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Sample records for 40-km time trial

  1. Ad-libitum drinking and performance during a 40-km cycling time trial in the heat.

    PubMed

    Berkulo, Meriam A R; Bol, Susan; Levels, Koen; Lamberts, Robert P; Daanen, Hein A M; Noakes, Timothy D

    2016-01-01

    The aim of this study was to investigate if drinking ad-libitum can counteract potential negative effects of a hypohydrated start caused by fluid restriction during a 40-km time trial (TT) in the heat. Twelve trained males performed one 40-km cycling TT euhydrated (EU: no water during the TT) and two 40-km cycling TTs hypohydrated. During one hypohydrated trial no fluid was ingested (HYPO), during the other trial ad-libitum water ingestion was allowed (FLUID). Ambient temperature was 35.2 ± 0.2 °C, relative humidity 51 ± 3% and airflow 7 m·s(-1). Body mass (BM) was determined at the start of the test, and before and after the TT. During the TT, power output, heart rate (HR), gastrointestinal temperature, mean skin temperature, rating of perceived exertion (RPE), thermal sensation, thermal comfort and thirst sensation were measured. Prior to the start of the TT, BM was 1.2% lower in HYPO and FLUID compared to EU. During the TT, BM loss in FLUID was lower compared to EU and HYPO (1.0 ± 0.8%, 2.7 ± 0.2% and 2.6 ± 0.3%, respectively). Hydration status had no effect on power output (EU: 223 ± 32 W, HYPO: 217 ± 39 W, FLUID: 224 ± 35 W), HR, gastrointestinal temperature, mean skin temperature, RPE, thermal sensation and thermal comfort. Thirst sensation was higher in HYPO than in EU and FLUID. It was concluded that hypohydration did not adversely affect performance during a 40-km cycling TT in the heat. Therefore, whether or not participants consumed fluid during exercise did not influence their TT performance. PMID:25675355

  2. Time-Domain Moment Tensors for shallow ( h ≤ 40 km) earthquakes in the broader Aegean Sea for the years 2006 and 2007: The database of the Aristotle University of Thessaloniki

    NASA Astrophysics Data System (ADS)

    Roumelioti, Zafeiria; Kiratzi, Anastasia; Benetatos, Christoforos

    2011-03-01

    We present a catalog of moment tensor (MT) solutions and moment magnitudes, Mw, for 119 shallow ( h ≤ 40 km) earthquakes in Greece and its surrounding lands (34°N-42°N, 19°E-30°E) for the years 2006 and 2007, computed with the 1D Time-Domain Moment Tensor inversion method (TDMT_INV code of Dreger, 2003). Magnitudes range from 3.2 ≤ Mw ≤ 5.7. Green's functions (GF) have been pre-computed to build a library, for a number of velocity profiles applicable to the broader Aegean Sea region, to be used in the inversion of observed broad band waveforms (10-50 s). All MT solutions are the outcome of a long series of tests of different reported source locations and hypocenter depths. Quality factors have been assigned to each MT solution based on the number of stations used in the inversion and the goodness of fit between observed and synthetic waveforms. In general, the focal mechanisms are compatible with previous knowledge on the seismotectonics of the Aegean area. The new data provide evidence for strike-slip faulting along NW-SE trending structures at the lower part of Axios basin, close to the heavily industrialized, and presently subsiding, region of the city of Thessaloniki. Normal faulting along E-W trending planes is observed at the Strimon basin, and in Orfanou Gulf in northern Greece. A sequence of events in the east Aegean Sea close to the coastline with western Anatolia sheds light on an active structure bounding the north coastline of Psara-Chios Islands about 20-25 km in length exhibiting right lateral strike-slip faulting.

  3. Estimating worldwide solar radiation resources on a 40km grid

    SciTech Connect

    Maxwell, E.L.; George, R.L.; Brady, E.H.

    1996-11-01

    During 1995, the National Renewable Energy Laboratory (NREL), initiated the Data Grid Task under the auspices of DOE`s Resource Assessment Program. A data grid is a framework of uniformly spaced locations (grid points) for which data are available. Estimates of monthly averages of direct normal, diffuse horizontal, and global horizontal daily-total solar radiation energy (kWh/m{sup 2}) are being made for each point on a grid covering the US, Mexico, the Caribbean, and southern Canada. The grid points are separated by approximately 40 km. Using interpolation methods, the digital data grid can be used to estimate solar resources at any location. The most encouraging result to date has been the location of sources providing worldwide data for most of the input parameters required for modeling daily total solar radiation. This is a multiyear task expected to continue through the rest of this century.

  4. Positive effect of lower body compression garments on subsequent 40-kM cycling time trial performance.

    PubMed

    de Glanville, Kieran M; Hamlin, Michael J

    2012-02-01

    This study aimed to investigate the effect of wearing graduated compression garments during recovery on subsequent 40-km time trial performance. In a randomized single-blind crossover experiment, 14 trained multisport male athletes (mean ± SD: age 33.8 ± 6.8 years, 40-km time 66:11 ± 2:10 minutes:seconds) were given a graduated full-leg-length compressive garment (76% Meryl Elastane, 24% Lycra) or a similar-looking noncompressive placebo garment (92% Polyester, 8% Spandex) to wear continuously for 24 hours after performing an initial 40-km time trial in their normal cycling attire. After the 24-hour recovery period, the compression (or placebo) garments were removed, and a second 40-km time trial was then completed to gauge the effect of each garment on subsequent performance. One week later, the groups were reversed and testing procedures repeated. The participant's hydration status, nutritional intake, and training were similar before each set of trials. Performance time in the second time trial was substantially improved with compression compared with placebo garments (1.2 ± 0.4%, mean ± 90% confidence interval). This improvement resulted in a substantially higher average power output after wearing the compression garment compared with that after wearing the placebo garment (3.3 ± 1.1%). Differences in oxygen cost and rating of perceived exertion between groups were trivial or unclear. The wearing of graduated compressive garments during recovery is likely to be worthwhile and unlikely to be harmful for well-trained endurance athletes. PMID:22240553

  5. Effects of magnitude and frequency of variations in external power output on simulated cycling time-trial performance.

    PubMed

    Wells, Marc; Atkinson, Greg; Marwood, Simon

    2013-01-01

    Mechanical models of cycling time-trial performance have indicated adverse effects of variations in external power output on overall performance times. Nevertheless, the precise influences of the magnitude and number of these variations over different distances of time trial are unclear. A hypothetical cyclist (body mass 70 kg, bicycle mass 10 kg) was studied using a mathematical model of cycling, which included the effects of acceleration. Performance times were modelled over distances of 4-40 km, mean power outputs of 200-600 W, power variation amplitudes of 5-15% and variation frequencies of 2-32 per time-trial. Effects of a "fast-start" strategy were compared with those of a constant-power strategy. Varying power improved 4-km performance at all power outputs, with the greatest improvement being 0.90 s for ± 15% power variation. For distances of 16.1, 20 and 40 km, varying power by ± 15% increased times by 3.29, 4.46 and 10.43 s respectively, suggesting that in long-duration cycling in constant environmental conditions, cyclists should strive to reduce power variation to maximise performance. The novel finding of the present study is that these effects are augmented with increasing event distance, amplitude and period of variation. These two latter factors reflect a poor adherence to a constant speed. PMID:23711074

  6. Design concepts for the first 40 km a key step for the space elevator

    NASA Astrophysics Data System (ADS)

    Knapman, John M.; Swan, Peter A.

    2014-11-01

    The Marine Node for the Space Elevator Infrastructure is the base for all activities to load and unload the cargo and climbers. As the basic design of the space elevator power system is solar power only, the first 40 km is hazardous to operations and demands enclosed packaging of fragile tether climbers. A significant question is: how do we place a full-up tether climber, driven by solar power, above the atmosphere? Two approaches, starting at the Marine Node, allow the tether climber to initiate the climb with solar energy above the atmosphere. The third viable approach is to provide a platform at altitude for initiation of tether climb. These approaches would enable solar power to be the source of energy for climbing. The three approaches are: Option One and Two: Marine Node (MN) Starting Location. MN - Box Protection - use boxes to protect the fragile solar panel and power the climber directly with a power extension cord to climb out of the atmosphere. MN - Spring Forward - use the characteristics of the elastic factor of the tether material. Option Three: High Stage One-develop a platform at altitude. Dangers for the space elevator during the first 40 km in altitude are discussed, and the options to deploy the tether climber and its solar arrays from the ocean surface to the desired altitude are explained.

  7. NCAR Global Climate Four-Dimensional Data Assimilation (CFDDA) Hourly 40 km Reanalysis: a high-resolution dynamically downscaled climatography

    NASA Astrophysics Data System (ADS)

    Peng, G. S.; Hou, C. Y.; Rife, D. L.; Dattore, R.

    2014-12-01

    Wind energy cost models incur inaccuracies from uncertainty in ambient wind measurements and estimates. This inhibits the best possible investment in wind energy infrastructure and management systems. High-resolution temporal and spatial wind data needed for wind availability analysis—usually created with regional-scale models—have traditionally been proprietary and costly to obtain. Freely available global model data suffers from either lower spatial or temporal resolution, or both. Low spatial resolution fails to realistically represent wind speeds in complex terrain. Low temporal resolution fails to capture the full diurnal cycle of wind behavior. The NCAR Global Climate Four-Dimensional Data Assimilation (CFDDA) Hourly 40 km Reanalysis was developed in 2009-2010 by the Research Applications Laboratory (RAL) to provide the most accurate boundary layer wind estimates available at that time. CFDDA used 28 sigma levels, with 19 between the surface and 700 hPa, a four-fold improvement over the contemporary NWP models. The dataset spans 21 years, 1985-2005, providing hourly atmospheric parameters, including winds, on 28 vertical levels on a global 40 km grid. This presentation will introduce the modeling and assimilation strategy, highlight the available data content including the parameter set, and review the data access options available from the RDA. CFDDA project partners, Defense Threat Reduction Agency (DTRA), NCAR RAL and NCAR Mesoscale & Microscale Meteorology (MMM) divisions are offering this dataset to the public for free with minor restrictions. NCAR Research Data Archive (RDA), hosted by the Computational and Information Systems Laboratory, provides data support. It is available at http://rda.ucar.edu/datasets/ds604.0/

  8. Full 40 km crustal reflection seismic datasets in several Indonesian basins

    NASA Astrophysics Data System (ADS)

    Dinkelman, M. G.; Granath, J. W.; Christ, J. M.; Emmet, P. A.; Bird, D. E.

    2010-12-01

    sedimentary and burial metamorphosed sedimentary rock that we divide into two packages on the basis of seismic character. The upper is 8-15 km of undeformed late Precambrian sediments the top of which ties Eocambrian rocks in wells in offshore New Guinea. This package appears to correlate to the Wessel Group in northern Australia. The lower package is composed of 10-15 km of strongly bedded, presumably burial metamorphosed rocks that make up the bulk of the lower crust. These may equate to any of a number of northern Australian Mesoproterozoic basins. This lower package offlaps ‘pods’ of seismically transparent basement (?Paleoproterozoic or Archean) that make up at most the lowermost 15 km of the 40 km PSDM line. Both Precambrian packages appear to be craton-margin sedimentary wedges, the younger overlapping the older. The SE extent of the lowermost package is deformed in a thrust system which may mark the event that detached it from its original underlying oceanic or transitional crust during cratonization. The SPAN programs are important new data sets to clarify and in some cases solve outstanding problems in basin architecture and tectonic evolution.

  9. Pure Rotational Raman Lidar for Temperature Measurements from 5-40 Km Over Wuhan, China

    NASA Astrophysics Data System (ADS)

    Li, Yajuan; Song, Shalei; Yang, Yong; Li, Faquan; Cheng, Xuewu; Chen, Zhenwei; Liu, Linmei; McCormick, M. Patrick; Gong, Shunsheng

    2016-06-01

    In this paper a pure rotational Raman lidar (PRR) was established for the atmospheric temperature measurements from 5 km to 40 km over Wuhan, China (30.5°N, 114.5°E). To extract the expected PRR signals and simultaneously suppress the elastically backscattered light, a high-spectral resolution polychromator for light splitting and filtering was designed. Observational results revealed that the temperature difference measured by PRR lidar and the local radiosonde below 30 km was less than 3.0 K. The good agreement validated the reliability of the PRR lidar. With the 1-h integration and 150-m spatial resolution, the statistical temperature error for PRR lidar increases from 0.4 K at 10 km up to 4 K at altitudes of about 30 km. In addition, the whole night temperature profiles were obtained for study of the long-term observation of atmospheric fluctuations.

  10. Exhumation of an unusually large, ~3000 km3 coherent block of oceanic crust from >40 km depth

    NASA Astrophysics Data System (ADS)

    Barrow, Wendy; Metcalf, Rodney; Fairhurst, Robert

    2010-05-01

    The Central Metamorphic terrane (CMt) is an unusually large (~3000 km3) coherent block of mid-ocean ridge (MOR) metabasites; the first one of this scale reported with eclogite facies relicts, decompression assemblages, and thermobarometry indicating exhumation of the entire block from >40 km depth. The CMt is exposed in the eastern Klamath Mountains of northern California and is dominantly an amphibolite facies metabasite which represents remnant oceanic crust subducted in a mid-Paleozoic Pacific-type margin. Thermochronology indicates that the CMt was subsequently exhumed along the Trinity fault during an early Permian extensional event. Newly discovered relict textures with new thermobarometry results suggest the CMt metabasites record the retrograde segment of the P-T-deformation-time path during exhumation from hornblende eclogite facies P-T conditions. A decompression and cooling sequence consisting of rutile cores within ilmenite crystals mantled by titanite is observed in CMt amphibolite samples. Zr-in-rutile thermometry combined with experimental data for rutile stability in metabasites suggests that relict rutile crystals preserve early P-T conditions of ~600° C and >1.3 GPa. Transition from eclogite facies is further supported by ilmenite-plagioclase-amphibole symplectites suggesting replacement of garnet or omphacite during decompression. The dominant mineral assemblages and metamorphic fabrics indicate dynamic recrystallization of metabasites during declining P-T conditions through amphibolite - epidote amphibolite facies. Exhumation via extension along the Trinity fault is suggested by the coplanar relationship between metabasite decompression-related deformation fabrics and the Trinity fault. We propose that subducted oceanic crust (CMt) was subsequently exhumed as a large coherent block from depths >40 km. This is significant because the conversion of mafic oceanic crust to eclogite produces the negative buoyancy (relative to mantle peridotite) that

  11. 28 Gb/s duobinary signal transmission over 40 km based on 10 GHz DML and PIN for 100 Gb/s PON.

    PubMed

    Li, Zhengxuan; Yi, Lilin; Wang, Xiaodong; Hu, Weisheng

    2015-08-10

    In this paper, we demonstrate the direct modulation and direct detection of 28-Gb/s duobinary signal for the future downstream capacity upgrade in next generation passive optical network (PON). Commercial 10-GHz directly modulated laser (DML) and PIN with a combined modulation bandwidth of ~7 GHz are used as transmitter and receiver respectively. In order to mitigate the chromatic dispersion induced signal distortion, an optical delay interferometer (DI) is employed to narrow down the signal spectrum, thereby realizing 40-km single mode fiber (SMF) transmission in C-band. Besides, the chirp-induced spectral broadening of the directly modulated signal enables a higher launch power than external modulation schemes, which increases the loss budget of the system. As a result, 31-dB loss budget is achieved, supporting 64 users with 40-km reach. Also, as the transceivers in both optical line terminal (OLT) and optical network unit (ONU) are commercial l0-GHz devices, the proposed scheme is compatible with 40-Gb/s time and wavelength division multiplexing passive optical network (TWDM-PON) systems, providing a cost-efficient alternative for the development of 100G PON. PMID:26367880

  12. Scaling maximal oxygen uptake to predict cycling time-trial performance in the field: a non-linear approach.

    PubMed

    Nevill, A M; Jobson, S A; Palmer, G S; Olds, T S

    2005-08-01

    The purpose of the present article is to identify the most appropriate method of scaling VO2max for differences in body mass when assessing the energy cost of time-trial cycling. The data from three time-trial cycling studies were analysed (N = 79) using a proportional power-function ANCOVA model. The maximum oxygen uptake-to-mass ratio found to predict cycling speed was VO2max(m)(-0.32) precisely the same as that derived by Swain for sub-maximal cycling speeds (10, 15 and 20 mph). The analysis was also able to confirm a proportional curvilinear association between cycling speed and energy cost, given by (VO2max(m)(-0.32))0.41. The model predicts, for example, that for a male cyclist (72 kg) to increase his average speed from 30 km h(-1) to 35 km h(-1), he would require an increase in VO2max from 2.36 l min(-1) to 3.44 l min(-1), an increase of 1.08 l min(-1). In contrast, for the cyclist to increase his mean speed from 40 km h(-1) to 45 km h(-1), he would require a greater increase in VO2max from 4.77 l min(-1) to 6.36 l min(-1), i.e. an increase of 1.59 l min(-1). The model is also able to accommodate other determinants of time-trial cycling, e.g. the benefit of cycling with a side wind (5% faster) compared with facing a predominately head/tail wind (P<0.05). Future research could explore whether the same scaling approach could be applied to, for example, alternative measures of recording power output to improve the prediction of time-trial cycling performance. PMID:15906080

  13. Timing and Completeness of Trial Results Posted at ClinicalTrials.gov and Published in Journals

    PubMed Central

    Riveros, Carolina; Dechartres, Agnes; Perrodeau, Elodie; Haneef, Romana; Boutron, Isabelle; Ravaud, Philippe

    2013-01-01

    Background The US Food and Drug Administration Amendments Act requires results from clinical trials of Food and Drug Administration–approved drugs to be posted at ClinicalTrials.gov within 1 y after trial completion. We compared the timing and completeness of results of drug trials posted at ClinicalTrials.gov and published in journals. Methods and Findings We searched ClinicalTrials.gov on March 27, 2012, for randomized controlled trials of drugs with posted results. For a random sample of these trials, we searched PubMed for corresponding publications. Data were extracted independently from ClinicalTrials.gov and from the published articles for trials with results both posted and published. We assessed the time to first public posting or publishing of results and compared the completeness of results posted at ClinicalTrials.gov versus published in journal articles. Completeness was defined as the reporting of all key elements, according to three experts, for the flow of participants, efficacy results, adverse events, and serious adverse events (e.g., for adverse events, reporting of the number of adverse events per arm, without restriction to statistically significant differences between arms for all randomized patients or for those who received at least one treatment dose). From the 600 trials with results posted at ClinicalTrials.gov, we randomly sampled 50% (n = 297) had no corresponding published article. For trials with both posted and published results (n = 202), the median time between primary completion date and first results publicly posted was 19 mo (first quartile = 14, third quartile = 30 mo), and the median time between primary completion date and journal publication was 21 mo (first quartile = 14, third quartile = 28 mo). Reporting was significantly more complete at ClinicalTrials.gov than in the published article for the flow of participants (64% versus 48% of trials, p<0.001), efficacy results (79% versus 69%, p = 0

  14. Polycyclic aromatic hydrocarbons in the airborne particulate matter at a location 40 km north of Bangkok, Thailand

    NASA Astrophysics Data System (ADS)

    Kim Oanh, N. T.; Bætz Reutergårdh, L.; Dung, N. Tr.; Yu, M.-H.; Yao, W.-X.; Co, H. X.

    Total suspended particulate matter in ambient air was sampled by high-volume samplers at four sites at the Asian Institute of Technology campus, west of the Phahonyothin Road, Phathumthani Province, 40 km North of Bangkok, Thailand. The concentrations of 18 polycyclic aromatic hydrocarbons (PAH), were measured by gas chromatography with flame ionisation and/or liquid chromatography with fluorescence detection. The PAH profile with relatively high concentrations of benzo(ghi)perylene and coronene, decreasing with the distance from the road, suggested a substantial contribution from the traffic. The concentrations in the core of the campus were in the same range as those reported for residential areas in the Bangkok Metropolitan.

  15. Discovering New Global Climate Patterns: Curating a 21-Year High Temporal (Hourly) and Spatial (40km) Resolution Reanalysis Dataset

    NASA Astrophysics Data System (ADS)

    Hou, C. Y.; Dattore, R.; Peng, G. S.

    2014-12-01

    The National Center for Atmospheric Research's Global Climate Four-Dimensional Data Assimilation (CFDDA) Hourly 40km Reanalysis dataset is a dynamically downscaled dataset with high temporal and spatial resolution. The dataset contains three-dimensional hourly analyses in netCDF format for the global atmospheric state from 1985 to 2005 on a 40km horizontal grid (0.4°grid increment) with 28 vertical levels, providing good representation of local forcing and diurnal variation of processes in the planetary boundary layer. This project aimed to make the dataset publicly available, accessible, and usable in order to provide a unique resource to allow and promote studies of new climate characteristics. When the curation project started, it had been five years since the data files were generated. Also, although the Principal Investigator (PI) had generated a user document at the end of the project in 2009, the document had not been maintained. Furthermore, the PI had moved to a new institution, and the remaining team members were reassigned to other projects. These factors made data curation in the areas of verifying data quality, harvest metadata descriptions, documenting provenance information especially challenging. As a result, the project's curation process found that: Data curator's skill and knowledge helped make decisions, such as file format and structure and workflow documentation, that had significant, positive impact on the ease of the dataset's management and long term preservation. Use of data curation tools, such as the Data Curation Profiles Toolkit's guidelines, revealed important information for promoting the data's usability and enhancing preservation planning. Involving data curators during each stage of the data curation life cycle instead of at the end could improve the curation process' efficiency. Overall, the project showed that proper resources invested in the curation process would give datasets the best chance to fulfill their potential to

  16. How Have Cancer Clinical Trial Eligibility Criteria Evolved Over Time?

    PubMed Central

    Yaman, Anil; Chakrabarti, Shreya; Sen, Anando; Weng, Chunhua

    2016-01-01

    Knowledge reuse of cancer trial designs may benefit from a temporal understanding of the evolution of the target populations of cancer studies over time. Therefore, we conducted a retrospective analysis of the trends of cancer trial eligibility criteria between 1999 and 2014. The yearly distributions of eligibility concepts for chemicals and drugs, procedures, observations, and medical conditions extracted from free-text eligibility criteria of 32,000 clinical trials for 89 cancer types were analyzed. We identified the concepts that trend upwards or downwards in all or selected cancer types, and the concepts that show anomalous trends for some cancers. Later, concept trends were studied in a disease-specific manner and illustrated for breast cancer. Criteria trends observed in this study are also validated and interpreted using evidence from the existing medical literature. This study contributes a method for concept trend analysis and original knowledge of the trends in cancer clinical trial eligibility criteria.

  17. How Have Cancer Clinical Trial Eligibility Criteria Evolved Over Time?

    PubMed

    Yaman, Anil; Chakrabarti, Shreya; Sen, Anando; Weng, Chunhua

    2016-01-01

    Knowledge reuse of cancer trial designs may benefit from a temporal understanding of the evolution of the target populations of cancer studies over time. Therefore, we conducted a retrospective analysis of the trends of cancer trial eligibility criteria between 1999 and 2014. The yearly distributions of eligibility concepts for chemicals and drugs, procedures, observations, and medical conditions extracted from free-text eligibility criteria of 32,000 clinical trials for 89 cancer types were analyzed. We identified the concepts that trend upwards or downwards in all or selected cancer types, and the concepts that show anomalous trends for some cancers. Later, concept trends were studied in a disease-specific manner and illustrated for breast cancer. Criteria trends observed in this study are also validated and interpreted using evidence from the existing medical literature. This study contributes a method for concept trend analysis and original knowledge of the trends in cancer clinical trial eligibility criteria. PMID:27570681

  18. Diet, lifestyle, and nonstatin trials: review of time to benefit.

    PubMed

    Denke, Margo A

    2005-09-01

    How rapidly benefits accrue from nonstatin, lipid-lowering therapies is a 21st-century question posed to data collected in the 20th century. The 3 early dietary trials conducted in institutional settings where diet was strictly controlled demonstrate that, compared with a control diet, cholesterol-lowering diets reduce coronary event rates over several years. These data do not reveal whether a more homogeneous high-risk population would demonstrate an earlier time to benefit. Dietary counseling trials of men with coronary disease conducted in the 1950s and 1960s failed to demonstrate a consistent benefit from dietary therapy, in part because of confounding factors from methodologic flaws in trial design. By the 1980s and 1990s, improvements in trial design, such as larger numbers of subjects, control of confounding risk factors, and limiting trial end points to those directly attributable to atherosclerotic events, were in place. Subsequently, 5 randomized clinical trials showed a consistent benefit of dietary therapy, with significant reductions by 1 to 2 years in fatal events, nonfatal events, and total mortality; 2 of these studies, each including omega-3 fatty acids as part of the dietary intervention, reported a rapid and significant time to benefit (within 3 to 6 months). Additional lifestyle benefits of cardiac rehabilitation (a surrogate for physical activity) and smoking cessation clearly show long-term benefit at 1 and 5 years, respectively. Nonstatin drug and surgical therapies either have shown no significant benefit (estrogen, dextrothyroxine) or benefit after 1 to 5 years of therapy (intestinal bypass surgery, cholestyramine, clofibrate, niacin, and a combination of niacin and clofibrate). In conclusion, rapid time to benefit has been observed in older lifestyle and nonstatin trials that have included omega-3 fatty acids as a component of dietary therapy. Lifestyle changes in diet, physical activity, weight loss, and smoking cessation remain important

  19. Anatomy of an ancient subduction interface at 40 km depth: Insights from P-T-t-d data, and geodynamic implications (Dent Blanche, Western Alps)

    NASA Astrophysics Data System (ADS)

    Angiboust, Samuel; Glodny, Johannes; Oncken, Onno; Chopin, Christian

    2014-05-01

    An exhumed metamorphic suture zone over 40 km long is exposed in the Dent Blanche Region of the Western Alps belt, along the Swiss-Italian border. In this region, the metasediment-bearing ophiolitic remnants of the Liguro-Piemontese ocean (Tsaté complex) are overthrusted by a continental, km-sized complex (Dent Blanche Tectonic System: DBTS) of Austro-Alpine affinity. The DBTS represents a strongly deformed composite terrane with independent tectonic slices of continental and oceanic origin. In order to better understand the nature and the geodynamic meaning of the shear zone at the base of the DBTS (Dent Blanche Thrust, DBT) we re-evaluated the pressure-temperature-time-deformation (P-T-t-d) history of these two units using modern thermobarometric tools, Rb/Sr deformation ages and field relationships. Our results show that the Tsaté complex is formed by a stack of km-thick calcschists-bearing tectonic slices, having experienced variable maximum burial temperatures of between 360°C and 490°C at depths of ca. 25-40 km, between 41 Ma and 37 Ma. The Arolla gneissic mylonites constituting the base of the DBTS experienced a continuous record of protracted high-pressure (12-14 kbar), top-to-NW D1 deformation at 450-500°C between 43 and 55 Ma. Some of these primary, peak metamorphic fabrics have been sheared (top-to-SE D2) and backfolded during exhumation and collisional overprint (20 km depth, 35-40 Ma) leading to the regional greenschist facies retrogression particularly prominent within Tsaté metasediments. The final juxtaposition of the DBTS with the Tsaté complex occurred between 350 and 500°C during this later, exhumation-related D2 event. Although some exhumation-related deformation partially reworked D1 primary features, we emphasize that the DBT can be viewed as a remnant of the Alpine early Eocene blueschist-facies subduction interface region. The DBT therefore constitutes the deeper equivalent of some shallower portions of the Alpine subduction

  20. Time to prerandomization monthly seizure count in perampanel trials

    PubMed Central

    Gil-Nagel, Antonio; Malerba, Stefano; Kramer, Lynn; Kumar, Dinesh; Bagiella, Emilia

    2015-01-01

    Objective: To determine whether a novel endpoint of time to prerandomization monthly seizure count could be used to differentiate efficacious and nonefficacious therapies in clinical trials of new add-on antiepileptic drugs (AEDs). Methods: This analysis used data from 3 randomized, double-blind, placebo-controlled phase III trials of perampanel as an add-on therapy in patients with epilepsy who were experiencing refractory partial seizures: studies 304 (ClinicalTrials.gov identifier NCT00699972), 305 (NCT00699582), and 306 (NCT00700310). Time to prerandomization monthly seizure count was evaluated post hoc for each trial, and findings were compared with the original primary outcomes (median percent change in seizure frequency and 50% responder rate). Outcomes were assessed for all partial-onset seizures, secondarily generalized (SG) tonic-clonic seizures only, and complex partial plus SG (CP + SG) seizures. Results: Perampanel 4–12 mg significantly prolonged median time to prerandomization monthly seizure count, generally by more than 1 week, compared with placebo, across all 3 studies, consistent with the original primary outcomes. Analysis of SG seizures only, and CP + SG seizures, also indicated a significantly prolonged median time to prerandomization monthly seizure count with perampanel 8 mg and 12 mg compared with placebo. Conclusions: Time to prerandomization monthly seizure count is a promising novel alternative to the standard endpoints of median percent change in seizure frequency and 50% responder rates used in trials of add-on AEDs. Use of this endpoint could reduce exposure to placebo or ineffective treatments, thereby facilitating trial recruitment and improving safety. PMID:25878175

  1. Effects of differentiated music on cycling time trial.

    PubMed

    Lim, H B T; Atkinson, G; Karageorghis, C I; Eubank, M R; Eubank, M M

    2009-06-01

    The aim of this study was to investigate the effects of music introduced and removed during a 10-km cycling time trial with reference to Rejeski's parallel processing theory and Karageorghis, Terry and Lane's conceptual framework for the prediction of responses to asynchronous music during sub-maximal exercise. A range of performance variables, ratings of perceived exertion, positive affect, negative affect, and blood lactate were assessed. Eleven males (mean age=24.9, s=6.1 years) completed a 10-km time trial under three conditions; no music, music played initially then removed between 5-10 km, and music played between 5-10 km only. Variables of time, power, cadence, speed, RPE, blood lactate, positive and negative affect were analysed using a ConditionxDistance ANOVA. There was no significant main effect for music conditions for the performance variables, perceived exertion, blood lactate, and affect (p>0.05). Nevertheless, a significant interaction effect for ConditionxDistance was found for cycling speed, with participants cycling 1-1.25 km/h faster at the start of the music introduced time trial than in both the music removed and no music time trials (p<0.05). The results indicate that performance and affect during a 10 km time trial are influenced by the introduction and/or removal of music during exercise and this finding can be used to extend current theory as it does not specifically address the periodic use music. The fact that participants exercised harder when they expected music to be introduced at a later stage illustrates the behavioural influences that music can engender during self-paced exercise. PMID:19199201

  2. Time Trials--An AP Physics Challenge Lab

    ERIC Educational Resources Information Center

    Jones, David

    2009-01-01

    I have come to the conclusion that for high school physics classroom and laboratory experiences, simpler is better! In this paper I describe a very simple and effective lab experience that my AP students have thoroughly enjoyed year after year. I call this lab exercise "Time Trials." The experiment is simple in design and it is a lot of fun for…

  3. Effect of Overhydration on Time-Trial Swim Performance.

    ERIC Educational Resources Information Center

    Maresh, Carl M.; Bergeron, Michael E.; Kenefick, Robert W.; Castellani, John W.; Hoffman, Jay R.; Armstrong, Lawrence E.

    2001-01-01

    Examined whether moderate overhydration would enhance the performance of otherwise euhydrated collegiate swimmers during two 183-meter time-trial swims held 3 days apart. Participants swam in alternate, randomized euhydrated, and overhydrated states. Results indicated that euhydration before an intense, short-duration swim was adequate for peak…

  4. Driving mechanisms for >40 km of exhumation during contraction and extension in a continental arc, Cascades core, Washington

    USGS Publications Warehouse

    Paterson, S.R.; Miller, R.B.; Alsleben, H.; Whitney, D.L.; Valley, P.M.; Hurlow, H.

    2004-01-01

    In the NW North American Cordillera, the Cascades core region of the Coast Plutonic Complex underwent Late Cretaceous (>96 Ma to locally 73 Ma) SW-NE contraction and crustal thickening followed by dextral transpression (???73 to 55 Ma), then transtension (3 mm /yr) by local thrusting in regions undergoing crustal thickening. In the central part of the core (Chelan block), >40 km of exhumation occurred between 91 and 45 Ma, about half of which occurred during early contraction (driven by thrusting) and half during top-to-north, arc-oblique shear during reactivation of a midcrustal Cretaceous thrust, the Dinkelman decollement. The footwall of this thrust consists of the Swakane Biotite Gneiss, a Cretaceous, metaclastic assemblage with recorded pressures of 10-12 kbar, no arc-related magmatism, and structures dominated by pervasive top-to-north shearing. The hanging wall consists of the Napeequa Complex, an oceanic assemblage with recorded pressures of 6-12 kbar, voluminous arc-related magmatism, and complex structures indicating early top-to-WSW shearing, younger top-to-north shearing, and widespread folding. In the Napeequa, top-to-north shearing started by 73 Ma during melt-present conditions at pressures ???6 kbar. Top-to-north shearing in both hanging wall and footwall continued during exhumation (???1.6 mm/yr) and cooling to greenschist facies conditions during which slip became increasingly localized, eventually resulting in formation of pseudotachylite on discrete slip surfaces. We suggest that arc-oblique extension was driven by along-arc heterogeneity in displacements/ erosion, initially during transpression and underplating of continental sediments, and later during transtension. Copyright 2004 by the American Geophysical Union.

  5. A new global meso-beta-scale (40 km) downscaled climatography: Improving decision making for societal and ecological applications

    NASA Astrophysics Data System (ADS)

    Rife, D.

    2009-12-01

    NCAR’s Research Applications Laboratory has developed a new global climatography for emergency management applications and renewable energy applications. The dataset consists of 21 years of hourly, global dynamically-downscaled reanalyses (40 km grid increment) from 1985 to 2005. The downscaling was performed with NCAR’s Climate Four Dimensional Data Assimilation System (ClimoFDDA), which was originally based upon the Penn State/NCAR MM5 model, and is now based on NCAR’s WRF Model. For the 21-year climatography presented herein, ClimoFDDA used global-scale data from the NCEP-DOE Reanalysis, standard surface and upper observations, and satellite-derived estimates of winds, temperature, and humidity to downscale the global climate information to meso-beta-scale, while fully accounting for topographic variations and surface characteristics (e.g., crop lands, lakes, dense urban areas, etc.). The presenter will describe the motivation, technical approach, and characteristics of this unique dataset. He will then show several examples of this dataset's utility for greatly enhancing decision making for renewable energy applications and emergency management applications, including: (a) assessing the interannual variability of wind power generation potential, (b) evaluating weather extremes (worst and best case scenarios), (c) relative frequency (return period) of winds at “operationally significant” thresholds, (d) wind climatographies at remote locations (distant from observation stations), (e) “regime-appropriate” uncertainty estimates that account for the variability of weather patterns, and (f) the diurnal constancy of winds at any point on the globe. This re-analysis dataset provides a new opportunity to address basic questions for an array of socioeconomic and ecological applications that were previously out of reach due to the coarse-scale representation (both spatial and temporal) of previous datasets.

  6. Driving mechanisms for >40 km of exhumation during contraction and extension in a continental arc, Cascades core, Washington

    NASA Astrophysics Data System (ADS)

    Paterson, Scott R.; Miller, Robert B.; Alsleben, Helge; Whitney, Donna L.; Valley, Peter M.; Hurlow, Hugh

    2004-06-01

    In the NW North American Cordillera, the Cascades core region of the Coast Plutonic Complex underwent Late Cretaceous (>96 Ma to locally 73 Ma) SW-NE contraction and crustal thickening followed by dextral transpression (˜73 to 55 Ma), then transtension (<55 Ma). Exhumation occurred during all three phases. During contraction, slow exhumation (˜0.6 mm/yr) occurred along the margins of the core, driven by isostatic rebound and erosion, and faster exhumation (>3 mm/yr) by local thrusting in regions undergoing crustal thickening. In the central part of the core (Chelan block), >40 km of exhumation occurred between 91 and 45 Ma, about half of which occurred during early contraction (driven by thrusting) and half during top-to-north, arc-oblique shear during reactivation of a midcrustal Cretaceous thrust, the Dinkelman decollement. The footwall of this thrust consists of the Swakane Biotite Gneiss, a Cretaceous, metaclastic assemblage with recorded pressures of 10-12 kbar, no arc-related magmatism, and structures dominated by pervasive top-to-north shearing. The hanging wall consists of the Napeequa Complex, an oceanic assemblage with recorded pressures of 6-12 kbar, voluminous arc-related magmatism, and complex structures indicating early top-to-WSW shearing, younger top-to-north shearing, and widespread folding. In the Napeequa, top-to-north shearing started by 73 Ma during melt-present conditions at pressures ≥6 kbar. Top-to-north shearing in both hanging wall and footwall continued during exhumation (˜1.6 mm/yr) and cooling to greenschist facies conditions during which slip became increasingly localized, eventually resulting in formation of pseudotachylite on discrete slip surfaces. We suggest that arc-oblique extension was driven by along-arc heterogeneity in displacements/erosion, initially during transpression and underplating of continental sediments, and later during transtension.

  7. The effects of caffeinated "energy shots" on time trial performance.

    PubMed

    Schubert, Matthew Mark; Astorino, Todd Anthony; Azevedo, John Leal

    2013-06-01

    An emerging trend in sports nutrition is the consumption of energy drinks and "energy shots". Energy shots may prove to be a viable pre-competition supplement for runners. Six male runners (mean ± SD age and VO2max: 22.5 ± 1.8 years and 69.1 ± 5.7 mL·kg-1·min-1) completed three trials [placebo (PLA; 0 mg caffeine), Guayakí Yerba Maté Organic Energy Shot™ (YM; 140 mg caffeine), or Red Bull Energy Shot™ (RB; 80 mg caffeine)]. Treatments were ingested following a randomized, placebo-controlled crossover design. Participants ran a five kilometer time trial on a treadmill. No differences (p > 0.05) in performance were detected with RB (17.55 ± 1.01 min) or YM ingestion (17.86 ± 1.59 min) compared to placebo (17.44 ± 1.25 min). Overall, energy shot ingestion did not improve time-trial running performance in trained runners. PMID:23743969

  8. Investigation of fiber dispersion impairment in 400GbE discrete multi-tone system for reach enhancement up to 40 km

    NASA Astrophysics Data System (ADS)

    Okabe, Ryo; Tanaka, Toshiki; Nishihara, Masato; Kai, Yutaka; Takahara, Tomoo; Chen, Hao; Yan, Weizhen; Tao, Zhenning; Rasmussen, Jens C.

    2015-01-01

    Discrete multi-tone (DMT) technology is an attractive modulation technique for short reach optical transmission system. One of the main factors that limit system performance is fiber dispersion, which is strongly influenced by the chirp characteristics of transmitters. We investigated the fiber dispersion impairment in a 400GbE (4 × 116.1-Gb/s) DMT system on LAN-WDM grid for reach enhancement up to 40 km through experiments and numerical simulations.

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

    PubMed

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

    2016-07-01

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

  10. Hemofiltration treatment for sepsis: is it time for controlled trials?

    PubMed

    Rogiers, P

    1999-11-01

    While the use of hemofiltration to treat septic shock has potential benefits, the existing studies are difficult to compare because of their variety of inclusion criteria. The concept is to remove the various mediators of severe sepsis and septic shock, such as cytokines and eicosanoids, so that acute renal failure and the resultant multi-organ failure and possible death can be delayed or prevented. The dilemmas include: (a) hemofiltration cannot distinguish between these pro-inflammatory mediators as they are of similar molecular weights, and thus it is difficult to determine which one or combination should be eliminated for the best hemodynamics; (b) timing of the hemofiltration to remove a particular cytokine may make a difference in patient outcome; (c) the most efficacious convection rate of ultrafiltration has not been determined yet; (d) since these mediators quickly saturate the membrane, it should be frequently changed, and thus biocompatibility, availability and costs are added issues; (e) the choice of buffer is different according to the diagnosis of these critically ill patients. Before designing clinical trials, further experimentation is necessary to explore these problems. PMID:10560816

  11. Age-related differences in the neural correlates of trial-to-trial variations of reaction time.

    PubMed

    Adleman, Nancy E; Chen, Gang; Reynolds, Richard C; Frackman, Anna; Razdan, Varun; Weissman, Daniel H; Pine, Daniel S; Leibenluft, Ellen

    2016-06-01

    Intra-subject variation in reaction time (ISVRT) is a developmentally-important phenomenon that decreases from childhood through young adulthood in parallel with the development of executive functions and networks. Prior work has shown a significant association between trial-by-trial variations in reaction time (RT) and trial-by-trial variations in brain activity as measured by the blood-oxygenated level-dependent (BOLD) response in functional magnetic resonance imaging (fMRI) studies. It remains unclear, however, whether such "RT-BOLD" relationships vary with age. Here, we determined whether such trial-by-trial relationships vary with age in a cross-sectional design. We observed an association between age and RT-BOLD relationships in 11 clusters located in visual/occipital regions, frontal and parietal association cortex, precentral/postcentral gyrus, and thalamus. Some of these relationships were negative, reflecting increased BOLD associated with decreased RT, manifesting around the time of stimulus presentation and positive several seconds later. Critically for present purposes, all RT-BOLD relationships increased with age. Thus, RT-BOLD relationships may reflect robust, measurable changes in the brain-behavior relationship across development. PMID:27239972

  12. Statistical Frequency-Dependent Analysis of Trial-to-Trial Variability in Single Time Series by Recurrence Plots

    PubMed Central

    Tošić, Tamara; Sellers, Kristin K.; Fröhlich, Flavio; Fedotenkova, Mariia; beim Graben, Peter; Hutt, Axel

    2016-01-01

    For decades, research in neuroscience has supported the hypothesis that brain dynamics exhibits recurrent metastable states connected by transients, which together encode fundamental neural information processing. To understand the system's dynamics it is important to detect such recurrence domains, but it is challenging to extract them from experimental neuroscience datasets due to the large trial-to-trial variability. The proposed methodology extracts recurrent metastable states in univariate time series by transforming datasets into their time-frequency representations and computing recurrence plots based on instantaneous spectral power values in various frequency bands. Additionally, a new statistical inference analysis compares different trial recurrence plots with corresponding surrogates to obtain statistically significant recurrent structures. This combination of methods is validated by applying it to two artificial datasets. In a final study of visually-evoked Local Field Potentials in partially anesthetized ferrets, the methodology is able to reveal recurrence structures of neural responses with trial-to-trial variability. Focusing on different frequency bands, the δ-band activity is much less recurrent than α-band activity. Moreover, α-activity is susceptible to pre-stimuli, while δ-activity is much less sensitive to pre-stimuli. This difference in recurrence structures in different frequency bands indicates diverse underlying information processing steps in the brain. PMID:26834580

  13. Frequency-specific coupling between trial-to-trial fluctuations of neural responses and response-time variability.

    PubMed

    Adamo, Nicoletta; Baumeister, Sarah; Hohmann, Sarah; Wolf, Isabella; Holz, Nathalie; Boecker, Regina; Laucht, Manfred; Banaschewski, Tobias; Brandeis, Daniel

    2015-08-01

    We assessed intra-individual variability of response times (RT) and single-trial P3 amplitudes following targets in healthy adults during a Flanker/NO-GO task. RT variability and variability of the neural responses coupled at the faster frequencies examined (0.07-0.17 Hz) at Pz, the target-P3 maxima, despite non-significant associations for overall variability (standard deviation, SD). Frequency-specific patterns of variability in the single-trial P3 may help to understand the neurophysiology of RT variability and its explanatory models of attention allocation deficits beyond intra-individual variability summary indices such as SD. PMID:25724293

  14. Time-Lag Bias in Trials of Pediatric Antidepressants: A Systematic Review and Meta-Analysis

    PubMed Central

    Reyes, Magdalena M.; Panza, Kaitlyn E.; Martin, Andrés; Bloch, Michael H.

    2013-01-01

    Objective To determine if there is evidence of a time-lag bias in the publication of pediatric antidepressant trials. Method We conducted a meta-analysis of published and unpublished randomized, placebo-controlled trials of serotonin reuptake inhibitors (SRIs) in subjects less than 18 years old with major depressive disorder. Our main outcomes were (1) time to publication of positive versus negative trials, and (2) proportion of treatment responders in trials with standard (< 3 years after study completion) versus delayed publication. Results We identified 15 randomized, placebo-controlled trials of SRIs for pediatric depression. Trials with negative findings had a significantly longer time to publication (median years ± standard deviation = 4.2 ±1.9) than trials with positive findings (2.2 ±0.9; log-rank χ2 = 4.35, p = 0.037). The estimated efficacy in trials with standard publication time (number needed to treat = 7, 95% CI: 5 – 11) was significantly greater than those with delayed publication (17, 95% CI: 9 – ∞; χ2 = 4.98, p = 0.025). The inflation-adjusted impact factor of journals for published trials with positive (15.33 ±11.01) and negative results (7.54 ±7.90) did not statistically differ (t = 1.4, df = 10, p = 0.17). Conclusions Despite a small number of trials of SRIs for pediatric antidepressants we found a significant evidence of time-lag bias in the publication of findings. This time-lag bias altered the perceived efficacy of pediatric antidepressants in the medical literature. Time-lag bias is not unique to child psychiatry and reflects a larger problem in scientific publishing. PMID:21156271

  15. Time-Lag Bias in Trials of Pediatric Antidepressants: A Systematic Review and Meta-Analysis

    ERIC Educational Resources Information Center

    Reyes, Magdalena M.; Panza, Kaitlyn E.; Martin, Andres; Bloch, Michael H.

    2011-01-01

    Objective: To determine whether there is evidence of a time-lag bias in the publication of pediatric antidepressant trials. Method: We conducted a meta-analysis of published and unpublished randomized placebo-controlled trials of serotonin reuptake inhibitors (SRIs) in subjects less than 18 years of age with major depressive disorder. Our main…

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

    PubMed

    Pierce, Jordan E; McDowell, Jennifer E

    2016-02-01

    Cognitive control optimizes responses to relevant task conditions by balancing bottom-up stimulus processing with top-down goal pursuit. It can be investigated using the ocular motor system by contrasting basic prosaccades (look toward a stimulus) with complex antisaccades (look away from a stimulus). Furthermore, the amount of time allotted between trials, the need to switch task sets, and the time allowed to prepare for an upcoming saccade all impact performance. In this study the relative probabilities of anti- and pro-saccades were manipulated across five blocks of interleaved trials, while the inter-trial interval and trial type cue duration were varied across subjects. Results indicated that inter-trial interval had no significant effect on error rates or reaction times (RTs), while a shorter trial type cue led to more antisaccade errors and faster overall RTs. Responses following a shorter cue duration also showed a stronger effect of trial type probability, with more antisaccade errors in blocks with a low antisaccade probability and slower RTs for each saccade task when its trial type was unlikely. A longer cue duration yielded fewer errors and slower RTs, with a larger switch cost for errors compared to a short cue duration. Findings demonstrated that when the trial type cue duration was shorter, visual motor responsiveness was faster and subjects relied upon the implicit trial probability context to improve performance. When the cue duration was longer, increased fixation-related activity may have delayed saccade motor preparation and slowed responses, guiding subjects to respond in a controlled manner regardless of trial type probability. PMID:26829023

  17. Using data of gradient magnetic surveys at altitudes of 20-40 km for the analysis of map errors and models of the geomagnetic field

    NASA Astrophysics Data System (ADS)

    Brekhov, Oleg; Tsvetkov, Yury

    2016-07-01

    Gradient geomagnetic survey at altitudes of 20-40 km from the board of stratospheric balloon have a high degree of accuracy. The data of the geomagnetic field (GMF), obtained with the help of high-precision proton magnetometer and GPS navigation receivers, are considered as a benchmark for the analysis of geomagnetic data. Gradient magnetic data is obtained by us on the balloon, allowed us to estimate the quality of the analytical models of International Geomagnetic Referent Field (IGRF) and to identify the causes of anomalous GMF map errors. Research data of magnetic anomalies map for the study area on the route length of 900 km showed that their spectrum has no harmonics with a wavelength more 130 km. This is a significant defect in a ground map. Defects of magnetic anomalies map are explained by the poor quality of the main GMF and low altitude aeromagnetic survey, as well as the presence of intense local magnetic anomalies, which does not allow reliable identifying the background of weak magnetic fields of deep sources. Using a balloon and satellite magnetic data allows creating an adequate model of the geomagnetic field up to 720.

  18. Evaluating adherence to the International Committee of Medical Journal Editors’ policy of mandatory, timely clinical trial registration

    PubMed Central

    Huser, Vojtech; Cimino, James J

    2013-01-01

    Objective To determine whether two specific criteria in Uniform Requirements for Manuscripts (URM) created by the International Committee of Medical Journal Editors (ICMJE)—namely, including the trial ID registration within manuscripts and timely registration of trials, are being followed. Materials and methods Observational study using computerized analysis of publicly available Medline article data and clinical trial registry data. We analyzed a purposive set of five ICMJE founding journals looking at all trial articles published in those journals during 2010–2011, and data from the ClinicalTrials.gov (CTG) trial registry. We measured adherence to trial ID inclusion policy as the percentage of trial journal articles that contained a valid trial ID within the article (journal-based sample). Adherence to timely registration was measured as the percentage of trials that registered the trial before enrolling the first participant within a 60-day grace period. We also examined timely registration rates by year of all phase II and higher interventional trials in CTG (registry-based sample). Results To determine trial ID inclusion, we analyzed 698 clinical trial articles in five journals. A total of 95.8% (661/690) of trial journal articles included the trial ID. In 88.3% the trial-article link is stored within a structured Medline field. To evaluate timely registration, we analyzed trials referenced by 451 articles from the selected five journals. A total of 60% (272/451) of articles were registered in a timely manner with an improving trend for trials initiated in later years (eg, 89% of trials that began in 2008 were registered in a timely manner). In the registry-based sample, the timely registration rates ranged from 56% for trials registered in 2006 to 72% for trials registered in 2011. Discussion Adherence to URM requirements for registration and trial ID inclusion increases the utility of PubMed and links it in an important way to clinical trial repositories

  19. Power Analysis for Trials with Discrete-Time Survival Endpoints

    ERIC Educational Resources Information Center

    Jozwiak, Katarzyna; Moerbeek, Mirjam

    2012-01-01

    Studies on event occurrence aim to investigate if and when subjects experience a particular event. The timing of events may be measured continuously using thin precise units or discretely using time periods. The latter metric of time is often used in social science research and the generalized linear model (GLM) is an appropriate model for data…

  20. The effect of a caffeinated mouth-rinse on endurance cycling time-trial performance.

    PubMed

    Doering, Thomas M; Fell, James W; Leveritt, Michael D; Desbrow, Ben; Shing, Cecilia M

    2014-02-01

    The purpose of this study was to investigate if acute caffeine exposure via mouth-rinse improved endurance cycling time-trial performance in well-trained cyclists. It was hypothesized that caffeine exposure at the mouth would enhance endurance cycling time-trial performance. Ten well-trained male cyclists (mean ± SD: 32.9 ± 7.5 years, 74.7 ± 5.3 kg, 176.8 ± 5.1cm, VO₂peak = 59.8 ± 3.5 ml·kg⁻¹·min⁻¹) completed two experimental time-trials following 24 hr of dietary and exercise standardization. A randomized, double-blind, placebo-controlled, cross-over design was employed whereby cyclists completed a time-trial in the fastest time possible, which was equivalent work to cycling at 75% of peak aerobic power output for 60 min. Cyclists were administered 25 ml mouth-rinses for 10 s containing either placebo or 35 mg of anhydrous caffeine eight times throughout the time-trial. Perceptual and physiological variables were recorded throughout. No significant improvement in time-trial performance was observed with caffeine (3918 ± 243 s) compared with placebo mouth-rinse (3940 ± 227 s). No elevation in plasma caffeine was detected due to the mouth-rinse conditions. Caffeine mouth-rinse had no significant effect on rating of perceived exertion, heart rate, rate of oxygen consumption or blood lactate concentration. Eight exposures of a 35 mg dose of caffeine at the buccal cavity for 10s does not significantly enhance endurance cycling time-trial performance, nor does it elevate plasma caffeine concentration. PMID:23980239

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-05-01

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

  3. Pacing strategies during a cycling time trial with simulated headwinds and tailwinds.

    PubMed

    Atkinson, G; Brunskill, A

    2000-10-01

    The aims of this study were to examine the effects of one self-selected and two enforced pacing strategies (constant and variable power output) on cycling performance during a time trial in which variable wind conditions were simulated. Seven male cyclists rode their own bicycles on a Computrainer cycle ergometer, which was programmed to simulate a 16.1 km time trial on a flat course with a 8.05 km h(-1) headwind in the first half of the race and a 8.05 km h(-1) tailwind in the second half of the race. Subjects rode an initial time trial (ITT) at a self-selected pace to the best of their ability. The mean power output from this trial was then used to calculate the pacing strategies in the subsequent two trials: Constant (C)--riders rode the whole time trial at this mean power output; and Variable (V)--riders rode the first headwind section at a power output 5% higher than the mean and then reduced the power output in the last 8.05 km so that the mean power output was the same as in the initial time trial and in trial C. Power output, heart rate and ratings of perceived exertion (RPE) were recorded every 1.61 km. Finish times, 8.05 km split times and blood lactate levels, pre- and post-exercise (to calculate delta lactate), were also recorded in each trial. In the ITT, riders chose a mean +/- SD power output of 267 +/- 56 W in the first 1.61 km which was 14% higher than the overall race mean +/- SD of 235 +/- 41 W. Power outputs then dropped to below the race mean after the first few kilometres. Mean +/- SD finish times in the C and V time trials were 1661 +/- 130 and 1659 +/- 135 s, respectively. These were significantly faster than the 1671 +/- 131 s recorded in the initial time trial (p = 0.009), even though overall mean power outputs were similar (234 - 235 W) between all trials (p = 0.26). Overall mean RPE and delta lactate were lowest in trial V (p < 0.05). Perceived exertion showed a pacing strategy by race split interaction (p < 0.0001), but it was not

  4. The effect of skin temperature on performance during a 7.5-km cycling time trial.

    PubMed

    Levels, Koen; de Koning, Jos J; Foster, Carl; Daanen, Hein A M

    2012-09-01

    Aerobic exercise performance is seriously compromised in the heat. Possibly, a high skin temperature causes a rating of perceived exertion (RPE)-mediated decrease in exercise intensity. The purpose of this study was to determine the effect of skin temperature on power output during a 7.5-km cycling time trial. Thirteen well-trained male subjects performed a 7.5-km cycling time trial at 15°C and 50% relative humidity (CONTROL), with radiative heat stress during the time trial, and with (PRECOOL) or without (HEAT) precooling. Heat stress was applied by infrared heaters positioned in front of the cycle ergometer between 1.5 and 6.0 km. Skin, rectal, and pill temperature, power output, heart rate, and RPE were measured during the trial. Despite the lower mean skin temperature at the start of the time trial for PRECOOL compared to HEAT (-2.1 ± 0.7°C; P < 0.01) and CONTROL (-1.8 ± 0.6°C; P < 0.05), and a greater increase in mean skin temperature during the heat stress period for PRECOOL (4.5 ± 1.0°C) and HEAT (3.9 ± 0.8°C) than for CONTROL (-0.3 ± 0.6°C; P < 0.01), no differences in power output were found between HEAT (273 ± 45 W) and CONTROL (284 ± 43 W; P = 0.11) and between HEAT and PRECOOL (266 ± 50 W; P = 0.47). Power output during the time trial was greater for CONTROL than for PRECOOL (P < 0.05). Additionally, no differences were observed in core temperature measures, HR, and RPE. Skin temperature does not affect the selection and modulation of exercise intensity in a 7.5-km cycling time trial. PMID:22270485

  5. Influence of spasmolytic treatment and amniotomy on delivery times: a factorial clinical trial.

    PubMed

    Guerresi, E; Gori, G; Beccari, A; Farro, M; Mazzanti, C

    1981-01-01

    In a double-blind factorial clinical trial in 300 patients (150 primiparae and 150 multiparae), the effects of amniotomy, rociverine, and butylscopolamine bromide administration on the course of labor were investigated. Rociverine significantly reduced the dilatation time and had no effect on the delivery time. Butylscopolamine bromide had no appreciable effect on the dilatation and expulsion times. Amniotomy resulted in a lengthening of the dilatation time and no significant change in the expulsion time. PMID:7008940

  6. Mouth rinsing with a carbohydrate solution does not influence cycle time trial performance in the heat.

    PubMed

    Watson, Phillip; Nichols, David; Cordery, Philip

    2014-09-01

    Ten endurance-trained males were recruited to examine the possible role of carbohydrate (CHO) receptors in the mouth influencing exercise performance in the heat. Volunteers completed an incremental test to exhaustion to determine peak oxygen uptake, a familiarisation trial, followed by 2 experimental trials. Trials consisted of a 1-h time trial undertaken in a climatic chamber maintained at 30 °C, 60% relative humidity. Immediately before, and at regular intervals throughout exercise, subjects ingested a bolus of water and then were provided with either a placebo (PLA) or a 6.4% glucose (CHO) solution to rinse in the mouth for 10 s before being expectorated. There was no difference in total work done between the PLA and CHO trials (758.8 ± 149.0 kJ; 762.6 ± 141.1 kJ; P = 0.951). Pacing was also similar, with no differences in power output apparent during the experimental trials (P = 0.546). Core temperature (P = 0.615), heart rate (P = 0.505), ratings of perceived exertion (P = 0.181), and perceived thermal stress (P = 0.416) were not influenced by the nature of the intervention. Blood glucose concentrations were similar during the CHO and PLA trials (P = 0.117). In contrast to the findings of several studies undertaken in temperate conditions, the present investigation failed to support role of oral sensing of CHO in influencing performance during prolonged exercise in warm conditions. PMID:25154896

  7. Conductive and evaporative precooling lowers mean skin temperature and improves time trial performance in the heat.

    PubMed

    Faulkner, S H; Hupperets, M; Hodder, S G; Havenith, G

    2015-06-01

    Self-paced endurance performance is compromised by moderate-to-high ambient temperatures that are evident in many competitive settings. It has become common place to implement precooling prior to competition in an attempt to alleviate perceived thermal load and performance decline. The present study aimed to investigate precooling incorporating different cooling avenues via either evaporative cooling alone or in combination with conductive cooling on cycling time trial performance. Ten trained male cyclists completed a time trial on three occasions in hot (35 °C) ambient conditions with the cooling garment prepared by (a) immersion in water (COOL, evaporative); (b) immersion in water and frozen (COLD, evaporative and conductive); or (c) no precooling (CONT). COLD improved time trial performance by 5.8% and 2.6% vs CONT and COOL, respectively (both P < 0.05). Power output was 4.5% higher for COLD vs CONT (P < 0.05). Mean skin temperature was lower at the onset of the time trial following COLD compared with COOL and CONT (both P < 0.05) and lasted for the first 20% of the time trial. Thermal sensation was perceived cooler following COOL and COLD. The combination of evaporative and conductive cooling (COLD) had the greatest benefit to performance, which is suggested to be driven by reduced skin temperature following cooling. PMID:25943669

  8. Dressing wear time after breast reconstruction: study protocol for a randomized controlled trial

    PubMed Central

    2013-01-01

    Background One of the major risk variables for surgical site infection is wound management. Understanding infection risk factors for breast operations is essential in order to develop infection-prevention strategies and improve surgical outcomes. The aim of this trial is to assess the influence of dressing wear time on surgical site infection rates and skin colonization. Patients’ perception at self-assessment will also be analyzed. Methods/Design This is a two-arm randomized controlled trial. Two hundred breast cancer patients undergoing immediate or delayed breast reconstruction will be prospectively enrolled. Patients will be randomly allocated to group I (dressing removed on postoperative day one) or group II (dressing removed on postoperative day six). Surgical site infections will be defined by standard criteria from the Centers for Disease Control and Prevention (CDC). Skin colonization will be assessed by culture of samples collected at predefined time points. Patients will score dressing wear time with regard to safety, comfort and convenience. Discussion The evidence to support dressing standards for breast surgery wounds is empiric and scarce. CDC recommends protecting, with a sterile dressing for 24 to 48 hours postoperatively, a primarily closed incision, but there is no recommendation to cover this kind of incision beyond 48 hours, or on the appropriate time to shower or bathe with an uncovered incision. The results of the ongoing trial may support standard recommendations regarding dressing wear time after breast reconstruction. Trial registration ClinicalTrials.gov identifier: http://NCT01148823. PMID:23432779

  9. Real-time monitoring for human clinical trials

    SciTech Connect

    Harker, Y.D.

    1995-11-01

    On August 3-4, 1994, an INEL team made measurements related to a real-time monitoring system for use on the epithermal beam facility at the BMRR. BNL has installed two fission chambers in front of the beam collimator, which are to monitor the beam coming from the reactor. These two monitors are located with one just above the 16-cm dia. front aperture and the other is just below. The fission chambers contain depleted uranium, but because of the small amount of U-235 present, they respond to thermal and near thermal neutrons rather than fast neutrons. This feature combined with their relatively small size (0.6 cm dia x 4 cm long) makes them very good monitors in the BMRR epithermal neutron beam. The INEL team worked with H.B. Lui (BNL) in performing initial tests of these monitors and established the settings to achieve stable operation. The main purpose of the measurement studies was to establish a basis for a monitoring method that tracks the dose the patient is receiving rather than the neutron fluence being delivered down the beam line.

  10. Effect of Time of Day on Performance, Hormonal and Metabolic Response during a 1000-M Cycling Time Trial

    PubMed Central

    Fernandes, Alan Lins; Lopes-Silva, João Paulo; Bertuzzi, Rômulo; Casarini, Dulce Elena; Arita, Danielle Yuri; Bishop, David John; Lima-Silva, Adriano Eduardo

    2014-01-01

    The aim of this study was to determine the effect of time of day on performance, pacing, and hormonal and metabolic responses during a 1000-m cycling time-trial. Nine male, recreational cyclists visited the laboratory four times. During the 1st visit the participants performed an incremental test and during the 2nd visit they performed a 1000-m cycling familiarization trial. On the 3rd and 4th visits, the participants performed a 1000-m TT at either 8 am or 6 pm, in randomized, repeated-measures, crossover design. The time to complete the time trial was lower in the evening than in the morning (88.2±8.7 versus 94.7±10.9 s, respectively, p<0.05), but there was no significant different in pacing. However, oxygen uptake and aerobic mechanical power output at 600 and 1000 m tended to be higher in the evening (p<0.07 and 0.09, respectively). There was also a main effect of time of day for insulin, cortisol, and total and free testosterone concentration, which were all higher in the morning (+60%, +26%, +31% and +22%, respectively, p<0.05). The growth hormone, was twofold higher in the evening (p<0.05). The plasma glucose was ∼11% lower in the morning (p<0.05). Glucagon, norepinephrine, epinephrine and lactate were similar for the morning and evening trials (p>0.05), but the norepinephrine response to the exercise was increased in the morning (+46%, p<0.05), and it was accompanied by a 5-fold increase in the response of glucose. Muscle recruitment, as measured by electromyography, was similar between morning and evening trials (p>0.05). Our findings suggest that performance was improved in the evening, and it was accompanied by an improved hormonal and metabolic milieu. PMID:25289885

  11. Effects of radiant heat exposure on pacing pattern during a 15-km cycling time trial.

    PubMed

    Levels, Koen; de Koning, Jos; Broekhuijzen, Iris; Zwaan, Tamara; Foster, Carl; Daanen, Hein

    2014-01-01

    The goal of this study was to investigate the effects of different durations of skin temperature manipulation on pacing patterns and performance during a 15-km cycling time trial. Nineteen well-trained men completed three 15-km cycling time trials in 18 °C and 50% relative humidity with 4.5-km (short-heat), 9.0-km (long-heat) or without (control) radiant heat exposure applied by infrared heaters after 1.5 km in the time trial. During the time trials, power output, mean skin temperature, rectal temperature, heart rate and rating of perceived exertion were assessed. The radiant heat exposure resulted in higher mean skin temperature during the time trial for short-heat (35.0 ± 0.6 °C) and long-heat (35.3 ± 0.5 °C) than for control (32.5 ± 1.0 °C; P < 0.001), whereas rectal temperature was similar (P = 0.55). The mean power output was less for short-heat (273 ± 8 W; P = 0.001) and long-heat (271 ± 9 W; P = 0.02) than for control (287 ± 7 W), but pacing patterns did not differ (P = 0.55). Heart rate was greatest in control (177 ± 9 beats · min(-1); P < 0.001), whereas the rating of perceived exertion remained similar. We concluded that a radiant heat exposure and associated higher skin temperature reduced overall performance, but did not modify pacing pattern during a 15-km cycling time trial, regardless of the duration of the exposure. PMID:24405217

  12. Field-measured drag area is a key correlate of level cycling time trial performance

    PubMed Central

    Peterman, James E.; Lim, Allen C.; Ignatz, Ryan I.; Edwards, Andrew G.

    2015-01-01

    Drag area (Ad) is a primary factor determining aerodynamic resistance during level cycling and is therefore a key determinant of level time trial performance. However, Ad has traditionally been difficult to measure. Our purpose was to determine the value of adding field-measured Ad as a correlate of level cycling time trial performance. In the field, 19 male cyclists performed a level (22.1 km) time trial. Separately, field-determined Ad and rolling resistance were calculated for subjects along with projected frontal area assessed directly (AP) and indirectly (Est AP). Also, a graded exercise test was performed to determine \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$\\dot {V}{O}_{2}$\\end{document}V˙O2 peak, lactate threshold (LT), and economy. \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$\\dot {V}{O}_{2}$\\end{document}V˙O2 peak (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$\\mathrm{l}~\\min ^{-1}$\\end{document}lmin−1) and power at LT were significantly correlated to power measured during the time trial (r = 0.83 and 0.69, respectively) but were not significantly correlated to performance time (r = − 0.42 and −0.45). The correlation with performance time improved significantly (p < 0.05) when these variables were normalized to Ad. Of note, Ad alone was better correlated to performance time (r = 0.85, p < 0.001) than any combination of non-normalized physiological

  13. Mouth Rinsing with Maltodextrin Solutions Fails to Improve Time Trial Endurance Cycling Performance in Recreational Athletes.

    PubMed

    Kulaksız, Tuğba Nilay; Koşar, Şükran Nazan; Bulut, Suleyman; Güzel, Yasemin; Willems, Marcus Elisabeth Theodorus; Hazir, Tahir; Turnagöl, Hüseyin Hüsrev

    2016-01-01

    The carbohydrate (CHO) concentration of a mouth rinsing solution might influence the CHO sensing receptors in the mouth, with consequent activation of brain regions involved in reward, motivation and regulation of motor activity. The purpose of the present study was to examine the effects of maltodextrin mouth rinsing with different concentrations (3%, 6% and 12%) after an overnight fast on a 20 km cycling time trial performance. Nine recreationally active, healthy males (age: 24 ± 2 years; V ˙ O 2 m a x : 47 ± 5 mL·kg(-1)·min(-1)) participated in this study. A double-blind, placebo-controlled randomized study was conducted. Participants mouth-rinsed every 2.5 km for 5 s. Maltodextrin mouth rinse with concentrations of 3%, 6% or 12% did not change time to complete the time trial and power output compared to placebo (p > 0.05). Time trial completion times were 40.2 ± 4.0, 40.1 ± 3.9, 40.1 ± 4.4, and 39.3 ± 4.2 min and power output 205 ± 22, 206 ± 25, 210 ± 24, and 205 ± 23 W for placebo, 3%, 6%, and 12% maltodextrin conditions, respectively. Heart rate, lactate, glucose, and rating of perceived exertion did not differ between trials (p > 0.05). In conclusion, mouth rinsing with different maltodextrin concentrations after an overnight fast did not affect the physiological responses and performance during a 20 km cycling time trial in recreationally active males. PMID:27171108

  14. Mouth Rinsing with Maltodextrin Solutions Fails to Improve Time Trial Endurance Cycling Performance in Recreational Athletes

    PubMed Central

    Kulaksız, Tuğba Nilay; Koşar, Şükran Nazan; Bulut, Suleyman; Güzel, Yasemin; Willems, Marcus Elisabeth Theodorus; Hazir, Tahir; Turnagöl, Hüseyin Hüsrev

    2016-01-01

    The carbohydrate (CHO) concentration of a mouth rinsing solution might influence the CHO sensing receptors in the mouth, with consequent activation of brain regions involved in reward, motivation and regulation of motor activity. The purpose of the present study was to examine the effects of maltodextrin mouth rinsing with different concentrations (3%, 6% and 12%) after an overnight fast on a 20 km cycling time trial performance. Nine recreationally active, healthy males (age: 24 ± 2 years; V˙O2max: 47 ± 5 mL·kg−1·min−1) participated in this study. A double-blind, placebo-controlled randomized study was conducted. Participants mouth-rinsed every 2.5 km for 5 s. Maltodextrin mouth rinse with concentrations of 3%, 6% or 12% did not change time to complete the time trial and power output compared to placebo (p > 0.05). Time trial completion times were 40.2 ± 4.0, 40.1 ± 3.9, 40.1 ± 4.4, and 39.3 ± 4.2 min and power output 205 ± 22, 206 ± 25, 210 ± 24, and 205 ± 23 W for placebo, 3%, 6%, and 12% maltodextrin conditions, respectively. Heart rate, lactate, glucose, and rating of perceived exertion did not differ between trials (p > 0.05). In conclusion, mouth rinsing with different maltodextrin concentrations after an overnight fast did not affect the physiological responses and performance during a 20 km cycling time trial in recreationally active males. PMID:27171108

  15. [Clinical trial requests of indigenous diagnostic imaging ultrasound devices in first-time registration application].

    PubMed

    Guo, Zhaojun; Cao, Guofang; Tao, Kan

    2012-11-01

    This article introduces the clinical requests of indigenous diagnostic imaging ultrasound devices in first-time registration application and the clinical trial requests in Technical Review Guidance of Ultrasound Imaging Diagnostic Devices (category III) Registration and puts forward some questions of the guidance's implementation. It is hoped to help concerned people. PMID:23461122

  16. Space-by-time decomposition for single-trial decoding of M/EEG activity.

    PubMed

    Delis, Ioannis; Onken, Arno; Schyns, Philippe G; Panzeri, Stefano; Philiastides, Marios G

    2016-06-01

    We develop a novel methodology for the single-trial analysis of multichannel time-varying neuroimaging signals. We introduce the space-by-time M/EEG decomposition, based on Non-negative Matrix Factorization (NMF), which describes single-trial M/EEG signals using a set of non-negative spatial and temporal components that are linearly combined with signed scalar activation coefficients. We illustrate the effectiveness of the proposed approach on an EEG dataset recorded during the performance of a visual categorization task. Our method extracts three temporal and two spatial functional components achieving a compact yet full representation of the underlying structure, which validates and summarizes succinctly results from previous studies. Furthermore, we introduce a decoding analysis that allows determining the distinct functional role of each component and relating them to experimental conditions and task parameters. In particular, we demonstrate that the presented stimulus and the task difficulty of each trial can be reliably decoded using specific combinations of components from the identified space-by-time representation. When comparing with a sliding-window linear discriminant algorithm, we show that our approach yields more robust decoding performance across participants. Overall, our findings suggest that the proposed space-by-time decomposition is a meaningful low-dimensional representation that carries the relevant information of single-trial M/EEG signals. PMID:27033682

  17. Syllable-Timed Speech Treatment for School-Age Children Who Stutter: A Phase I Trial

    ERIC Educational Resources Information Center

    Andrews, Cheryl; O'Brian, Sue; Harrison, Elisabeth; Onslow, Mark; Packman, Ann; Menzies, Ross

    2012-01-01

    Purpose: This clinical trial determined the outcomes of a simple syllable-timed speech (STS) treatment for school-age children who stutter. Method: Participants were 10 children, ages 6-11 years, who stutter. Treatment involved training the children and their parents to use STS at near normal speech rates. The technique was practiced in the clinic…

  18. Effects of Time between Trials on Rats' and Pigeons' Choices with Probabilistic Delayed Reinforcers

    ERIC Educational Resources Information Center

    Mazur, James E.; Biondi, Dawn R.

    2011-01-01

    Parallel experiments with rats and pigeons examined reasons for previous findings that in choices with probabilistic delayed reinforcers, rats' choices were affected by the time between trials whereas pigeons' choices were not. In both experiments, the animals chose between a standard alternative and an adjusting alternative. A choice of the…

  19. Exact solutions of the time-fractional Fisher equation by using modified trial equation method

    NASA Astrophysics Data System (ADS)

    Tandogan, Yusuf Ali; Bildik, Necdet

    2016-06-01

    In this study, modified trial equation method has been proposed to obtain precise solutions of nonlinear fractional differential equation. Using the modified test equation method, we obtained some new exact solutions of the time fractional nonlinear Fisher equation. The obtained results are classified as a soliton solution, singular solutions, rational function solutions and periodic solutions.

  20. Uncertainty of trial timing enhances acquisition of conditioned eyeblinks in anxiety vulnerable individuals.

    PubMed

    Allen, M T; Myers, C E; Servatius, R J

    2016-05-01

    Recent work has found that behaviorally inhibited (BI) individuals exhibit enhanced eyeblink conditioning in omission and yoked training as well as with schedules of partial reinforcement. We hypothesized that spacing CS-US paired trials over a longer period of time by extending and varying the inter-trial interval (ITI) would facilitate learning. All participants completed the Adult Measure of Behavioural Inhibition (AMBI) and were grouped as behaviorally inhibited (BI) and non-behaviorally inhibited (NI) based on a median split score of 15.5. All participants received 3 US alone trials and 30CS-US paired trials for acquisition training and 20CS alone trials for extinction training in one session. Conditioning stimuli were a 500 ms tone conditioned stimulus (CS) and a 50-ms air puff unconditional stimulus (US). Participants were randomly assigned to receive a short ITI (mean=30+/- 5s), a long ITI (mean=57+/- 5s) or a variable long ITI (mean=57 s, range 25-123 s). No significant ITI effects were observed for acquisition or extinction. Overall, anxiety vulnerable individuals exhibited enhanced conditioned eyeblink responses as compared to non-vulnerable individuals. This enhanced acquisition of CRs was significant in spaced training with a variable long ITI, but not the short or long ITI. There were no significant effects of ITI or BI on extinction. These findings are interpreted based on the idea that uncertainty plays a role in anxiety and can enhance associative learning in anxiety vulnerable individuals. PMID:26873040

  1. Time Regained: When People Stop a Physical Activity Program, How Does Their Time Use Change? A Randomised Controlled Trial

    PubMed Central

    Gomersall, Sjaan; Maher, Carol; English, Coralie; Rowlands, Alex; Olds, Tim

    2015-01-01

    The aim of this study was to investigate how previously inactive adults who had participated in a structured, partly supervised 6-week exercise program restructured their time budgets when the program ended. Using a randomised controlled trial design, 129 previously inactive adults were recruited and randomly allocated to one of three groups: a Moderate or Extensive six-week physical activity intervention (150 and 300 additional minutes of exercise per week, respectively) or a Control group. Additional physical activity was accumulated through both group and individual exercise sessions with a wide range of activities. Use of time and time spent in energy expenditure zones was measured using a computerised 24-h self-report recall instrument, the Multimedia Activity Recall for Children and Adults, and accelerometry at baseline, mid- and end-program and at 3- and 6-months follow up. At final follow up, all significant changes in time use domains had returned to within 20 minutes of baseline levels (Physical Activity 1-2 min/d, Active Transport 3-9 min/d, Self-Care 0-2 min/d, Television/Videogames 13-18 min/d in the Moderate and Extensive group, relative to Controls, respectively, p>0.05). Similarly, all significant changes in time spent in the moderate energy expenditure zone had returned to within 1-3 min/d baseline levels (p>0.05), however time spent in vigorous physical activity according to accelerometry estimates remained elevated, although the changes were small in magnitude (1 min/d in the Moderate and Extensive groups, relative to Controls, p=0.01). The results of this study demonstrate strong recidivist patterns in physical activity, but also in other aspects of time use. In designing and determining the effectiveness of exercise interventions, future studies would benefit from considering the whole profile of time use, rather than focusing on individual activities. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12610000248066 PMID

  2. The impact of homicide trials on the forensic pathologist's time--the Fulton County experience.

    PubMed

    Hanzlick, R

    1997-05-01

    Subpoenas received for criminal trials related to homicides in Fulton County (Atlanta) Georgia were tracked in a computer database for an 18 month period in order to determine the proportion of forensic pathologist worktime required for testimony in homicide cases. The number of subpoenas received annually amounted to 64% of the average number of homicides occurring annually. Testimony was required in about 33% of cases in which a subpoena was received, and, therefore, the number of testimony appearances per year was about 21% of the average annual number of homicides. Assuming a 40 hour work week for 52 weeks per year and an average of 3 hours of time preparing for, traveling to, and testifying in court, the time required of the forensic pathologist to testify in homicide trials amounted to about 2% of a full-time-equivalent. Although the time required for testimony in homicide cases may vary among jurisdictions because of the nature of its homicides, distance and travel time to court, and other factors, the data presented here may be used to estimate the impact of homicide trial court time on forensic pathology practice. PMID:9144948

  3. Sodium supplementation has no effect on endurance performance during a cycling time-trial in cool conditions: a randomised cross-over trial

    PubMed Central

    2013-01-01

    Background Sodium ingestion during exercise may exert beneficial effects on endurance performance by either its ability to attenuate the decrease in plasma volume or reduce the risk of Exercise Associated Hyponatremia (EAH). This study aimed to investigate the effect of sodium supplements on endurance performance during a 72 km road cycling time-trial in cool conditions (13.8 ± 2.0°C). Methods Nine well-trained cyclists (5 male, 4 female) participated in this randomized, double-blinded cross-over study, receiving either a 700 mg.h-1 salt capsule, or a corn flour placebo during the time trial. Water was ingested ad-libitum throughout the time trial. Measurements were taken pre, post, and 40 min following time-trials, analysing blood, sweat, and urinary hydration and sodium concentration. Results Sodium supplements had no effect on time-trial performance (overall time = 171 min sodium vs. 172 min placebo; p = 0.46). There was also no effect on the change in plasma sodium concentration from pre to post time trial between trials (relative plasma [Na+] change (pre-post): sodium = 0.56%, placebo = 0.47%; p = 0.60). The greatest difference observed was a significantly change in plasma volume from pre to post exercise between the salt and the placebo trial (p = 0.02), which corresponded with an increased thirst with sodium supplementation. Conclusion Sodium supplements therefore do not improving performance during exercise of approximately 3 h duration in cool conditions. PMID:23731903

  4. Efficient Bayesian Joint Models for Group Randomized Trials with Multiple Observation Times and Multiple Outcomes

    PubMed Central

    Xu, Xinyi; Pennell, Michael L.; Lu, Bo; Murray, David M.

    2013-01-01

    Summary In this paper, we propose a Bayesian method for Group Randomized Trials (GRTs) with multiple observation times and multiple outcomes of different types. We jointly model these outcomes using latent multivariate normal linear regression, which allows treatment effects to change with time and accounts for 1.) intra-class correlation (ICC) within groups 2.) the correlation between different outcomes measured on the same subject and 3.) the over-time correlation (OTC) of each outcome. Moreover we develop a set of innovative priors for the variance components which yield direct inference on the correlations, avoid undesirable constraints, and allow utilization of information from previous studies. We illustrate through simulations that our model can improve estimation efficiency (lower posterior standard deviations) of ICCs and treatment effects relative to single outcome models and models with diffuse priors on the variance components. We also demonstrate the methodology using body composition data collected in the Trial of Activity in Adolescent Girls (TAAG). PMID:22733563

  5. Mental time travel: effects of trial duration on episodic and semantic content.

    PubMed

    Cole, Scott N; Gill, Natalie C L; Conway, Martin A; Morrison, Catriona M

    2012-01-01

    Studies exploring mental time travel commonly use cue-word paradigms to elicit past and future autobiographical events. However, the effect of trial duration (how long participants are allowed to describe events) on the relationship between episodic and nonepisodic detail and episodic specificity (i.e., whether longer durations increase event specificity) has not been examined. To resolve these issues, a cue-word study was devised whereby participants described past and future events under three randomly administered time constraints: short (1-min), standard (3-min), and long (5-min) durations. Findings indicated that an individual's capacity for episodic and nonepisodic thought for the past and future were unrelated. This lends supports to the idea that independent mechanisms are responsible for episodic and semantic information. This study also offers clarity concerning the effect of different trial durations on episodic specificity, which may aid the design of future studies of mental time travel. PMID:23190177

  6. Evaluating the optimal timing of surgical antimicrobial prophylaxis: study protocol for a randomized controlled trial

    PubMed Central

    2014-01-01

    Background 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. Methods/Design 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

  7. Between-Trial Forgetting Due to Interference and Time in Motor Adaptation.

    PubMed

    Kim, Sungshin; Oh, Youngmin; Schweighofer, Nicolas

    2015-01-01

    Learning a motor task with temporally spaced presentations or with other tasks intermixed between presentations reduces performance during training, but can enhance retention post training. These two effects are known as the spacing and contextual interference effect, respectively. Here, we aimed at testing a unifying hypothesis of the spacing and contextual interference effects in visuomotor adaptation, according to which forgetting between trials due to either spaced presentations or interference by another task will promote between-trial forgetting, which will depress performance during acquisition, but will promote retention. We first performed an experiment with three visuomotor adaptation conditions: a short inter-trial-interval (ITI) condition (SHORT-ITI); a long ITI condition (LONG-ITI); and an alternating condition with two alternated opposite tasks (ALT), with the same single-task ITI as in LONG-ITI. In the SHORT-ITI condition, there was fastest increase in performance during training and largest immediate forgetting in the retention tests. In contrast, in the ALT condition, there was slowest increase in performance during training and little immediate forgetting in the retention tests. Compared to these two conditions, in the LONG-ITI, we found intermediate increase in performance during training and intermediate immediate forgetting. To account for these results, we fitted to the data six possible adaptation models with one or two time scales, and with interference in the fast, or in the slow, or in both time scales. Model comparison confirmed that two time scales and some degree of interferences in either time scale are needed to account for our experimental results. In summary, our results suggest that retention following adaptation is modulated by the degree of between-trial forgetting, which is due to time-based decay in single adaptation task and interferences in multiple adaptation tasks. PMID:26599075

  8. Physiological and Anthropometrical Predictors of 15-Kilometer Time Trial Cycling Performance Time.

    ERIC Educational Resources Information Center

    Miller, Frank R.; Manfredi, Thomas G.

    1987-01-01

    A study assessing the relationship between physiological and anthropometrical variables and cycling performance time found that anaerobic threshhold and body circumference ratio correlated highly with cycling performance time. (Author/CB)

  9. Sensitivity Analysis of Per-Protocol Time-to-Event Treatment Efficacy in Randomized Clinical Trials

    PubMed Central

    Gilbert, Peter B.; Shepherd, Bryan E.; Hudgens, Michael G.

    2013-01-01

    Summary Assessing per-protocol treatment effcacy on a time-to-event endpoint is a common objective of randomized clinical trials. The typical analysis uses the same method employed for the intention-to-treat analysis (e.g., standard survival analysis) applied to the subgroup meeting protocol adherence criteria. However, due to potential post-randomization selection bias, this analysis may mislead about treatment efficacy. Moreover, while there is extensive literature on methods for assessing causal treatment effects in compliers, these methods do not apply to a common class of trials where a) the primary objective compares survival curves, b) it is inconceivable to assign participants to be adherent and event-free before adherence is measured, and c) the exclusion restriction assumption fails to hold. HIV vaccine efficacy trials including the recent RV144 trial exemplify this class, because many primary endpoints (e.g., HIV infections) occur before adherence is measured, and nonadherent subjects who receive some of the planned immunizations may be partially protected. Therefore, we develop methods for assessing per-protocol treatment efficacy for this problem class, considering three causal estimands of interest. Because these estimands are not identifiable from the observable data, we develop nonparametric bounds and semiparametric sensitivity analysis methods that yield estimated ignorance and uncertainty intervals. The methods are applied to RV144. PMID:24187408

  10. Nitrate supplementation's improvement of 10-km time-trial performance in trained cyclists.

    PubMed

    Cermak, Naomi M; Gibala, Martin J; van Loon, Luc J C

    2012-02-01

    Six days of dietary nitrate supplementation in the form of beetroot juice (~0.5 L/d) has been reported to reduce pulmonary oxygen uptake (VO₂) during submaximal exercise and increase tolerance of high-intensity work rates, suggesting that nitrate can be a potent ergogenic aid. Limited data are available regarding the effect of nitrate ingestion on athletic performance, and no study has investigated the potential ergogenic effects of a small-volume, concentrated dose of beetroot juice. The authors tested the hypothesis that 6 d of nitrate ingestion would improve time-trial performance in trained cyclists. Using a double-blind, repeated-measures crossover design, 12 male cyclists (31±3 yr, VO2peak=58±2 ml·kg⁻¹·min⁻¹, maximal power [Wmax]=342±10 W) ingested 140 ml/d of concentrated beetroot (~8 mmol/d nitrate) juice (BEET) or a placebo (nitrate-depleted beetroot juice; PLAC) for 6 d, separated by a 14-d washout. After supplementation on Day 6, subjects performed 60 min of submaximal cycling (2×30 min at 45% and 65% Wmax, respectively), followed by a 10-km time trial. Time-trial performance (953±18 vs. 965±18 s, p<.005) and power output (294±12 vs. 288±12 W, p<.05) improved after BEET compared with PLAC supplementation. Submaximal VO₂ was lower after BEET (45% Wmax=1.92±0.06 vs. 2.02±0.09 L/min, 65% Wmax 2.94±0.12 vs. 3.11±0.12 L/min) than with PLAC (main effect, p<.05). Whole-body fuel selection and plasma lactate, glucose, and insulin concentrations did not differ between treatments. Six days of nitrate supplementation reduced VO₂ during submaximal exercise and improved time-trial performance in trained cyclists. PMID:22248502

  11. Analysis of Time to Event Outcomes in Randomized Controlled Trials by Generalized Additive Models

    PubMed Central

    Argyropoulos, Christos; Unruh, Mark L.

    2015-01-01

    Background Randomized Controlled Trials almost invariably utilize the hazard ratio calculated with a Cox proportional hazard model as a treatment efficacy measure. Despite the widespread adoption of HRs, these provide a limited understanding of the treatment effect and may even provide a biased estimate when the assumption of proportional hazards in the Cox model is not verified by the trial data. Additional treatment effect measures on the survival probability or the time scale may be used to supplement HRs but a framework for the simultaneous generation of these measures is lacking. Methods By splitting follow-up time at the nodes of a Gauss Lobatto numerical quadrature rule, techniques for Poisson Generalized Additive Models (PGAM) can be adopted for flexible hazard modeling. Straightforward simulation post-estimation transforms PGAM estimates for the log hazard into estimates of the survival function. These in turn were used to calculate relative and absolute risks or even differences in restricted mean survival time between treatment arms. We illustrate our approach with extensive simulations and in two trials: IPASS (in which the proportionality of hazards was violated) and HEMO a long duration study conducted under evolving standards of care on a heterogeneous patient population. Findings PGAM can generate estimates of the survival function and the hazard ratio that are essentially identical to those obtained by Kaplan Meier curve analysis and the Cox model. PGAMs can simultaneously provide multiple measures of treatment efficacy after a single data pass. Furthermore, supported unadjusted (overall treatment effect) but also subgroup and adjusted analyses, while incorporating multiple time scales and accounting for non-proportional hazards in survival data. Conclusions By augmenting the HR conventionally reported, PGAMs have the potential to support the inferential goals of multiple stakeholders involved in the evaluation and appraisal of clinical trial

  12. The Role of Time-Limited Trials in Dialysis Decision Making in Critically Ill Patients.

    PubMed

    Scherer, Jennifer S; Holley, Jean L

    2016-02-01

    Technologic advances, such as continuous RRT, provide lifesaving therapy for many patients. AKI in the critically ill patient, a fatal diagnosis in the past, is now often a survivable condition. Dialysis decision making for the critically ill patient with AKI is complex. What was once a question solely of survival now is nuanced by an individual's definition of quality of life, personal values, and short- and long-term prognoses. Clinical evaluation of AKI in the critically ill is multifaceted. Treatment decision making requires consideration of the natural evolution of the patient's AKI within the context of the global prognosis. Situations are often marked by prognostic uncertainty and clinical unknowns. In the face of these uncertainties, establishment of patient-directed therapies is imperative. A time-limited trial of continuous RRT in this setting is often appropriate but difficult to execute. Using patient preferences as a clinical guide, a proper time-limited trial requires assessment of prognosis, elicitation of patient values, strong communication skills, clear documentation, and often, appropriate integration of palliative care services. A well conducted time-limited trial can avoid interprofessional conflict and provide support for the patient, family, and staff. PMID:26450932

  13. Effects of time between trials on rats' and pigeons' choices with probabilistic delayed reinforcers.

    PubMed

    Mazur, James E; Biondi, Dawn R

    2011-01-01

    Parallel experiments with rats and pigeons examined reasons for previous findings that in choices with probabilistic delayed reinforcers, rats' choices were affected by the time between trials whereas pigeons' choices were not. In both experiments, the animals chose between a standard alternative and an adjusting alternative. A choice of the standard alternative led to a short delay (1 s or 3 s), and then food might or might not be delivered. If food was not delivered, there was an "interlink interval," and then the animal was forced to continue to select the standard alternative until food was delivered. A choice of the adjusting alternative always led to food after a delay that was systematically increased and decreased over trials to estimate an indifference point--a delay at which the two alternatives were chosen about equally often. Under these conditions, the indifference points for both rats and pigeons increased as the interlink interval increased from 0 s to 20 s, indicating decreased preference for the probabilistic reinforcer with longer time between trials. The indifference points from both rats and pigeons were well described by the hyperbolic-decay model. In the last phase of each experiment, the animals were not forced to continue selecting the standard alternative if food was not delivered. Under these conditions, rats' choices were affected by the time between trials whereas pigeons' choices were not, replicating results of previous studies. The differences between the behavior of rats and pigeons appears to be the result of procedural details, not a fundamental difference in how these two species make choices with probabilistic delayed reinforcers. PMID:21541170

  14. Effects of Time between Trials on Rats' and Pigeons' Choices with Probabilistic Delayed Reinforcers

    PubMed Central

    Mazur, James E; Biondi, Dawn R

    2011-01-01

    Parallel experiments with rats and pigeons examined reasons for previous findings that in choices with probabilistic delayed reinforcers, rats' choices were affected by the time between trials whereas pigeons' choices were not. In both experiments, the animals chose between a standard alternative and an adjusting alternative. A choice of the standard alternative led to a short delay (1 s or 3 s), and then food might or might not be delivered. If food was not delivered, there was an “interlink interval,” and then the animal was forced to continue to select the standard alternative until food was delivered. A choice of the adjusting alternative always led to food after a delay that was systematically increased and decreased over trials to estimate an indifference point—a delay at which the two alternatives were chosen about equally often. Under these conditions, the indifference points for both rats and pigeons increased as the interlink interval increased from 0 s to 20 s, indicating decreased preference for the probabilistic reinforcer with longer time between trials. The indifference points from both rats and pigeons were well described by the hyperbolic-decay model. In the last phase of each experiment, the animals were not forced to continue selecting the standard alternative if food was not delivered. Under these conditions, rats' choices were affected by the time between trials whereas pigeons' choices were not, replicating results of previous studies. The differences between the behavior of rats and pigeons appears to be the result of procedural details, not a fundamental difference in how these two species make choices with probabilistic delayed reinforcers. PMID:21541170

  15. Impact of a thrombolysis research trial on time to treatment for acute myocardial infarction in the emergency department.

    PubMed

    Boisjolie, C R; Sharkey, S W; Cannon, C P; Brunette, D; Haugland, J M; Thatcher, J L; Henry, T D

    1995-08-15

    Because time to treatment in AMI is a critical factor in long-term outcome, it is important that complex trials designed to improve reperfusion therapy do not delay the time to treatment. Participation in the TIMI 5 trial did not significantly prolong our door-to-needle time. These results indicate that, if done carefully, complex, labor-intensive studies can be performed within a reasonable time limit. Care should be taken to design protocols incorporating easy drug preparation, informed consent by the ED, and efficiency of trial initiation. PMID:7639167

  16. Escalation with Overdose Control Using Time to Toxicity for Cancer Phase I Clinical Trials

    PubMed Central

    Tighiouart, Mourad; Liu, Yuan; Rogatko, André

    2014-01-01

    Escalation with overdose control (EWOC) is a Bayesian adaptive phase I clinical trial design that produces consistent sequences of doses while controlling the probability that patients are overdosed. However, this design does not take explicitly into account the time it takes for a patient to exhibit dose limiting toxicity (DLT) since the occurrence of DLT is ascertained within a predetermined window of time. Models to estimate the Maximum Tolerated Dose (MTD) that use the exact time when the DLT occurs are expected to be more precise than those where the variable of interest is categorized as presence or absence of DLT, given that information is lost in the process of categorization of the variable. We develop a class of parametric models for time to toxicity data in order to estimate the MTD efficiently, and present extensive simulations showing that the method has good design operating characteristics relative to the original EWOC and a version of time to event EWOC (TITE-EWOC) which allocates weights to account for the time it takes for a patient to exhibit DLT. The methodology is exemplified by a cancer phase I clinical trial we designed in order to estimate the MTD of Veliparib (ABT-888) in combination with fixed doses of gemcitabine and intensity modulated radiation therapy in patients with locally advanced, un-resectable pancreatic cancer. PMID:24663812

  17. Performance during a 20-km cycling time-trial after caffeine ingestion

    PubMed Central

    2014-01-01

    Background The objective of this study was to analyze the effect of caffeine ingestion on the performance and physiological variables associated with fatigue in 20-km cycling time trials. Methods In a double-blind placebo-controlled crossover study, 13 male cyclists (26 ± 10 y, 71 ± 9 kg, 176 ± 6 cm) were randomized into 2 groups and received caffeine (CAF) capsules (6 mg.kg−1) or placebo (PLA) 60 min before performing 20-km time trials. Distance, speed, power, rpm, rating of perceived exertion (RPE), electromyography (EMG) of the quadriceps muscles and heart rate (HR) were continuously measured during the tests. In addition, BRUMS questionnaire was applied before and after the tests. Results Significant interactions were found in power and speed (P = 0.001), which were significantly higher at the end of the test (final 2 km) after CAF condition. A main effect of time (P = 0.001) was observed for RPE and HR, which increased linearly until the end of exercise in both conditions. The time taken to complete the test was similar in both conditions (PLA = 2191 ± 158 s vs. CAF = 2181 ± 194 s, P = 0.61). No significant differences between CAF and PLA conditions were identified for speed, power, rpm, RPE, EMG, HR, and BRUMS (P > 0.05). Conclusion The results suggest that caffeine intake 60 min before 20-km time trials has no effect on the performance or physiological responses of cyclists. PMID:25302056

  18. Smartphone Mobile Application Delivering Personalized, Real-Time Sun Protection Advice: A Randomized Clinical Trial

    PubMed Central

    Buller, David B.; Berwick, Marianne; Lantz, Kathy; Buller, Mary Klein; Shane, James; Kane, Ilima; Liu, Xia

    2014-01-01

    Importance Mobile smart phones are rapidly emerging as an effective means of communicating with many Americans. Using mobile applications, they can access remote databases, track time and location, and integrate user input to provide tailored health information. Objective A smart phone mobile application providing personalized, real-time sun protection advice was evaluated in a randomized trial. Design The trial was conducted in 2012 and had a randomized pretest-posttest controlled design with a 10-week follow-up. Setting Data was collected from a nationwide population-based survey panel. Participants The trial enrolled a sample of n=604 non-Hispanic and Hispanic adults from the Knowledge Panel® aged 18 or older who owned an Android smart phone. Intervention The mobile application provided advice on sun protection (i.e., protection practices and risk of sunburn) and alerts (to apply/reapply sunscreen and get out of the sun), hourly UV Index, and vitamin D production based on the forecast UV Index, phone's time and location, and user input. Main Outcomes and Measures Percent of days using sun protection and time spent outdoors (days and minutes) in the midday sun and number of sunburns in the past 3 months were collected. Results Individuals in the treatment group reported more shade use but less sunscreen use than controls. Those who used the mobile app reported spending less time in the sun and using all protection behaviors combined more. Conclusions and Relevance The mobile application improved some sun protection. Use of the mobile application was lower than expected but associated with increased sun protection. Providing personalized advice when and where people are in the sun may help reduce sun exposure. PMID:25629710

  19. Single-trial prediction of reaction time variability from MEG brain activity.

    PubMed

    Ohata, Ryu; Ogawa, Kenji; Imamizu, Hiroshi

    2016-01-01

    Neural activity prior to movement onset contains essential information for predictive assistance for humans using brain-machine-interfaces (BMIs). Even though previous studies successfully predicted different goals for upcoming movements, it is unclear whether non-invasive recording signals contain the information to predict trial-by-trial behavioral variability under the same movement. In this paper, we examined the predictability of subsequent short or long reaction times (RTs) from magnetoencephalography (MEG) signals in a delayed-reach task. The difference in RTs was classified significantly above chance from 550 ms before the go-signal onset using the cortical currents in the premotor cortex. Significantly above-chance classification was performed in the lateral prefrontal and the right inferior parietal cortices at the late stage of the delay period. Thus, inter-trial variability in RTs is predictable information. Our study provides a proof-of-concept of the future development of non-invasive BMIs to prevent delayed movements. PMID:27250872

  20. Single-trial prediction of reaction time variability from MEG brain activity

    PubMed Central

    Ohata, Ryu; Ogawa, Kenji; Imamizu, Hiroshi

    2016-01-01

    Neural activity prior to movement onset contains essential information for predictive assistance for humans using brain-machine-interfaces (BMIs). Even though previous studies successfully predicted different goals for upcoming movements, it is unclear whether non-invasive recording signals contain the information to predict trial-by-trial behavioral variability under the same movement. In this paper, we examined the predictability of subsequent short or long reaction times (RTs) from magnetoencephalography (MEG) signals in a delayed-reach task. The difference in RTs was classified significantly above chance from 550 ms before the go-signal onset using the cortical currents in the premotor cortex. Significantly above-chance classification was performed in the lateral prefrontal and the right inferior parietal cortices at the late stage of the delay period. Thus, inter-trial variability in RTs is predictable information. Our study provides a proof-of-concept of the future development of non-invasive BMIs to prevent delayed movements. PMID:27250872

  1. Effect of intermittent hypoxic training on 20 km time trial and 30 s anaerobic performance.

    PubMed

    Hamlin, M J; Marshall, H C; Hellemans, J; Ainslie, P N; Anglem, N

    2010-08-01

    This study aimed to verify whether the "live low, train high" approach is beneficial for endurance and/or anaerobic cycling performance. Sixteen well-trained athletes completed 90 min of endurance training (60-70% of heart rate reserve), followed by two 30-s all-out sprints (Wingate test), daily, for 10 consecutive days. Nine subjects [intermittent hypoxic training (IHT) group] trained with an F(I)O(2) set to produce arterial oxygen saturations of approximately 88-82%, while seven subjects (placebo group) trained while breathing a normal gas mixture (F(I)O(2)=0.21). Four performance tests were conducted at sea level including a familiarization and baseline trial, followed by repeat trials at 2 and 9 days post-intervention. Relative to the placebo group, the mean power during the 30-s Wingate test increased by 3.0% (95% confidence limits, CL +/- 3.5%) 2 days, and 1.7% (+/- 3.8%) 9 days post-IHT. Changes in other performance variables (30 s peak power, 20 km mean power and 20 km oxygen cost) were unclear. During the time trial, the IHT participants' blood lactate concentration, respiratory exchange ratio, and SpO(2), relative to the placebo group, was substantially increased at 2 days post-intervention. The addition of IHT to the normal training program of well-trained athletes produced worthwhile gains in 30 s sprint performance possibly through enhanced glycolysis. PMID:19793215

  2. Evolving spike-timing-dependent plasticity for single-trial learning in robots.

    PubMed

    Di Paolo, Ezequiel A

    2003-10-15

    Single-trial learning is studied in an evolved robot model of synaptic spike-timing-dependent plasticity (STDP). Robots must perform positive phototaxis but must learn to perform negative phototaxis in the presence of a short-lived aversive sound stimulus. STDP acts at the millisecond range and depends asymmetrically on the relative timing of pre- and post-synaptic spikes. Although it has been involved in learning models of input prediction, these models require the iterated presentation of the input pattern, and it is hard to see how this mechanism could sustain single-trial learning over a time-scale of tens of seconds. An incremental evolutionary approach is used to answer this question. The evolved robots succeed in learning the appropriate behaviour, but learning does not depend on achieving the right synaptic configuration but rather the right pattern of neural activity. Robot performance during positive phototaxis is quite robust to loss of spike-timing information, but in contrast, this loss is catastrophic for learning negative phototaxis where entrained firing is common. Tests show that the final weight configuration carries no information about whether a robot is performing one behaviour or the other. Fixing weights, however, has the effect of degrading performance, thus demonstrating that plasticity is used to sustain the neural activity corresponding both to the normal phototaxis condition and to the learned behaviour. The implications and limitations of this result are discussed. PMID:14599321

  3. Single-trial time-frequency analysis of electrocortical signals: baseline correction and beyond.

    PubMed

    Hu, L; Xiao, P; Zhang, Z G; Mouraux, A; Iannetti, G D

    2014-01-01

    Event-related desynchronization (ERD) and synchronization (ERS) of electrocortical signals (e.g., electroencephalogram [EEG] and magnetoencephalogram) reflect important aspects of sensory, motor, and cognitive cortical processing. The detection of ERD and ERS relies on time-frequency decomposition of single-trial electrocortical signals, to identify significant stimulus-induced changes in power within specific frequency bands. Typically, these changes are quantified by expressing post-stimulus EEG power as a percentage of change relative to pre-stimulus EEG power. However, expressing post-stimulus EEG power relative to pre-stimulus EEG power entails two important and surprisingly neglected issues. First, it can introduce a significant bias in the estimation of ERD/ERS magnitude. Second, it confuses the contribution of pre- and post-stimulus EEG power. Taking the human electrocortical responses elicited by transient nociceptive stimuli as an example, we demonstrate that expressing ERD/ERS as the average percentage of change calculated at single-trial level introduces a positive bias, resulting in an overestimation of ERS and an underestimation of ERD. This bias can be avoided using a single-trial baseline subtraction approach. Furthermore, given that the variability in ERD/ERS is not only dependent on the variability in post-stimulus power but also on the variability in pre-stimulus power, an estimation of the respective contribution of pre- and post-stimulus EEG variability is needed. This can be achieved using a multivariate linear regression (MVLR) model, which could be optimally estimated using partial least square (PLS) regression, to dissect and quantify the relationship between behavioral variables and pre- and post-stimulus EEG activities. In summary, combining single-trial baseline subtraction approach with PLS regression can be used to achieve a correct detection and quantification of ERD/ERS. PMID:24084069

  4. Effects of dietary nitrate, caffeine, and their combination on 20-km cycling time trial performance.

    PubMed

    Glaister, Mark; Pattison, John R; Muniz-Pumares, Daniel; Patterson, Stephen D; Foley, Paul

    2015-01-01

    The aim of this study was to examine the acute supplementation effects of dietary nitrate, caffeine, and their combination on 20-km cycling time trial performance. Using a randomized, counterbalanced, double-blind Latin-square design, 14 competitive female cyclists (age: 31 ± 7 years; height: 1.69 ± 0.07 m; body mass: 61.6 ± 6.0 kg) completed four 20-km time trials on a racing bicycle fitted to a turbo trainer. Approximately 2.5 hours before each trial, subjects consumed a 70-ml dose of concentrated beetroot juice containing either 0.45 g of dietary nitrate or with the nitrate content removed (placebo). One hour before each trial, subjects consumed a capsule containing either 5 mg·kg of caffeine or maltodextrin (placebo). There was a significant effect of supplementation on power output (p = 0.001), with post hoc tests revealing higher power outputs in caffeine (205 ± 21 W) vs. nitrate (194 ± 22 W) and placebo (194 ± 25 W) trials only. Caffeine-induced improvements in power output corresponded with significantly higher measures of heart rate (caffeine: 166 ± 12 b·min vs. placebo: 159 ± 15 b·min; p = 0.02), blood lactate (caffeine: 6.54 ± 2.40 mmol·L vs. placebo: 4.50 ± 2.11 mmol·L; p < 0.001), and respiratory exchange ratio (caffeine: 0.95 ± 0.04 vs. placebo: 0.91 ± 0.05; p = 0.03). There were no effects (p ≥ 0.05) of supplementation on cycling cadence, rating of perceived exertion, (Equation is included in full-text article.), or integrated electromyographic activity. The results of this study support the well-established beneficial effects of caffeine supplementation on endurance performance. In contrast, acute supplementation with dietary nitrate seems to have no effect on endurance performance and adds nothing to the benefits afforded by caffeine supplementation. PMID:24978834

  5. Respiratory frequency is strongly associated with perceived exertion during time trials of different duration.

    PubMed

    Nicolò, Andrea; Marcora, Samuele M; Sacchetti, Massimo

    2016-07-01

    In order to provide further insight into the link between respiratory frequency (fR) and the rating of perceived exertion (RPE), the present study investigated the effect of exercise duration on perceptual and physiological responses during self-paced exercise. Nine well-trained competitive male cyclists (23 ± 3 years) performed a preliminary incremental ramp test and three randomised self-paced time trials (TTs) differing in exercise duration (10, 20 and 30 min). Both RPE and fR increased almost linearly over time, with a less-pronounced rate of increase when absolute exercise duration increased. However, when values were expressed against relative exercise duration, no between-trial differences were found in either RPE or fR. Conversely, between-trial differences were observed for minute ventilation ([Formula: see text]E), [Formula: see text]O2 and heart rate (HR), when values were expressed against relative exercise duration. Unlike the relationship between RPE and both [Formula: see text]E and HR, the relationship between RPE and fR was not affected by exercise duration. In conclusion, fR, but not [Formula: see text]E, HR or [Formula: see text]O2, shows a strong relationship to RPE and a similar time course, irrespective of exercise duration. These findings indicate that fR is the best correlate of RPE during self-paced exercise, at least among the parameters and for the range of durations herein investigated. PMID:26503587

  6. The effects of Red Bull energy drink compared with caffeine on cycling time-trial performance.

    PubMed

    Quinlivan, Alannah; Irwin, Christopher; Grant, Gary D; Anoopkumar-Dukie, Sheilandra; Skinner, Tina; Leveritt, Michael; Desbrow, Ben

    2015-10-01

    This study investigated the ergogenic effects of a commercial energy drink (Red Bull) or an equivalent dose of anhydrous caffeine in comparison with a noncaffeinated control beverage on cycling performance. Eleven trained male cyclists (31.7 ± 5.9 y 82.3 ± 6.1 kg, VO2max = 60.3 ± 7.8 mL · kg-1 · min-1) participated in a double-blind, placebo-controlled, crossover-design study involving 3 experimental conditions. Participants were randomly administered Red Bull (9.4 mL/kg body mass [BM] containing 3 mg/kg BM caffeine), anhydrous caffeine (3 mg/kg BM given in capsule form), or a placebo 90 min before commencing a time trial equivalent to 1 h cycling at 75% peak power output. Carbohydrate and fluid volumes were matched across all trials. Performance improved by 109 ± 153 s (2.8%, P = .039) after Red Bull compared with placebo and by 120 ± 172 s (3.1%, P = .043) after caffeine compared with placebo. No significant difference (P > .05) in performance time was detected between Red Bull and caffeine treatments. There was no significant difference (P > .05) in mean heart rate or rating of perceived exertion among the 3 treatments. This study demonstrated that a moderate dose of caffeine consumed as either Red Bull or in anhydrous form enhanced cycling time-trial performance. The ergogenic benefits of Red Bull energy drink are therefore most likely due to the effects of caffeine, with the other ingredients not likely to offer additional benefit. PMID:25710190

  7. Operating Room Time Savings with the Use of Splint Packs: A Randomized Controlled Trial

    PubMed Central

    Gonzalez, Tyler A.; Bluman, Eric M.; Palms, David; Smith, Jeremy T.; Chiodo, Christopher P.

    2016-01-01

    Background: The most expensive variable in the operating room (OR) is time. Lean Process Management is being used in the medical field to improve efficiency in the OR. Streamlining individual processes within the OR is crucial to a comprehensive time saving and cost-cutting health care strategy. At our institution, one hour of OR time costs approximately $500, exclusive of supply and personnel costs. Commercially prepared splint packs (SP) contain all components necessary for plaster-of-Paris short-leg splint application and have the potential to decrease splint application time and overall costs by making it a more lean process. We conducted a randomized controlled trial comparing OR time savings between SP use and bulk supply (BS) splint application. Methods: Fifty consecutive adult operative patients on whom post-operative short-leg splint immobilization was indicated were randomized to either a control group using BS or an experimental group using SP. One orthopaedic surgeon (EMB) prepared and applied all of the splints in a standardized fashion. Retrieval time, preparation time, splint application time, and total splinting time for both groups were measured and statistically analyzed. Results: The retrieval time, preparation time and total splinting time were significantly less (p<0.001) in the SP group compared with the BS group. There was no significant difference in application time between the SP group and BS group. Conclusion: The use of SP made the process of splinting more lean. This has resulted in an average of 2 minutes 52 seconds saved in total splinting time compared to BS, making it an effective cost-cutting and time saving technique. For high volume ORs, use of splint packs may contribute to substantial time and cost savings without impacting patient safety. PMID:26894212

  8. The effect of music on 10-km cycle time-trial performance.

    PubMed

    Hagen, Jana; Foster, Carl; Rodríguez-Marroyo, Jose; de Koning, Jos J; Mikat, Richard P; Hendrix, Charles R; Porcari, John P

    2013-01-01

    Music is widely used as an ergogenic aid in sport, but there is little evidence of its effectiveness during closed-loop athletic events. In order to determine the effectiveness of music as an ergogenic aid, well-trained and task-habituated cyclists performed 10-km cycle time trials either while listening to self-selected motivational music or with auditory input blocked. There were no statistically significant differences in performance time or physiological or psychological markers related to music (time-trial duration17.75 ± 2.10 vs 17.81 ± 2.06 min, mean power output 222 ± 66 vs 220 ± 65 W, peak heart rate184 ± 9 vs 183 ± 8 beats/min, peak blood lactate12.1 ± 2.6 vs 11.9 ± 2.1 mmol/L, and final rating of perceived exertion 8.4 ± 1.5 vs 8.5 ± 1.6). It is concluded that during exercise at competitive intensity, there is no meaningful effect of music on either performance or physiology. PMID:22868289

  9. Predicting analysis time in events-driven clinical trials using accumulating time-to-event surrogate information.

    PubMed

    Wang, Jianming; Ke, Chunlei; Yu, Zhinuan; Fu, Lei; Dornseif, Bruce

    2016-05-01

    For clinical trials with time-to-event endpoints, predicting the accrual of the events of interest with precision is critical in determining the timing of interim and final analyses. For example, overall survival (OS) is often chosen as the primary efficacy endpoint in oncology studies, with planned interim and final analyses at a pre-specified number of deaths. Often, correlated surrogate information, such as time-to-progression (TTP) and progression-free survival, are also collected as secondary efficacy endpoints. It would be appealing to borrow strength from the surrogate information to improve the precision of the analysis time prediction. Currently available methods in the literature for predicting analysis timings do not consider utilizing the surrogate information. In this article, using OS and TTP as an example, a general parametric model for OS and TTP is proposed, with the assumption that disease progression could change the course of the overall survival. Progression-free survival, related both to OS and TTP, will be handled separately, as it can be derived from OS and TTP. The authors seek to develop a prediction procedure using a Bayesian method and provide detailed implementation strategies under certain assumptions. Simulations are performed to evaluate the performance of the proposed method. An application to a real study is also provided. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26689725

  10. Clinical Trial Decisions in Difficult Circumstances: Parental Consent Under Time Pressure.

    PubMed

    Jansen-van der Weide, Marijke C; Caldwell, Patrina H Y; Young, Bridget; de Vries, Martine C; Willems, Dick L; Van't Hoff, William; Woolfall, Kerry; van der Lee, Johanna H; Offringa, Martin

    2015-10-01

    Treatments and interventions used to care for children in emergencies should be based on strong evidence. Well-designed clinical trials investigating these interventions for children are therefore indispensable. Parental informed consent is a key ethical requirement for the enrollment of children in such studies. However, if time is limited because of an urgent need for intervention, there are additional ethical challenges to adequately support the informed consent process. The acute situation and associated psychological impact may compromise the ability of parents to give informed consent. Little evidence exists to guide the process of consent seeking for a child's research participation when time is limited. It is also unclear in what circumstances alternatives to prospective informed consent could be applied. This article describes possible options to manage the informed consent process in an appropriate, practical, and, we believe, ethical way when time is limited. PMID:26416935

  11. Acute whole body UVA irradiation combined with nitrate ingestion enhances time trial performance in trained cyclists.

    PubMed

    Muggeridge, David J; Sculthorpe, Nicholas; Grace, Fergal M; Willis, Gareth; Thornhill, Laurence; Weller, Richard B; James, Philip E; Easton, Chris

    2015-08-01

    Dietary nitrate supplementation has been shown to increase nitric oxide (NO) metabolites, reduce blood pressure (BP) and enhance exercise performance. Acute exposure to ultraviolet (UV)-A light also increases NO bioavailability and reduces BP. We conducted a randomized, counterbalanced placebo-controlled trial to determine the effects of UV-A light alone and in combination with nitrate on the responses to sub-maximal steady-state exercise and time trial (TT) performance. Nine cyclists (VO2max 53.1 ± 4.4 ml/kg/min) completed five performance trials comprising 10 min submaximal steady-state cycling followed by a 16.1 km TT. Following a familiarization the final four trials were preceded, in random order, by either (1) Nitrate gels (NIT) + UV-A, (2) Placebo (PLA) + UV-A, (3) NIT + Sham light (SHAM) and (4) PLA + SHAM (control). The NIT gels (2 × 60 ml gels, ~8.1 mmol nitrate) or a low-nitrate PLA were ingested 2.5 h prior to the trial. The light exposure consisted of 20 J/cm(2) whole body irradiation with either UV-A or SHAM light. Plasma nitrite was measured pre- and post-irradiation and VO2 was measured continuously during steady-state exercise. Plasma nitrite was higher for NIT + SHAM (geometric mean (95% CI), 332 (292-377) nM; P = 0.029) and NIT + UV-A (456 (312-666) nM; P = 0.014) compared to PLA + SHAM (215 (167-277) nM). Differences between PLA + SHAM and PLA + UV-A (282 (248-356) nM) were small and non-significant. During steady-state exercise VO2 was reduced following NIT + UVA (P = 0.034) and tended to be lower in NIT + SHAM (P = 0.086) but not PLA + UV-A (P = 0.381) compared to PLA + SHAM. Performance in the TT was significantly faster following NIT + UV-A (mean ± SD 1447 ± 41 s P = 0.005; d = 0.47), but not PLA + UV-A (1450 ± 40 s; d = 0.41) or NIT + SHAM (1455 ± 47 s; d = 0.28) compared to PLA + SHAM (1469 ± 52 s). These findings demonstrate that exposure to UV-A light alone does not alter the physiological responses to exercise or improve

  12. Randomized clinical trial of the timing it right stroke family support program: research protocol

    PubMed Central

    2014-01-01

    Background Family caregivers provide invaluable support to stroke survivors during their recovery, rehabilitation, and community re-integration. Unfortunately, it is not standard clinical practice to prepare and support caregivers in this role and, as a result, many experience stress and poor health that can compromise stroke survivor recovery and threaten the sustainability of keeping the stroke survivor at home. We developed the Timing it Right Stroke Family Support Program (TIRSFSP) to guide the timing of delivering specific types of education and support to meet caregivers’ evolving needs. The objective of this multi-site randomized controlled trial is to determine if delivering the TIRSFSP across the stroke care continuum improves caregivers’ sense of being supported and emotional well-being. Methods/design Our multi-site single-blinded randomized controlled trial will recruit 300 family caregivers of stroke survivors from urban and rural acute care hospitals. After completing a baseline assessment, participants will be randomly allocated to one of three groups: 1) TIRSFSP guided by a stroke support person (health care professional with stroke care experience), delivered in-person during acute care and by telephone for approximately the first six to 12 months post-stroke, 2) caregiver self-directed TIRSFSP with an initial introduction to the program by a stroke support person, or 3) standard care receiving the educational resource “Let’s Talk about Stroke” prepared by the Heart and Stroke Foundation. Participants will complete three follow-up quantitative assessments 3, 6, and 12-months post-stroke. These include assessments of depression, social support, psychological well-being, stroke knowledge, mastery (sense of control over life), caregiving assistance provided, caregiving impact on everyday life, and indicators of stroke severity and disability. Qualitative methods will also be used to obtain information about caregivers’ experiences with the

  13. A Randomized Trial of Time-Limited Antiretroviral Therapy in Acute/Early HIV Infection

    PubMed Central

    Margolick, Joseph B.; Apuzzo, Linda; Singer, Joel; Wong, Hubert; Lee, Terry; Gallant, Joel E.; El-Helou, Phillippe; Loutfy, Mona R.; Rachlis, Anita; Fraser, Christopher; Kasper, Kenneth; Tremblay, Cécile; Tossonian, Harout; Conway, Brian

    2015-01-01

    Background It has been proposed that initiation of antiretroviral treatment (ART) very soon after establishment of HIV infection may be beneficial by improving host control of HIV replication and delaying disease progression. Methods People with documented HIV infection of less than 12 months’ duration in Baltimore MD and seven Canadian sites were randomized to either a) observation and deferred ART, or b) immediate treatment with ART for 12 months. All subjects not receiving ART were followed quarterly and permanent ART was initiated according to contemporaneous treatment guidelines. The endpoint of the trial was total ART-free time from study entry until initiation of permanent ART. Results One hundred thirteen people were randomized, 56 to the observation arm and 57 to the immediate treatment arm. Twenty-three had acute (<2 months) infection and 90 early (2–12 months) infection. Of those randomized to the immediate treatment arm, 37 completed 12 months of ART according to protocol, 9 declined to stop ART after 12 months, and 11 were nonadherent to the protocol or lost to follow-up. Comparing those in the observation arm to either those who completed 12 months of ART or all 56 who were randomized to immediate ART, there was no significant difference between the arms in treatment-free interval after study entry, which was about 18 months in both arms. Conclusions This study did not find a benefit from administration of a brief, time-limited (12-month) course of ART in acute or early HIV infection. Trial Registration ClinicalTrials.gov NCT00106171 PMID:26600459

  14. Assessing potentially time-dependent treatment effect from clinical trials and observational studies for survival data, with applications to the Women's Health Initiative combined hormone therapy trial

    PubMed Central

    Yang, Song; Prentice, Ross L.

    2015-01-01

    For risk and benefit assessment in clinical trials and observational studies with time-to-event data, the Cox model has usually been the model of choice. When the hazards are possibly non-proportional, a piece-wise Cox model over a partition of the time axis may be considered. Here we propose to analyze clinical trials or observational studies with time-to-event data using a certain semiparametric model. The model allows for a time-dependent treatment effect. It includes the important proportional hazards model as a sub-model, and can accommodate various patterns of time-dependence of the hazard ratio. After estimation of the model parameters using a pseudo-likelihood approach, simultaneous confidence intervals for the hazard ratio function are established using a Monte Carlo method to assess the time-varying pattern of the treatment effect. To assess the overall treatment effect, estimated average hazard ratio and its confidence intervals are also obtained. The proposed methods are applied to data from the Women's Health Initiative. To compare the WHI clinical trial and observational study, we use the propensity score in building the regression model. Compared to the piece-wise Cox model, the proposed model yields a better model fit and does not require partitioning of the time axis. PMID:25689356

  15. Pancreatitis of biliary origin, optimal timing of cholecystectomy (PONCHO trial): study protocol for a randomized controlled trial

    PubMed Central

    2012-01-01

    Background After an initial attack of biliary pancreatitis, cholecystectomy minimizes the risk of recurrent biliary pancreatitis and other gallstone-related complications. Guidelines advocate performing cholecystectomy within 2 to 4 weeks after discharge for mild biliary pancreatitis. During this waiting period, the patient is at risk of recurrent biliary events. In current clinical practice, surgeons usually postpone cholecystectomy for 6 weeks due to a perceived risk of a more difficult dissection in the early days following pancreatitis and for logistical reasons. We hypothesize that early laparoscopic cholecystectomy minimizes the risk of recurrent biliary pancreatitis or other complications of gallstone disease in patients with mild biliary pancreatitis without increasing the difficulty of dissection and the surgical complication rate compared with interval laparoscopic cholecystectomy. Methods/Design PONCHO is a randomized controlled, parallel-group, assessor-blinded, superiority multicenter trial. Patients are randomly allocated to undergo early laparoscopic cholecystectomy, within 72 hours after randomization, or interval laparoscopic cholecystectomy, 25 to 30 days after randomization. During a 30-month period, 266 patients will be enrolled from 18 hospitals of the Dutch Pancreatitis Study Group. The primary endpoint is a composite endpoint of mortality and acute re-admissions for biliary events (that is, recurrent biliary pancreatitis, acute cholecystitis, symptomatic/obstructive choledocholithiasis requiring endoscopic retrograde cholangiopancreaticography including cholangitis (with/without endoscopic sphincterotomy), and uncomplicated biliary colics) occurring within 6 months following randomization. Secondary endpoints include the individual endpoints of the composite endpoint, surgical and other complications, technical difficulty of cholecystectomy and costs. Discussion The PONCHO trial is designed to show that early laparoscopic cholecystectomy

  16. Characterizing the developmental profile of effort-induced motor overflow across a timed trial.

    PubMed

    Addamo, Patricia K; Farrow, Maree; Bradshaw, John L; Moss, Simon; Georgiou-Karistianis, Nellie

    2013-01-01

    Motor overflow is overt involuntary movement that accompanies voluntary movement. This study investigated the change in overflow production across a timed trial and the factors that affected this profile. Seventeen children (aged 8-11 years), 17 young adults (aged 18-35 years), and 17 older adults (aged 60-80 years) performed a 5-s finger pressing task by exerting 33% or 66% of their maximal force output using either index finger. Overflow was recorded as force from the alternative index finger. Young adult overflow remained stable over the 5 s. The rate of overflow increase over time was significantly greater for children than young adults. There was also a tendency for a greater overflow increase in older adults than in young adults. This overflow gradient was also greater in the right hand, particularly for children. These findings indicate that the neurological processes underlying overflow production are age dependent. Overflow progressed in a dynamic fashion over the course of a trial in children and older adults, probably because of increased bilateral cortical activation and the facilitation of motor task performance. This study is unique in quantitatively capturing the dynamic profile of overflow production in healthy participants across the life span. PMID:23858955

  17. The effect of time trial cycling position on physiological and aerodynamic variables.

    PubMed

    Fintelman, D M; Sterling, M; Hemida, H; Li, F-X

    2015-01-01

    To reduce aerodynamic resistance cyclists lower their torso angle, concurrently reducing Peak Power Output (PPO). However, realistic torso angle changes in the range used by time trial cyclists have not yet been examined. Therefore the aim of this study was to investigate the effect of torso angle on physiological parameters and frontal area in different commonly used time trial positions. Nineteen well-trained male cyclists performed incremental tests on a cycle ergometer at five different torso angles: their preferred torso angle and at 0, 8, 16 and 24°. Oxygen uptake, carbon dioxide expiration, minute ventilation, gross efficiency, PPO, heart rate, cadence and frontal area were recorded. The frontal area provides an estimate of the aerodynamic drag. Overall, results showed that lower torso angles attenuated performance. Maximal values of all variables, attained in the incremental test, decreased with lower torso angles (P < 0.001). The 0° torso angle position significantly affected the metabolic and physiological variables compared to all other investigated positions. At constant submaximal intensities of 60, 70 and 80% PPO, all variables significantly increased with increasing intensity (P < 0.0001) and decreasing torso angle (P < 0.005). This study shows that for trained cyclists there should be a trade-off between the aerodynamic drag and physiological functioning. PMID:25658151

  18. Multicomponent intervention to reduce daily sedentary time: a randomised controlled trial

    PubMed Central

    Carr, Lucas J; Karvinen, Kristina; Peavler, Mallory; Smith, Rebecca; Cangelosi, Kayla

    2013-01-01

    Objectives To test the efficacy of a multicomponent technology intervention for reducing daily sedentary time and improving cardiometabolic disease risk among sedentary, overweight university employees. Design Blinded, randomised controlled trial. Setting A large south-eastern university in the USA. Participants 49 middle-aged, primarily female, sedentary and overweight adults working in sedentary jobs enrolled in the study. A total of 40 participants completed the study. Interventions Participants were randomised to either: (1) an intervention group (N=23; 47.6+9.9 years; 94.1% female; 33.2+4.5 kg/m2); (2) or wait-list control group (N=17; 42.6+8.9 years; 86.9% female; 31.7+4.9 kg/m2). The intervention group received a theory-based, internet-delivered programme, a portable pedal machine at work and a pedometer for 12 weeks. The wait-list control group maintained their behaviours for 12 weeks. Outcome measures Primary (sedentary and physical activity behaviour measured objectively through StepWatch) and secondary (heart rate, blood pressure, height, weight, waist circumference, per cent body fat, cardiorespiratory fitness, fasting lipids) outcomes were measured at baseline and postintervention (12 weeks). Exploratory outcomes including intervention compliance and process evaluation measures were also assessed postintervention. Results Compared to controls, the intervention group reduced daily sedentary time (mean change (95%CI): −58.7 min/day (−118.4 to 0.99; p<0.01)) after adjusting for baseline values and monitor wear time. Intervention participants logged on to the website 71.3% of all intervention days, used the pedal machine 37.7% of all working intervention days and pedalled an average of 31.1 min/day. Conclusions These findings suggest that the intervention was engaging and resulted in reductions in daily sedentary time among full-time sedentary employees. These findings hold public health significance due to the growing number of

  19. The effect of dehydration on muscle metabolism and time trial performance during prolonged cycling in males.

    PubMed

    Logan-Sprenger, Heather M; Heigenhauser, George J F; Jones, Graham L; Spriet, Lawrence L

    2015-08-01

    This study combined overnight fluid restriction with lack of fluid intake during prolonged cycling to determine the effects of dehydration on substrate oxidation, skeletal muscle metabolism, heat shock protein 72 (Hsp72) response, and time trial (TT) performance. Nine males cycled at ~65% VO2peak for 90 min followed by a TT (6 kJ/kg BM) either with fluid (HYD) or without fluid (DEH). Blood samples were taken every 20 min and muscle biopsies were taken at 0, 45, and 90 min of exercise and after the TT. DEH subjects started the trial with a -0.6% BM from overnight fluid restriction and were dehydrated by 1.4% after 45 min, 2.3% after 90 min of exercise, and 3.1% BM after the TT. There were no significant differences in oxygen uptake, carbon dioxide production, or total sweat loss between the trials. However, physiological parameters (heart rate [HR], rate of perceived exertion, core temperature [Tc], plasma osmolality [Posm], plasma volume [Pvol] loss, and Hsp72), and carbohydrate (CHO) oxidation and muscle glycogen use were greater during 90 min of moderate cycling when subjects progressed from 0.6% to 2.3% dehydration. TT performance was 13% slower when subjects began 2.3% and ended 3.1% dehydrated. Throughout the TT, Tc, Posm, blood and muscle lactate [La], and serum Hsp72 were higher, even while working at a lower power output (PO). The accelerated muscle glycogen use during 90 min of moderate intensity exercise with DEH did not affect subsequent TT performance, rather augmented Tc, RPE and the additional physiological factors were more important in slowing performance when dehydrated. PMID:26296770

  20. The effect of dehydration on muscle metabolism and time trial performance during prolonged cycling in males

    PubMed Central

    Logan-Sprenger, Heather M; Heigenhauser, George JF; Jones, Graham L; Spriet, Lawrence L

    2015-01-01

    This study combined overnight fluid restriction with lack of fluid intake during prolonged cycling to determine the effects of dehydration on substrate oxidation, skeletal muscle metabolism, heat shock protein 72 (Hsp72) response, and time trial (TT) performance. Nine males cycled at ∼65% VO2peak for 90 min followed by a TT (6 kJ/kg BM) either with fluid (HYD) or without fluid (DEH). Blood samples were taken every 20 min and muscle biopsies were taken at 0, 45, and 90 min of exercise and after the TT. DEH subjects started the trial with a −0.6% BM from overnight fluid restriction and were dehydrated by 1.4% after 45 min, 2.3% after 90 min of exercise, and 3.1% BM after the TT. There were no significant differences in oxygen uptake, carbon dioxide production, or total sweat loss between the trials. However, physiological parameters (heart rate [HR], rate of perceived exertion, core temperature [Tc], plasma osmolality [Posm], plasma volume [Pvol] loss, and Hsp72), and carbohydrate (CHO) oxidation and muscle glycogen use were greater during 90 min of moderate cycling when subjects progressed from 0.6% to 2.3% dehydration. TT performance was 13% slower when subjects began 2.3% and ended 3.1% dehydrated. Throughout the TT, Tc, Posm, blood and muscle lactate [La], and serum Hsp72 were higher, even while working at a lower power output (PO). The accelerated muscle glycogen use during 90 min of moderate intensity exercise with DEH did not affect subsequent TT performance, rather augmented Tc, RPE and the additional physiological factors were more important in slowing performance when dehydrated. PMID:26296770

  1. Single and combined effects of beetroot juice and caffeine supplementation on cycling time trial performance.

    PubMed

    Lane, Stephen C; Hawley, John A; Desbrow, Ben; Jones, Andrew M; Blackwell, James R; Ross, Megan L; Zemski, Adam J; Burke, Louise M

    2014-09-01

    Both caffeine and beetroot juice have ergogenic effects on endurance cycling performance. We investigated whether there is an additive effect of these supplements on the performance of a cycling time trial (TT) simulating the 2012 London Olympic Games course. Twelve male and 12 female competitive cyclists each completed 4 experimental trials in a double-blind Latin square design. Trials were undertaken with a caffeinated gum (CAFF) (3 mg·kg(-1) body mass (BM), 40 min prior to the TT), concentrated beetroot juice supplementation (BJ) (8.4 mmol of nitrate (NO3(-)), 2 h prior to the TT), caffeine plus beetroot juice (CAFF+BJ), or a control (CONT). Subjects completed the TT (females: 29.35 km; males: 43.83 km) on a laboratory cycle ergometer under conditions of best practice nutrition: following a carbohydrate-rich pre-event meal, with the ingestion of a carbohydrate-electrolyte drink and regular oral carbohydrate contact during the TT. Compared with CONT, power output was significantly enhanced after CAFF+BJ and CAFF (3.0% and 3.9%, respectively, p < 0.01). There was no effect of BJ supplementation when used alone (-0.4%, p = 0.6 compared with CONT) or when combined with caffeine (-0.9%, p = 0.4 compared with CAFF). We conclude that caffeine (3 mg·kg(-1) BM) administered in the form of a caffeinated gum increased cycling TT performance lasting ∼50-60 min by ∼3%-4% in both males and females. Beetroot juice supplementation was not ergogenic under the conditions of this study. PMID:25154895

  2. Time-related trends in variability of cIMT changes in statin trials

    PubMed Central

    Davidson, Michael H.; Tomassini, Joanne E.; Jensen, Erin; Neff, David; Polis, Adam B.; Tershakovec, Andrew M.

    2015-01-01

    This brief article provides complementary data supporting the results reported in “Changing Characteristics of Statin-related cIMT Trials from 1988 to 2006” [1]. That article described time-related trends in baseline factors and study characteristics that may have influenced the variability of carotid intima media thickness (cIMT) endpoints (mean of mean and maximum common carotid artery [CCA]/cIMT) in published statin trials. In this brief report, additional details for the studies included in the analysis, and further supporting data, including mean of the maximum CCA/cIMT changes and subgroup data (mean and maximum CCA/cIMT) are provided. For the analysis, study-level data was extracted from 17 statin cIMT trials conducted during 1988–2006, selected on the basis of having at least one statin monotherapy arm in the absence of mixed therapy, and baseline- and study-end values for mean mean and mean maximum CCA/cIMT endpoints. The baseline mean CCA/cIMT, maximum mean CCA/cIMT and LDL-C levels, and annualized cIMT changes were estimated for the overall studies, those conducted before/after 2000, and in risk-based subgroups. Interestingly, all 8 studies conducted before 2000 were significant for cIMT change in which patients did not receive prior LLT; whereas after 2000, the results were more variable and in 4 of 6 trials that did not show a significant cIMT change, patients had received prior treatment. Baseline mean maximum cIMT and LDL-C levels, and annualized changes in studies conducted before 2000 were higher than those conducted after 2000, similar to the results reported in the original article for the mean mean cIMT endpoint. These findings were consistent across study populations of patients with CHD risk versus those without, and in studies with greater LDL-C reductions and with thickened baseline cIMT at study entry for both mean and maximum cIMT changes. Taken together, these results are consistent with trends in recent years toward greater use of

  3. Augmented case-only designs for randomized clinical trials with failure time endpoints

    PubMed Central

    2015-01-01

    Summary Under suitable assumptions and by exploiting the independence between inherited genetic susceptibility and treatment assignment, the case-only design yields efficient estimates for subgroup treatment effects and gene-treatment interaction in a Cox model. However it cannot provide estimates of the genetic main effect and baseline hazards, that are necessary to compute the absolute disease risk. For two-arm, placebo-controlled trials with rare failure time endpoints, we consider augmenting the case-only design with random samples of controls from both arms, as in the classical case-cohort sampling scheme, or with a random sample of controls from the active treatment arm only. The latter design is motivated by vaccine trials for cost-effective use of resources and specimens so that host genetics and vaccine-induced immune responses can be studied simultaneously in a bigger set of participants. We show that these designs can identify all parameters in a Cox model and that the efficient case-only estimator can be incorporated in a two-step plug-in procedure. Results in simulations and a data example suggest that incorporating case-only estimators in the classical case-cohort design improves the precision of all estimated parameters; sampling controls only in the active treatment arm attains a similar level of efficiency. PMID:26347982

  4. Time to benefit for colorectal cancer screening: survival meta-analysis of flexible sigmoidoscopy trials

    PubMed Central

    Boscardin, W John; Stijacic-Cenzer, Irena; Lee, Sei J

    2015-01-01

    Objective To determine the time to benefit of using flexible sigmoidoscopy for colorectal cancer screening. Design Survival meta-analysis. Data sources A Cochrane Collaboration systematic review published in 2013, Medline, and Cochrane Library databases. Eligibility criteria Randomized controlled trials comparing screening flexible sigmoidoscopy with no screening. Trials with fewer than 100 flexible sigmoidoscopy screenings were excluded. Results Four studies were eligible (total n=459 814). They were similar for patients’ age (50-74 years), length of follow-up (11.2-11.9 years), and relative risk for colorectal cancer related mortality (0.69-0.78 with flexible sigmoidoscopy screening). For every 1000 people screened at five and 10 years, 0.3 and 1.2 colorectal cancer related deaths, respectively, were prevented. It took 4.3 years (95% confidence interval 2.8 to 5.8) to observe an absolute risk reduction of 0.0002 (one colorectal cancer related death prevented for every 5000 flexible sigmoidoscopy screenings). It took 9.4 years (7.6 to 11.3) to observe an absolute risk reduction of 0.001 (one colorectal cancer related death prevented for every 1000 flexible sigmoidoscopy screenings). Conclusion Our findings suggest that screening flexible sigmoidoscopy is most appropriate for older adults with a life expectancy greater than approximately 10 years. PMID:25881903

  5. Scanning Lidar Measurements of the Full-Scale RDD Field Trial Puff Plumes.

    PubMed

    Cao, Xiaoying; Roy, Gilles

    2016-05-01

    A vertically scanning lidar (light/radar) was used to measure the time evolution of clouds generated by a small explosive device. Vertical sweeps were performed at a downwind distance of 105 m from the detonation. The measured quantity obtained from the lidar was the light extinction coefficient. This quantity is directly proportional to the aerosol concentration. The background aerosol value was set to 0.0001 m (-1) (assuming a visibility of 40 km), and assuming the scattering properties of the explosively generated cloud is the same as the background aerosol, the authors found that the instantaneous maximal local concentration of aerosol in the cloud did not exceed 500 times the background aerosol value, and the instantaneous concentration was typically less than five times the background aerosol value. In the two trials that were done, the volumes of the clouds were reasonably close at 2,700 m(3) and 4,000 m(3), respectively. PMID:27023031

  6. Aerodynamics of a cycling team in a time trial: does the cyclist at the front benefit?

    NASA Astrophysics Data System (ADS)

    Íñiguez-de-la Torre, A.; Íñiguez, J.

    2009-11-01

    When seasonal journeys take place in nature, birds and fishes migrate in groups. This provides them not only with security but also a considerable saving of energy. The power they need to travel requires overcoming aerodynamic or hydrodynamic drag forces, which can be substantially reduced when the group travels in an optimal arrangement. Also in this area, humans imitate nature, which is especially evident in the practice of outdoor sports and motor competitions. Cycle races, in which speeds of up to 15 m s-1 are frequent, offer great opportunities to appreciate the advantage of travelling in a group. Here we present a brief analysis of the aerodynamics of a cycling team in a time-trial challenge, showing how each rider is favoured according to his position in the group. We conclude that the artificial tail wind created by the team also benefits the cyclist at the front by about 5%.

  7. The analysis and forecasting of male cycling time trial records established within England and Wales.

    PubMed

    Dyer, Bryce; Hassani, Hossein; Shadi, Mehran

    2016-01-01

    The format of cycling time trials in England, Wales and Northern Ireland, involves riders competing individually over several fixed race distances of 10-100 miles in length and using time constrained formats of 12 and 24 h in duration. Drawing on data provided by the national governing body that covers the regions of England and Wales, an analysis of six male competition record progressions was undertaken to illustrate its progression. Future forecasts are then projected through use of the Singular Spectrum Analysis technique. This method has not been applied to sport-based time series data before. All six records have seen a progressive improvement and are non-linear in nature. Five records saw their highest level of record change during the 1950-1969 period. Whilst new record frequency generally has reduced since this period, the magnitude of performance improvement has generally increased. The Singular Spectrum Analysis technique successfully provided forecasted projections in the short to medium term with a high level of fit to the time series data. PMID:26708927

  8. Real-Time Predictions of Reservoir Size and Rebound Time during Antiretroviral Therapy Interruption Trials for HIV

    PubMed Central

    Rosenbloom, Daniel I. S.; Goldstein, Edward; Hanhauser, Emily; Kuritzkes, Daniel R.

    2016-01-01

    Monitoring the efficacy of novel reservoir-reducing treatments for HIV is challenging. The limited ability to sample and quantify latent infection means that supervised antiretroviral therapy (ART) interruption studies are generally required. Here we introduce a set of mathematical and statistical modeling tools to aid in the design and interpretation of ART-interruption trials. We show how the likely size of the remaining reservoir can be updated in real-time as patients continue off treatment, by combining the output of laboratory assays with insights from models of reservoir dynamics and rebound. We design an optimal schedule for viral load sampling during interruption, whereby the frequency of follow-up can be decreased as patients continue off ART without rebound. While this scheme can minimize costs when the chance of rebound between visits is low, we find that the reservoir will be almost completely reseeded before rebound is detected unless sampling occurs at least every two weeks and the most sensitive viral load assays are used. We use simulated data to predict the clinical trial size needed to estimate treatment effects in the face of highly variable patient outcomes and imperfect reservoir assays. Our findings suggest that large numbers of patients—between 40 and 150—will be necessary to reliably estimate the reservoir-reducing potential of a new therapy and to compare this across interventions. As an example, we apply these methods to the two “Boston patients”, recipients of allogeneic hematopoietic stem cell transplants who experienced large reductions in latent infection and underwent ART-interruption. We argue that the timing of viral rebound was not particularly surprising given the information available before treatment cessation. Additionally, we show how other clinical data can be used to estimate the relative contribution that remaining HIV+ cells in the recipient versus newly infected cells from the donor made to the residual reservoir

  9. Real-Time Predictions of Reservoir Size and Rebound Time during Antiretroviral Therapy Interruption Trials for HIV.

    PubMed

    Hill, Alison L; Rosenbloom, Daniel I S; Goldstein, Edward; Hanhauser, Emily; Kuritzkes, Daniel R; Siliciano, Robert F; Henrich, Timothy J

    2016-04-01

    Monitoring the efficacy of novel reservoir-reducing treatments for HIV is challenging. The limited ability to sample and quantify latent infection means that supervised antiretroviral therapy (ART) interruption studies are generally required. Here we introduce a set of mathematical and statistical modeling tools to aid in the design and interpretation of ART-interruption trials. We show how the likely size of the remaining reservoir can be updated in real-time as patients continue off treatment, by combining the output of laboratory assays with insights from models of reservoir dynamics and rebound. We design an optimal schedule for viral load sampling during interruption, whereby the frequency of follow-up can be decreased as patients continue off ART without rebound. While this scheme can minimize costs when the chance of rebound between visits is low, we find that the reservoir will be almost completely reseeded before rebound is detected unless sampling occurs at least every two weeks and the most sensitive viral load assays are used. We use simulated data to predict the clinical trial size needed to estimate treatment effects in the face of highly variable patient outcomes and imperfect reservoir assays. Our findings suggest that large numbers of patients-between 40 and 150-will be necessary to reliably estimate the reservoir-reducing potential of a new therapy and to compare this across interventions. As an example, we apply these methods to the two "Boston patients", recipients of allogeneic hematopoietic stem cell transplants who experienced large reductions in latent infection and underwent ART-interruption. We argue that the timing of viral rebound was not particularly surprising given the information available before treatment cessation. Additionally, we show how other clinical data can be used to estimate the relative contribution that remaining HIV+ cells in the recipient versus newly infected cells from the donor made to the residual reservoir that

  10. Lower theta inter-trial phase coherence during performance monitoring is related to higher reaction time variability: a lifespan study.

    PubMed

    Papenberg, Goran; Hämmerer, Dorothea; Müller, Viktor; Lindenberger, Ulman; Li, Shu-Chen

    2013-12-01

    Trial-to-trial reaction time (RT) variability is consistently higher in children and older adults than in younger adults. Converging evidence also indicates that higher RT variability is (a) associated with lower behavioral performance on complex cognitive tasks, (b) distinguishes patients with neurological deficits from healthy individuals, and also (c) predicts longitudinal cognitive decline in older adults. However, so far the processes underlying increased RT variability are poorly understood. Previous evidence suggests that control signals in the medial frontal cortex (MFC) are reflected in theta band activity and may implicate the coordination of distinct brain areas during performance monitoring. We hypothesized that greater trial-to-trial variability in theta power during performance monitoring may be associated with greater behavioral variability in response latencies. We analyzed event-related theta oscillations assessed during a cued-Go/NoGo task in a lifespan sample covering the age range from middle childhood to old age. Our results show that theta inter-trial coherence during NoGo trials increases from childhood to early adulthood, and decreases from early adulthood to old age. Moreover, in all age groups, individuals with higher variability in medial frontal stimulus-locked theta oscillations showed higher trial-to-trial RT variability behaviorally. Importantly, this effect was strongest at high performance monitoring demands and independent of motor response execution as well as theta power. Taken together, our findings reveal that lower theta inter-trial coherence is related to greater behavioral variability within and across age groups. These results hint at the possibility that more variable MFC control may be associated with greater performance fluctuations. PMID:23876249

  11. Cause, timing, and location of death in the Single Ventricle Reconstruction trial

    PubMed Central

    Ohye, Richard G.; Schonbeck, Julie V.; Eghtesady, Pirooz; Laussen, Peter C.; Pizarro, Christian; Shrader, Peter; Frank, Deborah U.; Graham, Eric M.; Hill, Kevin D.; Jacobs, Jeffrey P.; Kanter, Kirk R.; Kirsh, Joel A.; Lambert, Linda M.; Lewis, Alan B.; Ravishankar, Chitra; Tweddell, James S.; Williams, Ismee A.; Pearson, Gail D.

    2012-01-01

    Objectives The Single Ventricle Reconstruction trial randomized 555 subjects with a single right ventricle undergoing the Norwood procedure at 15 North American centers to receive either a modified Blalock-Taussig shunt or right ventricle-to-pulmonary artery shunt. Results demonstrated a rate of death or cardiac transplantation by 12 months postrandomization of 36% for the modified Blalock-Taussig shunt and 26% for the right ventricle-to-pulmonary artery shunt, consistent with other publications. Despite this high mortality rate, little is known about the circumstances surrounding these deaths. Methods There were 164 deaths within 12 months postrandomization. A committee adjudicated all deaths for cause and recorded the timing, location, and other factors for each event. Results The most common cause of death was cardiovascular (42%), followed by unknown cause (24%) and multisystem organ failure (7%). The median age at death for subjects dying during the 12 months was 1.6 months (interquartile range, 0.6 to 3.7 months), with the highest number of deaths occurring during hospitalization related to the Norwood procedure. The most common location of death was at a Single Ventricle Reconstruction trial hospital (74%), followed by home (13%). There were 29 sudden, unexpected deaths (18%), although in retrospect, 12 were preceded by a prodrome. Conclusions In infants with a single right ventricle undergoing staged repair, the majority of deaths within 12 months of the procedure are due to cardiovascular causes, occur in a hospital, and within the first few months of life. Increased understanding of the circumstances surrounding the deaths of these single ventricle patients may reduce the high mortality rate. (J Thorac Cardiovasc Surg 2012;144:907-14) PMID:22901498

  12. Rejection positivity predicts trial-to-trial reaction times in an auditory selective attention task: a computational analysis of inhibitory control

    PubMed Central

    Chen, Sufen; Melara, Robert D.

    2014-01-01

    A series of computer simulations using variants of a formal model of attention (Melara and Algom, 2003) probed the role of rejection positivity (RP), a slow-wave electroencephalographic (EEG) component, in the inhibitory control of distraction. Behavioral and EEG data were recorded as participants performed auditory selective attention tasks. Simulations that modulated processes of distractor inhibition accounted well for reaction-time (RT) performance, whereas those that modulated target excitation did not. A model that incorporated RP from actual EEG recordings in estimating distractor inhibition was superior in predicting changes in RT as a function of distractor salience across conditions. A model that additionally incorporated momentary fluctuations in EEG as the source of trial-to-trial variation in performance precisely predicted individual RTs within each condition. The results lend support to the linking proposition that RP controls the speed of responding to targets through the inhibitory control of distractors. PMID:25191244

  13. Acute prior heavy strength exercise bouts improve the 20-km cycling time trial performance.

    PubMed

    Silva, Renato A S; Silva-Júnior, Fernando L; Pinheiro, Fabiano A; Souza, Patrícia F M; Boullosa, Daniel A; Pires, Flávio O

    2014-09-01

    This study verified if a prior 5 repetition maximum (5RM) strength exercise would improve the cycling performance during a 20-km cycling time trial (TT20km). After determination of the 5RM leg press exercise load, 11 trained cyclists performed a TT20km in a control condition and 10-minute after 4 sets of 5RM strength exercise bouts (potentiation condition). Oxygen uptake, blood lactate concentration, ratings of perceived exertion (RPE), and power output data were recorded during the TT20km. Cycling economy index was assessed before the TT20km, and pacing strategy was analyzed assuming a "J-shaped" power output distribution profile. Results were a 6.1% reduction (p ≤ 0.05) in the time to complete the TT20km, a greater cycling economy (p < 0.01), and power output in the first 10% of the TT20km (i.e., trend; p = 0.06) in the potentiation condition. However, no differences were observed in pacing strategy, physiological parameters, and RPE between the conditions. These results suggest that 5RM strength exercise bouts improve the performance in a subsequent TT20km. PMID:24584047

  14. Time controlled pulsatile transdermal delivery of nicotine: A phase I feasibility trial in male smokers.

    PubMed

    Hammann, Felix; Kummer, Oliver; Guercioni, Stefania; Imanidis, Georgios; Drewe, Juergen

    2016-06-28

    Nicotine substitution is a mainstay component in smoking cessation schemes. Current products including patches are poorly effective mainly because they do not give smokers the same pharmacokinetic profile of nicotine as cigarette consumption. This work evaluates a new computer operated delivery system for time controlled pulsatile transdermal administration of nicotine in a phase I clinical trial with twelve heavy smoking male volunteers. The device was affixed to the ventral side of the leading lower arm of the subjects and was programmed to deliver two pulses of drug within 16h with three delivery rates in a consecutive dose escalation study. Tolerability of the three increasing doses of nicotine was established. Plasma concentration of nicotine exhibited two peaks and one trough and reached therapeutically effective levels that behaved linearly with the drug load concentration of the device. In vivo input rate, delivered amount and elimination kinetics were deduced by pharmacokinetic modeling to analyze device performance. Timing, dose and duration of delivery were controlled by system operation parameters. Hence, feasibility of controlled pulsatile delivery of nicotine at predetermined intervals was demonstrated. After additional optimization, preprogrammed or on demand administration to meet individualized and circadian replacement needs should improve smoking cessation efficacy. PMID:27090163

  15. The effect of β-alanine supplementation on cycling time trials of different length.

    PubMed

    Bellinger, Phillip M; Minahan, Clare L

    2016-10-01

    The varying results reported in response to β-alanine supplementation may be related to the duration and nature of the exercise protocol employed. We investigated the effects of β-alanine supplementation on a wide range of cycling performance tests in order to produce a clear concise set of criteria for its efficacy. Fourteen trained cyclists (Age = 24.8 ± 6.7 years; VO2max = 65.4 ± 10.2 mL·kg·min(-1)) participated in this placebo-controlled, double-blind study. Prior to supplementation, subjects completed two (familiarization and baseline) supramaximal cycling bouts until exhaustion (120% pre-supplementation VO2max) and two 1-, 4- and 10-km cycling time trial (TT). Subjects then supplemented orally for 4 weeks with 6.4 g/d placebo or β-alanine and repeated the battery of performance tests. Blood lactate was measured pre-exercise, post-exercise and 5  min post-exercise. β-alanine supplementation elicited significant increases in time to exhaustion (TTE) (17.6 ± 11.5 s; p = 0.013, effect compared with placebo) and was likely to be beneficial to 4-km TT performance time (-7.8 ± 8.1 s; 94% likelihood), despite not being statistically different (p = 0.060). Performance times in the 1- and 10-km TT were not affected by treatment. For the highly trained cyclists in the current study, β-alanine supplementation significantly extended supramaximal cycling TTE and may have provided a worthwhile improvement to 4-km TT performance. However, 1- and 10-km cycling TT performance appears to be unaffected by β-alanine supplementation. PMID:26652037

  16. Covariate Adjustment Strategy Increases Power in the Randomized Controlled Trial With Discrete-Time Survival Endpoints

    ERIC Educational Resources Information Center

    Safarkhani, Maryam; Moerbeek, Mirjam

    2013-01-01

    In a randomized controlled trial, a decision needs to be made about the total number of subjects for adequate statistical power. One way to increase the power of a trial is by including a predictive covariate in the model. In this article, the effects of various covariate adjustment strategies on increasing the power is studied for discrete-time…

  17. Changes in Clinical Trials Methodology Over Time: A Systematic Review of Six Decades of Research in Psychopharmacology

    PubMed Central

    Brunoni, André R.; Tadini, Laura; Fregni, Felipe

    2010-01-01

    Background There have been many changes in clinical trials methodology since the introduction of lithium and the beginning of the modern era of psychopharmacology in 1949. The nature and importance of these changes have not been fully addressed to date. As methodological flaws in trials can lead to false-negative or false-positive results, the objective of our study was to evaluate the impact of methodological changes in psychopharmacology clinical research over the past 60 years. Methodology/Principal Findings We performed a systematic review from 1949 to 2009 on MEDLINE and Web of Science electronic databases, and a hand search of high impact journals on studies of seven major drugs (chlorpromazine, clozapine, risperidone, lithium, fluoxetine and lamotrigine). All controlled studies published 100 months after the first trial were included. Ninety-one studies met our inclusion criteria. We analyzed the major changes in abstract reporting, study design, participants' assessment and enrollment, methodology and statistical analysis. Our results showed that the methodology of psychiatric clinical trials changed substantially, with quality gains in abstract reporting, results reporting, and statistical methodology. Recent trials use more informed consent, periods of washout, intention-to-treat approach and parametric tests. Placebo use remains high and unchanged over time. Conclusions/Significance Clinical trial quality of psychopharmacological studies has changed significantly in most of the aspects we analyzed. There was significant improvement in quality reporting and internal validity. These changes have increased study efficiency; however, there is room for improvement in some aspects such as rating scales, diagnostic criteria and better trial reporting. Therefore, despite the advancements observed, there are still several areas that can be improved in psychopharmacology clinical trials. PMID:20209133

  18. Time-Based Physical Activity Interventions for Weight Loss: A Randomized Trial

    PubMed Central

    Jakicic, John M.; Rickman, Amy D.; Lang, Wei; Davis, Kelliann K.; Gibbs, Bethany Barone; Neiberg, Rebecca; Marcus, Marsha D.

    2014-01-01

    Purpose To examine whether enhancing standard behavior weight loss interventions (SBWP) with additional strategies at the initiation of the intervention (ADOPT) or providing the additional strategies at predetermined times over the intervention period (MAINTAIN) enhances 18 month weight loss. Methods This was a clinical trial with participants (n=195; age= 43.2±8.6 yrs; BMI= 33.0±3.4 kg/m2) randomized to SBWP, ADOPT, or MAINTAIN. All were prescribed an energy restricted diet and physical activity, with group intervention sessions delivered over 18 months. ADOPT received additional phone contact (months 1–3), supervised exercise (months 1–6), and behavior campaigns (months 4–9). MAINTAIN received additional phone contact (months 4–6), supervised exercise (months 7–12), and behavior campaigns (months 13–18). Results There was a significant Group X Time interaction for weight loss (p=0.0032). SBWP lost 9.3±0.9, 7.8±1.1, and 5.9±1.2 kg at 6, 12, and 18 months, respectively. ADOPT lost 8.9±0.9, 7.6±1.2, and 5.8±1.2 kg, and MAINTAIN lost 9.7±0.9, 11.0±1.2, and 9.0±1.2 kg at 6, 12, and 18 months, respectively. The Group X Time interaction for SBWP vs. MAINTAIN (p=0.0033) and ADOPT vs. MAINTAIN (p=0.0075) was significant. There was a significant Group X Time interaction for change in fitness (p=0.0060). The Group X Time interaction for MAINTAIN vs. ADOPT (p=0.0018) was significant with a trend for MAINTAIN vs. SBWP (p=0.0525). Conclusions MAINTAIN improved 18-month weight loss compared to SBWP and ADOPT, with statistical trends that MAINTAIN resulted in greater improvements in fitness. These results suggest that time-based strategies emphasizing physical activity conferred greater benefits when delivered later and over the full course of intervention. This provides valuable information for the implementation of time-based strategies to improve long-term weight loss and fitness in overweight and obese adults. PMID:25160843

  19. Five-Kilometers Time Trial: Preliminary Validation of a Short Test for Cycling Performance Evaluation

    PubMed Central

    Dantas, Jose Luiz; Pereira, Gleber; Nakamura, Fabio Yuzo

    2015-01-01

    Background: The five-kilometer time trial (TT5km) has been used to assess aerobic endurance performance without further investigation of its validity. Objectives: This study aimed to perform a preliminary validation of the TT5km to rank well-trained cyclists based on aerobic endurance fitness and assess changes of the aerobic endurance performance. Materials and Methods: After the incremental test, 20 cyclists (age = 31.3 ± 7.9 years; body mass index = 22.7 ± 1.5 kg/m2; maximal aerobic power = 360.5 ± 49.5 W) performed the TT5km twice, collecting performance (time to complete, absolute and relative power output, average speed) and physiological responses (heart rate and electromyography activity). The validation criteria were pacing strategy, absolute and relative reliability, validity, and sensitivity. Sensitivity index was obtained from the ratio between the smallest worthwhile change and typical error. Results: The TT5km showed high absolute (coefficient of variation < 3%) and relative (intraclass coefficient correlation > 0.95) reliability of performance variables, whereas it presented low reliability of physiological responses. The TT5km performance variables were highly correlated with the aerobic endurance indices obtained from incremental test (r > 0.70). These variables showed adequate sensitivity index (> 1). Conclusions: TT5km is a valid test to rank the aerobic endurance fitness of well-trained cyclists and to differentiate changes on aerobic endurance performance. Coaches can detect performance changes through either absolute (± 17.7 W) or relative power output (± 0.3 W.kg-1), the time to complete the test (± 13.4 s) and the average speed (± 1.0 km.h-1). Furthermore, TT5km performance can also be used to rank the athletes according to their aerobic endurance fitness. PMID:26448846

  20. Cross-sectional study of Pfizer-sponsored clinical trials: assessment of time to publication and publication history

    PubMed Central

    Fay, Lorna

    2016-01-01

    Objective To estimate the proportion of Pfizer-sponsored clinical trials that completed in 2010 and are published as manuscripts in the peer-reviewed literature, and to assess the manuscript development history. Design Retrospective, cross-sectional analysis. Setting Clinical trials registered in ClinicalTrials.gov that completed in 2010 for approved, Pfizer prescription products in patients or vaccines in healthy participants. Main outcome measures The proportion of studies for which the primary outcome(s) was published and the median time from study completion to publication. The manuscript development history included the number of times a manuscript was submitted before it was accepted for publication. Results Among registered clinical trials for which Pfizer was the sponsor that completed in 2010, 76 met all inclusion criteria. The primary outcome(s) for 65 (85%) studies was published in 71 manuscripts; the median time to publication was 31 months (range 3–63 months). Of the remaining 11 studies, 2 had been submitted to at least one journal, 2 had not yet been submitted and 7 had no plans to publish because the study had terminated early due to recruitment challenges. Manuscripts accepted at the first choice journal were published at median time of 28 months (range 8–63, n=31), those accepted at second choice journal were published at 32 months (3–45, n=19), and for those accepted at third choice journal, it was 40 months (range 24–53, n=13). Conclusions The publication rate and median time to publication from study completion for Pfizer-sponsored studies were comparable to those previously reported for combined analyses of industry and non-industry sectors. Opportunities exist for sponsors, authors and journals to explore ideas that would facilitate more timely publication for clinical trial results. However, to be effective, such changes may need to revisit the entire publication process. PMID:27431904

  1. The effect of exercise training with an additional inspiratory load on inspiratory muscle fatigue and time-trial performance.

    PubMed

    McEntire, Serina J; Smith, Joshua R; Ferguson, Christine S; Brown, Kelly R; Kurti, Stephanie P; Harms, Craig A

    2016-08-01

    The purpose was to determine the effect of moderate-intensity exercise training (ET) on inspiratory muscle fatigue (IMF) and if an additional inspiratory load during ET (ET+IL) would further improve inspiratory muscle strength, IMF, and time-trial performance. 15 subjects were randomly divided to ET (n=8) and ET+IL groups (n=7). All subjects completed six weeks of exercise training three days/week at ∼70%V̇O2peak for 30min. The ET+IL group breathed through an inspiratory muscle trainer (15% PImax) during exercise. 5-mile, and 30-min time-trials were performed pre-training, weeks three and six. Inspiratory muscle strength increased (p<0.05) for both groups to a similar (p>0.05) extent. ET and ET+IL groups improved (p<0.05) 5-mile time-trial performance (∼10% and ∼18%) and the ET+IL group was significantly faster than ET at week 6. ET and ET+IL groups experienced less (p<0.05) IMF compared to pre-training following the 5-mile time-trial. In conclusion, these data suggest ET leads to less IMF, ET+IL improves inspiratory muscle strength and IMF, but not different than ET alone. PMID:27195511

  2. Effect of Heat and Heat Acclimatization on Cycling Time Trial Performance and Pacing

    PubMed Central

    RACINAIS, SEBASTIEN; PÉRIARD, JULIEN D.; KARLSEN, ANDERS; NYBO, LARS

    2015-01-01

    ABSTRACT Purpose This study aimed to determine the effects of heat acclimatization on performance and pacing during outdoor cycling time trials (TT, 43.4 km) in the heat. Methods Nine cyclists performed three TT in hot ambient conditions (TTH, approximately 37°C) on the first (TTH-1), sixth (TTH-2), and 14th (TTH-3) days of training in the heat. Data were compared with the average of two TT in cool condition (approximately 8°C) performed before and after heat acclimatization (TTC). Results TTH-1 (77 ± 6 min) was slower (P = 0.001) than TTH-2 (69 ± 5 min), and both were slower (P < 0.01) than TTC and TTH-3 (66 ± 3 and 66 ± 4 min, respectively), without differences between TTC and TTH-3 (P > 0.05). The cyclists initiated the first 20% of all TT at a similar power output, irrespective of climate and acclimatization status; however, during TTH-1, they subsequently had a marked decrease in power output, which was partly attenuated after 6 d of acclimatization and was further reduced after 14 d. HR was higher during the first 20% of TTH-1 than that in the other TT (P < 0.05), but there were no differences between conditions from 30% onward. Final rectal temperature was similar in all TTH (40.2°C ± 0.4°C, P = 1.000) and higher than that in TTC (38.5°C ± 0.6°C, P < 0.001). Conclusions After 2 wk of acclimatization, trained cyclists are capable of completing a prolonged TT in a similar time in the heat compared with cool conditions, whereas in the unacclimatized state, they experienced a marked decrease in power output during the TTH. PMID:24977692

  3. Improving time-lapse seismic repeatability: CO2CRC Otway site permanent geophone array field trials

    NASA Astrophysics Data System (ADS)

    Pevzner, Roman; Dupuis, Christian; Shulakova, Valeriya; Urosevic, Milovan; Lumley, David

    2013-04-01

    The proposed Stage 2C of the CO2CRC Otway project involves injection of a small amount (around 15,000 tonnes) of CO2/CH4 gas mixture into saline acquifer (Paaratte formation) at the depth of ~1.5 km. The seismic time-lapse signal will depend largely on the formation properties and the injection scenario, but is likely to be relatively weak. In order to improve time-lapse seismic monitoring capabilities by decreasing the noise level, a buried receiver arrays can be used. A small-scale trial of such an array was conducted at Otway site in June 2012. A set of 25 geophones was installed in 3 m deep boreholes in parallel to the same number of surface geophones. In addition, four geophones were placed into boreholes of 1 to 12 m depth. In order to assess the gain in the signal-to-noise ratio and repeatability, both active and passive seismic surveys were carried out. The surveys were conducted in relatively poor weather conditions, with rain, strong wind and thunderstorms increasing the noise level. We found that noise level for buried geophones is on average 20 dB lower compared to the surface ones. Furthermore, the combination of active and passive experiments has allowed us to perform a detailed classification of various noise sources. Acknowledgement The authors acknowledge the funding provided by the Australian government through its CRC program to support this CO2CRC research project. We also acknowledge the CO2CRC's corporate sponsors and the financial assistance provided through Australian National Low Emissions Coal Research and Development (ANLEC R&D). ANLEC R&D is supported by Australian Coal Association Low Emissions Technology Limited and the Australian Government through the Clean Energy Initiative.

  4. Screen-time Weight-loss Intervention Targeting Children at Home (SWITCH): A randomized controlled trial study protocol

    PubMed Central

    2011-01-01

    Background Approximately one third of New Zealand children and young people are overweight or obese. A similar proportion (33%) do not meet recommendations for physical activity, and 70% do not meet recommendations for screen time. Increased time being sedentary is positively associated with being overweight. There are few family-based interventions aimed at reducing sedentary behavior in children. The aim of this trial is to determine the effects of a 24 week home-based, family oriented intervention to reduce sedentary screen time on children's body composition, sedentary behavior, physical activity, and diet. Methods/Design The study design is a pragmatic two-arm parallel randomized controlled trial. Two hundred and seventy overweight children aged 9-12 years and primary caregivers are being recruited. Participants are randomized to intervention (family-based screen time intervention) or control (no change). At the end of the study, the control group is offered the intervention content. Data collection is undertaken at baseline and 24 weeks. The primary trial outcome is child body mass index (BMI) and standardized body mass index (zBMI). Secondary outcomes are change from baseline to 24 weeks in child percentage body fat; waist circumference; self-reported average daily time spent in physical and sedentary activities; dietary intake; and enjoyment of physical activity and sedentary behavior. Secondary outcomes for the primary caregiver include change in BMI and self-reported physical activity. Discussion This study provides an excellent example of a theory-based, pragmatic, community-based trial targeting sedentary behavior in overweight children. The study has been specifically designed to allow for estimation of the consistency of effects on body composition for Māori (indigenous), Pacific and non-Māori/non-Pacific ethnic groups. If effective, this intervention is imminently scalable and could be integrated within existing weight management programs. Trial

  5. Analysis of Classical Time-Trial Performance and Technique-Specific Physiological Determinants in Elite Female Cross-Country Skiers

    PubMed Central

    Sandbakk, Øyvind; Losnegard, Thomas; Skattebo, Øyvind; Hegge, Ann M.; Tønnessen, Espen; Kocbach, Jan

    2016-01-01

    The present study investigated the contribution of performance on uphill, flat, and downhill sections to overall performance in an international 10-km classical time-trial in elite female cross-country skiers, as well as the relationships between performance on snow and laboratory-measured physiological variables in the double poling (DP) and diagonal (DIA) techniques. Ten elite female cross-country skiers were continuously measured by a global positioning system device during an international 10-km cross-country skiing time-trial in the classical technique. One month prior to the race, all skiers performed a 5-min submaximal and 3-min self-paced performance test while roller skiing on a treadmill, both in the DP and DIA techniques. The time spent on uphill (r = 0.98) and flat (r = 0.91) sections of the race correlated most strongly with the overall 10-km performance (both p < 0.05). Approximately 56% of the racing time was spent uphill, and stepwise multiple regression revealed that uphill time explained 95.5% of the variance in overall performance (p < 0.001). Distance covered during the 3-min roller-skiing test and body-mass normalized peak oxygen uptake (VO2peak) in both techniques showed the strongest correlations with overall time-trial performance (r = 0.66–0.78), with DP capacity tending to have greatest impact on the flat and DIA capacity on uphill terrain (all p < 0.05). Our present findings reveal that the time spent uphill most strongly determine classical time-trial performance, and that the major portion of the performance differences among elite female cross-country skiers can be explained by variations in technique-specific aerobic power. PMID:27536245

  6. Analysis of Classical Time-Trial Performance and Technique-Specific Physiological Determinants in Elite Female Cross-Country Skiers.

    PubMed

    Sandbakk, Øyvind; Losnegard, Thomas; Skattebo, Øyvind; Hegge, Ann M; Tønnessen, Espen; Kocbach, Jan

    2016-01-01

    The present study investigated the contribution of performance on uphill, flat, and downhill sections to overall performance in an international 10-km classical time-trial in elite female cross-country skiers, as well as the relationships between performance on snow and laboratory-measured physiological variables in the double poling (DP) and diagonal (DIA) techniques. Ten elite female cross-country skiers were continuously measured by a global positioning system device during an international 10-km cross-country skiing time-trial in the classical technique. One month prior to the race, all skiers performed a 5-min submaximal and 3-min self-paced performance test while roller skiing on a treadmill, both in the DP and DIA techniques. The time spent on uphill (r = 0.98) and flat (r = 0.91) sections of the race correlated most strongly with the overall 10-km performance (both p < 0.05). Approximately 56% of the racing time was spent uphill, and stepwise multiple regression revealed that uphill time explained 95.5% of the variance in overall performance (p < 0.001). Distance covered during the 3-min roller-skiing test and body-mass normalized peak oxygen uptake (VO2peak) in both techniques showed the strongest correlations with overall time-trial performance (r = 0.66-0.78), with DP capacity tending to have greatest impact on the flat and DIA capacity on uphill terrain (all p < 0.05). Our present findings reveal that the time spent uphill most strongly determine classical time-trial performance, and that the major portion of the performance differences among elite female cross-country skiers can be explained by variations in technique-specific aerobic power. PMID:27536245

  7. METHODS AND BASELINE CARDIOVASCULAR DATA FROM THE EARLY VERSUS LATE INTERVENTION TRIAL WITH ESTRADIOL TESTING THE MENOPAUSAL HORMONE TIMING HYPOTHESIS

    PubMed Central

    Hodis, Howard N.; Mack, Wendy J.; Shoupe, Donna; Azen, Stanley P.; Stanczyk, Frank Z.; Hwang-Levine, Juliana; Budoff, Matthew J.; Henderson, Victor W.

    2014-01-01

    Objective To present methods and baseline data from the Early versus Late Intervention Trial with Estradiol (ELITE), the only clinical trial designed to specifically test the timing hypothesis of postmenopausal hormone therapy (HT). The timing hypothesis posits that HT effects depend on the temporal initiation of HT relative to time-since-menopause. Methods ELITE is a randomized, double-blinded, placebo-controlled trial with a 2x2 factorial design. 643 healthy postmenopausal women without cardiovascular disease were randomized to oral estradiol or placebo for up to 6-7 years according to number of years-since-menopause, <6 years or ≥10 years. Carotid artery intima-media thickness (CIMT) and cardiac computed tomography were conducted to determine HT effects on subclinical atherosclerosis across menopause strata. Results Participants in the early and late postmenopausal strata were well-separated by mean age, 55.4 versus 65.4 years and median time-since-menopause, 3.5 versus 14.3 years, respectively. The expected risk factors were associated with CIMT at baseline in both strata (age, blood pressure and body mass index). In the early but not in the late postmenopausal group, there were significant associations between CIMT and factors that may play a role in responsiveness of atherosclerosis progression according to timing of HT initiation. These include LDL-C, HDLC, sex hormone binding globulin and serum total estradiol. Conclusion The ELITE randomized controlled trial is timely and unique. Baseline data indicate that ELITE is well-positioned to test the HT timing hypothesis in relation to atherosclerosis progression and coronary artery disease. (NCT00114517; www.clinicaltrials.gov) PMID:25380275

  8. Effect of Sodium Phosphate Supplementation on Cycling Time Trial Performance and VO2 1 and 8 Days Post Loading

    PubMed Central

    Brewer, Cameron P.; Dawson, Brian; Wallman, Karen E.; Guelfi, Kym J.

    2014-01-01

    This study examined the effect of 6 days of sodium phosphate (SP) (50 mg·kg·FFM-1·day-1) or placebo (PL) supplementation in trained cyclists on either 100 kJ (23.9 Kcal) (~3-4 min) or 250 kJ (59.7 Kcal) (~10-12 min) time trials performances both 1 and 8 days post-supplementation. Trials were performed in a counterbalanced crossover design, with a 28-day washout period between supplementation phases. No significant differences, moderate-large ES (d) or likely (or greater) smallest worthwhile change (SWC) values were recorded for time to completion and mean power output on days 1 and 8 post-supplementation, both within and between SP and PL for either the 100 or 250 kJ (23.9 or 59.7 Kcal) trials. In the 100 kJ (23.9 Kcal) trial (only) first minute VO2 tended to be higher in SP8 than both PL8 (d = 0.60; 88/10/2 SWC) and SP1 (d = 0.47: 82/15/3 SWC), as was mean VO2 (PL8: d = 0.77; 93/6/1 SWC and SP1: d = 0.84; 90/8/3 SWC). No significant differences were found for heart rate, ratings of perceived exertion and blood lactate post-exercise within or between any trials, while serum phosphate values were not different before or after supplementation with SP or PL. In conclusion, this study showed a tendency for increased VO2 in a short duration (100 kJ/ 23.9 Kcal: ~3-4 min) cycling test on day 8 after SP supplementation, but no differences in 100 or 250 kJ (23.9 or 59.7 Kcal) time trials performances were observed. Key Points Studies investigating the effects of sodium phosphate loading on shorter duration (<15 min) and higher intensity exercise performance are lacking, as is research on how long any ergogenic effect may last. Loading did not improve cycling time trial (~3-4 min and 10-12 min) performance either 1 or 8 days after supplementation. Future studies should investigate the effect of sodium phosphate loading on repeated sprints and simulated cycling road race performance over extended durations (>30 min), where it may be likely to have a more beneficial effect

  9. Prediction of accrual closure date in multi-center clinical trials with discrete-time Poisson process models

    PubMed Central

    Tang, Gong; Kong, Yuan; Chang, Chung-Chou Ho; Kong, Lan; Costantino, Joseph P.

    2016-01-01

    In a phase III multi-center cancer clinical trial or large public health studies, sample size is predetermined to achieve desired power and study participants are enrolled from tens or hundreds of participating institutions. As the accrual is closing to the target size, the coordinating data center needs to project the accrual closure date based on the observed accrual pattern and notify the participating sites several weeks in advance. In the past, projections were simply based on some crude assessment and conservative measures were incorporated in order to achieve the target accrual size. This approach often resulted in excessive accrual size and subsequently unnecessary financial burden on the study sponsors. Here we proposed a discrete-time Poisson process-based method to estimate the accrual rate at time of projection and subsequently the trial closure date. To ensure that target size would be reached with high confidence, we also proposed a conservative method for the closure date projection. The proposed method was illustrated through the analysis of the accrual data of NSABP trial B-38. The results showed that application of proposed method could help to save considerable amount of expenditure in patient management without compromising the accrual goal in multi-center clinical trials. PMID:22411544

  10. Effect of oral nitrate supplementation on pulmonary hemodynamics during exercise and time trial performance in normoxia and hypoxia: a randomized controlled trial

    PubMed Central

    Bourdillon, Nicolas; Fan, Jui-Lin; Uva, Barbara; Müller, Hajo; Meyer, Philippe; Kayser, Bengt

    2015-01-01

    Background: Hypoxia-induced pulmonary vasoconstriction increases pulmonary arterial pressure (PAP) and may impede right heart function and exercise performance. This study examined the effects of oral nitrate supplementation on right heart function and performance during exercise in normoxia and hypoxia. We tested the hypothesis that nitrate supplementation would attenuate the increase in PAP at rest and during exercise in hypoxia, thereby improving exercise performance. Methods: Twelve trained male cyclists [age: 31 ± 7 year (mean ± SD)] performed 15 km time-trial cycling (TT) and steady-state submaximal cycling (50, 100, and 150 W) in normoxia and hypoxia (11% inspired O2) following 3-day oral supplementation with either placebo or sodium nitrate (0.1 mmol/kg/day). We measured TT time-to-completion, muscle tissue oxygenation during TT and systolic right ventricle to right atrium pressure gradient (RV-RA gradient: index of PAP) during steady state cycling. Results: During steady state exercise, hypoxia elevated RV-RA gradient (p > 0.05), while oral nitrate supplementation did not alter RV-RA gradient (p > 0.05). During 15 km TT, hypoxia lowered muscle tissue oxygenation (p < 0.05). Nitrate supplementation further decreased muscle tissue oxygenation during 15 km TT in hypoxia (p < 0.05). Hypoxia impaired time-to-completion during TT (p < 0.05), while no improvements were observed with nitrate supplementation in normoxia or hypoxia (p > 0.05). Conclusion: Our findings indicate that oral nitrate supplementation does not attenuate acute hypoxic pulmonary vasoconstriction nor improve performance during time trial cycling in normoxia and hypoxia. PMID:26528189

  11. Alternative Calculations of Individual Patient Time in Therapeutic Range While Taking Warfarin: Results From the ROCKET AF Trial

    PubMed Central

    Singer, Daniel E.; Hellkamp, Anne S.; Yuan, Zhong; Lokhnygina, Yuliya; Patel, Manesh R.; Piccini, Jonathan P.; Hankey, Graeme J.; Breithardt, Günter; Halperin, Jonathan L.; Becker, Richard C.; Hacke, Werner; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A. A.; Califf, Robert M.

    2015-01-01

    Background In the ROCKET AF (Rivaroxaban–Once‐daily, oral, direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) trial, marked regional differences in control of warfarin anticoagulation, measured as the average individual patient time in the therapeutic range (iTTR) of the international normalized ratio (INR), were associated with longer inter‐INR test intervals. The standard Rosendaal approach can produce biased low estimates of TTR after an appropriate dose change if the follow‐up INR test interval is prolonged. We explored the effect of alternative calculations of TTR that more immediately account for dose changes on regional differences in mean iTTR in the ROCKET AF trial. Methods and Results We used an INR imputation method that accounts for dose change. We compared group mean iTTR values between our dose change–based method with the standard Rosendaal method and determined that the differences between approaches depended on the balance of dose changes that produced in‐range INRs (“corrections”) versus INRs that were out of range in the opposite direction (“overshoots”). In ROCKET AF, the overall mean iTTR of 55.2% (Rosendaal) increased up to 3.1% by using the dose change–based approach, depending on assumptions. However, large inter‐regional differences in anticoagulation control persisted. Conclusions TTR, the standard measure of control of warfarin anticoagulation, depends on imputing daily INR values for the vast majority of follow‐up days. Our TTR calculation method may better reflect the impact of warfarin dose changes than the Rosendaal approach. In the ROCKET AF trial, this dose change–based approach led to a modest increase in overall mean iTTR but did not materially affect the large inter‐regional differences previously reported. Clinical Trial Registration URL: ClinicalTrials.gov. Unique identifier: NCT00403767. PMID:25736441

  12. Rationale and study design for a randomised controlled trial to reduce sedentary time in adults at risk of type 2 diabetes mellitus: project stand (Sedentary Time ANd diabetes)

    PubMed Central

    2011-01-01

    Background The rising prevalence of Type 2 Diabetes Mellitus (T2DM) is a major public health problem. There is an urgent need for effective lifestyle interventions to prevent the development of T2DM. Sedentary behaviour (sitting time) has recently been identified as a risk factor for diabetes, often independent of the time spent in moderate-to-vigorous physical activity. Project STAND (Sedentary Time ANd Diabetes) is a study which aims to reduce sedentary behaviour in younger adults at high risk of T2DM. Methods/Design A reduction in sedentary time is targeted using theory driven group structured education. The STAND programme is subject to piloting and process evaluation in line with the MRC framework for complex interventions. Participants are encouraged to self-monitor and self-regulate their behaviour. The intervention is being assessed in a randomised controlled trial with 12 month follow up. Inclusion criteria are a) aged 18-40 years with a BMI in the obese range; b) 18-40 years with a BMI in the overweight range plus an additional risk factor for T2DM. Participants are randomised to the intervention (n = 89) or control (n = 89) arm. The primary outcome is a reduction in sedentary behaviour at 12 months as measured by an accelerometer (count < 100/min). Secondary outcomes include physical activity, sitting/lying time using the ActivPAL posture monitor, fasting and 2 h oral glucose tolerance test, lipids, inflammatory biomarkers, body weight, waist circumference, blood pressure, illness perceptions, and efficacy beliefs for behaviour change. Conclusions This is the first UK trial to address sedentary behaviour change in a population of younger adults at risk of T2DM. The results will provide a platform for the development of a range of future multidisciplinary interventions in this rapidly expanding high-risk population. Trial registration Current controlled trials ISRCTN08434554, MRC project 91409. PMID:22151909

  13. Inspiratory muscle training improves cycling time-trial performance and anaerobic work capacity but not critical power.

    PubMed

    Johnson, Michael A; Sharpe, Graham R; Brown, Peter I

    2007-12-01

    We examined whether inspiratory muscle training (IMT) improved cycling time-trial performance and changed the relationship between limit work (W (lim)) and limit time (T (lim)), which is described by the parameters critical power (CP) and anaerobic work capacity (AWC). Eighteen male cyclists were assigned to either a pressure-threshold IMT or sham hypoxic-training placebo (PLC) group. Prior to and following a 6 week intervention subjects completed a 25-km cycling time-trial and three constant-power tests to establish the W (lim)-T (lim) relationship. Constant-power tests were prescribed to elicit exercise intolerance within 3-10 (Ex1), 10-20 (Ex2), and 20-30 (Ex3) min. Maximal inspiratory mouth pressure increased by (mean +/- SD) 17.1 +/- 12.2% following IMT (P < 0.01) and was accompanied by a 2.66 +/- 2.51% improvement in 25-km time-trial performance (P < 0.05); there were no changes following PLC. Constant-power cycling endurance was unchanged following PLC, as was CP (pre vs. post: 249 +/- 32 vs. 250 +/- 32 W) and AWC (30.7 +/- 12.7 vs. 30.1 +/- 12.5 kJ). Following IMT Ex1 and Ex3 cycling endurance improved by 18.3 +/- 15.1 and 15.3 +/- 19.1% (P < 0.05), respectively, CP was unchanged (264 +/- 62 vs. 263 +/- 61 W), but AWC increased from 24.8 +/- 5.6 to 29.0 +/- 8.4 kJ (P < 0.05). In conclusion, these data provide novel evidence that improvements in constant-power and cycling time-trial performance following IMT in cyclists may be explained, in part, by an increase in AWC. PMID:17874123

  14. Randomised Trials or the Test of Time? The Story of Human Albumin Administration.

    ERIC Educational Resources Information Center

    Roberts, Ian

    2000-01-01

    Conducted a systematic review of randomized controlled trials of the administration of human albumin in critically ill patients. Findings raised serious concerns about the safety of an intervention that has been widely used in health care around the world. Findings illustrate the importance of systematic reviews in health care and other areas of…

  15. Amyloid-based immunotherapy for Alzheimer's disease in the time of prevention trials: the way forward.

    PubMed

    Panza, Francesco; Solfrizzi, Vincenzo; Imbimbo, Bruno P; Tortelli, Rosanna; Santamato, Andrea; Logroscino, Giancarlo

    2014-03-01

    Both active and passive anti-β-amyloid (Aβ) immunotherapies for the treatment of Alzheimer's disease (AD) have demonstrated clearance of brain Aβ deposits. Among passive immunotherapeutics, two Phase III clinical trials in mild-to-moderate AD patients with bapineuzumab, a humanized monoclonal antibody directed at the N-terminal sequence of Aβ, were disappointing. Also solanezumab, directed at the mid-region of Aβ, failed in two Phase III trials in mild-to-moderate AD. Another Phase III trial with solanezumab is ongoing in mildly affected AD patients based on encouraging results in this subgroup. Second-generation active Aβ vaccines (CAD106, ACC-001, and Affitope AD02) and new passive anti-Aβ immunotherapies (gantenerumab and crenezumab) have been developed and are under clinical testing. These new anti-Aβ immunotherapies are being tested in prodromal AD, in presymptomatic subjects with AD-related mutations, or in asymptomatic subjects at risk of developing AD. These primary and secondary prevention trials will definitely test the Aβ cascade hypothesis of AD. PMID:24490853

  16. Improvements in Cycling but Not Handcycling 10 km Time Trial Performance in Habitual Caffeine Users.

    PubMed

    Graham-Paulson, Terri; Perret, Claudio; Goosey-Tolfrey, Victoria

    2016-01-01

    Caffeine supplementation during whole-/lower-body exercise is well-researched, yet evidence of its effect during upper-body exercise is equivocal. The current study explored the effects of caffeine on cycling/handcycling 10 km time trial (TT) performance in habitual caffeine users. Eleven recreationally trained males (mean (SD) age 24 (4) years, body mass 85.1 (14.6) kg, cycling/handcycling peak oxygen uptake ( V · peak) 42.9 (7.3)/27.6 (5.1) mL∙kg∙min(-1), 160 (168) mg/day caffeine consumption) completed two maximal incremental tests and two familiarization sessions. During four subsequent visits, participants cycled/handcycled for 30 min at 65% mode-specific V · peak (preload) followed by a 10 km TT following the ingestion of 4 mg∙kg(-1) caffeine (CAF) or placebo (PLA). Caffeine significantly improved cycling (2.0 (2.0)%; 16:35 vs. 16:56 min; p = 0.033) but not handcycling (1.8 (3.0)%; 24:10 vs. 24:36 min; p = 0.153) TT performance compared to PLA. The improvement during cycling can be attributed to the increased power output during the first and last 2 km during CAF. Higher blood lactate concentration (Bla) was reported during CAF compared to PLA (p < 0.007) and was evident 5 min post-TT during cycling (11.2 ± 2.6 and 8.8 ± 3.2 mmol/L; p = 0.001) and handcycling (10.6 ± 2.5 and 9.2 ± 2.9 mmol/L; p = 0.006). Lower overall ratings of perceived exertion (RPE) were seen following CAF during the preload (p < 0.05) but not post-TT. Lower peripheral RPE were reported at 20 min during cycling and at 30 min during handcycling, and lower central RPE was seen at 30 min during cycling (p < 0.05). Caffeine improved cycling but not handcycling TT performance. The lack of improvement during handcycling may be due to the smaller active muscle mass, elevated (Bla) and/or participants' training status. PMID:27348000

  17. Improvements in Cycling but Not Handcycling 10 km Time Trial Performance in Habitual Caffeine Users

    PubMed Central

    Graham-Paulson, Terri; Perret, Claudio; Goosey-Tolfrey, Victoria

    2016-01-01

    Caffeine supplementation during whole-/lower-body exercise is well-researched, yet evidence of its effect during upper-body exercise is equivocal. The current study explored the effects of caffeine on cycling/handcycling 10 km time trial (TT) performance in habitual caffeine users. Eleven recreationally trained males (mean (SD) age 24 (4) years, body mass 85.1 (14.6) kg, cycling/handcycling peak oxygen uptake (V·peak) 42.9 (7.3)/27.6 (5.1) mL∙kg∙min−1, 160 (168) mg/day caffeine consumption) completed two maximal incremental tests and two familiarization sessions. During four subsequent visits, participants cycled/handcycled for 30 min at 65% mode-specific V·peak (preload) followed by a 10 km TT following the ingestion of 4 mg∙kg−1 caffeine (CAF) or placebo (PLA). Caffeine significantly improved cycling (2.0 (2.0)%; 16:35 vs. 16:56 min; p = 0.033) but not handcycling (1.8 (3.0)%; 24:10 vs. 24:36 min; p = 0.153) TT performance compared to PLA. The improvement during cycling can be attributed to the increased power output during the first and last 2 km during CAF. Higher blood lactate concentration (Bla) was reported during CAF compared to PLA (p < 0.007) and was evident 5 min post-TT during cycling (11.2 ± 2.6 and 8.8 ± 3.2 mmol/L; p = 0.001) and handcycling (10.6 ± 2.5 and 9.2 ± 2.9 mmol/L; p = 0.006). Lower overall ratings of perceived exertion (RPE) were seen following CAF during the preload (p < 0.05) but not post-TT. Lower peripheral RPE were reported at 20 min during cycling and at 30 min during handcycling, and lower central RPE was seen at 30 min during cycling (p < 0.05). Caffeine improved cycling but not handcycling TT performance. The lack of improvement during handcycling may be due to the smaller active muscle mass, elevated (Bla) and/or participants’ training status. PMID:27348000

  18. The potential influence of perception of achievement on performance in volitional time-to-exhaustion cycle ergometer trials.

    PubMed

    Lorimer, Ross; Babraj, John

    2013-06-01

    The purpose of this short communication was to report the findings of an investigation of the potential influence of spontaneous goal setting on subjects undertaking maximal fitness testing. Subjects were asked to complete a single incremental volitional time-to-exhaustion cycle ergometer trial. The final minute of the trial, after the last increase in increment in resistance, was broken down into six 10-second intervals and a frequency count made of how many subjects stopped within each interval. A chi-square test was used to determine that there was a significant difference between the expected and the observed frequencies (p < 0.05), with 45% of subjects stopping in the first interval (0-10 seconds) and 0% within the last interval (51-60 seconds). Reflections of the subjects revealed that those who were close to exhaustion but near to reaching the next increment of resistance were more likely to "push on." However, despite having been told to keep going as long as they could, subjects upon reaching that increment stopped almost immediately as they believed they could not manage to reach the next increment. This suggests a potential psychological element related to goal achievement that influences performance in incremental volitional time-to-exhaustion cycle ergometer trials. Practically, this means that the information participants have available on which to base goals (level of increment, time, etc.) needs to be minimized to prevent spontaneous goal setting. PMID:23037613

  19. KRAS and Colorectal Cancer: Ethical and Pragmatic Issues in Effecting Real-Time Change in Oncology Clinical Trials and Practice

    PubMed Central

    Goldberg, Richard M.; Grothey, Axel; Mooney, Margaret; Roach, Nancy; Saltz, Leonard B.; Welch, John J.; Wood, William A.; Meropol, Neal J.

    2011-01-01

    Systemic therapy has led to a median survival time for patients with advanced colorectal cancer (CRC) almost fourfold longer than that expected with best supportive care, an outcome achieved through combining chemotherapeutic and targeted biologic agents. Although the latter can include anti–epidermal growth factor receptor antibodies, such as cetuximab and panitumumab, we now have strong evidence that patients whose tumors harbor mutated KRAS will not benefit from this class of agent. Acceptance of the reliability and importance of the KRAS data took several years to evolve, however, for a variety of reasons. The timeline from the presentation and publication of small, retrospective phase II studies to widespread acceptance of the KRAS predictive value and changes in behavior—specifically, modifications of ongoing national trials in advanced/metastatic CRC, changes in national guidelines and practice patterns, and adjustments to the labeled indications for the monoclonal antibodies—was lengthy. In this commentary, we discuss whether or not the process of data disclosure regarding KRAS status and treatment of advanced CRC patients was effective in permitting timely decisions regarding ongoing publicly funded clinical trials and whether or not such decisions were rational and ethical. The overall goals are to highlight lessons learned regarding early disclosure of clinical trial results, as well as vetting and adoption of new scientific data, and to propose modifications for handling similar situations in the future. PMID:21737577

  20. Impact of Withholding Breastfeeding at the Time of Vaccination on the Immunogenicity of Oral Rotavirus Vaccine—A Randomized Trial

    PubMed Central

    Ali, Asad; Kazi, Abdul Momin; Cortese, Margaret M.; Fleming, Jessica A.; Moon, SungSil; Parashar, Umesh D.; Jiang, Baoming; McNeal, Monica M.; Steele, Duncan; Bhutta, Zulfiqar; Zaidi, Anita K. M.

    2015-01-01

    Background Breast milk contains anti-rotavirus IgA antibodies and other innate immune factors that inhibit rotavirus replication in vitro. These factors could diminish the immunogenicity of oral rotavirus vaccines, particularly if breastfeeding occurs close to the time of vaccine administration. Methods Between April 2011 and November 2012, we conducted an open label, randomized trial to compare the immunogenicity of Rotarix (RV1) in infants whose breastfeeding was withheld one hour before through one hour after vaccination with that in infants breastfed at the time of vaccination. The trial was conducted in the peri-urban area of Ibrahim Hyderi in Karachi, Pakistan. Both groups received three doses of RV1 at 6, 10 and 14 weeks of age. Seroconversion (anti-rotavirus IgA antibodies ≥20 U/mL in subjects seronegative at 6 weeks of age) following three vaccine doses (6, 10 and 14 weeks) was determined at 18 weeks of age (primary objective) and seroconversion following two doses (6 and 10 weeks) was determined at 14 weeks of age (secondary objective). Results Four hundred eligible infants were randomly assigned in a 1:1 ratio between the withholding breastfeeding and immediate breastfeeding arms. Overall, 353 (88.3%) infants completed the study according to protocol; 181 in the withholding breastfeeding group and 172 in the immediate breastfeeding group. After three RV1 doses, anti-rotavirus IgA antibody seroconversion was 28.2% (95% CI: 22.1; 35.1) in the withholding arm and 37.8% (95% CI: 30.9; 45.2) in the immediate breastfeeding arm (difference: -9.6% [95% CI: -19.2; 0.2] p=0.07). After two doses of RV1, seroconversion was 16.6% (95% CI: 11.9; 22.7) in the withholding arm and 29.1% (95% CI: 22.8, 36.3) in the immediate breastfeeding arm (difference: -12.5% [95% CI: -21.2,-3.8] p=0.005). Conclusions Withholding breastfeeding around the time of RV1 vaccine administration did not lead to increased anti-rotavirus IgA seroconversion compared with that seen with a

  1. Joint modeling tumor burden and time to event data in oncology trials.

    PubMed

    Shen, Ye; Anderson, Aparna; Sinha, Ritwik; Li, Yang

    2014-01-01

    The tumor burden (TB) process is postulated to be the primary mechanism through which most anticancer treatments provide benefit. In phase II oncology trials, the biologic effects of a therapeutic agent are often analyzed using conventional endpoints for best response, such as objective response rate and progression-free survival, both of which causes loss of information. On the other hand, graphical methods including spider plot and waterfall plot lack any statistical inference when there is more than one treatment arm. Therefore, longitudinal analysis of TB data is well recognized as a better approach for treatment evaluation. However, longitudinal TB process suffers from informative missingness because of progression or death. We propose to analyze the treatment effect on tumor growth kinetics using a joint modeling framework accounting for the informative missing mechanism. Our approach is illustrated by multisetting simulation studies and an application to a nonsmall-cell lung cancer data set. The proposed analyses can be performed in early-phase clinical trials to better characterize treatment effect and thereby inform decision-making. PMID:25044957

  2. Preventive home visits postpone mortality – a controlled trial with time-limited results

    PubMed Central

    Sahlen, Klas-Göran; Dahlgren, Lars; Hellner, Britt Mari; Stenlund, Hans; Lindholm, Lars

    2006-01-01

    Background There is a debate on whether preventive home visits to older people have any impact. This study was undertaken to investigate whether preventive home visits by professional health workers to older persons can postpone mortality in a Swedish context. Method A controlled trial in a small community in the north of Sweden. Participants are healthy pensioners aged 75 years and over. 196 pensioners were selected as the intervention group and 346 as the control group. The intervention, two visits per year, lasted two years. Results During the intervention, mortality was 27 per 1000 in the intervention group and 48 per 1000 in the control group. The incidence rate ratio for the control group IR2000–2001 was 1,79 (95%CI = 0,94–3,40). Analysing the data with an "on treatment approach" gave a significant result, 2,31 (95%CI = 1,07–5,02) After the trial the difference between the groups disappeared. Conclusion Preventive home visits in a healthy older population can postpone mortality in a Swedish context if they are carried out by professional health-workers in a structured way. When the home visit programme ended the effect on mortality disappeared. These findings are dependent on contextual factors that make it difficult to form general policy recommendations. PMID:16945128

  3. Statistics in review. Part 2: generalised linear models, time-to-event and time-series analysis, evidence synthesis and clinical trials.

    PubMed

    Moran, John L; Solomon, Patricia J

    2007-06-01

    In Part I, we reviewed graphical display and data summary, followed by a consideration of linear regression models. Generalised linear models, structured in terms of an exponential response distribution and link function, are now introduced, subsuming logistic and Poisson regression. Time-to-event ("survival") analysis is developed from basic principles of hazard rate, and survival, cumulative distribution and density functions. Semi-parametric (Cox) and parametric (accelerated failure time) regression models are contrasted. Time-series analysis is explicated in terms of trend, seasonal, and other cyclical and irregular components, and further illustrated by development of a classical Box-Jenkins ARMA (autoregressive moving average) model for monthly ICU-patient hospital mortality rates recorded over 11 years. Multilevel (random-effects) models and principles of meta-analysis are outlined, and the review concludes with a brief consideration of important statistical aspects of clinical trials: sample size determination, interim analysis and "early stopping". PMID:17536991

  4. Analysing Time to Event Data in Dementia Prevention Trials: The Example of the GuidAge Study of EGb761.

    PubMed

    Scherrer, B; Andrieu, S; Ousset, P J; Berrut, G; Dartigues, J F; Dubois, B; Pasquier, F; Piette, F; Robert, P; Touchon, J; Garnier, P; Mathiex-Fortunet, H; Vellas, B

    2015-12-01

    Time-to-event analysis is frequently used in medical research to investigate potential disease-modifying treatments in neurodegenerative diseases. Potential treatment effects are generally evaluated using the logrank test, which has optimal power and sensitivity when the treatment effect (hazard ratio) is constant over time. However, there is generally no prior information as to how the hazard ratio for the event of interest actually evolves. In these cases, the logrank test is not necessarily the most appropriate to use. When the hazard ratio is expected to decrease or increase over time, alternative statistical tests such as the Fleming-Harrington test, provide a better sensitivity. An example of this comes from a large, five-year randomised, placebo-controlled prevention trial (GuidAge) in 2854 community-based subjects making spontaneous memory complaints to their family physicians, which evaluated whether treatment with EGb761 can modify the risk of developing AD. The primary outcome measure was the time to conversion from memory complaint to Alzheimer's type dementia. Although there was no significant difference in the hazard function of conversion between the two treatment groups according to the preplanned logrank test, a significant treatment-by-time interaction for the incidence of AD was observed in a protocol-specified subgroup analysis, suggesting that the hazard ratio is not constant over time. For this reason, additional post hoc analyses were performed using the Fleming-Harrington test to evaluate whether there was a signal of a late effect of EGb761. Applying the Fleming-Harrington test, the hazard function for conversion to dementia in the placebo group was significantly different from that in the EGb761 treatment group (p = 0.0054), suggesting a late effect of EGb761. Since this was a post hoc analysis, no definitive conclusions can be drawn as to the effectiveness of the treatment. This post hoc analysis illustrates the interest of performing

  5. Effect of the Use and Timing of Bone Marrow Mononuclear Cell Delivery on Left Ventricular Function After Acute Myocardial Infarction: The TIME Randomized Trial

    PubMed Central

    Traverse, Jay H.; Henry, Timothy D.; Pepine, Carl J.; Willerson, James T.; Zhao, David X.M.; Ellis, Stephen G.; Forder, John R.; Anderson, R. David; Hatzopoulos, Antonis K.; Penn, Marc S.; Perin, Emerson C.; Chambers, Jeffrey; Baran, Kenneth W.; Raveendran, Ganesh; Lambert, Charles; Lerman, Amir; Simon, Daniel I.; Vaughan, Douglas E.; Lai, Dejian; Gee, Adrian P.; Taylor, Doris A.; Cogle, Christopher R.; Thomas, James D.; Olson, Rachel E.; Bowman, Sherry; Francescon, Judy; Geither, Carrie; Handberg, Eileen; Kappenman, Casey; Westbrook, Lynette; Piller, Linda B.; Simpson, Lara M.; Baraniuk, Sarah; Loghin, Catalin; Aguilar, David; Richman, Sara; Zierold, Claudia; Spoon, Daniel B.; Bettencourt, Judy; Sayre, Shelly L.; Vojvodic, Rachel W.; Skarlatos, Sonia I.; Gordon, David J.; Ebert, Ray F.; Kwak, Minjung; Moyé, Lemuel A.; Simari, Robert D.

    2013-01-01

    Context While the delivery of cell therapy following ST segment myocardial infarction (STEMI) has been evaluated in previous clinical trials, the influence of the timing of cell delivery on the effect on left ventricular (LV) function has not been analyzed in a trial that randomly designated the time of delivery. Objective To determine 1) the effect of intracoronary autologous bone marrow mononuclear cell (BMC) delivery following STEMI on recovery of global and regional LV function and 2) if timing of BMC delivery (3 versus 7 days following reperfusion) influences this effect. Design, Setting, and Patients Between July 17, 2008 and November 15, 2011, 120 patients were enrolled in a randomized, 2×2 factorial, double-blind, placebo-controlled trial of the National Heart, Lung, and Blood Institute (NHLBI)-sponsored Cardiovascular Cell Therapy Research Network (CCTRN) of patients with LV dysfunction (LV Ejection Fraction (LVEF) ≤45%) following successful primary percutaneous coronary intervention (PCI) of anterior STEMI. Interventions Intracoronary infusion of 150 × 106 BMCs or placebo (randomized 2:1 BMC:placebo) within 12 hours of aspiration and processing administered at Day 3 or Day 7 (randomized 1:1) post-PCI. Main Outcome Measures Co-primary endpoints were: 1) Change in global (LVEF) and regional (wall motion) LV function in infarct and border zones at 6 months measured by cardiac magnetic resonance imaging and 2) Change in LV function as affected by timing of treatment on Day 3 versus Day 7. Secondary endpoints included major adverse cardiovascular events as well as changes in LV volumes and infarct size. Results Patient mean age was 56.9±10.9 years with 87.5% male. At 6 months, LVEF increased similarly in both BMC (45.2±10.6 to 48.3±13.3 %) and placebo groups (44.5±10.8 to 47.8±13.6 %). No detectable treatment effect on regional LV function was observed in either infarct or border zones. Differences between therapy groups in the change in global LV

  6. Measuring Time to Biochemical Failure in the TROG 96.01 Trial: When Should the Clock Start Ticking?

    SciTech Connect

    Denham, James W.; Steigler, Allison; Kumar, Mahesh; Lamb, David S.; Joseph, David; Spry, Nigel A.; Tai, Keen-Hun; Atkinson, Chris; Turner, Sandra FRANZCR; Greer, Peter B.; Gleeson, Paul S.; D'Este, Catherine

    2009-11-15

    Purpose: We sought to determine whether short-term neoadjuvant androgen deprivation (STAD) duration influences the optimal time point from which Phoenix fail (time to biochemical failure; TTBF) should be measured. Methods and Materials: In the Trans-Tasman Radiation Oncology Group 96.01 trial, men with locally advanced prostate cancer were randomized to 3 or 6 months STAD before and during prostatic irradiation (XRT) or to XRT alone. The prognostic value of TTBF measured from the end of radiation (ERT) and randomization were compared using Cox models. Results: Between 1996 and 2000, 802 eligible patients were randomized. In 436 men with Phoenix failure, TTBF measured from randomization was a powerful predictor of prostate cancer-specific survival and marginally more accurate than TTBF measured from ERT in Cox models. Insufficient data were available to confirm that TTBF measured from testosterone recovery may also be a suitable option. Conclusions: TTBF measured from randomization (commencement of therapy) performed well in this trial dataset and will be a convenient option if this finding holds in other datasets that include long-term androgen deprivation data.

  7. Timing and extent of response in colorectal cancer: critical review of current data and implication for future trials.

    PubMed

    Aprile, Giuseppe; Fontanella, Caterina; Bonotto, Marta; Rihawi, Karim; Lutrino, Stefania Eufemia; Ferrari, Laura; Casagrande, Mariaelena; Ongaro, Elena; Berretta, Massimiliano; Avallone, Antonio; Rosati, Gerardo; Giuliani, Francesco; Fasola, Gianpiero

    2015-10-01

    The identification of new surrogate endpoints for advanced colorectal cancer is becoming crucial and, along with drug development, it represents a research field increasingly studied. Although overall survival (OS) remains the strongest trial endpoint available, it requires larger sample size and longer periods of time for an event to happen. Surrogate endpoints such as progression free survival (PFS) or response rate (RR) may overcome these issues but, as such, they need to be prospectively validated before replacing the real endpoints; moreover, they often bear many other limitations. In this narrative review we initially discuss the role of time-to-event endpoints, objective response and response rate as surrogates of OS in the advanced colorectal cancer setting, discussing also how such measures are influenced by the tumor assessment criteria currently employed. We then report recent data published about early tumor shrinkage and deepness of response, which have recently emerged as novel potential endpoint surrogates, discussing their strengths and weaknesses and providing a critical comment. Despite being very compelling, the role of such novel response measures is yet to be confirmed and their surrogacy with OS still needs to be further investigated within larger and well-designed trials. PMID:26308250

  8. Timing and extent of response in colorectal cancer: critical review of current data and implication for future trials

    PubMed Central

    Aprile, Giuseppe; Fontanella, Caterina; Bonotto, Marta; Rihawi, Karim; Lutrino, Stefania Eufemia; Ferrari, Laura; Casagrande, Mariaelena; Ongaro, Elena; Berretta, Massimiliano; Avallone, Antonio; Rosati, Gerardo; Giuliani, Francesco; Fasola, Gianpiero

    2015-01-01

    The identification of new surrogate endpoints for advanced colorectal cancer is becoming crucial and, along with drug development, it represents a research field increasingly studied. Although overall survival (OS) remains the strongest trial endpoint available, it requires larger sample size and longer periods of time for an event to happen. Surrogate endpoints such as progression free survival (PFS) or response rate (RR) may overcome these issues but, as such, they need to be prospectively validated before replacing the real endpoints; moreover, they often bear many other limitations. In this narrative review we initially discuss the role of time-to-event endpoints, objective response and response rate as surrogates of OS in the advanced colorectal cancer setting, discussing also how such measures are influenced by the tumor assessment criteria currently employed. We then report recent data published about early tumor shrinkage and deepness of response, which have recently emerged as novel potential endpoint surrogates, discussing their strengths and weaknesses and providing a critical comment. Despite being very compelling, the role of such novel response measures is yet to be confirmed and their surrogacy with OS still needs to be further investigated within larger and well-designed trials. PMID:26308250

  9. Detrended Fluctuation Analysis and Adaptive Fractal Analysis of Stride Time Data in Parkinson's Disease: Stitching Together Short Gait Trials

    PubMed Central

    Liebherr, Magnus; Haas, Christian T.

    2014-01-01

    Variability indicates motor control disturbances and is suitable to identify gait pathologies. It can be quantified by linear parameters (amplitude estimators) and more sophisticated nonlinear methods (structural information). Detrended Fluctuation Analysis (DFA) is one method to measure structural information, e.g., from stride time series. Recently, an improved method, Adaptive Fractal Analysis (AFA), has been proposed. This method has not been applied to gait data before. Fractal scaling methods (FS) require long stride-to-stride data to obtain valid results. However, in clinical studies, it is not usual to measure a large number of strides (e.g., strides). Amongst others, clinical gait analysis is limited due to short walkways, thus, FS seem to be inapplicable. The purpose of the present study was to evaluate FS under clinical conditions. Stride time data of five self-paced walking trials ( strides each) of subjects with PD and a healthy control group (CG) was measured. To generate longer time series, stride time sequences were stitched together. The coefficient of variation (CV), fractal scaling exponents (DFA) and (AFA) were calculated. Two surrogate tests were performed: A) the whole time series was randomly shuffled; B) the single trials were randomly shuffled separately and afterwards stitched together. CV did not discriminate between PD and CG. However, significant differences between PD and CG were found concerning and . Surrogate version B yielded a higher mean squared error and empirical quantiles than version A. Hence, we conclude that the stitching procedure creates an artificial structure resulting in an overestimation of true . The method of stitching together sections of gait seems to be appropriate in order to distinguish between PD and CG with FS. It provides an approach to integrate FS as standard in clinical gait analysis and to overcome limitations such as short walkways. PMID:24465708

  10. Predictions of future dangerousness in capital murder trials: is it time to "disinvent the wheel"?

    PubMed

    Edens, John F; Buffington-Vollum, Jacqueline K; Keilen, Andrea; Roskamp, Phillip; Anthony, Christine

    2005-02-01

    Although recent U.S. Supreme Court decisions regarding the death penalty (e.g., Atkins v. Virginia, 2002) have renewed interest in mental health issues, one topic that has not received much attention recently is the ongoing use of expert testimony to support claims that defendants represent a "continuing threat to society." In this article, we (a) review prior research relevant to determining the accuracy of clinical predictions that capital defendants will commit future acts of criminal violence; (b) summarize new data from current and former death row inmates in Texas that bolster the claim that such predictions are gross overestimates of risk; and (c) review extant research addressing the potential utility of various risk assessment instruments that increasingly are being used to reinforce clinical predictions in capital trials. Despite significant recent advances in the field of risk assessment, clinical assertions that a defendant is likely to commit future violent acts appear to be highly inaccurate and ethically questionable at best. Moreover, available research offers little support for the claim that the accuracy of these predictions will be appreciably improved by relying on more structured risk assessment measures that have some demonstrated predictive validity in other contexts. PMID:15865332

  11. Measuring social integration in a pilot randomized controlled trial of critical time: intervention-task shifting in Latin America

    PubMed Central

    Baumgartner, Joy Noel; da Silva, Tatiana Fernandes Carpinteiro; Valencia, Eliecer; Susser, Ezra

    2013-01-01

    Global mental health movements increasingly highlight the importance of social integration for individuals living with severe mental illnesses. However, this important individual-level outcome is rarely measured in programs. As part of RedeAmericas, a pilot regional randomized controlled trial of critical time intervention — task shifting — will be conducted, which includes social integration as an outcome measure. It is a time-limited care coordination model to enhance continuity of support for people with severe mental illness during critical periods of transition. Given the challenges of measuring social integration, particularly for a multi-country study with unique cultural contexts, this paper has described the measurement approach used to create a composite measure that uses items from disability and quality of life instruments in addition to other key items. PMID:24288454

  12. Measuring social integration in a pilot randomized controlled trial of critical time: intervention-task shifting in Latin America.

    PubMed

    Baumgartner, Joy Noel; da Silva, Tatiana Fernandes Carpinteiro; Valencia, Eliecer; Susser, Ezra

    2012-01-01

    Global mental health movements increasingly highlight the importance of social integration for individuals living with severe mental illnesses. However, this important individual-level outcome is rarely measured in programs. As part of RedeAmericas, a pilot regional randomized controlled trial of critical time intervention - task shifting - will be conducted, which includes social integration as an outcome measure. It is a time-limited care coordination model to enhance continuity of support for people with severe mental illness during critical periods of transition. Given the challenges of measuring social integration, particularly for a multi-country study with unique cultural contexts, this paper has described the measurement approach used to create a composite measure that uses items from disability and quality of life instruments in addition to other key items. PMID:24288454

  13. A Follow up Randomized Controlled Trial of "Time to Read": A Volunteer Mentoring Program

    ERIC Educational Resources Information Center

    Miller, Sarah; Connolly, Paul; Maguire, Lisa K.

    2011-01-01

    "Time to Read" is a volunteer mentoring program that recruits volunteers from the local business community to spend one hour of company time each week working on a one-to-one basis with primary school children aged 8 to 9 years with the aim of improving reading skills. The authors first evaluated the program in 2006-8 using a randomized controlled…

  14. A Phase III Randomized Trial of the Timing of Meloxicam With Iodine-125 Prostate Brachytherapy

    SciTech Connect

    Crook, Juanita; Patil, Nikhilesh; Wallace, Kris; Borg, Jette; Zhou, David; Ma, Clement; Pond, Greg

    2010-06-01

    Purpose: Nonsteroidal anti-inflammatory medication is used to reduce prostate edema and urinary symptoms following prostate brachytherapy. We hypothesized that a cyclooxygenase-2 (COX-2) inhibitor regimen started 1 week prior to seed implant might diminish the inflammatory response, thus reducing edema, retention rates, and symptom severity. Methods and Materials: From March 2004 to February 2008, 316 men consented to an institutional review board-approved randomized study of a 4-week course of meloxicam, 7.5 mg orally twice per day, starting either on the day of implant or 1 week prior to implant. Brachytherapy was performed using iodine-125 seeds and was preplanned and performed under transrectal ultrasound (TRUS) and fluoroscopic guidance. Prostate volume obtained by MR imaging at 1 month was compared to baseline prostate volume obtained by TRUS planimetry and expressed as an edema factor. The trial endpoints were prostate edema at 1 month, International Prostate Symptom Score (IPSS) questionnaire results at 1 and 3 months, and any need for catheterization. Results: Results for 300 men were analyzed. Median age was 61 (range, 45-79 years), and median TRUS prostate volume was 35.7 cc (range, 18.1-69.5 cc). Median IPSS at baseline was 5 (range, 0-24) and was 15 at 1 month, 16 at 3 months, and 10 at 6 months. Catheterization was required for 7% of patients (6.2% day 0 arm vs. 7.9% day -7 arm; p = 0.65). The median edema factor at 1 month was 1.02 (range, 0.73-1.7). 1.01 day 0 arm vs. 1.05 day -7 arm. Baseline prostate volume remained the primary predictor of postimplant urinary retention. Conclusions: Starting meloxicam 1 week prior to brachytherapy compared to starting immediately after the procedure did not reduce 1-month edema, improve IPSSs at 1 or 3 months, or reduce the need for catheterization.

  15. Reducing office workers’ sitting time: rationale and study design for the Stand Up Victoria cluster randomized trial

    PubMed Central

    2013-01-01

    Background Excessive time spent in sedentary behaviours (sitting or lying with low energy expenditure) is associated with an increased risk for type 2 diabetes, cardiovascular disease and some cancers. Desk-based office workers typically accumulate high amounts of daily sitting time, often in prolonged unbroken bouts. The Stand Up Victoria study aims to determine whether a 3-month multi-component intervention in the office setting reduces workplace sitting, particularly prolonged, unbroken sitting time, and results in improvements in cardio-metabolic biomarkers and work-related outcomes, compared to usual practice. Methods/Design A two-arm cluster-randomized controlled trial (RCT), with worksites as the unit of randomization, will be conducted in 16 worksites located in Victoria, Australia. Work units from one organisation (Department of Human Services, Australian Government) will be allocated to either the multi-component intervention (organisational, environmental [height-adjustable workstations], and individual behavioural strategies) or to a usual practice control group. The recruitment target is 160 participants (office-based workers aged 18–65 years and working at least 0.6 full time equivalent) per arm. At each assessment (0- [baseline], 3- [post intervention], and 12-months [follow-up]), objective measurement via the activPAL3 activity monitor will be used to assess workplace: sitting time (primary outcome); prolonged sitting time (sitting time accrued in bouts of ≥30 minutes); standing time; sit-to-stand transitions; and, moving time. Additional outcomes assessed will include: non-workplace activity; cardio-metabolic biomarkers and health indicators (including fasting glucose, lipids and insulin; anthropometric measures; blood pressure; and, musculoskeletal symptoms); and, work-related outcomes (presenteeism, absenteeism, productivity, work performance). Incremental cost-effectiveness and identification of both workplace and individual

  16. The effect of time on CPR and automated external defibrillator skills in the Public Access Defibrillation Trial

    PubMed Central

    Christenson, Jim; Nafziger, Sarah; Compton, Scott; Vijayaraghavan, Kris; Slater, Brian; Ledingham, Robert; Powell, Judy; McBurnie, Mary Ann

    2009-01-01

    Background The time to skill deterioration between primary training/retraining and further retraining in Cardiopulmonary resuscitation (CPR) and automated external defibrillation (AED) for lay-persons is unclear. The Public Access Defibrillation (PAD) Trial was a multi-center randomized controlled trial evaluating survival after CPR-only vs. CPR+AED delivered by onsite non-medical volunteer responders in out-of-hospital cardiac arrest. Aims This sub-study evaluated the relationship of time between primary training/retraining and further retraining on volunteer performance during pretest AED and CPR skill evaluation. Methods Volunteers at 1260 facilities in 24 North American regions underwent training/retraining according to facility randomization, which included an initial session and a refresher session at approximately 6 months. Before the next retraining, a CPR and AED skill test was completed for 2729 volunteers. Primary outcome for the study was assessment of global competence of CPR or AED performance (adequate vs not adequate) using Chi-square tests for trends by time interval (3, 6, 9, and 12 months). Confirmatory (GEE) logistic regression analysis, adjusted for site and potential confounders. Results The proportion of volunteers judged to be competent did not diminish by interval (3,6,9,12 months) for either CPR or AED skills. After adjusting for site and potential confounders, longer intervals before to further retraining was associated with a slightly lower likelihood of performing adequate CPR but not with AED scores. Conclusions After primary training/retraining, the CPR skills of targeted lay responders deteriorate nominally but 80% remain competent up to one year. AED skills do not significantly deteriorate and 90% of volunteers remain competent up to one year. PMID:17303309

  17. Subacute dietary toxicities of dicrotophos and dieldrin in time-replicated trials with young ring-necked pheasants and mallards

    USGS Publications Warehouse

    Hill, E.F.

    1982-01-01

    The dietary toxicities of (E)-phosphoric acid 3-(dimethylamino)-1-methyl-3-oxo-1-propenyl dimethyl ester (dicrotophos) and 3,4,5,6,9,9-hexachloro-1a,2,2a,3,6,6a,7,7a-octahydro-2,7:3,6-dimethanonaphth[2,3-b]oxirene (dieldrin) to 10-day-old ring-necked pheasants (Phasianus colchicus) and 5-day-old mallards (Anas platyrhynchos) were compared in five time-replicated trials. Toxicities were calculated as median lethal concentrations (LC50s) based on 5 days of ad libitum feeding on geometrically spaced concentrations of toxicant. The LC50s were more uniform for dieldrin than for dicrotophos with both species and more uniform for pheasants than for mallards with both compounds. The LC50s of dieldrin and dicrotophos averaged 59 [standard deviation (SD) = 4.4] and 45 ppm (SD = 5.0) for pheasants, and 156 (SD = 24.9) and 102 ppm (SD = 24.9) for mallards. Changes in LC50s between successive trials, although possibly haphazard, were nearly always in the same direction for both compounds with both species. Feeding rates at various concentrations of equivalent potency gave meaningful insight into the sensitivity and vulnerability of both species to these insecticides. Comparisons of 5 and 10-day-old mallards demonstrated the importance of age differences to interpretation of short-term subacute toxicity data. For example, at 5 days dicrotophos was 1.5 times more toxic than dieldrin, but at 10 days dieldrin was 2.6 times more toxic. These differences are explained.

  18. A Randomised Controlled Trial to Reduce Sedentary Time in Young Adults at Risk of Type 2 Diabetes Mellitus: Project STAND (Sedentary Time ANd Diabetes)

    PubMed Central

    Biddle, Stuart J. H.; Edwardson, Charlotte L.; Wilmot, Emma G.; Yates, Thomas; Gorely, Trish; Bodicoat, Danielle H.; Ashra, Nuzhat; Khunti, Kamlesh; Nimmo, Myra A.; Davies, Melanie J.

    2015-01-01

    Aims Type 2 diabetes mellitus (T2DM), a serious and prevalent chronic disease, is traditionally associated with older age. However, due to the rising rates of obesity and sedentary lifestyles, it is increasingly being diagnosed in the younger population. Sedentary (sitting) behaviour has been shown to be associated with greater risk of cardio-metabolic health outcomes, including T2DM. Little is known about effective interventions to reduce sedentary behaviour in younger adults at risk of T2DM. We aimed to investigate, through a randomised controlled trial (RCT) design, whether a group-based structured education workshop focused on sitting reduction, with self-monitoring, reduced sitting time. Methods Adults aged 18–40 years who were either overweight (with an additional risk factor for T2DM) or obese were recruited for the Sedentary Time ANd Diabetes (STAND) RCT. The intervention programme comprised of a 3-hour group-based structured education workshop, use of a self-monitoring tool, and follow-up motivational phone call. Data were collected at three time points: baseline, 3 and 12 months after baseline. The primary outcome measure was accelerometer-assessed sedentary behaviour after 12 months. Secondary outcomes included other objective (activPAL) and self-reported measures of sedentary behaviour and physical activity, and biochemical, anthropometric, and psycho-social variables. Results 187 individuals (69% female; mean age 33 years; mean BMI 35 kg/m2) were randomised to intervention and control groups. 12 month data, when analysed using intention-to-treat analysis (ITT) and per-protocol analyses, showed no significant difference in the primary outcome variable, nor in the majority of the secondary outcome measures. Conclusions A structured education intervention designed to reduce sitting in young adults at risk of T2DM was not successful in changing behaviour at 12 months. Lack of change may be due to the brief nature of such an intervention and lack of focus

  19. A Single-Center Randomized Controlled Trial Evaluating Timing of Preparation for Capsule Enteroscopy

    PubMed Central

    Black, Katherine R.; Truss, Wiley; Joiner, Cynthia I.; Peter, Shajan

    2015-01-01

    Background/Aims Intestinal lavage (IL) administration immediately before capsule enteroscopy (CE) is superior to lavage the day before the procedure. We aimed to determine the effect of IL timing on CE diagnostic yield. Methods Patients referred for CE were randomized prospectively into two equal groups according to the timing of IL with 2 L of polyethylene glycol solution. Group A and B underwent IL over 2 hours beginning 14 and 4 hours, respectively, before the scheduled CE. The primary outcome measure was preparation quality, measured with a predetermined validated grading scale. Results A total of 34 patients were randomized. The frequency of mucosal abnormalities (77% vs. 82%, p=not significant [NS]) and diagnostic yield (47% vs. 53%, p=NS) were similar between the two groups. Moreover, no significant association between the quality of small bowel preparation and the timing at which the purgative for IL was administered was observed (overall fluid transparency, p=0.936; overall mucosal invisibility, p=0.091). Conclusions Day-before IL is equivalent to same-day IL in terms of overall preparation quality, proportion of complete studies to cecum, small bowel transit time, frequency of identified mucosal abnormalities, and overall diagnostic yield. PMID:26064824

  20. The Microcomputer as Tachistoscope: Trials and Tribulations of Timing on the TRS-80.

    ERIC Educational Resources Information Center

    Mapou, Robert L.

    In this paper a hardware/software system is described which permits the use of the Radio Shack TRS-80 Model I as a tachistoscope in perceptual-cognitive research. Hardware requirements and configuration, problems in developing software routines to handle reaction and stimulus timing using the TRS-80, and the development of a routine for…

  1. Timing the therapeutic window of opportunity in early rheumatoid arthritis: proposal for definitions of disease duration in clinical trials.

    PubMed

    Raza, Karim; Saber, Tajvur P; Kvien, Tore K; Tak, Paul P; Gerlag, Danielle M

    2012-12-01

    The effects of treatment in early rheumatoid arthritis (RA) and the consequences of delayed therapy represent important areas for research. The concept of a 'window of opportunity' is now well established and considerable attention has been paid to when it might close. However, in order to study how long the window of opportunity lasts, the timing of its opening must be precisely defined. An analysis of definitions of 'onset' in clinical studies reveals imprecision and heterogeneity, making accurate assessment of this important concept of the 'window of opportunity' very difficult. In this paper we propose that, in clinical trials in early RA, data on durations since onset of symptoms and onset of joint swelling as well as disease duration based on fulfilment of classification criteria should be routinely presented. PMID:22941769

  2. A logrank test-based method for sizing clinical trials with two co-primary time-to-event endpoints.

    PubMed

    Sugimoto, Tomoyuki; Sozu, Takashi; Hamasaki, Toshimitsu; Evans, Scott R

    2013-07-01

    We discuss sample size determination for clinical trials evaluating the joint effects of an intervention on two potentially correlated co-primary time-to-event endpoints. For illustration, we consider the most common case, a comparison of two randomized groups, and use typical copula families to model the bivariate endpoints. A correlation structure of the bivariate logrank statistic is specified to account for the correlation among the endpoints, although the between-group comparison is performed using the univariate logrank statistic. We propose methods to calculate the required sample size to compare the two groups and evaluate the performance of the methods and the behavior of required sample sizes via simulation. PMID:23307913

  3. Protocol for the CHEST Australia Trial: a phase II randomised controlled trial of an intervention to reduce time-to-consult with symptoms of lung cancer

    PubMed Central

    Murray, Sonya R; Murchie, Peter; Campbell, Neil; Walter, Fiona M; Mazza, Danielle; Habgood, Emily; Kutzer, Yvonne; Martin, Andrew; Goodall, Stephen; Barnes, David J

    2015-01-01

    Introduction Lung cancer is the most common cancer worldwide, with 1.3 million new cases diagnosed every year. It has one of the lowest survival outcomes of any cancer because over two-thirds of patients are diagnosed when curative treatment is not possible. International research has focused on screening and community interventions to promote earlier presentation to a healthcare provider to improve early lung cancer detection. This paper describes the protocol for a phase II, multisite, randomised controlled trial, for patients at increased risk of lung cancer in the primary care setting, to facilitate early presentation with symptoms of lung cancer. Methods/analysis The intervention is based on a previous Scottish CHEST Trial that comprised of a primary-care nurse consultation to discuss and implement a self-help manual, followed by self-monitoring reminders to improve symptom appraisal and encourage help-seeking in patients at increased risk of lung cancer. We aim to recruit 550 patients from two Australian states: Western Australia and Victoria. Patients will be randomised to the Intervention (a health consultation involving a self-help manual, monthly prompts and spirometry) or Control (spirometry followed by usual care). Eligible participants are long-term smokers with at least 20 pack years, aged 55 and over, including ex-smokers if their cessation date was less than 15 years ago. The primary outcome is consultation rate for respiratory symptoms. Ethics and dissemination Ethical approval has been obtained from The University of Western Australia's Human Research Ethics Committee (RA/4/1/6018) and The University of Melbourne Human Research Committee (1 441 433). A summary of the results will be disseminated to participants and we plan to publish the main trial outcomes in a single paper. Further publications are anticipated after further data analysis. Findings will be presented at national and international conferences from late 2016. Trial

  4. Family-based interventions for reducing sedentary time in youth: a systematic review of randomized controlled trials.

    PubMed

    Marsh, S; Foley, L S; Wilks, D C; Maddison, R

    2014-02-01

    Family involvement in interventions to reduce sedentary time may help foster appropriate long-term screen-based habits in children. This review systematically synthesized evidence from randomized controlled trials of interventions with a family component that targeted reduction of sedentary time, including TV viewing, video games and computer use, in children. MEDLINE, PubMed, PsycInfo, CINAHL and Embase were searched from inception through March 2012. Seventeen articles were considered eligible and included in the review. Studies were judged to be at low-to-moderate risk of bias. Despite inconsistent study results, level of parental involvement, rather than the setting itself, appeared an important determinant of intervention success. Studies including a parental component of medium-to-high intensity were consistently associated with statistically significant changes in sedentary behaviours. Participant age was also identified as a determinant of intervention outcomes; all three studies conducted in pre-school children demonstrated significant decreases in sedentary time. Finally, TV exposure appeared to be related to changes in energy intake rather than physical activity. Future studies should assess the effects of greater parental involvement and child age on success of sedentary behaviour interventions. More research is required to better understand the relationship between screen time and health behaviours, particularly energy intake. PMID:24102891

  5. Effect of Paralysis at the Time of ProSeal Laryngeal Mask Airway Insertion on Pharyngolaryngeal Morbidities. A Randomized Trial

    PubMed Central

    Shin, Hyun-Jung; Oh, Ah-Young; Park, Hee-Pyoung; Hwang, Jung-Won

    2015-01-01

    Neuromuscular block results in the loss of muscular tone in the upper airway, which might contribute to the increased postoperative airway morbidity followed by ProSeal laryngeal mask airway (PLMA) insertion. We compared the pharyngolaryngeal discomfort exerted by the PLMA according to the neuromuscular block. One hundred sixty patients undergoing surgery for breast disease or inguinal hernia were anesthetized with propofol and remifentanil by target controlled infusion. Rocuronium 0.6 mg/kg (NMBA group, n = 80) or normal saline (No-NMBA group, n = 80) was administered after the loss of consciousness, and one anesthesiologist inserted the PLMA. Postoperative pharyngolaryngeal discomfort was evaluated at postoperative 1 h. Traumatic event was recorded based on the blood trace on the surface of the PLMA cuff. Insertion time, insertion attempt number, sealing pressure, and fiberoptic brochoscopic grades were evaluated. Patients’ characteristics and the PLMA insertion condition (insertion time, successful insertion attempt number, fiberoptic bronchoscopic grade, and sealing pressure) were similar between the two groups. The PLMA can be successfully inserted in non-paralyzed patients with less postoperative pharyngolaryngeal discomfort than when a neuromuscular blocking agent is used (13.8% vs. 30.0%, P = 0.021). The incidence of traumatic events is also reduced when no neuromuscular blocking agent is used (16.3% vs. 32.5%, P = 0.026). Regardless of whether or not a surgical procedure requires muscular relaxation, there is no need to administer neuromuscular blocking agents solely for the purpose of PLMA insertion. Trial Registration ClinicalTrials.gov NCT01035021 PMID:26252522

  6. Determining probability distributions of parameter performances for time-series model calibration: A river system trial

    NASA Astrophysics Data System (ADS)

    Kim, Shaun Sang Ho; Hughes, Justin Douglas; Chen, Jie; Dutta, Dushmanta; Vaze, Jai

    2015-11-01

    A calibration method is presented that uses a sub-period resampling method to estimate probability distributions of performance for different parameter sets. Where conventional calibration methods implicitly identify the best performing parameterisations on average, the new method looks at the consistency of performance during sub-periods. The method is implemented with the conceptual river reach algorithms within the Australian Water Resources Assessments River (AWRA-R) model in the Murray-Darling Basin, Australia. The new method is tested for 192 reaches in a cross-validation scheme and results are compared to a traditional split-sample calibration-validation implementation. This is done to evaluate the new technique's ability to predict daily streamflow outside the calibration period. The new calibration method produced parameterisations that performed better in validation periods than optimum calibration parameter sets for 103 reaches and produced the same parameterisations for 35 reaches. The method showed a statistically significant improvement to predictive performance and potentially provides more rational flux terms over traditional split-sample calibration methods. Particular strengths of the proposed calibration method is that it avoids extra weighting towards rare periods of good agreement and also prevents compensating biases through time. The method can be used as a diagnostic tool to evaluate stochasticity of modelled systems and used to determine suitable model structures of different time-series models. Although the method is demonstrated using a hydrological model, the method is not limited to the field of hydrology and could be adopted for many different time-series modelling applications.

  7. Clinical trials of fluvoxamine vs chlorimipramine with single and three times daily dosing

    PubMed Central

    De Wilde, J. E.; Mertens, C.; Wakelin, J. S.

    1983-01-01

    1 Two double-blind, randomised studies were performed to compare the efficacy of fluvoxamine and chlorimipramine in depressed patients. In the first study the effects of a single daily dosage of between 100 and 300 mg of fluvoxamine were compared with those of chlorimipramine at a dosage of 50-150 mg daily in 43 out-patients with endogenous depression. 2 In a second study using three times daily dosing with a daily dosage of 150-300 mg for both fluvoxamine and chlorimipramine, 30 in-patients with unipolar or bipolar depression were assessed. 3 Four weeks of treatment with single daily dosing resulted in a mean improvement of 61.4% (± s.d. 31.7) on the Hamilton Rating Scale for Depression (HAMD) for fluvoxamine and of 65.3% (± s.d. 25.8) for chlorimipramine. In the study with three times daily dosing the mean results were 72.9% (± s.d. 22.3) improvement for fluvoxamine and 62.1% (± s.d. 28.5) for chlorimipramine. 4 At similar dosages, fluvoxamine had significantly less untoward effects on blood pressure than chlorimipramine. Anticholinergic effects were also fewer in the fluvoxamine group, as were nervous system symptoms, with the latter difference reaching statistical significance (P = 0.02). 5 We conclude that fluvoxamine, given in a single daily dose of 150-250 mg, provides antidepressant efficacy similar to chlorimipramine. At this dosage it may be expected to produce less anticholinergic effects and have less influence on blood pressure than chlorimipramine. PMID:6407503

  8. Methods for testing theory and evaluating impact in randomized field trials: intent-to-treat analyses for integrating the perspectives of person, place, and time.

    PubMed

    Brown, C Hendricks; Wang, Wei; Kellam, Sheppard G; Muthén, Bengt O; Petras, Hanno; Toyinbo, Peter; Poduska, Jeanne; Ialongo, Nicholas; Wyman, Peter A; Chamberlain, Patricia; Sloboda, Zili; MacKinnon, David P; Windham, Amy

    2008-06-01

    Randomized field trials provide unique opportunities to examine the effectiveness of an intervention in real world settings and to test and extend both theory of etiology and theory of intervention. These trials are designed not only to test for overall intervention impact but also to examine how impact varies as a function of individual level characteristics, context, and across time. Examination of such variation in impact requires analytical methods that take into account the trial's multiple nested structure and the evolving changes in outcomes over time. The models that we describe here merge multilevel modeling with growth modeling, allowing for variation in impact to be represented through discrete mixtures--growth mixture models--and nonparametric smooth functions--generalized additive mixed models. These methods are part of an emerging class of multilevel growth mixture models, and we illustrate these with models that examine overall impact and variation in impact. In this paper, we define intent-to-treat analyses in group-randomized multilevel field trials and discuss appropriate ways to identify, examine, and test for variation in impact without inflating the Type I error rate. We describe how to make causal inferences more robust to misspecification of covariates in such analyses and how to summarize and present these interactive intervention effects clearly. Practical strategies for reducing model complexity, checking model fit, and handling missing data are discussed using six randomized field trials to show how these methods may be used across trials randomized at different levels. PMID:18215473

  9. Experiential Virtual Scenarios With Real-Time Monitoring (Interreality) for the Management of Psychological Stress: A Block Randomized Controlled Trial

    PubMed Central

    Pallavicini, Federica; Morganti, Luca; Serino, Silvia; Scaratti, Chiara; Briguglio, Marilena; Crifaci, Giulia; Vetrano, Noemi; Giulintano, Annunziata; Bernava, Giuseppe; Tartarisco, Gennaro; Pioggia, Giovanni; Raspelli, Simona; Cipresso, Pietro; Vigna, Cinzia; Grassi, Alessandra; Baruffi, Margherita; Wiederhold, Brenda; Riva, Giuseppe

    2014-01-01

    Background The recent convergence between technology and medicine is offering innovative methods and tools for behavioral health care. Among these, an emerging approach is the use of virtual reality (VR) within exposure-based protocols for anxiety disorders, and in particular posttraumatic stress disorder. However, no systematically tested VR protocols are available for the management of psychological stress. Objective Our goal was to evaluate the efficacy of a new technological paradigm, Interreality, for the management and prevention of psychological stress. The main feature of Interreality is a twofold link between the virtual and the real world achieved through experiential virtual scenarios (fully controlled by the therapist, used to learn coping skills and improve self-efficacy) with real-time monitoring and support (identifying critical situations and assessing clinical change) using advanced technologies (virtual worlds, wearable biosensors, and smartphones). Methods The study was designed as a block randomized controlled trial involving 121 participants recruited from two different worker populations—teachers and nurses—that are highly exposed to psychological stress. Participants were a sample of teachers recruited in Milan (Block 1: n=61) and a sample of nurses recruited in Messina, Italy (Block 2: n=60). Participants within each block were randomly assigned to the (1) Experimental Group (EG): n=40; B1=20, B2=20, which received a 5-week treatment based on the Interreality paradigm; (2) Control Group (CG): n=42; B1=22, B2=20, which received a 5-week traditional stress management training based on cognitive behavioral therapy (CBT); and (3) the Wait-List group (WL): n=39, B1=19, B2=20, which was reassessed and compared with the two other groups 5 weeks after the initial evaluation. Results Although both treatments were able to significantly reduce perceived stress better than WL, only EG participants reported a significant reduction (EG=12% vs CG=0

  10. A First-Time-In-Human Phase I Clinical Trial of Bispecific Antibody-Targeted, Paclitaxel-Packaged Bacterial Minicells

    PubMed Central

    Rosenthal, Mark; McArthur, Grant A.; Pattison, Scott T.; Pattison, Stacey L.; MacDiarmid, Jennifer; Brahmbhatt, Himanshu; Scott, Andrew M.

    2015-01-01

    Background We have harnessed a novel biological system, the bacterial minicell, to deliver cancer therapeutics to cancer cells. Preclinical studies showed that epidermal growth factor receptor (EGFR)-targeted, paclitaxel-loaded minicells (EGFRminicellsPac) have antitumor effects in xenograft models. To examine the safety of the minicell delivery system, we initiated a first-time-in-human, open-label, phase I clinical study of EGFRminicellsPac in patients with advanced solid tumors. Methodology Patients received 5 weekly infusions followed by a treatment free week. Seven dose levels (1x108, 1x109, 3x109, 1x1010, 1.5x1010, 2x1010, 5x1010) were evaluated using a 3+3 dose-escalation design. Primary objectives were safety, tolerability and determination of the maximum tolerated dose. Secondary objectives were assessment of immune/inflammatory responses and antitumor activity. Principal Findings Twenty eight patients were enrolled, 22 patients completed at least one cycle of EGFRminicellsPac; 6 patients did not complete a cycle due to rapidly progressive disease. A total of 236 doses was delivered over 42 cycles, with a maximum of 45 doses administered to a single patient. Most common treatment-related adverse events were rigors and pyrexia. No deaths resulted from treatment-related adverse events and the maximum tolerated dose was defined as 1x1010 EGFRminicellsPac. Surprisingly, only a mild self-limiting elevation in the inflammatory cytokines IL-6, IL-8 and TNFα and anti-inflammatory IL-10 was observed. Anti-LPS antibody titers peaked by dose 3 and were maintained at that level despite repeat dosing with the bacterially derived minicells. Ten patients (45%; n = 22) achieved stable disease as their best response. Conclusions/Significance This is the first study in humans of a novel biological system that can provide targeted delivery of a range of chemotherapeutic drugs to solid tumor cells. Bispecific antibody-targeted minicells, packaged with the chemotherapeutic

  11. Positive Pacing Strategies Are Utilized by Elite Male and Female Para-cyclists in Short Time Trials in the Velodrome

    PubMed Central

    Wright, Rachel L.

    2016-01-01

    In para-cycling, competitors are classed based on functional impairment resulting in cyclists with neurological and locomotor impairments competing against each other. In Paralympic competition, classes are combined by using a factoring adjustment to race times to produce the overall medallists. Pacing in short-duration track cycling events is proposed to utilize an “all-out” strategy in able-bodied competition. However, pacing in para-cycling may vary depending on the level of impairment. Analysis of the pacing strategies employed by different classification groups may offer scope for optimal performance; therefore, this study investigated the pacing strategy adopted during the 1-km time trial (TT) and 500-m TT in elite C1 to C3 para-cyclists and able-bodied cyclists. Total times and intermediate split times (125-m intervals; measured to 0.001 s) were obtained from the C1-C3 men's 1-km TT (n = 28) and women's 500-m TT (n = 9) from the 2012 Paralympic Games and the men's 1-km TT (n = 19) and women's 500-m TT (n = 12) from the 2013 UCI World Track Championships from publically available video. Split times were expressed as actual time, factored time (for the para-cyclists) and as a percentage of total time. A two-way analysis of variance was used to investigate differences in split times between the different classifications and the able-bodied cyclists in the men's 1-km TT and between the para-cyclists and able-bodied cyclists in the women's 500-m TT. The importance of position at the first split was investigated with Kendall's Tau-b correlation. The first 125-m split time was the slowest for all cyclists, representing the acceleration phase from a standing start. C2 cyclists were slowest at this 125-m split, probably due to a combination of remaining seated in this acceleration phase and a high proportion of cyclists in this group being trans-femoral amputees. Not all cyclists used aero-bars, preferring to use drop, flat or bullhorn handlebars. Split times

  12. Positive Pacing Strategies Are Utilized by Elite Male and Female Para-cyclists in Short Time Trials in the Velodrome.

    PubMed

    Wright, Rachel L

    2015-01-01

    In para-cycling, competitors are classed based on functional impairment resulting in cyclists with neurological and locomotor impairments competing against each other. In Paralympic competition, classes are combined by using a factoring adjustment to race times to produce the overall medallists. Pacing in short-duration track cycling events is proposed to utilize an "all-out" strategy in able-bodied competition. However, pacing in para-cycling may vary depending on the level of impairment. Analysis of the pacing strategies employed by different classification groups may offer scope for optimal performance; therefore, this study investigated the pacing strategy adopted during the 1-km time trial (TT) and 500-m TT in elite C1 to C3 para-cyclists and able-bodied cyclists. Total times and intermediate split times (125-m intervals; measured to 0.001 s) were obtained from the C1-C3 men's 1-km TT (n = 28) and women's 500-m TT (n = 9) from the 2012 Paralympic Games and the men's 1-km TT (n = 19) and women's 500-m TT (n = 12) from the 2013 UCI World Track Championships from publically available video. Split times were expressed as actual time, factored time (for the para-cyclists) and as a percentage of total time. A two-way analysis of variance was used to investigate differences in split times between the different classifications and the able-bodied cyclists in the men's 1-km TT and between the para-cyclists and able-bodied cyclists in the women's 500-m TT. The importance of position at the first split was investigated with Kendall's Tau-b correlation. The first 125-m split time was the slowest for all cyclists, representing the acceleration phase from a standing start. C2 cyclists were slowest at this 125-m split, probably due to a combination of remaining seated in this acceleration phase and a high proportion of cyclists in this group being trans-femoral amputees. Not all cyclists used aero-bars, preferring to use drop, flat or bullhorn handlebars. Split times

  13. Stress and Fatigue Management Using Balneotherapy in a Short-Time Randomized Controlled Trial

    PubMed Central

    Razbadauskas, Artūras; Sąlyga, Jonas; Martinkėnas, Arvydas

    2016-01-01

    Objective. To investigate the influence of high-salinity geothermal mineral water on stress and fatigue. Method. 180 seamen were randomized into three groups: geothermal (65), music (50), and control (65). The geothermal group was administered 108 g/L salinity geothermal water bath for 2 weeks five times a week. Primary outcome was effect on stress and fatigue. Secondary outcomes were the effect on cognitive function, mood, and pain. Results. The improvements after balneotherapy were a reduction in the number and intensity of stress-related symptoms, a reduction in pain and general, physical, and mental fatigue, and an improvement in stress-related symptoms management, mood, activation, motivation, and cognitive functions with effect size from 0.8 to 2.3. In the music therapy group, there were significant positive changes in the number of stress symptoms, intensity, mood, pain, and activity with the effect size of 0.4 to 1.1. The researchers did not observe any significant positive changes in the control group. The comparison between the groups showed that balneotherapy was superior to music therapy and no treatment group. Conclusions. Balneotherapy is beneficial for stress and fatigue reduction in comparison with music or no therapy group. Geothermal water baths have a potential as an efficient approach to diminish stress caused by working or living conditions. PMID:27051455

  14. Stress and Fatigue Management Using Balneotherapy in a Short-Time Randomized Controlled Trial.

    PubMed

    Rapolienė, Lolita; Razbadauskas, Artūras; Sąlyga, Jonas; Martinkėnas, Arvydas

    2016-01-01

    Objective. To investigate the influence of high-salinity geothermal mineral water on stress and fatigue. Method. 180 seamen were randomized into three groups: geothermal (65), music (50), and control (65). The geothermal group was administered 108 g/L salinity geothermal water bath for 2 weeks five times a week. Primary outcome was effect on stress and fatigue. Secondary outcomes were the effect on cognitive function, mood, and pain. Results. The improvements after balneotherapy were a reduction in the number and intensity of stress-related symptoms, a reduction in pain and general, physical, and mental fatigue, and an improvement in stress-related symptoms management, mood, activation, motivation, and cognitive functions with effect size from 0.8 to 2.3. In the music therapy group, there were significant positive changes in the number of stress symptoms, intensity, mood, pain, and activity with the effect size of 0.4 to 1.1. The researchers did not observe any significant positive changes in the control group. The comparison between the groups showed that balneotherapy was superior to music therapy and no treatment group. Conclusions. Balneotherapy is beneficial for stress and fatigue reduction in comparison with music or no therapy group. Geothermal water baths have a potential as an efficient approach to diminish stress caused by working or living conditions. PMID:27051455

  15. Randomized Trial of Psychological Interventions to Preventing Postpartum Depression among Iranian First-time Mothers

    PubMed Central

    Fathi-Ashtiani, Ali; Ahmadi, Ahmad; Ghobari-Bonab, Bagher; Azizi, Mohammed Parsa; Saheb-Alzamani, Sayeh Moosavi

    2015-01-01

    Background: The current study was conducted to examine the effect of cognitive behavior therapy on the reduction postpartum mood disorder and increasing the self-esteem of at-risk Iranian mothers. Methods: In this quasi-experimental study, 135 at-risk mothers were selected from the population by means of cluster sampling and randomly assigned into one of two groups: Intervention (n = 64), or control (n = 71). The control group received usual medical care, and the intervention group received an eight sessions’ cognitive behavior program during pregnancy. Assessments were administered at two time points (pretest at the beginning of the third trimester and posttest at 2 weeks postpartum). Beck anxiety, beck depression, Edinburgh postpartum depression, (PPD) Coopersmith self-esteem, and religious attitude questionnaire were used to collect data. Results: The mean age of participants was 25.8 ± 3.7 years. One-third of them had either bachelor or higher degrees in education (33%). About two-third of participants were unemployment with similar distribution in both the groups (intervention = 80%, control = 83%). The majority (70%) of the participants had cesarean section deliveries. There were no statistically significant differences respects to sociodemographic characteristics between the control and intervention groups (P > 0.05). The multivariate analysis of covariance results showed that the average scores of PPD were reduced significantly in the intervention group (P < 0.001). Also while the mean score of anxiety in the intervention group decreased from 23.31 (standard error [SE] =12.11) to 16.64 (SE = 8.33) and self-esteem increased from 29.09 (SE = 3.51) to 31.81 (SE = 2.76), no change was statistically significant in comparison to the control group. Conclusions: According to the findings of the present study, cognitive behavior intervention is effective in reducing PPD in at-risk mothers. PMID:26682030

  16. The feasibility, time savings and economic impact of a designated time appointment system at a busy HIV care clinic in Kenya: a randomized controlled trial

    PubMed Central

    Kwena, Zachary A; Njoroge, Betty W; Cohen, Craig R; Oyaro, Patrick; Shikari, Rosemary; Kibaara, Charles K; Bukusi, Elizabeth A

    2015-01-01

    Introduction As efforts are made to reach universal access to ART in Kenya, the problem of congestion at HIV care clinics is likely to worsen. We evaluated the feasibility and the economic benefits of a designated time appointment system as a solution to decongest HIV care clinics. Methods This was an explanatory two-arm open-label randomized controlled trial that enrolled 354 consenting participants during their normal clinic days and followed-up at subsequent clinic appointments for up to nine months. Intervention arm participants were given specific dates and times to arrive at the clinic for their next appointment while those in the control arm were only given the date and had the discretion to decide on the time to arrive as is the standard practice. At follow-up visits, we recorded arrival and departure times and asked the monetary value of work participants engaged in before and after clinic. We conducted multiple imputation to replace missing data in our primary outcome variables to allow for intention-to-treat analysis; and analyzed the data using Mann–Whitney U test. Results Overall, 72.1% of the intervention participants arrived on time, 13.3% arrived ahead of time and 14.6% arrived past scheduled time. Intervention arm participants spent a median of 65 [interquartile range (IQR), 52–87] minutes at the clinic compared to 197 (IQR, 173–225) minutes for control participants (p<0.01). Furthermore, intervention arm participants were more productively engaged on their clinic days valuing their cumulative work at a median of USD 10.5 (IQR, 60.0–16.8) compared to participants enrolled in the control arm who valued their work at USD 8.3 (IQR, 5.5–12.9; p=0.02). Conclusions A designated time appointment system is feasible and provides substantial time savings associated with greater economic productivity for HIV patients attending a busy HIV care clinic. PMID:26163505

  17. Tracking real-time neural activation of conceptual knowledge using single-trial event-related potentials.

    PubMed

    Amsel, Ben D

    2011-04-01

    Empirically derived semantic feature norms categorized into different types of knowledge (e.g., visual, functional, auditory) can be summed to create number-of-feature counts per knowledge type. Initial evidence suggests several such knowledge types may be recruited during language comprehension. The present study provides a more detailed understanding of the timecourse and intensity of influence of several such knowledge types on real-time neural activity. A linear mixed-effects model was applied to single trial event-related potentials for 207 visually presented concrete words measured on total number of features (semantic richness), imageability, and number of visual motion, color, visual form, smell, taste, sound, and function features. Significant influences of multiple feature types occurred before 200ms, suggesting parallel neural computation of word form and conceptual knowledge during language comprehension. Function and visual motion features most prominently influenced neural activity, underscoring the importance of action-related knowledge in computing word meaning. The dynamic time courses and topographies of these effects are most consistent with a flexible conceptual system wherein temporally dynamic recruitment of representations in modal and supramodal cortex are a crucial element of the constellation of processes constituting word meaning computation in the brain. PMID:21219919

  18. Metabolic consequences of β-alanine supplementation during exhaustive supramaximal cycling and 4000-m time-trial performance.

    PubMed

    Bellinger, Phillip M; Minahan, Clare L

    2016-08-01

    The present study investigated the effects of β-alanine supplementation on the resultant blood acidosis, lactate accumulation, and energy provision during supramaximal-intensity cycling, as well as the aerobic and anaerobic contribution to power output during a 4000-m cycling time trial (TT). Seventeen trained cyclists (maximal oxygen uptake = 4.47 ± 0.55 L·min(-1)) were administered 6.4 g of β-alanine (n = 9) or placebo (n = 8) daily for 4 weeks. Participants performed a supramaximal cycling test to exhaustion (equivalent to 120% maximal oxygen uptake) before (PreExh) and after (PostExh) the 4-week supplementation period, as well as an additional postsupplementation supramaximal cycling test identical in duration and power output to PreExh (PostMatch). Anaerobic capacity was quantified and blood pH, lactate, and bicarbonate concentrations were measured pre-, immediately post-, and 5 min postexercise. Subjects also performed a 4000-m cycling TT before and after supplementation while the aerobic and anaerobic contributions to power output were quantified. β-Alanine supplementation increased time to exhaustion (+12.8 ± 8.2 s; P = 0.041) and anaerobic capacity (+1.1 ± 0.7 kJ; P = 0.048) in PostExh compared with PreExh. Performance time in the 4000-m TT was reduced following β-alanine supplementation (-6.3 ± 4.6 s; P = 0.034) and the mean anaerobic power output was likely to be greater (+6.2 ± 4.5 W; P = 0.035). β-Alanine supplementation increased time to exhaustion concomitant with an augmented anaerobic capacity during supramaximal intensity cycling, which was also mirrored by a meaningful increase in the anaerobic contribution to power output during a 4000-m cycling TT, resulting in an enhanced overall performance. PMID:27467218

  19. Optimal power-to-mass ratios when predicting flat and hill-climbing time-trial cycling.

    PubMed

    Nevill, A M; Jobson, S A; Davison, R C R; Jeukendrup, A E

    2006-07-01

    The purpose of this article was to establish whether previously reported oxygen-to-mass ratios, used to predict flat and hill-climbing cycling performance, extend to similar power-to-mass ratios incorporating other, often quick and convenient measures of power output recorded in the laboratory [maximum aerobic power (W(MAP)), power output at ventilatory threshold (W(VT)) and average power output (W(AVG)) maintained during a 1 h performance test]. A proportional allometric model was used to predict the optimal power-to-mass ratios associated with cycling speeds during flat and hill-climbing cycling. The optimal models predicting flat time-trial cycling speeds were found to be (W(MAP)m(-0.48))(0.54), (W(VT)m(-0.48))(0.46) and (W(AVG)m(-0.34))(0.58) that explained 69.3, 59.1 and 96.3% of the variance in cycling speeds, respectively. Cross-validation results suggest that, in conjunction with body mass, W(MAP) can provide an accurate and independent prediction of time-trial cycling, explaining 94.6% of the variance in cycling speeds with the standard deviation about the regression line, s=0.686 km h(-1). Based on these models, there is evidence to support that previously reported VO2-to-mass ratios associated with flat cycling speed extend to other laboratory-recorded measures of power output (i.e. Wm(-0.32)). However, the power-function exponents (0.54, 0.46 and 0.58) would appear to conflict with the assumption that the cyclists' speeds should be proportional to the cube root (0.33) of power demand/expended, a finding that could be explained by other confounding variables such as bicycle geometry, tractional resistance and/or the presence of a tailwind. The models predicting 6 and 12% hill-climbing cycling speeds were found to be proportional to (W(MAP)m(-0.91))(0.66), revealing a mass exponent, 0.91, that also supports previous research. PMID:16685550

  20. Preconception Low Dose Aspirin and Time to Pregnancy: Findings From the Effects of Aspirin in Gestation and Reproduction Randomized Trial

    PubMed Central

    Mumford, Sunni L.; Schliep, Karen C.; Sjaarda, Lindsey A.; Stanford, Joseph B.; Lesher, Laurie L.; Wactawski-Wende, Jean; Lynch, Anne M.; Townsend, Janet M.; Perkins, Neil J.; Zarek, Shvetha M.; Tsai, Michael Y.; Chen, Zhen; Faraggi, David; Galai, Noya; Silver, Robert M.

    2015-01-01

    Objective: The objective was to determine the effect of preconception-initiated daily low-dose aspirin (LDA; 81 mg/day) treatment on time to pregnancy in women with a history of pregnancy loss. Design: This was a multicenter, block-randomized, double-blind, placebo-controlled trial. Participants were block-randomized by center and eligibility stratum. Setting: The study was conducted at four U.S.A. medical centers (2007–2012). Participants: Participants women aged 18–40 years actively attempting pregnancy, stratified by eligibility criteria: the “original” stratum, women with one loss <20 weeks' gestation during the previous year; and the “expanded” stratum, women with one or two previous losses of any gestational age regardless of time since loss. Intervention: Daily LDA was compared with matching placebo for up to six menstrual cycles of attempting pregnancy. Main Outcome Measure: Time to hCG detected pregnancy and clinically confirmed pregnancy, analyzed by intention-to-treat, was measured. Results: Of the 1228 women randomly assigned to LDA (n = 615) or placebo (n = 613), 410 (67%) women receiving LDA achieved pregnancy compared to 382 (63%) receiving placebo, corresponding to a fecundability odds ratio (FOR) of 1.14 (95% CI: 0.97, 1.33). Among women in the original stratum (n = 541), LDA was associated with increased fecundability compared to placebo (FOR: 1.28; 95%CI: 1.02, 1.62). Conclusions: Preconception-initiated LDA treatment resulted in a nonsignificant increase in fecundability of 14% in women with a history of 1–2 pregnancy losses, and a significant increase of 28% in women with a history of only one pregnancy loss of <20 weeks' gestation in the preceding year. Preconception-initiated LDA may increase fecundability in certain women with a recent early pregnancy loss. PMID:25710565

  1. Clinical Trial Participation and Time to Treatment Among Adolescents and Young Adults With Cancer: Does Age at Diagnosis or Insurance Make a Difference?

    PubMed Central

    Parsons, Helen M.; Harlan, Linda C.; Seibel, Nita L.; Stevens, Jennifer L.; Keegan, Theresa H.M.

    2011-01-01

    Purpose Because adolescent and young adult (AYA) patients with cancer have experienced variable improvement in survival over the past two decades, enhancing the quality and timeliness of cancer care in this population has emerged as a priority area. To identify current trends in AYA care, we examined patterns of clinical trial participation, time to treatment, and provider characteristics in a population-based sample of AYA patients with cancer. Methods Using the National Cancer Institute Patterns of Care Study, we used multivariate logistic regression to evaluate demographic and provider characteristics associated with clinical trial enrollment and time to treatment among 1,358 AYA patients with cancer (age 15 to 39 years) identified through the Surveillance, Epidemiology, and End Results Program. Results In our study, 14% of patients age 15 to 39 years had enrolled onto a clinical trial; participation varied by type of cancer, with the highest participation in those diagnosed with acute lymphoblastic leukemia (37%) and sarcoma (32%). Multivariate analyses demonstrated that uninsured, older patients and those treated by nonpediatric oncologists were less likely to enroll onto clinical trials. Median time from pathologic confirmation to first treatment was 3 days, but this varied by race/ethnicity and cancer site. In multivariate analyses, advanced cancer stage and outpatient treatment alone were associated with longer time from pathologic confirmation to treatment. Conclusion Our study identified factors associated with low clinical trial participation in AYA patients with cancer. These findings support the continued need to improve access to clinical trials and innovative treatments for this population, which may ultimately translate into improved survival. PMID:21931022

  2. Managing clinical trials.

    PubMed

    Farrell, Barbara; Kenyon, Sara; Shakur, Haleema

    2010-01-01

    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. PMID:20626885

  3. Preliminary clinical trial in percutaneous nephrolithotomy using a real-time navigation system for percutaneous kidney access

    NASA Astrophysics Data System (ADS)

    Rodrigues, Pedro L.; Moreira, António H. J.; Rodrigues, Nuno F.; Pinho, A. C. M.; Fonseca, Jaime C.; Lima, Estevão.; Vilaça, João. L.

    2014-03-01

    Background: Precise needle puncture of renal calyces is a challenging and essential step for successful percutaneous nephrolithotomy. This work tests and evaluates, through a clinical trial, a real-time navigation system to plan and guide percutaneous kidney puncture. Methods: A novel system, entitled i3DPuncture, was developed to aid surgeons in establishing the desired puncture site and the best virtual puncture trajectory, by gathering and processing data from a tracked needle with optical passive markers. In order to navigate and superimpose the needle to a preoperative volume, the patient, 3D image data and tracker system were previously registered intraoperatively using seven points that were strategically chosen based on rigid bone structures and nearby kidney area. In addition, relevant anatomical structures for surgical navigation were automatically segmented using a multi-organ segmentation algorithm that clusters volumes based on statistical properties and minimum description length criterion. For each cluster, a rendering transfer function enhanced the visualization of different organs and surrounding tissues. Results: One puncture attempt was sufficient to achieve a successful kidney puncture. The puncture took 265 seconds, and 32 seconds were necessary to plan the puncture trajectory. The virtual puncture path was followed correctively until the needle tip reached the desired kidney calyceal. Conclusions: This new solution provided spatial information regarding the needle inside the body and the possibility to visualize surrounding organs. It may offer a promising and innovative solution for percutaneous punctures.

  4. Effect of Practical Precooling on Neuromuscular Function and 5-km Time-Trial Performance in Hot, Humid Conditions Among Well-Trained Male Runners.

    PubMed

    Randall, Carla A; Ross, Emma Z; Maxwell, Neil S

    2015-07-01

    This study investigated whether torso and thigh precooling during a warm-up effects neuromuscular function and 5-km time-trial performance in hot, humid conditions. Eight well-trained male runners completed 3 randomized time-trials in 32.2 ± 0.8° C and 48.6 ± 6.7% relative humidity. A 30-minute warm-up was completed with no cooling (Control), precooling by an ice vest (Vest), or ice packs covering the thighs (Packs). Before the warm-up and after the time-trial, supramaximal femoral nerve stimulation was delivered during and following maximal isometric contractions. Core and skin temperature, heart rate, and perceptual ratings were recorded before and during the warm-up and time-trial. Overall performance time was improved in Packs compared with Control (1,407 ± 80 seconds vs. 1,492 ± 88 seconds; p ≤ 0.05) but not in Vest (1,444 ± 71 seconds; p > 0.05). In Packs, a higher exercise intensity (p ≤ 0.05) and less cumulative time (p < 0.01) were evident during the last kilometer compared with Control. Maximum voluntary force, voluntary activation, muscle contractility, and membrane excitability were not different after exercise or between conditions. Ten minutes after the warm-up, skin temperature was lower in Vest and Packs compared with Control (p < 0.01). Thermal strain and body heat content change was lower in Vest and Packs, respectively (p ≤ 0.05). Findings indicate that torso and thigh precooling during a warm-up reduces thermoregulatory strain. However, thigh opposed to torso precooling provides greater performance improvements. Neuromuscular function did not aid performance, indicating that transient changes in afferent feedback and muscle recruitment may enhance endurance trial performance. PMID:26102259

  5. Multicentre randomised control trial comparing real time teledermatology with conventional outpatient dermatological care: societal cost-benefit analysis

    PubMed Central

    Wootton, R; Bloomer, S E; Corbett, R; Eedy, D J; Hicks, N; Lotery, H E; Mathews, C; Paisley, J; Steele, K; Loane, M A

    2000-01-01

    Objectives Comparison of real time teledermatology with outpatient dermatology in terms of clinical outcomes, cost-benefits, and patient reattendance. Design Randomised controlled trial with a minimum follow up of three months. Setting Four health centres (two urban, two rural) and two regional hospitals. Subjects 204 general practice patients requiring referral to dermatology services; 102 were randomised to teledermatology consultation and 102 to traditional outpatient consultation. Main outcome measures Reported clinical outcome of initial consultation, primary care and outpatient reattendance data, and cost-benefit analysis of both methods of delivering care. Results No major differences were found in the reported clinical outcomes of teledermatology and conventional dermatology. Of patients randomised to teledermatology, 55 (54%) were managed within primary care and 47 (46%) required at least one hospital appointment. Of patients randomised to the conventional hospital outpatient consultation, 46 (45%) required at least one further hospital appointment, 15 (15%) required general practice review, and 40 (39%) no follow up visits. Clinical records showed that 42 (41%) patients seen by teledermatology attended subsequent hospital appointments compared with 41 (40%) patients seen conventionally. The net societal cost of the initial consultation was £132.10 per patient for teledermatology and £48.73 for conventional consultation. Sensitivity analysis revealed that if each health centre had allocated one morning session a week to teledermatology and the average round trip to hospital had been 78 km instead of 26 km, the costs of the two methods of care would have been equal. Conclusions Real time teledermatology was clinically feasible but not cost effective compared with conventional dermatological outpatient care. However, if the equipment were purchased at current prices and the travelling distances greater, teledermatology would be a cost effective alternative

  6. Beyond the futility argument: the fair process approach and time-limited trials for managing dialysis conflict.

    PubMed

    Rinehart, Ann

    2013-11-01

    Futility is an ancient concept arising from Greek mythology that was resurrected for its medical application in the 1980s with the proliferation of many lifesaving technologies, including dialysis and renal transplantation. By that time, the domineering medical paternalism that characterized the pre-1960s physician-patient relationship morphed into assertive patient autonomy, and some patients began to claim the right to demand aggressive, high-technology interventions, despite physician disapproval. To counter this power struggle, the establishment of a precise definition of futility offered hope for a futility policy that would allow physicians to justify withholding or withdrawing treatment, despite patient and family objections. This article reviews the various attempts made to define medical futility and describes their limited applicability to dialysis. When futility concerns arise, physicians should recognize the opportunity to address conflict, using best practice communication skills. Physicians would also benefit from understanding the ethical principles of respect for patient autonomy, beneficence, nonmaleficence, justice, and professional integrity that underlie medical decision-making. Also reviewed is the use of a fair process approach or time-limited trial when conflict resolution cannot be achieved. These topics are addressed in the Renal Physician Association's clinical practice guideline Shared Decision-Making in the Appropriate Initiation and Withdrawal from Dialysis, with which nephrologists should be well versed. A case presentation of intractable calciphylaxis in a new dialysis patient illustrates the pitfalls of physicians not fully appreciating the ethics of medical decision-making and failing to use effective conflict management approaches in the clinical practice guideline. PMID:23868900

  7. Sex differences in atazanavir pharmacokinetics and associations with time to clinical events: AIDS Clinical Trials Group Study A5202

    PubMed Central

    Venuto, Charles S.; Mollan, Katie; Ma, Qing; Daar, Eric S.; Sax, Paul E.; Fischl, Margaret; Collier, Ann C.; Smith, Kimberly Y.; Tierney, Camlin; Morse, Gene D.

    2014-01-01

    Objectives It is uncertain whether HIV-1 antiretroviral exposure and clinical response varies between males and females or different race/ethnic groups. We describe ritonavir-enhanced atazanavir pharmacokinetics in relation to virological failure, safety and tolerability in treatment-naive individuals to investigate potential differences. Methods Plasma samples were collected from participants in AIDS Clinical Trials Group Study A5202 for measurement of antiretroviral concentrations. Individual estimates of apparent oral clearance of atazanavir (L/h) were calculated from a one-compartment model and divided into tertiles as slow (<7), middle (7 to <9; reference group) and fast (≥9). Associations between atazanavir clearance and clinical outcomes were estimated with a hazard ratio (HR) from Cox proportional hazards models. Interactions between atazanavir clearance and sex, race/ethnicity and NRTIs were investigated for each of the outcomes. Results Among 786 participants, average atazanavir clearance was slower in females (n = 131) than males (n = 655). Atazanavir clearance was associated with time to virological failure (P = 0.053) and this relationship differed significantly by sex (P = 0.003). Females in the fast atazanavir clearance group had shorter time to virological failure (HR 3.49; 95% CI 1.24–9.84) compared with the middle (reference) atazanavir clearance group. Among males, the slow atazanavir clearance group had a higher risk of virological failure (HR 2.10; 95% CI 1.16–3.77). Conclusions Atazanavir clearance differed by sex. Females with fast clearance and males with slow clearance had increased risk of virological failure. PMID:25159623

  8. Evaluation of the UP4FUN Intervention: A Cluster Randomized Trial to Reduce and Break Up Sitting Time in European 10-12-Year-Old Children

    PubMed Central

    Vik, Frøydis N.; Lien, Nanna; Berntsen, Sveinung; De Bourdeaudhuij, Ilse; Grillenberger, Monika; Manios, Yannis; Kovacs, Eva; Chinapaw, Mai J. M.; Brug, Johannes; Bere, Elling

    2015-01-01

    Background The UP4FUN intervention is a family-involved school-based intervention aiming at reducing and breaking up sitting time at home (with special emphasis on screen time), and breaking up sitting time in school among 10–12 year olds in Europe. The purpose of the present paper was to evaluate its short term effects. Methodology/Principal Findings A total of 3147 pupils from Belgium, Germany, Greece, Hungary and Norway participated in a school-randomized controlled trial. The intervention included 1–2 school lessons per week for a period of six weeks, along with assignments for the children and their parents. Screen time and breaking up sitting time were registered by self-report and total sedentary time and breaking up sitting time by accelerometry. The effect of the intervention on these behaviors was evaluated by multilevel regression analyses. All analyses were adjusted for baseline values and gender. Significance level was p≤0.01. No significant intervention effects were observed, neither for self-reported TV/DVD or computer/game console time, nor for accelerometer-assessed total sedentary time and number of breaks in sitting time. The intervention group, however, reported more positive attitudes towards (β = 0.25 (95% CI 0.11, 0.38)) and preferences/liking for (β = 0.20 (95% CI 0.08, 0.32)) breaking up sitting time than the control group. Conclusions/Significance No significant intervention effect on self-reported screen time or accelerometer-assessed sedentary time or breaks in sitting time was observed, but positive effects on beliefs regarding breaking up sitting time were found in favor of the intervention group. Overall, these results do not warrant wider dissemination of the present UP4FUN intervention. Trial Registration International Standard Randomized Controlled Trial Number Registry ISRCTN34562078 PMID:25826704

  9. Effectiveness of behavioral graded activity after first-time lumbar disc surgery: short term results of a randomized controlled trial.

    PubMed

    Ostelo, R W J G; de Vet, H C W; Berfelo, M W; Kerckhoffs, M R; Vlaeyen, J W S; Wolters, P M J C; van den Brandt, P A

    2003-12-01

    Behavioral approaches to treating patients following lumbar disc surgery are becoming increasingly popular. The treatment method is based on the assumption that pain and pain disability are not only influenced by somatic pathology, if found, but also by psychological and social factors. A recent study highlighted the effectiveness of cognitive-behavioral interventions, as compared to no treatment, for chronic low back patients. However, to the authors' knowledge, there is no randomized controlled trial that evaluates a behavioral program for patients following lumbar disc surgery. The purpose of this study was to assess the effectiveness of a behavioral graded activity (BGA) program compared to usual care (UC) in physiotherapy following first-time lumbar disc surgery. The BGA program was a patient-tailored intervention based upon operant therapy. The essence of the BGA is to teach patients that it is safe to increase activity levels. The study was designed as a randomized controlled trial. Assessments were carried out before and after treatment by an observer blinded to treatment allocation. Patients suffering residual symptoms restricting their activities of daily living and/or work at the 6 weeks post-surgery consultation by the neurosurgeon were included. The exclusion criteria were: complications during surgery, any relevant underlying pathology, and any contraindication to physiotherapy or the BGA program. Primary outcome measures were the patient's Global Perceived Effect and the functional status. Secondary measures were: fear of movement, viewing pain as extremely threatening, pain, severity of the main complaint, range of motion, and relapses. Physiotherapists in the BGA group received proper training. Between November 1997 and December 1999, 105 patients were randomized; 53 into the UC group and 52 into the BGA group. The unadjusted analysis shows a 19.3% (95% CI: 0.1 to 38.5) statistically significant difference to the advantage of the UC group on Global

  10. A Randomized Controlled Trial to Evaluate the Benefits of a Multimedia Educational Program for First-Time Hearing Aid Users

    PubMed Central

    Brandreth, Marian; Brassington, William; Leighton, Paul; Wharrad, Heather

    2016-01-01

    Objectives: The aims of this study were to (1) develop a series of short interactive videos (or reusable learning objects [RLOs]) covering a broad range of practical and psychosocial issues relevant to the auditory rehabilitation for first-time hearing aid users; (2) establish the accessibility, take-up, acceptability and adherence of the RLOs; and (3) assess the benefits and cost-effectiveness of the RLOs. Design: The study was a single-center, prospective, randomized controlled trial with two arms. The intervention group (RLO+, n = 103) received the RLOs plus standard clinical service including hearing aid(s) and counseling, and the waitlist control group (RLO−, n = 100) received standard clinical service only. The effectiveness of the RLOs was assessed 6-weeks posthearing aid fitting. Seven RLOs (total duration 1 hr) were developed using a participatory, community of practice approach involving hearing aid users and audiologists. RLOs included video clips, illustrations, animations, photos, sounds and testimonials, and all were subtitled. RLOs were delivered through DVD for TV (50.6%) and PC (15.2%), or via the internet (32.9%). Results: RLO take-up was 78%. Adherence overall was at least 67%, and 97% in those who attended the 6-week follow-up. Half the participants watched the RLOs two or more times, suggesting self-management of their hearing loss, hearing aids, and communication. The RLOs were rated as highly useful and the majority of participants agreed the RLOs were enjoyable, improved their confidence and were preferable to written information. Postfitting, there was no significant between-group difference in the primary outcome measure, overall hearing aid use. However, there was significantly greater hearing aid use in the RLO+ group for suboptimal users. Furthermore, the RLO+ group had significantly better knowledge of practical and psychosocial issues, and significantly better practical hearing aid skills than the RLO− group. Conclusions: The RLOs

  11. Harnessing Technology to Improve Clinical Trials: Study of Real-Time Informatics to Collect Data, Toxicities, Image Response Assessments, and Patient-Reported Outcomes in a Phase II Clinical Trial

    PubMed Central

    Pietanza, M. Catherine; Basch, Ethan M.; Lash, Alex; Schwartz, Lawrence H.; Ginsberg, Michelle S.; Zhao, Binsheng; Shouery, Marwan; Shaw, Mary; Rogak, Lauren J.; Wilson, Manda; Gabow, Aaron; Latif, Marcia; Lin, Kai-Hsiung; Wu, Qinfei; Kass, Samantha L.; Miller, Claire P.; Tyson, Leslie; Sumner, Dyana K.; Berkowitz-Hergianto, Alison; Sima, Camelia S.; Kris, Mark G.

    2013-01-01

    Purpose In clinical trials, traditional monitoring methods, paper documentation, and outdated collection systems lead to inaccuracies of study information and inefficiencies in the process. Integrated electronic systems offer an opportunity to collect data in real time. Patients and Methods We created a computer software system to collect 13 patient-reported symptomatic adverse events and patient-reported Karnofsky performance status, semi-automated RECIST measurements, and laboratory data, and we made this information available to investigators in real time at the point of care during a phase II lung cancer trial. We assessed data completeness within 48 hours of each visit. Clinician satisfaction was measured. Results Forty-four patients were enrolled, for 721 total visits. At each visit, patient-reported outcomes (PROs) reflecting toxicity and disease-related symptoms were completed using a dedicated wireless laptop. All PROs were distributed in batch throughout the system within 24 hours of the visit, and abnormal laboratory data were available for review within a median of 6 hours from the time of sample collection. Manual attribution of laboratory toxicities took a median of 1 day from the time they were accessible online. Semi-automated RECIST measurements were available to clinicians online within a median of 2 days from the time of imaging. All clinicians and 88% of data managers felt there was greater accuracy using this system. Conclusion Existing data management systems can be harnessed to enable real-time collection and review of clinical information during trials. This approach facilitates reporting of information closer to the time of events, and improves efficiency, and the ability to make earlier clinical decisions. PMID:23630218

  12. Influence of acute dietary nitrate supplementation on 50 mile time trial performance in well-trained cyclists.

    PubMed

    Wilkerson, Daryl P; Hayward, Giles M; Bailey, Stephen J; Vanhatalo, Anni; Blackwell, Jamie R; Jones, Andrew M

    2012-12-01

    Dietary nitrate supplementation has been reported to improve short distance time trial (TT) performance by 1-3 % in club-level cyclists. It is not known if these ergogenic effects persist in longer endurance events or if dietary nitrate supplementation can enhance performance to the same extent in better trained individuals. Eight well-trained male cyclists performed two laboratory-based 50 mile TTs: (1) 2.5 h after consuming 0.5 L of nitrate-rich beetroot juice (BR) and (2) 2.5 h after consuming 0.5 L of nitrate-depleted BR as a placebo (PL). BR significantly elevated plasma [NO(2) (-)] (BR: 472 ± 96 vs. PL: 379 ± 94 nM; P < 0.05) and reduced completion time for the 50 mile TT by 0.8 % (BR: 136.7 ± 5.6 vs. PL: 137.9 ± 6.4 min), which was not statistically significant (P > 0.05). There was a significant correlation between the increased post-beverage plasma [NO(2) (-)] with BR and the reduction in TT completion time (r = -0.83, P = 0.01). Power output (PO) was not different between the conditions at any point (P > 0.05) but oxygen uptake ([Formula: see text]O(2)) tended to be lower in BR (P = 0.06), resulting in a significantly greater PO/[Formula: see text]O(2) ratio (BR: 67.4 ± 5.5 vs. PL: 65.3 ± 4.8 W L min(-1); P < 0.05). In conclusion, acute dietary supplementation with beetroot juice did not significantly improve 50 mile TT performance in well-trained cyclists. It is possible that the better training status of the cyclists in this study might reduce the physiological and performance response to NO(3) (-) supplementation compared with the moderately trained cyclists tested in earlier studies. PMID:22526247

  13. Quality of life assessment among HIV-positive persons entering the INSIGHT Strategic Timing of AntiRetroviral Treatment trial

    PubMed Central

    Lifson, Alan R.; Grandits, Greg; Gardner, Edward M.; Wolff, Marcelo; Pulik, Piotr; Williams, Ian; Burman, William J.

    2014-01-01

    Objectives With HIV treatment prolonging survival and HIV managed as a chronic illness, quality of life (QOL) is important to evaluate in persons living with HIV (PLWH). We assessed QOL at study entry in the Strategic Timing of AntiRetroviral Treatment clinical trial of antiretroviral-naive PLWH with >500 CD4 cells/μL. Methods QOL was assessed with: 1) visual analogue scale (VAS) for self-assessment of overall current health; 2) SF-12V2 Health Survey®, summarised into eight individual QOL domains plus component summary scores for physical health (PCS) and mental health (MCS). The VAS and eight domain scores were scaled 0–100. Mean QOL measures were calculated overall and by demographic, clinical and behavioural factors. Results 4631 participants completed the VAS and 4119 the SF-12. Mean VAS score was 80.9 ±15.7. Mean SF-12 domain scores were lowest for vitality (66.3 ±26.4) and mental health (68.6 ±21.4), and highest for physical functioning (89.3 ±23.0) and bodily pain (88.0 ±21.4). Using multiple linear regression, PCS scores were lower (p<0.001) for Asians, North Americans, females, older age, less education, longer duration of known HIV, alcoholism/substance dependence, and body mass index ≥30 kg/m2. MCS scores were highest (p<0.001) for Africans, South Americans, and older age and lowest for females, current smokers, and alcoholism/ substance dependence. Conclusions In this primarily healthy population, QOL was mostly favorable, emphasising importance that HIV treatments do not negatively impact QOL. Self-assessed physical health was higher than mental health. Factors such as older age and geographic region have different influences on perceived physical and mental health. PMID:25711327

  14. The Improving Rural Cancer Outcomes (IRCO) Trial: a factorial cluster-randomised controlled trial of a complex intervention to reduce time to diagnosis in rural patients with cancer in Western Australia: a study protocol

    PubMed Central

    Emery, Jon D; Gray, Victoria; Walter, Fiona M; Cheetham, Shelley; Croager, Emma J; Slevin, Terry; Saunders, Christobel; Threlfall, Tim; Auret, Kirsten; Nowak, Anna K; Geelhoed, Elizabeth; Bulsara, Max; Holman, C D'Arcy J

    2014-01-01

    Introduction While overall survival for most common cancers in Australia is improving, the rural–urban differential has been widening, with significant excess deaths due to lung, colorectal, breast and prostate cancer in regional Australia. Internationally a major focus on understanding variations in cancer outcomes has been later presentation to healthcare and later diagnosis. Approaches to reducing time to diagnosis of symptomatic cancer include public symptom awareness campaigns and interventions in primary care to improve early cancer detection. This paper reports the protocol of a factorial cluster-randomised trial of community and general practice (GP) level interventions to reduce the time to diagnosis of cancer in rural Western Australia (WA). Methods and analysis The community intervention is a symptom awareness campaign tailored for rural Australians delivered through a community engagement model. The GP intervention includes a resource card with symptom risk assessment charts and local referral pathways implemented through multiple academic detailing visits and case studies. Participants are eligible if recently diagnosed with breast, colorectal, lung or prostate cancer who reside in specific regions of rural WA with a planned sample size of 1350. The primary outcome is the Total Diagnostic Interval, defined as the duration from first symptom (or date of cancer screening test) to cancer diagnosis. Secondary outcomes include cancer stage, healthcare utilisation, disease-free status, survival at 2 and 5 years and cost-effectiveness. Ethics and dissemination Ethics approval has been granted by the University of Western Australia and from all relevant hospital recruitment sites in WA. Results Results of this trial will be reported in peer-reviewed publications and in conference presentations. Trial registration number Australian New Zealand Clinical Trials Registry (ANZCTR). ACTRN12610000872033. PMID:25231496

  15. The Early External Cephalic Version (ECV) 2 Trial: an international multicentre randomised controlled trial of timing of ECV for breech pregnancies

    PubMed Central

    Hutton, EK; Hannah, ME; Ross, SJ; Delisle, M-F; Carson, GD; Windrim, R; Ohlsson, A; Willan, AR; Gafni, A; Sylvestre, G; Natale, R; Barrett, Y; Pollard, JK; Dunn, MS; Turtle, P

    2011-01-01

    Objective To investigate whether initiating external cephalic version (ECV) earlier in pregnancy might increase the rate of successful ECV procedures, and be more effective in decreasing the rate of non-cephalic presentation at birth and of caesarean section. Design An unblinded multicentred randomised controlled trial. Setting A total of 1543 women were randomised from 68 centres in 21 countries. Population Women with a singleton breech fetus at a gestational age of 330/7 weeks (231 days) to 356/7 weeks (251 days) of gestation were included. Methods Participants were randomly assigned to having a first ECV procedure between the gestational ages of 340/7 (238 days) and 356/7 weeks of gestation (early ECV group) or at or after 370/7 (259 days) weeks of gestation (delayed ECV group). Main outcome measures The primary outcome was the rate of caesarean section; the secondary outcome was the rate of preterm birth. Results Fewer fetuses were in a non-cephalic presentation at birth in the early ECV group (314/765 [41.1%] versus 377/768 [49.1%] in the delayed ECV group; relative risk [RR] 0.84, 95% CI 0.75, 0.94, P = 0.002). There were no differences in rates of caesarean section (398/765 [52.0%] versus 430/768 [56.0%]; RR 0.93, 95% CI 0.85, 1.02, P = 0.12) or in risk of preterm birth (50/765 [6.5%] versus 34/768 [4.4%]; RR 1.48, 95% CI 0.97, 2.26, P = 0.07) between groups. Conclusion External cephalic version at 34–35 weeks versus 37 or more weeks of gestation increases the likelihood of cephalic presentation at birth but does not reduce the rate of caesarean section and may increase the rate of preterm birth. PMID:21291506

  16. A Randomized Trial Comparing Part-time Patching with Observation for Intermittent Exotropia in Children 12 to 35 Months Old

    PubMed Central

    Mohney, Brian G.; Cotter, Susan A.; Chandler, Danielle L.; Holmes, Jonathan M.; Chen, Angela M.; Melia, Michele; Donahue, Sean P.; Wallace, David K.; Kraker, Raymond T.; Christian, Melanie L.; Suh, Donny W.

    2015-01-01

    Objective To determine the effectiveness of part-time patching for treating intermittent exotropia (IXT) in young children Design Multicenter, randomized clinical trial Participants Two hundred one children 12 to 35-months-old with untreated IXT meeting the following criteria: 1) IXT at distance OR constant exotropia at distance and either IXT or exophoria at near; 2) ≥15 prism diopter (Δ) exodeviation at distance or near by prism and alternate cover test (PACT) but at least 10Δ exodeviation at distance by PACT. Methods Participants were randomly assigned to either observation (no treatment for 6 months) or patching prescribed for 3 hours daily for 5 months, followed by 1 month of no patching. Main Outcome Measure The primary outcome was deterioration, defined as constant exotropia measuring at least 10Δ at distance and near or receipt of non-protocol treatment for IXT. Results Of the 177 participants (88%) completing the 6-month primary outcome examination, deterioration occurred in 4.6% (4 of 87) of the participants in the observation group and in 2.2% (2 of 90) of the participants in the patching group (difference = 2.4%; P = 0.27, 95% confidence interval (CI) = -3.8% to +9.4%). Motor deterioration occurred in 2.3% (2 of 87) of the observation group and in 2.2% (2 of 90) of the patching group (difference = 0.08%, P = 0.55, 95% CI = -5.8% to +6.1%). For the observation and patching groups respectively, 6-month mean PACT measurements were 27.9Δ versus 24.9Δ at distance (P = 0.02) and 19.3Δ versus 17.0Δ at near (P = 0.10); 6-month mean exotropia control scores were 2.8 vs. 2.3 points at distance (P = 0.02), and 1.4 vs. 1.1 points at near (P = 0.26). Conclusion Among children 12 to 35 months of age with previously untreated IXT, deterioration over 6 months was uncommon, with or without patching treatment. There was insufficient evidence to recommend part-time patching for the treatment of IXT in children in this age group. PMID:26072346

  17. A Randomized Trial Comparing Part-time Patching with Observation for Children 3–10 Years Old with Intermittent Exotropia

    PubMed Central

    Cotter, Susan A.; Mohney, Brian G.; Chandler, Danielle L.; Holmes, Jonathan M.; Repka, Michael X.; Melia, Michele; Wallace, David K.; Beck, Roy W.; Birch, Eileen E.; Kraker, Raymond T.; Tamkins, Susanna M.; Miller, Aaron M.; Sala, Nicholas A.; Glaser, Stephen R.

    2014-01-01

    Objective To determine the effectiveness of prescribed part-time patching for treatment of intermittent exotropia in children Design Multicenter, randomized clinical trial Participants Three hundred fifty-eight children aged 3 to < 11 years old with previously untreated (except for refractive correction) intermittent exotropia (IXT) and near stereoacuity of 400 arcsec or better were enrolled. Intermittent exotropia met the following criteria: 1) constant or intermittent exotropia at distance and either intermittent exotropia or exophoria at near; 2) exodeviation (tropia or phoria) of at least 15 prism diopters (Δ) at distance or near by prism and alternate cover test (PACT); and 3) exodeviation of at least 10Δ at distance by PACT. Methods Participants were randomly assigned to either observation (no treatment for 6 months) or patching for 3 hours per day for 5 months, with a 1-month washout period of no patching before the 6-month primary outcome exam. Main Outcome Measure The primary outcome was deterioration at either the 3-month or the 6-month follow-up visit, defined as: 1) constant exotropia measuring at least 10Δ at distance and near by simultaneous prism and cover test, and/or 2) near stereoacuity decreased by at least 2 octaves from baseline, both assessed by a masked examiner and confirmed by a retest. Participants who were prescribed any non-randomized treatment without first meeting either deterioration criteria were also counted as having deteriorated. Results Of the 324 (91%) participants completing the 6-month primary outcome exam, deterioration occurred in 10 (6.1%) of the 165 participants in the observation group (3 of these 10 started treatment without meeting deterioration criteria) and in 1 (0.6%) of the 159 participants in the part-time patching group (difference = 5.4%, lower limit of one-sided exact 95% confidence interval = 2.0%; p value from one-sided hypothesis test = 0.004). Conclusion Deterioration of previously untreated childhood IXT

  18. What motivates participation in HIV cure trials? A call for real-time assessment to improve informed consent

    PubMed Central

    Peay, Holly L; Henderson, Gail E

    2015-01-01

    HIV cure research, a diverse set of studies aimed at eradicating or greatly reducing HIV in latent reservoirs, has become a strategic priority for global AIDS research. However, in early-phase HIV cure research there are ethical challenges related to the uncertainty around potential risks and the risk–benefit balance. Similar to clinical trials in other disease areas, these concerns may impact clinical trial participants' comprehension and decision making. Here we suggest attention to the terminology used to describe HIV cure research that may promote therapeutic misconception, and exploration of the decision-making influences and processes of those who accept and decline participation in HIV cure trials. These data will facilitate efforts to improve protocols and informed consent based on an understanding of participant preferences and needs. PMID:25866844

  19. A controlled time-series trial of clinical reminders: using computerized firm systems to make quality improvement research a routine part of mainstream practice.

    PubMed Central

    Goldberg, H. I.; Neighbor, W. E.; Cheadle, A. D.; Ramsey, S. D.; Diehr, P.; Gore, E.

    2000-01-01

    OBJECTIVE: To explore the feasibility of conducting unobtrusive interventional research in community practice settings by integrating firm-system techniques with time-series analysis of relational-repository data. STUDY SETTING: A satellite teaching clinic divided into two similar, but geographically separated, primary care group practices called firms. One firm was selected by chance to receive the study intervention. Forty-two providers and 2,655 patients participated. STUDY DESIGN: A nonrandomized controlled trial of computer-generated preventive reminders. Net effects were determined by quantitatively combining population-level data from parallel experimental and control interrupted time series extending over two-month baseline and intervention periods. DATA COLLECTION: Mean rates at which mammography, colorectal cancer screening, and cholesterol testing were performed on patients due to receive each maneuver at clinic visits were the trial's outcome measures. PRINCIPAL FINDINGS: Mammography performance increased on the experimental firm by 154 percent (0.24 versus 0.61, p = .03). No effect on fecal occult blood testing was observed. Cholesterol ordering decreased on both the experimental (0.18 versus 0.1 1, p = .02) and control firms (0.13 versus 0.07, p = .03) coincident with national guidelines retreating from recommending screening for young adults. A traditional uncontrolled interrupted time-series design would have incorrectly attributed the experimental-firm decrease to the introduction of reminders. The combined analysis properly indicated that no net prompting effect had occurred, as the difference between firms in cholesterol testing remained stochastically stable over time (0.05 versus 0.04, p = .75). A logistic-regression analysis applied to individual-level data produced equivalent findings. The trial incurred no supplementary data collection costs. CONCLUSIONS: The apparent validity and practicability of our reminder implementation study should

  20. Omission of the bladder flap at caesarean section reduces delivery time without increased morbidity: a meta-analysis of randomised controlled trials.

    PubMed

    O'Neill, Heidi A; Egan, Grace; Walsh, Colin A; Cotter, Amanda M; Walsh, Stewart R

    2014-03-01

    Caesarean section (CS) is the most common major surgical procedure performed worldwide. Traditionally, creation of a bladder flap (BF) has been a routine surgical step at CS although recent randomised controlled trials (RCTs) have begun to question its value. We performed a meta-analysis of RCTs examining the benefits of BF formation at CS. Pubmed, Medline, Embase, CINAHL Plus(®), Web of Science Reference and Cochrane Databases online were searched in March 2012 using combinations of the terms "c(a)esarean", "bladder", "flap" and "technique". Citations identified in the primary search were screened for eligibility. Online clinical registries (www.clinicaltrials.gov, www.controlled-trials.com and www.ukcrc.org.) were also searched. The primary outcome was bladder injury. Secondary outcomes were skin incision-delivery interval, total operating time, blood loss and duration of hospitalisation. Pooled outcome measures (odds ratio [OR] and weighted mean difference [WMD]) were calculated using a random effects model. Three published RCTs and one unpublished trial identified from an online trial registry were included (n=581 women). All four trials excluded very preterm and emergency CS. Omission of the BF step at CS reduced the skin incision-delivery interval (WMD 1.27min; p=0.0001). No differences were found for bladder injury (pooled OR 0.96), total operating time (WMD 3.5min), blood loss (WMD 42ml) or duration of hospitalisation (WMD 0.07 days). Omission of the BF at elective CS does not appear to increase the rate of peri-operative complications and improves the skin incision-delivery interval. The role of BF formation in very preterm procedures and emergency intrapartum CS needs further study. PMID:24411951

  1. End points for adjuvant therapy trials: has the time come to accept disease-free survival as a surrogate end point for overall survival?

    PubMed

    Gill, Sharlene; Sargent, Daniel

    2006-06-01

    The intent of adjuvant therapy is to eradicate micro-metastatic residual disease following curative resection with the goal of preventing or delaying recurrence. The time-honored standard for demonstrating efficacy of new adjuvant therapies is an improvement in overall survival (OS). This typically requires phase III trials of large sample size with lengthy follow-up. With the intent of reducing the cost and time of completing such trials, there is considerable interest in developing alternative or surrogate end points. A surrogate end point may be employed as a substitute to directly assess the effects of an intervention on an already accepted clinical end point such as mortality. When used judiciously, surrogate end points can accelerate the evaluation of new therapies, resulting in the more timely dissemination of effective therapies to patients. The current review provides a perspective on the suitability and validity of disease-free survival (DFS) as an alternative end point for OS. Criteria for establishing surrogacy and the advantages and limitations associated with the use of DFS as a primary end point in adjuvant clinical trials and as the basis for approval of new adjuvant therapies are discussed. PMID:16794241

  2. Computerized patient identification for the EMBRACA clinical trial using real-time data from the PRAEGNANT network for metastatic breast cancer patients.

    PubMed

    Hein, Alexander; Gass, Paul; Walter, Christina Barbara; Taran, Florin-Andrei; Hartkopf, Andreas; Overkamp, Friedrich; Kolberg, Hans-Christian; Hadji, Peyman; Tesch, Hans; Ettl, Johannes; Wuerstlein, Rachel; Lounsbury, Debra; Lux, Michael P; Lüftner, Diana; Wallwiener, Markus; Müller, Volkmar; Belleville, Erik; Janni, Wolfgang; Fehm, Tanja N; Wallwiener, Diethelm; Ganslandt, Thomas; Ruebner, Matthias; Beckmann, Matthias W; Schneeweiss, Andreas; Fasching, Peter A; Brucker, Sara Y

    2016-07-01

    As breast cancer is a diverse disease, clinical trials are becoming increasingly diversified and are consequently being conducted in very small subgroups of patients, making study recruitment increasingly difficult. The aim of this study was to assess the use of data from a remote data entry system that serves a large national registry for metastatic breast cancer. The PRAEGNANT network is a real-time registry with an integrated biomaterials bank that was designed as a scientific study and as a means of identifying patients who are eligible for clinical trials, based on clinical and molecular information. Here, we report on the automated use of the clinical data documented to identify patients for a clinical trial (EMBRACA) for patients with metastatic breast cancer. The patients' charts were assessed by two independent physicians involved in the clinical trial and also by a computer program that tested patients for eligibility using a structured query language script. In all, 326 patients from two study sites in the PRAEGNANT network were included in the analysis. Using expert assessment, 120 of the 326 patients (37 %) appeared to be eligible for inclusion in the EMBRACA study; with the computer algorithm assessment, a total of 129 appeared to be eligible. The sensitivity of the computer algorithm was 0.87 and its specificity was 0.88. Using computer-based identification of patients for clinical trials appears feasible. With the instrument's high specificity, its application in a large cohort of patients appears to be feasible, and the workload for reassessing the patients is limited. PMID:27283834

  3. Impact of Global Geographic Region on Time in Therapeutic Range on Warfarin Anticoagulant Therapy: Data From the ROCKET AF Clinical Trial

    PubMed Central

    Singer, Daniel E.; Hellkamp, Anne S.; Piccini, Jonathan P.; Mahaffey, Kenneth W.; Lokhnygina, Yuliya; Pan, Guohua; Halperin, Jonathan L.; Becker, Richard C.; Breithardt, Günter; Hankey, Graeme J.; Hacke, Werner; Nessel, Christopher C.; Patel, Manesh R.; Califf, Robert M.; Fox, Keith A. A.

    2013-01-01

    Background Vitamin K antagonist (VKA) therapy remains the most common method of stroke prevention in patients with atrial fibrillation. Time in therapeutic range (TTR) is a widely cited measure of the quality of VKA therapy. We sought to identify factors associated with TTR in a large, international clinical trial. Methods and Results TTR (international normalized ratio [INR] 2.0 to 3.0) was determined using standard linear interpolation in patients randomized to warfarin in the ROCKET AF trial. Factors associated with TTR at the individual patient level (i‐TTR) were determined via multivariable linear regression. Among 6983 patients taking warfarin, recruited from 45 countries grouped into 7 regions, the mean i‐TTR was 55.2% (SD 21.3%) and the median i‐TTR was 57.9% (interquartile range 43.0% to 70.6%). The mean time with INR <2 was 29.1% and the mean time with an INR >3 was 15.7%. While multiple clinical features were associated with i‐TTR, dominant determinants were previous warfarin use (mean i‐TTR of 61.1% for warfarin‐experienced versus 47.4% in VKA‐naïve patients) and geographic region where patients were managed (mean i‐TTR varied from 64.1% to 35.9%). These effects persisted in multivariable analysis. Regions with the lowest i‐TTRs had INR distributions shifted toward lower INR values and had longer inter‐INR test intervals. Conclusions Independent of patient clinical features, the regional location of medical care is a dominant determinant of variation in i‐TTR in global studies of warfarin. Regional differences in mean i‐TTR are heavily influenced by subtherapeutic INR values and are associated with reduced frequency of INR testing. Clinical Trial Registration URL: ClinicalTrials.gov. Unique identifier: NCT00403767. PMID:23525418

  4. Randomised controlled trial of improvisational music therapy's effectiveness for children with autism spectrum disorders (TIME-A): study protocol

    PubMed Central

    2012-01-01

    Background Previous research has suggested that music therapy may facilitate skills in areas typically affected by autism spectrum disorders such as social interaction and communication. However, generalisability of previous findings has been restricted, as studies were limited in either methodological accuracy or the clinical relevance of their approach. The aim of this study is to determine effects of improvisational music therapy on social communication skills of children with autism spectrum disorders. An additional aim of the study is to examine if variation in dose of treatment (i.e., number of music therapy sessions per week) affects outcome of therapy, and to determine cost-effectiveness. Methods/Design Children aged between 4;0 and 6;11 years who are diagnosed with autism spectrum disorder will be randomly assigned to one of three conditions. Parents of all participants will receive three sessions of parent counselling (at 0, 2, and 5 months). In addition, children randomised to the two intervention groups will be offered individual, improvisational music therapy over a period of five months, either one session (low-intensity) or three sessions (high-intensity) per week. Generalised effects of music therapy will be measured using standardised scales completed by blinded assessors (Autism Diagnostic Observation Schedule, ADOS) and parents (Social Responsiveness Scale, SRS) before and 2, 5, and 12 months after randomisation. Cost effectiveness will be calculated as man years. A group sequential design with first interim look at N = 235 will ensure both power and efficiency. Discussion Responding to the need for more rigorously designed trials examining the effectiveness of music therapy in autism spectrum disorders, this pragmatic trial sets out to generate findings that will be well generalisable to clinical practice. Addressing the issue of dose variation, this study's results will also provide information on the relevance of session frequency for therapy

  5. Joint modeling of longitudinal ordinal data and competing risks survival times and analysis of the NINDS rt-PA stroke trial

    PubMed Central

    Li, Ning; Elashoff, Robert M.; Li, Gang; Saver, Jeffrey

    2009-01-01

    SUMMARY Existing joint models for longitudinal and survival data are not applicable for longitudinal ordinal outcomes with possible non-ignorable missing values caused by multiple reasons. We propose a joint model for longitudinal ordinal measurements and competing risks failure time data, in which a partial proportional odds model for the longitudinal ordinal outcome is linked to the event times by latent random variables. At the survival endpoint, our model adopts the competing risks framework to model multiple failure types at the same time. The partial proportional odds model, as an extension of the popular proportional odds model for ordinal outcomes, is more flexible and at the same time provides a tool to test the proportional odds assumption. We use a likelihood approach and derive an EM algorithm to obtain the maximum likelihood estimates of the parameters. We further show that all the parameters at the survival endpoint are identifiable from the data. Our joint model enables one to make inference for both the longitudinal ordinal outcome and the failure times simultaneously. In addition, the inference at the longitudinal endpoint is adjusted for possible non-ignorable missing data caused by the failure times. We apply the method to the NINDS rt-PA stroke trial. Our study considers the modified Rankin Scale only. Other ordinal outcomes in the trial, such as the Barthel and Glasgow scales can be treated in the same way. PMID:19943331

  6. A randomized trial of prophylactic uterosacral ligament suspension at the time of hysterectomy for Prevention of Vaginal Vault Prolapse (PULS): design and methods.

    PubMed

    Alperin, Marianna; Weinstein, Milena; Kivnick, Seth; Duong, Thinh H; Menefee, Shawn

    2013-07-01

    The primary aim of this randomized trial is to evaluate whether a standardized uterosacral ligament suspension colpopexy (USLSC), added to a planned hysterectomy for an indication other than pelvic organ prolapse (POP), decreases the rate of subsequent vaginal vault prolapse in women without preoperative symptomatic POP. Secondary aims include comparison of perioperative complications, urinary, bowel and sexual functions between subjects with and without concomitant USLSC. If shown to be beneficial, the cost-effectiveness of prophylactic USLSC at the time of hysterectomy will be evaluated. This trial will be performed at 4 centers across the United States. The data will be analyzed by the data-coordinating center of the Southern California Kaiser Permanente. Standardized questionnaires and objective measurements will be obtained. The patients and providers performing assessments are masked to treatment assignment. The primary outcome, defined as absence of POP at/distal to the hymen on Pelvic Organ Prolapse Quantitative examination, will be determined 12 months post-operatively. Secondary outcomes include: no prolapse symptoms by questionnaires, and no treatment for POP besides the prophylactic study intervention. Additional follow-up occurs annually for a total of 5 years. Accrual is projected to take 3 years. Given cost and morbidity of surgical repair of post-hysterectomy prolapse, preventive strategies are of outmost importance. The risks and benefits of prophylactic USLSC have never been studied prospectively. This trial is designed to determine if USLSC is an appropriate clinical adjunct at the time of hysterectomy, with subsequent reduction of symptomatic POP. PMID:23587538

  7. A Phase II Randomized Controlled Trial Comparing Safety, Procedure Time, and Cost of the PrePex™ Device to Forceps Guided Surgical Circumcision in Zimbabwe

    PubMed Central

    Tshimanga, Mufuta; Mangwiro, Tonderayi; Mugurungi, Owen; Xaba, Sinokuthemba; Murwira, Munyaradzi; Kasprzyk, Danuta; Montaño, Daniel E.; Nyamukapa, Daisy; Tambashe, Basile; Chatikobo, Pesanai; Gundidza, Patricia; Gwinji, Gerald

    2016-01-01

    Background The World Health Organization (WHO) and the Joint United Nations Program on HIV/AIDS promote MC (male circumcision) as a key HIV prevention strategy where HIV prevalence and incidence are high and MC prevalence is low. In Zimbabwe, to achieve the 1.26 million circumcisions needed to be performed by 2015 to achieve optimal MC coverage, a new approach was needed. The primary objective of the current trial was to assess the performance (safety, procedure time, and cost) of the PrePex device compared to forceps-guided surgical circumcision. Methods and Findings This Phase II, randomized, open-label trial in Zimbabwe involved healthy, non-circumcised adult male volunteers who were randomly assigned to the PrePex device (n = 160) or surgical arm (n = 80). Three doctors and 4 nurses, all certified on both circumcision methods, performed the procedures. The PrePex device procedure involves a plastic ring with a rubber O-ring that necrotizes the foreskin to facilitate easy and minimally invasive removal. Total procedure time was the primary endpoint. Adverse event (AE) data were also gathered for 90 days post-procedure. All 80 participants in the surgical arm and 158 participants in the PrePex arm achieved complete circumcision. The total procedure time for the PrePex device was approximately one-third of the total surgical procedure (4.8 minutes, Standard Deviation [SD]: 1.2 versus 14.6 minutes; SD: 4.2; p<0.00001). There were 2 AEs for 2 participants (rate of 1.3%, 95% Confidence Interval: 0.0025–4.53%), which were resolved with simple intervention. The AEs were device related, including 1 case of pain leading to device removal and 1 case of removal of the device. Conclusions The trial supports previous studies’ conclusions that the PrePex procedure is safe, quick, easy to apply, and effective in terms of procedure time as an alternative to traditional surgical circumcision. The PrePex device has great potential for use in overburdened health systems and in

  8. Menstrual cycle phase and carbohydrate ingestion alter immune response following endurance exercise and high intensity time trial performance test under hot conditions

    PubMed Central

    2014-01-01

    Background Sex hormones are known to regulate some responses during exercise. Evaluation of the differences in exercise response with regard to menstrual cycle will help understand the menstrual cycle phase specific adaptations to exercise and athletic performance. Methods We investigated the effects of menstrual cycle phase and carbohydrate (CHO) ingestion on immune response during endurance exercise at 30°C. Six healthy women completed 4 trials comprising 90 min of cycling at 50% peak aerobic power V˙O2peak and a high intensity time trial performance test (POST). They ingested a placebo- or CHO-containing beverage during the trials, which were performed during both the follicular and luteal phases of the menstrual cycle. In all trials, thermoregulatory, cardiorespiratory, and immune responses were measured during exercise and after POST. Results Although the thermoregulatory responses differed between the menstrual cycle phases, the cardiorespiratory responses were not different. After placebo ingestion, leukocyte concentration (cells/μL) at POST (15.9 × 103) in the luteal phase was significantly higher than that in the follicular phase (12.9 × 103). The rise in leukocyte concentration was attenuated upon CHO ingestion, and the difference between menstrual cycle phases disappeared. A significant positive correlation was found between leukocyte concentration and serum free fatty acid concentrations. Interleukin-6, calprotectin, and myeloperoxidase concentrations significantly increased at POST in all trials, but no significant differences were observed between menstrual cycle phase or beverage type. Concentrations of other cytokines did not change during exercise in any of the 4 trials. Menstrual cycle phase and beverage type had no significant effect on the POST outcome. Thus, differences in leukocyte mobilization between menstrual cycle phases could result from the effect of sex hormones on substrate utilization. Conclusions The menstrual cycle

  9. Reducing bed rest time from five to three hours does not increase complications after cardiac catheterization: the THREE CATH Trial 1

    PubMed Central

    Matte, Roselene; Hilário, Thamires de Souza; Reich, Rejane; Aliti, Graziella Badin; Rabelo-Silva, Eneida Rejane

    2016-01-01

    Abstract Objective: to compare the incidence of vascular complications in patients undergoing transfemoral cardiac catheterization with a 6F introducer sheath followed by 3-hour versus 5-hour rest. Methods: randomized clinical trial. Subjects in the intervention group (IG) ambulated 3 hours after sheath removal, versus 5 hours in the control group (CG). All patients remained in the catheterization laboratory for 5 hours and were assessed hourly, and were contacted 24, 48, and 72 h after hospital discharge. Results: the sample comprised 367 patients in the IG and 363 in the GC. During cath lab stay, hematoma was the most common complication in both groups, occurring in 12 (3%) IG and 13 (4%) CG subjects (P=0.87). Bleeding occurred in 4 (1%) IG and 6 (2%) CG subjects (P=0.51), and vasovagal reaction in 5 (1.4%) IG and 4 (1.1%) CG subjects (P=0.75). At 24-h, 48-h, and 72-h bruising was the most commonly reported complication in both groups. None of the comparisons revealed any significant between-group differences. Conclusion: the results of this trial show that reducing bed rest time to 3 hours after elective cardiac catheterization is safe and does not increase complications as compared with a 5-hour rest. ClinicalTrials.gov Identifier: NCT-01740856 PMID:27463113

  10. The effect of foot reflexology on physiologic parameters and mechanical ventilation weaning time in patients undergoing open-heart surgery: A clinical trial study.

    PubMed

    Ebadi, Abbas; Kavei, Parastoo; Moradian, Seyyed Tayyeb; Saeid, Yaser

    2015-08-01

    The aim of this study was to investigate the efficacy of foot reflexology on physiological parameters and mechanical ventilation weaning time in patients undergoing open-heart surgery. This was a double blind three-group randomized controlled trial. Totally, 96 patients were recruited and randomly allocated to the experimental, placebo, and the control groups. Study groups respectively received foot reflexology, simple surface touching, and the routine care of the study setting. Physiological parameters (pulse rate, respiratory rate, systolic and diastolic blood pressures, mean arterial pressure, percutaneous oxygen saturation) and weaning time were measured. The study groups did not differ significantly in terms of physiological parameters (P value > 0.05). However, the length of weaning time in the experimental group was significantly shorter than the placebo and the control groups (P value < 0.05). The study findings demonstrated the efficiency of foot reflexology in shortening the length of weaning time. PMID:26256138

  11. Beetroot Juice Improves On-Water 500 M Time-Trial Performance, and Laboratory-Based Paddling Economy in National and International-Level Kayak Athletes.

    PubMed

    Peeling, Peter; Cox, Gregory R; Bullock, Nicola; Burke, Louise M

    2015-06-01

    We assessed the ingestion of a beetroot juice supplement (BR) on 4-min laboratory-based kayak performance in national level male (n = 6) athletes (Study A), and on 500 m on-water kayak time-trial (TT) performance in international level female (n = 5) athletes (Study B). In Study A, participants completed three laboratory-based sessions on a kayak ergometer, including a 7 × 4 min step test, and two 4 min maximal effort performance trials. Two and a half hours before the warm-up of each 4 min performance trial, athletes received either a 70 ml BR shot containing ~4.8 mmol of nitrate, or a placebo equivalent (BRPLA). The distance covered over the 4 min TT was not different between conditions; however, the average VO2 over the 4 min period was significantly lower in BR (p = .04), resulting in an improved exercise economy (p = .05). In Study B, participants completed two field-based 500 m TTs, separated by 4 days. Two hours before each trial, athletes received either two 70 ml BR shots containing ~9.6 mmol of nitrate, or a placebo equivalent (BRPLA). BR supplementation significantly enhanced TT performance by 1.7% (p = .01). Our results show that in national-level male kayak athletes, commercially available BR shots (70 ml) containing ~4.8 mmol of nitrate improved exercise economy during laboratory-based tasks predominantly reliant on the aerobic energy system. Furthermore, greater volumes of BR (140 ml; ~9.6 mmol nitrate) provided to international-level female kayak athletes resulted in enhancements to TT performance in the field. PMID:25202886

  12. Analysis of Workflow and Time to Treatment and the Effects on Outcome in Endovascular Treatment of Acute Ischemic Stroke: Results from the SWIFT PRIME Randomized Controlled Trial.

    PubMed

    Goyal, Mayank; Jadhav, Ashutosh P; Bonafe, Alain; Diener, Hans; Mendes Pereira, Vitor; Levy, Elad; Baxter, Blaise; Jovin, Tudor; Jahan, Reza; Menon, Bijoy K; Saver, Jeffrey L

    2016-06-01

    Purpose To study the relationship between functional independence and time to reperfusion in the Solitaire with the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke (SWIFT PRIME) trial in patients with disabling acute ischemic stroke who underwent endovascular therapy plus intravenous tissue plasminogen activator (tPA) administration versus tPA administration alone and to investigate variables that affect time spent during discrete steps. Materials and Methods Data were analyzed from the SWIFT PRIME trial, a global, multicenter, prospective study in which outcomes were compared in patients treated with intravenous tPA alone or in combination with the Solitaire device (Covidien, Irvine, Calif). Between December 2012 and November 2014, 196 patients were enrolled. The relation between time from (a) symptom onset to reperfusion and (b) imaging to reperfusion and clinical outcome was analyzed, along with patient and health system characteristics that affect discrete steps in patient workflow. Multivariable logistic regression was used to assess relationships between time and outcome; negative binomial regression was used to evaluate effects on workflow. The institutional review board at each site approved the trial. Patients provided written informed consent, or, at select sites, there was an exception from having to acquire explicit informed consent in emergency circumstances. Results In the stent retriever arm of the study, symptom onset to reperfusion time of 150 minutes led to 91% estimated probability of functional independence, which decreased by 10% over the next hour and by 20% with every subsequent hour of delay. Time from arrival at the emergency department to arterial access was 90 minutes (interquartile range, 69-120 minutes), and time to reperfusion was 129 minutes (interquartile range, 108-169 minutes). Patients who initially arrived at a referring facility had longer symptom onset to groin puncture times compared with

  13. Timing of eyewitness expert testimony, jurors' need for cognition, and case strength as determinants of trial verdicts.

    PubMed

    Leippe, Michael R; Eisenstadt, Donna; Rauch, Shannon M; Seib, Hope M

    2004-06-01

    In 2 experiments, college students read a murder-trial transcript that included or did not include court-appointed expert testimony about eyewitness memory. The testimony either preceded or followed the evidence, and the judge's final instructions reminded or did not remind jurors about the expert's testimony. Expert testimony decreased perceptions of guilt and eyewitness believability when it followed the evidence and preceded the judge's reminder. This effect occurred whether the prosecution case was moderately weak or moderately strong. Jurors' need for cognition (NC) was curvilinearly related to convictions in a strong case. Low and high NC jurors convicted less than did moderate NC jurors. Greater scrutiny by high NC jurors may make them more likely to consider evidence for the weaker side. PMID:15161410

  14. Analysis of failure time data with multilevel clustering, with application to the child vitamin a intervention trial in Nepal.

    PubMed

    Shih, Joanna H; Lu, Shou-En

    2007-09-01

    We consider the problem of estimating covariate effects in the marginal Cox proportional hazard model and multilevel associations for child mortality data collected from a vitamin A supplementation trial in Nepal, where the data are clustered within households and villages. For this purpose, a class of multivariate survival models that can be represented by a functional of marginal survival functions and accounts for hierarchical structure of clustering is exploited. Based on this class of models, an estimation strategy involving a within-cluster resampling procedure is proposed, and a model assessment approach is presented. The asymptotic theory for the proposed estimators and lack-of-fit test is established. The simulation study shows that the estimates are approximately unbiased, and the proposed test statistic is conservative under extremely heavy censoring but approaches the size otherwise. The analysis of the Nepal study data shows that the association of mortality is much greater within households than within villages. PMID:17825001

  15. Cycling Time Trial Performance 4 Hours After Glycogen-Lowering Exercise Is Similarly Enhanced by Recovery Nondairy Chocolate Beverages Versus Chocolate Milk.

    PubMed

    Upshaw, Adam U; Wong, Tiffany S; Bandegan, Arash; Lemon, Peter W

    2016-02-01

    Postexercise chocolate milk ingestion has been shown to enhance both glycogen resynthesis and subsequent exercise performance. To assess whether nondairy chocolate beverage ingestion post-glycogen-lowering exercise can enhance 20-km cycling time trial performance 4 hr later, eight healthy trained male cyclists (21.8 ± 2.3y, VO2max = 61.2 ± 1.4 ml·kg-1·min-1; M ± SD) completed a series of intense cycling intervals designed to lower muscle glycogen (Jentjens & Jeukendrup, 2003) followed by 4 hr of recovery and a subsequent 20-km cycling time trial. During the first 2 hr of recovery, participants ingested chocolate dairy milk (DAIRYCHOC), chocolate soy beverage (SOYCHOC), chocolate hemp beverage (HEMPCHOC), low-fat dairy milk (MILK), or a low-energy artificially sweetened, flavored beverage (PLACEBO) at 30-min intervals in a double-blind, counterbalanced repeated-measures design. All drinks, except the PLACEBO (247 kJ) were isoenergetic (2,107 kJ), and all chocolate-flavored drinks provided 1-g CHO·kg body mass-1·h-1. Fluid intake across treatments was equalized (2,262 ± 148 ml) by ingesting appropriate quantities of water based on drink intake. The CHO:PRO ratio was 4:1, 1.5:1, 4:1, and 6:1 for DAIRYCHOC, MILK, SOYCHOC, and HEMPCHOC, respectively. One-way analysis of variance with repeated measures showed time trial performance (DAIRYCHOC = 34.58 ± 2.5 min, SOYCHOC = 34.83 ± 2.2 min, HEMPCHOC = 34.88 ± 1.1 min, MILK = 34.47 ± 1.7 min) was enhanced similarly vs PLACEBO (37.85 ± 2.1) for all treatments (p = .019) These data suggest that postexercise macronutrient and total energy intake are more important for same-day 20-km cycling time trial performance after glycogen-lowering exercise than protein type or protein-to-carbohydrate ratio. PMID:26314086

  16. DiAs Web Monitoring: A Real-Time Remote Monitoring System Designed for Artificial Pancreas Outpatient Trials

    PubMed Central

    Place, Jérôme; Robert, Antoine; Brahim, Najib Ben; Patrick, Keith-Hynes; Farret, Anne; Marie-Josée, Pelletier; Buckingham, Bruce; Breton, Marc; Kovatchev, Boris; Renard, Eric

    2013-01-01

    Background Developments in an artificial pancreas (AP) for patients with type 1 diabetes have allowed a move toward performing outpatient clinical trials. “Home-like” environment implies specific protocol and system adaptations among which the introduction of remote monitoring is meaningful. We present a novel tool allowing multiple patients to monitor AP use in home-like settings. Methods We investigated existing systems, performed interviews of experienced clinical teams, listed required features, and drew several mockups of the user interface. The resulting application was tested on the bench before it was used in three outpatient studies representing 3480 h of remote monitoring. Results Our tool, called DiAs Web Monitoring (DWM), is a web-based application that ensures reception, storage, and display of data sent by AP systems. Continuous glucose monitoring (CGM) and insulin delivery data are presented in a colored chart to facilitate reading and interpretation. Several subjects can be monitored simultaneously on the same screen, and alerts are triggered to help detect events such as hypoglycemia or CGM failures. In the third trial, DWM received approximately 460 data per subject per hour: 77% for log messages, 5% for CGM data. More than 97% of transmissions were achieved in less than 5 min. Conclusions Transition from a hospital setting to home-like conditions requires specific AP supervision to which remote monitoring systems can contribute valuably. DiAs Web Monitoring worked properly when tested in our outpatient studies. It could facilitate subject monitoring and even accelerate medical and technical assessment of the AP. It should now be adapted for long-term studies with an enhanced notification feature. J Diabetes Sci Technol 2013;7(6):1427–1435 PMID:24351169

  17. Quasi-experimental trial of diabetes Self-Management Automated and Real-Time Telephonic Support (SMARTSteps) in a Medicaid managed care plan: study protocol

    PubMed Central

    2012-01-01

    Background Health information technology can enhance self-management and quality of life for patients with chronic disease and overcome healthcare barriers for patients with limited English proficiency. After a randomized controlled trial of a multilingual automated telephone self-management support program (ATSM) improved patient-centered dimensions of diabetes care in safety net clinics, we collaborated with a nonprofit Medicaid managed care plan to translate research into practice, offering ATSM as a covered benefit and augmenting ATSM to promote medication activation. This paper describes the protocol of the Self-Management Automated and Real-Time Telephonic Support Project (SMARTSteps). Methods/Design This controlled quasi-experimental trial used a wait-list variant of a stepped wedge design to enroll 362 adult health plan members with diabetes who speak English, Cantonese, or Spanish and receive care at 4 publicly-funded clinics. Through language-stratified randomization, participants were assigned to four intervention statuses: SMARTSteps-ONLY, SMARTSteps-PLUS, or wait-list for either intervention. In addition to usual primary care, intervention participants received 27 weekly calls in their preferred language with rotating queries and response-triggered education about self-care, medication adherence, safety concerns, psychological issues, and preventive services. Health coaches from the health plan called patients with out-of-range responses for collaborative goal setting and action planning. SMARTSteps-PLUS also included health coach calls to promote medication activation, adherence and intensification, if triggered by ATSM-reported non-adherence, refill non-adherence from pharmacy claims, or suboptimal cardiometabolic indicators. Wait-list patients crossed-over to SMARTSteps-ONLY or -PLUS at 6 months. For participants who agreed to structured telephone interviews at baseline and 6 months (n = 252), primary outcomes will be changes in quality of life and

  18. Peer-mentoring for first-time mothers from areas of socio-economic disadvantage: A qualitative study within a randomised controlled trial

    PubMed Central

    Murphy, Christine A; Cupples, Margaret E; Percy, Andrew; Halliday, Henry L; Stewart, Moira C

    2008-01-01

    Background Non-professional involvement in delivering health and social care support in areas of socio-economic deprivation is considered important in attempting to reduce health inequalities. However, trials of peer mentoring programmes have yielded inconsistent evidence of benefit: difficulties in implementation have contributed to uncertainty regarding their efficacy. We aimed to explore difficulties encountered in conducting a randomised controlled trial of a peer-mentoring programme for first-time mothers in socially disadvantaged areas, in order to provide information relevant to future research and practice. This paper describes the experiences of lay-workers, women and health professionals involved in the trial. Methods Thematic analysis of semi-structured interviews with women (n = 11) who were offered peer mentor support, lay-workers (n = 11) who provided mentoring and midwives (n = 2) who supervised the programme, which provided support, from first hospital antenatal visit to one year postnatal. Planned frequency of contact was two-weekly (telephone or home visit) but was tailored to individuals' needs. Results Despite lay-workers living in the same locality, they experienced difficulty initiating contact with women and this affected their morale adversely. Despite researchers' attempts to ensure that the role of the mentor was understood clearly it appeared that this was not achieved for all participants. Mentors attempted to develop peer-mentor relationships by offering friendship and sharing personal experiences, which was appreciated by women. Mentors reported difficulties developing relationships with those who lacked interest in the programme. External influences, including family and friends, could prevent or facilitate mentoring. Time constraints in reconciling flexible mentoring arrangements with demands of other commitments posed major personal difficulties for lay-workers. Conclusion Difficulties in initiating contact, developing peer

  19. Molecular Evolution of the HIV-1 Thai Epidemic between the Time of RV144 Immunogen Selection to the Execution of the Vaccine Efficacy Trial

    PubMed Central

    Tovanabutra, Sodsai; Rerks-Ngarm, Supachai; Nitayaphan, Sorachai; Eamsila, Chirapa; Kunasol, Prayura; Khamboonruang, Chirasak; Thongcharoen, Prasert; Namwat, Chawetsan; Premsri, Nakorn; Benenson, Michael; Morgan, Patricia; Bose, Meera; Sanders-Buell, Eric; Paris, Robert; Robb, Merlin L.; Birx, Deborah L.; De Souza, Mark S.; McCutchan, Francine E.; Michael, Nelson L.; Kim, Jerome H.

    2013-01-01

    The RV144 HIV-1 vaccine trial (Thailand, 2003 to 2009), using immunogens genetically matched to the regional epidemic, demonstrated the first evidence of efficacy for an HIV-1 vaccine. Here we studied the molecular evolution of the HIV-1 epidemic from the time of immunogen selection to the execution of the efficacy trial. We studied HIV-1 genetic diversity among 390 volunteers who were deferred from enrollment in RV144 due to preexisting HIV-1 infection using a multiregion hybridization assay, full-genome sequencing, and phylogenetic analyses. The subtype distribution was 91.7% CRF01_AE, 3.5% subtype B, 4.3% B/CRF01_AE recombinants, and 0.5% dual infections. CRF01_AE strains were 31% more diverse than the ones from the 1990s Thai epidemic. Sixty-nine percent of subtype B strains clustered with the cosmopolitan Western B strains. Ninety-three percent of B/CRF01_AE recombinants were unique; recombination breakpoint analysis showed that these strains were highly embedded within the larger network that integrates recombinants from East/Southeast Asia. Compared to Thai sequences from the early 1990s, the distance to the RV144 immunogens increased 52% to 68% for CRF01_AE Env immunogens and 12% to 29% for subtype B immunogens. Forty-three percent to 48% of CRF01_AE sequences differed from the sequence of the vaccine insert in Env variable region 2 positions 169 and 181, which were implicated in vaccine sieve effects in RV144. In conclusion, compared to the molecular picture at the early stages of vaccine development, our results show an overall increase in the genetic complexity of viruses in the Thai epidemic and in the distance to vaccine immunogens, which should be considered at the time of the analysis of the trial results. PMID:23576510

  20. Molecular evolution of the HIV-1 Thai epidemic between the time of RV144 immunogen selection to the execution of the vaccine efficacy trial.

    PubMed

    Kijak, Gustavo H; Tovanabutra, Sodsai; Rerks-Ngarm, Supachai; Nitayaphan, Sorachai; Eamsila, Chirapa; Kunasol, Prayura; Khamboonruang, Chirasak; Thongcharoen, Prasert; Namwat, Chawetsan; Premsri, Nakorn; Benenson, Michael; Morgan, Patricia; Bose, Meera; Sanders-Buell, Eric; Paris, Robert; Robb, Merlin L; Birx, Deborah L; De Souza, Mark S; McCutchan, Francine E; Michael, Nelson L; Kim, Jerome H

    2013-07-01

    The RV144 HIV-1 vaccine trial (Thailand, 2003 to 2009), using immunogens genetically matched to the regional epidemic, demonstrated the first evidence of efficacy for an HIV-1 vaccine. Here we studied the molecular evolution of the HIV-1 epidemic from the time of immunogen selection to the execution of the efficacy trial. We studied HIV-1 genetic diversity among 390 volunteers who were deferred from enrollment in RV144 due to preexisting HIV-1 infection using a multiregion hybridization assay, full-genome sequencing, and phylogenetic analyses. The subtype distribution was 91.7% CRF01_AE, 3.5% subtype B, 4.3% B/CRF01_AE recombinants, and 0.5% dual infections. CRF01_AE strains were 31% more diverse than the ones from the 1990s Thai epidemic. Sixty-nine percent of subtype B strains clustered with the cosmopolitan Western B strains. Ninety-three percent of B/CRF01_AE recombinants were unique; recombination breakpoint analysis showed that these strains were highly embedded within the larger network that integrates recombinants from East/Southeast Asia. Compared to Thai sequences from the early 1990s, the distance to the RV144 immunogens increased 52% to 68% for CRF01_AE Env immunogens and 12% to 29% for subtype B immunogens. Forty-three percent to 48% of CRF01_AE sequences differed from the sequence of the vaccine insert in Env variable region 2 positions 169 and 181, which were implicated in vaccine sieve effects in RV144. In conclusion, compared to the molecular picture at the early stages of vaccine development, our results show an overall increase in the genetic complexity of viruses in the Thai epidemic and in the distance to vaccine immunogens, which should be considered at the time of the analysis of the trial results. PMID:23576510

  1. Effectiveness of a primary care-based intervention to reduce sitting time in overweight and obese patients (SEDESTACTIV): a randomized controlled trial; rationale and study design

    PubMed Central

    2014-01-01

    Background There is growing evidence suggesting that prolonged sitting has negative effects on people’s weight, chronic diseases and mortality. Interventions to reduce sedentary time can be an effective strategy to increase daily energy expenditure. The purpose of this study is to evaluate the effectiveness of a six-month primary care intervention to reduce daily of sitting time in overweight and mild obese sedentary patients. Method/Design The study is a randomized controlled trial (RCT). Professionals from thirteen primary health care centers (PHC) will randomly invite to participate mild obese or overweight patients of both gender, aged between 25 and 65 years old, who spend 6 hours at least daily sitting. A total of 232 subjects will be randomly allocated to an intervention (IG) and control group (CG) (116 individuals each group). In addition, 50 subjects with fibromyalgia will be included. Primary outcome is: (1) sitting time using the activPAL device and the Marshall questionnaire. The following parameters will be also assessed: (2) sitting time in work place (Occupational Sitting and Physical Activity Questionnaire), (3) health-related quality of life (EQ-5D), (4) evolution of stage of change (Prochaska and DiClemente's Stages of Change Model), (5) physical inactivity (catalan version of Brief Physical Activity Assessment Tool), (6) number of steps walked (pedometer and activPAL), (7) control based on analysis (triglycerides, total cholesterol, HDL, LDL, glycemia and, glycated haemoglobin in diabetic patients) and (8) blood pressure and anthropometric variables. All parameters will be assessed pre and post intervention and there will be a follow up three, six and twelve months after the intervention. A descriptive analysis of all variables and a multivariate analysis to assess differences among groups will be undertaken. Multivariate analysis will be carried out to assess time changes of dependent variables. All the analysis will be done under the

  2. Prior low- or high-intensity exercise alters pacing strategy, energy system contribution and performance during a 4-km cycling time trial.

    PubMed

    Correia-Oliveira, Carlos Rafaell; Santos, Ralmony Alcantara; Silva-Cavalcante, Marcos David; Bertuzzi, Romulo; Kiss, Maria Augusta Peduti Dal'Molin; Bishop, David John; Lima-Silva, Adriano Eduardo

    2014-01-01

    We analyzed the influence of prior exercise designed to reduce predominantly muscle glycogen in either type I or II fibers on pacing and performance during a 4-km cycling time trial (TT). After preliminary and familiarization trials, in a randomized, repeated-measures crossover design, ten amateur cyclists performed: 1) an exercise designed to reduce glycogen of type I muscle fibers, followed by a 4-km TT (EX-FIB I); 2) an exercise designed to reduce glycogen of type II muscle fibers, followed by a 4-km TT (EX-FIB II) and; 3) a 4-km TT, without the prior exercise (CONT). The muscle-glycogen-reducing exercise in both EX-FIB I and EX-FIB II was performed in the evening, ∼12 h before the 4-km TT. Performance time was increased and power output (PO) was reduced in EX-FIB I (432.8±8.3 s and 204.9±10.9 W) and EX-FIB II (428.7±6.7 s and 207.5±9.1 W) compared to CONT (420.8±6.4 s and 218.4±9.3 W; P<0.01), without a difference between EX-FIB I and EX-FIB II (P>0.05). The PO was lower in EX-FIB I than in CONT at the beginning and middle of the trial (P<0.05). The mean aerobic contribution during EX-FIB I was also significantly lower than in CONT (P<0.05), but there was no difference between CONT and EX-FIB II or between EX-FIB I and EX-FIB II (P>0.05). The integrated electromyography was unchanged between conditions (P>0.05). Performance may have been impaired in EX-FIB I due a more conservative pacing at the beginning and middle, which was associated with a reduced aerobic contribution. In turn, the PO profile adopted in EX-FIB II was also reduced throughout the trial, but the impairment in performance may be attributed to a reduced glycolytic contribution (i.e. reduced lactate accumulation). PMID:25330452

  3. Prior Low- or High-Intensity Exercise Alters Pacing Strategy, Energy System Contribution and Performance during a 4-km Cycling Time Trial

    PubMed Central

    Correia-Oliveira, Carlos Rafaell; Santos, Ralmony Alcantara; Silva-Cavalcante, Marcos David; Bertuzzi, Romulo; Kiss, Maria Augusta Peduti Dal’Molin; Bishop, David John; Lima-Silva, Adriano Eduardo

    2014-01-01

    We analyzed the influence of prior exercise designed to reduce predominantly muscle glycogen in either type I or II fibers on pacing and performance during a 4-km cycling time trial (TT). After preliminary and familiarization trials, in a randomized, repeated-measures crossover design, ten amateur cyclists performed: 1) an exercise designed to reduce glycogen of type I muscle fibers, followed by a 4-km TT (EX-FIB I); 2) an exercise designed to reduce glycogen of type II muscle fibers, followed by a 4-km TT (EX-FIB II) and; 3) a 4-km TT, without the prior exercise (CONT). The muscle-glycogen-reducing exercise in both EX-FIB I and EX-FIB II was performed in the evening, ∼12 h before the 4-km TT. Performance time was increased and power output (PO) was reduced in EX-FIB I (432.8±8.3 s and 204.9±10.9 W) and EX-FIB II (428.7±6.7 s and 207.5±9.1 W) compared to CONT (420.8±6.4 s and 218.4±9.3 W; P<0.01), without a difference between EX-FIB I and EX-FIB II (P>0.05). The PO was lower in EX-FIB I than in CONT at the beginning and middle of the trial (P<0.05). The mean aerobic contribution during EX-FIB I was also significantly lower than in CONT (P<0.05), but there was no difference between CONT and EX-FIB II or between EX-FIB I and EX-FIB II (P>0.05). The integrated electromyography was unchanged between conditions (P>0.05). Performance may have been impaired in EX-FIB I due a more conservative pacing at the beginning and middle, which was associated with a reduced aerobic contribution. In turn, the PO profile adopted in EX-FIB II was also reduced throughout the trial, but the impairment in performance may be attributed to a reduced glycolytic contribution (i.e. reduced lactate accumulation). PMID:25330452

  4. The effect of real-time CPR feedback and post event debriefing on patient and processes focused outcomes: A cohort study: trial protocol

    PubMed Central

    2011-01-01

    Background Cardiac arrest affects 30-35, 000 hospitalised patients in the UK every year. For these patients to be given the best chance of survival, high quality cardiopulmonary resuscitation (CPR) must be delivered, however the quality of CPR in real-life is often suboptimal. CPR feedback devices have been shown to improve CPR quality in the pre-hospital setting and post-event debriefing can improve adherence to guidelines and CPR quality. However, the evidence for use of these improvement methods in hospital remains unclear. The CPR quality improvement initiative is a prospective cohort study of the Q-CPR real-time feedback device combined with post-event debriefing in hospitalised adult patients who sustain a cardiac arrest. Methods/design The primary objective of this trial is to assess whether a CPR quality improvement initiative will improve rate of return of sustained spontaneous circulation in in-hospital-cardiac-arrest patients. The study is set in one NHS trust operating three hospital sites. Secondary objectives will evaluate: any return of spontaneous circulation; survival to hospital discharge and patient cerebral performance category at discharge; quality of CPR variables and cardiac arrest team factors. Methods: All three sites will have an initial control phase before any improvements are implemented; site 1 will implement audiovisual feedback combined with post event debriefing, site 2 will implement audiovisual feedback only and site 3 will remain as a control site to measure any changes in outcome due to any other trust-wide changes in resuscitation practice. All adult patients sustaining a cardiac arrest and receiving resuscitation from the hospital cardiac arrest team will be included. Patients will be excluded if; they have a Do-not-attempt resuscitation order written and documented in their medical records, the cardiac arrest is not attended by a resuscitation team, the arrest occurs out-of-hospital or the patient has previously participated

  5. Meta-analysis of time-to-event outcomes from randomized trials using restricted mean survival time: application to individual participant data.

    PubMed

    Wei, Yinghui; Royston, Patrick; Tierney, Jayne F; Parmar, Mahesh K B

    2015-09-20

    Meta-analysis of time-to-event outcomes using the hazard ratio as a treatment effect measure has an underlying assumption that hazards are proportional. The between-arm difference in the restricted mean survival time is a measure that avoids this assumption and allows the treatment effect to vary with time. We describe and evaluate meta-analysis based on the restricted mean survival time for dealing with non-proportional hazards and present a diagnostic method for the overall proportional hazards assumption. The methods are illustrated with the application to two individual participant meta-analyses in cancer. The examples were chosen because they differ in disease severity and the patterns of follow-up, in order to understand the potential impacts on the hazards and the overall effect estimates. We further investigate the estimation methods for restricted mean survival time by a simulation study. PMID:26099573

  6. Preliminary Comparison of Two-Way Satellite Time and Frequency Transfer and GPS Common-View Time Transfer During the INTELSAT Field Trial

    NASA Technical Reports Server (NTRS)

    Davis, John A.; Lewandowski, W.; DeYoung, James A.; Kirchner, Dieter; Hetzel, Peter; deJong, Gerrit; Soering, A.; Baumont, F.; Klepczynski, William; McKinley, Angela Davis; Parker, Thomas E.; Bartle, K. A.; Ressler, Hubert; Robnik, R.; Veenstra, L.

    1996-01-01

    For a decade and a half Global Positioning System (GPS) common-view time transfer has greatly served the needs of primary timing laboratories for regular intercomparisons of remote atomic clocks. However, GPS as a one-way technique has natural limits and may not meet all challenges of the comparison of the coming new generation of atomic clocks. Two-way satellite time and frequency transfer (TWSTFT) is a promising technique which may successfully complement GPS. For two years, regular TWSTFT's have been performed between eight laboratories situated in both Europe and North America, using INTELSAT satellites. This has enabled an extensive direct comparison to be made between these two high performance time transfer methods. The performance of the TWSTFT and GPS common view methods are compared over a number of time-transfer links. These links use a variety of time-transfer hardware and atomic clocks and have baselines of substantially different lengths. The relative merits of the two time-transfer systems are discussed.

  7. Two-Arm Randomized Pilot Intervention Trial to Decrease Sitting Time and Increase Sit-To-Stand Transitions in Working and Non-Working Older Adults

    PubMed Central

    Kerr, Jacqueline; Takemoto, Michelle; Bolling, Khalisa; Atkin, Andrew; Carlson, Jordan; Rosenberg, Dori; Crist, Katie; Godbole, Suneeta; Lewars, Brittany; Pena, Claudia; Merchant, Gina

    2016-01-01

    Background Excessive sitting has been linked to poor health. It is unknown whether reducing total sitting time or increasing brief sit-to-stand transitions is more beneficial. We conducted a randomized pilot study to assess whether it is feasible for working and non-working older adults to reduce these two different behavioral targets. Methods Thirty adults (15 workers and 15 non-workers) age 50–70 years were randomized to one of two conditions (a 2-hour reduction in daily sitting or accumulating 30 additional brief sit-to-stand transitions per day). Sitting time, standing time, sit-to-stand transitions and stepping were assessed by a thigh worn inclinometer (activPAL). Participants were assessed for 7 days at baseline and followed while the intervention was delivered (2 weeks). Mixed effects regression analyses adjusted for days within participants, device wear time, and employment status. Time by condition interactions were investigated. Results Recruitment, assessments, and intervention delivery were feasible. The ‘reduce sitting’ group reduced their sitting by two hours, the ‘increase sit-to-stand’ group had no change in sitting time (p < .001). The sit-to-stand transition group increased their sit-to-stand transitions, the sitting group did not (p < .001). Conclusions This study was the first to demonstrate the feasibility and preliminary efficacy of specific sedentary behavioral goals. Trial Registration clinicaltrials.gov NCT02544867 PMID:26735919

  8. Clinical trial: assessment of regional gut transit times in healthy controls and patients with gastroparesis using wireless motility technology

    PubMed Central

    Sarosiek, I.; Selover, K. H.; Katz, L. A.; Semler, J. R.; Wilding, G. E.; Lackner, J. M.; Sitrin, M. D.; Kuo, B.; Chey, W. D.; Hasler, W. L.; Koch, K. L.; Parkman, H. P.; Sarosiek, J; Mccallum, R. W.

    2015-01-01

    BACKGROUND Wireless pH and pressure motility capsule (wireless motility capsule) technology provides a method to assess regional gastrointestinal transit times. AIMS Data from a multi-center study of gastroparetic patients and healthy controls was analyzed to: compare regional transit times measured by wireless motility capsule in healthy controls and gastroparetics (GP). METHODS 66 healthy controls and 34 patients with GP [15 diabetic and 19 idiopathic] swallowed wireless motility capsule together with standardized meal (255 kcal). Gastric emptying time (GET), small bowel transit time (SBTT), colon transit time (CTT), and whole gut transit time (WGTT) were calculated using the wireless motility capsule. RESULTS GET, CTT and WGTT but not SBTT were significantly longer in GP than in controls. Eighteen percent of gastroparetic patients had delayed WGTT. Both diabetic and idiopathic etiologies of gastroparetics had significantly slower WGTT (p<0.0001) in addition to significantly slower GET than healthy controls. Diabetic gastroparetics additionally had significantly slower CTT than healthy controls (p = 0.0054). CONCLUSIONS 1) In addition to assessing gastric emptying, regional transit times can be measured using wireless motility capsule. 2) The prolongation of CTT in gastroparetic patients indicates dysmotility beyond the stomach in GP is present and could be contributing to symptom presentation. PMID:19814743

  9. Effects of Cereal, Fruit and Vegetable Fibers on Human Fecal Weight and Transit Time: A Comprehensive Review of Intervention Trials

    PubMed Central

    de Vries, Jan; Birkett, Anne; Hulshof, Toine; Verbeke, Kristin; Gibes, Kernon

    2016-01-01

    Cereal fibers are known to increase fecal weight and speed transit time, but far less data are available on the effects of fruits and vegetable fibers on regularity. This study provides a comprehensive review of the impact of these three fiber sources on regularity in healthy humans. We identified English-language intervention studies on dietary fibers and regularity and performed weighted linear regression analyses for fecal weight and transit time. Cereal and vegetable fiber groups had comparable effects on fecal weight; both contributed to it more than fruit fibers. Less fermentable fibers increased fecal weight to a greater degree than more fermentable fibers. Dietary fiber did not change transit time in those with an initial time of <48 h. In those with an initial transit time ≥48 h, transit time was reduced by approximately 30 min per gram of cereal, fruit or vegetable fibers, regardless of fermentability. Cereal fibers have been studied more than any other kind in relation to regularity. This is the first comprehensive review comparing the effects of the three major food sources of fiber on bowel function and regularity since 1993. PMID:26950143

  10. Effects of Cereal, Fruit and Vegetable Fibers on Human Fecal Weight and Transit Time: A Comprehensive Review of Intervention Trials.

    PubMed

    de Vries, Jan; Birkett, Anne; Hulshof, Toine; Verbeke, Kristin; Gibes, Kernon

    2016-03-01

    Cereal fibers are known to increase fecal weight and speed transit time, but far less data are available on the effects of fruits and vegetable fibers on regularity. This study provides a comprehensive review of the impact of these three fiber sources on regularity in healthy humans. We identified English-language intervention studies on dietary fibers and regularity and performed weighted linear regression analyses for fecal weight and transit time. Cereal and vegetable fiber groups had comparable effects on fecal weight; both contributed to it more than fruit fibers. Less fermentable fibers increased fecal weight to a greater degree than more fermentable fibers. Dietary fiber did not change transit time in those with an initial time of <48 h. In those with an initial transit time ≥48 h, transit time was reduced by approximately 30 min per gram of cereal, fruit or vegetable fibers, regardless of fermentability. Cereal fibers have been studied more than any other kind in relation to regularity. This is the first comprehensive review comparing the effects of the three major food sources of fiber on bowel function and regularity since 1993. PMID:26950143

  11. Reproducibility of Outdoor Flat and Uphill Cycling Time Trials and Their Performance Correlates with Peak Power Output in Moderately Trained Cyclists

    PubMed Central

    Tan, Frankie H. Y.; Aziz, Abdul Rashid

    2005-01-01

    The aims of the present study were firstly to examine the reproducibility of outdoor flat and uphill cycling time trials (TT), and secondly to assess the relationship between peak power output (Wpeak) obtained in the laboratory and outdoor cycling performance in moderately trained cyclists. Eight competitive male cyclists first performed a progressive cycle ergometer test in the laboratory to determine Wpeak (W). Thereafter, they performed three 36 km TT (TT36) on a flat course on separate days and at the same time of the day. On a different day, they also performed three 1.4 km uphill TT (TT1.4) in a single day. The coefficient of variation (CV) values across three TT36 and TT1.4 ranged from 1.1 - 1.4% and 2.6 - 2.9%, for performance time (min) and mean power (W), respectively. The correlation between absolute Wpeak (W) obtained in the laboratory and mean power during TT36 and TT1.4 was 0.90 (p < 0.01) and 0.98 (p < 0.01), respectively. Absolute Wpeak (W) correlated significantly with performance time in TT36 (r = -0.72, p < 0.05) but not in TT1.4 (r = -0.52, p > 0.05). The correlation between relative Wpeak (W·kg-1) and performance time in TT36 and TT1.4 was r = -0.65 (p > 0.05) and r = -0.91 (p < 0.01), respectively. In conclusion, under stable environmental conditions, performance time and mean power are highly reproducible in moderately trained cyclists during outdoor cycling TT. Laboratory determined absolute Wpeak (W) may predict cycling performance on a flat course but relative Wpeak (W·kg-1) is a better predictor of performance during uphill cycling. Key Points Under stable environmental conditions, performance time and mean power are highly reproducible in moderately trained cyclists during outdoor flat and uphill cycling time trials. Laboratory determined peak power output (Wpeak) (W) may predict cycling performance on a flat course. Laboratory determined relative Wpeak (W·kg-1) is a better predictor of performance during uphill cycling PMID:24453532

  12. Collaborative trial validation studies of real-time PCR-based GMO screening methods for detection of the bar gene and the ctp2-cp4epsps construct.

    PubMed

    Grohmann, Lutz; Brünen-Nieweler, Claudia; Nemeth, Anne; Waiblinger, Hans-Ulrich

    2009-10-14

    Polymerase Chain Reaction (PCR)-based screening methods targeting genetic elements commonly used in genetically modified (GM) plants are important tools for the detection of GM materials in food, feed, and seed samples. To expand and harmonize the screening capability of enforcement laboratories, the German Federal Office of Consumer Protection and Food Safety conducted collaborative trials for interlaboratory validation of real-time PCR methods for detection of the phosphinothricin acetyltransferase (bar) gene from Streptomyces hygroscopicus and a construct containing the 5-enolpyruvylshikimate-3-phosphate synthase gene from Agrobacterium tumefaciens sp. strain CP4 (ctp2-cp4epsps), respectively. To assess the limit of detection, precision, and accuracy of the methods, laboratories had to analyze two sets of 18 coded genomic DNA samples of events LLRice62 and MS8 with the bar method and NK603 and GT73 with the ctp2-cp4epsps method at analyte levels of 0, 0.02, and 0.1% GM content, respectively. In addition, standard DNAs were provided to the laboratories to generate calibration curves for copy number quantification of the bar and ctp2-cp4epsps target sequences present in the test samples. The study design and the results obtained are discussed with respect to the difficult issue of developing general guidelines and concepts for the collaborative trial validation of qualitative PCR screening methods. PMID:19807158

  13. The P600-as-P3 hypothesis revisited: single-trial analyses reveal that the late EEG positivity following linguistically deviant material is reaction time aligned.

    PubMed

    Sassenhagen, Jona; Schlesewsky, Matthias; Bornkessel-Schlesewsky, Ina

    2014-10-01

    The P600, a late positive ERP component following linguistically deviant stimuli, is commonly seen as indexing structural, high-level processes, e.g. of linguistic (re)analysis. It has also been identified with the P3 (P600-as-P3 hypothesis), which is thought to reflect a systemic neuromodulator release facilitating behavioural shifts and is usually response time aligned. We investigated single-trial alignment of the P600 to response, a critical prediction of the P600-as-P3 hypothesis. Participants heard sentences containing morphosyntactic and semantic violations and responded via a button press. The elicited P600 was perfectly response aligned, while an N400 following semantic deviations was stimulus aligned. This is, to our knowledge, the first single-trial analysis of language processing data using within-sentence behavioural responses as temporal covariates. Results support the P600-as-P3 perspective and thus constitute a step towards a neurophysiological grounding of language-related ERPs. PMID:25151545

  14. Clinical Trials

    MedlinePlus

    Clinical trials are research studies that test how well new medical approaches work in people. Each study answers ... prevent, screen for, diagnose, or treat a disease. Clinical trials may also compare a new treatment to a ...

  15. Clinical Trials

    MedlinePlus

    Clinical trials are research studies that test how well new medical approaches work in people. Each study ... prevent, screen for, diagnose, or treat a disease. Clinical trials may also compare a new treatment to ...

  16. What Are Clinical Trials? | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Clinical Trials What Are Clinical Trials? Past Issues / Fall 2010 Table of Contents ... conducted all the time. The Different Phases of Clinical Trials Clinical trials related to drugs are classified ...

  17. Trial Watch

    PubMed Central

    Vacchelli, Erika; Aranda, Fernando; Eggermont, Alexander; Galon, Jérôme; Sautès-Fridman, Catherine; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2014-01-01

    In 1997, for the first time in history, a monoclonal antibody (mAb), i.e., the chimeric anti-CD20 molecule rituximab, was approved by the US Food and Drug Administration for use in cancer patients. Since then, the panel of mAbs that are approved by international regulatory agencies for the treatment of hematopoietic and solid malignancies has not stopped to expand, nowadays encompassing a stunning amount of 15 distinct molecules. This therapeutic armamentarium includes mAbs that target tumor-associated antigens, as well as molecules that interfere with tumor-stroma interactions or exert direct immunostimulatory effects. These three classes of mAbs exert antineoplastic activity via distinct mechanisms, which may or may not involve immune effectors other than the mAbs themselves. In previous issues of OncoImmunology, we provided a brief scientific background to the use of mAbs, all types confounded, in cancer therapy, and discussed the results of recent clinical trials investigating the safety and efficacy of this approach. Here, we focus on mAbs that primarily target malignant cells or their interactions with stromal components, as opposed to mAbs that mediate antineoplastic effects by activating the immune system. In particular, we discuss relevant clinical findings that have been published during the last 13 months as well as clinical trials that have been launched in the same period to investigate the therapeutic profile of hitherto investigational tumor-targeting mAbs. PMID:24605265

  18. Making Time for Instructional Leadership. Volume 2: The Feasibility of a Randomized Control Trial of the SAM Process

    ERIC Educational Resources Information Center

    Goldring, Ellen; Grissom, Jason A.; Neumerski, Christine M.; Murphy, Joseph; Blissett, Richard; Porter, Andy

    2015-01-01

    This three-volume report describes the "SAM (School Administration Manager) process," an approach that about 700 schools around the nation are using to direct more of principals' time and effort to improve teaching and learning in classrooms. Research has shown that a principal's instructional leadership is second only to teaching among…

  19. International ring trial for the validation of an event-specific Golden Rice 2 quantitative real-time polymerase chain reaction method.

    PubMed

    Jacchia, Sara; Nardini, Elena; Bassani, Niccolò; Savini, Christian; Shim, Jung-Hyun; Trijatmiko, Kurniawan; Kreysa, Joachim; Mazzara, Marco

    2015-05-27

    This article describes the international validation of the quantitative real-time polymerase chain reaction (PCR) detection method for Golden Rice 2. The method consists of a taxon-specific assay amplifying a fragment of rice Phospholipase D α2 gene, and an event-specific assay designed on the 3' junction between transgenic insert and plant DNA. We validated the two assays independently, with absolute quantification, and in combination, with relative quantification, on DNA samples prepared in haploid genome equivalents. We assessed trueness, precision, efficiency, and linearity of the two assays, and the results demonstrate that both the assays independently assessed and the entire method fulfill European and international requirements for methods for genetically modified organism (GMO) testing, within the dynamic range tested. The homogeneity of the results of the collaborative trial between Europe and Asia is a good indicator of the robustness of the method. PMID:25946377

  20. Organizational-Level Strategies With or Without an Activity Tracker to Reduce Office Workers’ Sitting Time: Rationale and Study Design of a Pilot Cluster-Randomized Trial

    PubMed Central

    Fjeldsoe, Brianna S; Young, Duncan C; Winkler, Elisabeth A H; Dunstan, David W; Straker, Leon M; Brakenridge, Christian J; Healy, Genevieve N

    2016-01-01

    Background The office workplace is a key setting in which to address excessive sitting time and inadequate physical activity. One major influence on workplace sitting is the organizational environment. However, the impact of organizational-level strategies on individual level activity change is unknown. Further, the emergence of sophisticated, consumer-targeted wearable activity trackers that facilitate real-time self-monitoring of activity, may be a useful adjunct to support organizational-level strategies, but to date have received little evaluation in this workplace setting. Objective The aim of this study is to evaluate the feasibility, acceptability, and effectiveness of organizational-level strategies with or without an activity tracker on sitting, standing, and stepping in office workers in the short (3 months, primary aim) and long-term (12 months, secondary aim). Methods This study is a pilot, cluster-randomized trial (with work teams as the unit of clustering) of two interventions in office workers: organizational-level support strategies (eg, visible management support, emails) or organizational-level strategies plus the use of a waist-worn activity tracker (the LUMOback) that enables self-monitoring of sitting, standing, and stepping time and enables users to set sitting and posture alerts. The key intervention message is to ‘Stand Up, Sit Less, and Move More.’ Intervention elements will be implemented from within the organization by the Head of Workplace Wellbeing. Participants will be recruited via email and enrolled face-to-face. Assessments will occur at baseline, 3, and 12 months. Time spent sitting, sitting in prolonged (≥30 minute) bouts, standing, and stepping during work hours and across the day will be measured with activPAL3 activity monitors (7 days, 24 hours/day protocol), with total sitting time and sitting time during work hours the primary outcomes. Web-based questionnaires, LUMOback recorded data, telephone interviews, and focus

  1. A phase II trial of personalized peptide vaccination in castration-resistant prostate cancer patients: prolongation of prostate-specific antigen doubling time

    PubMed Central

    2013-01-01

    Background Cancer vaccine is one of the attractive treatment modalities for patients with castration-resistant prostate cancer (CRPC). However, because of delayed immune responses, its clinical benefits, besides for overall survival (OS), are not well captured by the World Health Organization (WHO) and Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Several surrogate markers for evaluation of cancer vaccine, including prostate-specific antigen doubling time (PSADT), are currently sought. The purpose of this study was to assess prospectively the PSA kinetics and immune responses, as well as the efficacy, safety, and biomarkers of personalized peptide vaccination (PPV) in progressive CRPC. Methods One hundred patients with progressive CRPC were treated with PPV using 2–4 positive peptides from 31 candidate peptides determined by both human leukocyte antigen (HLA) class IA types and the levels of immunoglobulin G (IgG) against each peptide. The association between immune responses and PSADT as well as overall survival (OS) was studied. Results PPV was safe and well tolerated in all patients with a median survival time of 18.8 months. Peptide-specific IgG and T-cell responses strongly correlated with PSADT (p < 0.0001 and p = 0.0007, respectively), which in turn showed correlation with OS (p = 0.018). Positive IgG responses and prolongation of PSADT during PPV were also significantly associated with OS (p = 0.001 and p = 0.004) by multivariate analysis. Conclusions PSADT could be an appropriate surrogate marker for evaluation of the clinical benefit of cancer vaccine. Further randomized trials are needed to confirm these results. Trial registration UMIN000001850 PMID:24373380

  2. Association of a multibiomarker disease activity score at multiple time-points with radiographic progression in rheumatoid arthritis: results from the SWEFOT trial

    PubMed Central

    Hambardzumyan, Karen; Bolce, Rebecca J; Saevarsdottir, Saedis; Forslind, Kristina; Wallman, Johan K; Cruickshank, Scott E; Sasso, Eric H; Chernoff, David; van Vollenhoven, Ronald F

    2016-01-01

    Objectives In rheumatoid arthritis (RA), predictive biomarkers for subsequent radiographic progression (RP) could improve therapeutic choices for individual patients. We previously showed that the multibiomarker disease activity (MBDA) score in patients with newly diagnosed RA identified patients at risk for RP. We evaluated the MBDA score at multiple time-points as a predictor of RP during 2 years of follow-up. Methods A subset of patients with RA (N=220) from the Swedish Farmacotherapy (SWEFOT) trial were analysed for MBDA score, disease activity score of 28 joints (DAS28), C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) at baseline (BL), month 3 and year 1, for predicting RP based on modified Sharp/van der Heijde scores at BL, year 1 and year 2. Results Patients with persistently low MBDA (<30) scores or those with a decrease from moderate (30–44) to low MBDA scores, did not develop RP during 2 years of follow-up. The highest risk for RP during 2 years of follow-up (42%) was observed among patients with persistently high (>44) MBDA scores. Among methotrexate non-responders with a high MBDA score at BL or month 3, significantly more of those who received triple therapy had RP at year 2 compared with those who received antitumour necrosis factor therapy. Conclusions Measuring the MBDA score both before and during treatment in RA was useful for the assessment of individual patient risk for RP during 2 years of follow-up. In comparison with low CRP, ESR or DAS28, a low MBDA score at any time-point was associated with numerically lower proportions of RP. Trial registration number NCT00764725. PMID:26958364

  3. Real-time differential GPS/GLONASS trials in Europe using all-in-view 20-channel receivers

    NASA Astrophysics Data System (ADS)

    Capaccio, S.; Lowe, D.; Walsh, D. M. A.; Daly, P.

    Following the initial development of 20-channel, all-in-view Global Navigation Satellite System (GNSS), GPS/GLONASS/Inmarsat-3, receivers at the Institute of Satellite Navigation (ISN), University of Leeds, a modification programme has been undertaken to allow real-time differential corrections to be sent from one 20-channel receiver to another identical receiver using a serial link between them. The differential correction software incorporates the RTCM SC-104 and RTCA DO-217 format developed specifically for GPS and adjusted by the ISN to allow simultaneous GLONASS operation.After successful laboratory testing, real-time differential GNSS tests were successfully completed in static mode between Aberdeen and Leeds via the SkyFix differential data-link, and in dynamic mode at DTEO Boscombe Down using a C-band data-link between the ground and a receiver on board the DRA BAC 1-11 aircraft. The aims of the tests were, (i) to demonstrate real-time differential GNSS position-fixing, (ii) to establish the accuracy improvements brought about, and (iii) to examine the effects of data-link latency and satellite PDOP on the solution accuracy.

  4. To determine block establishment time of supraclavicular brachial plexus block using blunt versus short bevel needle: A prospective randomized trial

    PubMed Central

    Ahuja, V; Thapa, D; Gombar, S; Dhiman, D

    2016-01-01

    Background: Unintentional intraneural injection under ultrasound guidance (USG) with fine caliber needles and lower success rate with large caliber Tuohy needles in supraclavicular brachial plexus block (SCB) have been reported. Materials and Methods: We undertook study to standardize the use of 20-gauge short versus blunt bevel needle for SCB. After approval of Institutional Ethics Committee and written informed consent, patients were randomized using computer-generated random number table to either of the two groups; blunt bevel needle group (n = 30): SCB under USG using 20-gauge Tuohy needle or short bevel needle group (n = 30): SCB under USG using 20-gauge short bevel needle. The primary outcome of the study was time to establishment of sensory and motor block of individual nerves, and secondary outcome was tolerability and any adverse effects. Results: The time to establishment of sensory and motor block in individual nerve territory was similar in both the groups. The complete sensory and motor anesthesia was achieved in 78.3% patients and complete sensory and motor anesthesia after supplementary block was achieved in 86.6% patients. Paresthesias during SCB were recorded in 15 patients. Out of these eight patients were of blunt bevel group and seven patients were of short bevel group. None of the patients experienced any neurological adverse effects. Conclusion: The establishment of sensory and motor blockade of individual nerves was similar to 20-gauge short and blunt bevel needle under ultrasound guide with no neurological adverse events. PMID:27375378

  5. The better the story, the bigger the serving: narrative transportation increases snacking during screen time in a randomized trial

    PubMed Central

    2013-01-01

    Background Watching television and playing video games increase energy intake, likely due to distraction from satiety cues. A study comparing one hour of watching TV, playing typical video games, or playing motion-controlled video games found a difference across groups in energy intake, but the reasons for this difference are not clear. As a secondary analysis, we investigated several types of distraction to determine potential psychosocial mechanisms which may account for greater energy intake observed during sedentary screen time as compared to motion-controlled video gaming. Methods Feelings of enjoyment, engagement (mental immersion), spatial presence (the feeling of being in the game), and transportation (immersion in a narrative) were investigated in 120 young adults aged 18 – 35 (60 female). Results Only narrative transportation was associated with total caloric intake (ρ = .205, P = .025). Transportation was also higher in the TV group than in the gaming groups (P = .002) and higher in males than in females (P = .003). Transportation mediated the relationship between motion-controlled gaming (as compared to TV watching) and square root transformed energy intake (indirect effect = −1.34, 95% confidence interval −3.57, −0.13). No other distraction-related variables were associated with intake. Conclusions These results suggest that different forms of distraction may differentially affect eating behavior during screen time, and that narrative appears to be a particularly strong distractor. Future studies should further investigate the effects of narrative on eating behavior. PMID:23680389

  6. Implementing wait-time reductions under Ontario government benchmarks (Pay-for-Results): a Cluster Randomized Trial of the Effect of a Physician-Nurse Supplementary Triage Assistance team (MDRNSTAT) on emergency department patient wait times

    PubMed Central

    2013-01-01

    Background Internationally, emergency departments are struggling with crowding and its associated morbidity, mortality, and decreased patient and health-care worker satisfaction. The objective was to evaluate the addition of a MDRNSTAT (Physician (MD)-Nurse (RN) Supplementary Team At Triage) on emergency department patient flow and quality of care. Methods Pragmatic cluster randomized trial. From 131 weekday shifts (8:00–14:30) during a 26-week period, we randomized 65 days (3173 visits) to the intervention cluster with a MDRNSTAT presence, and 66 days (3163 visits) to the nurse-only triage control cluster. The primary outcome was emergency department length-of-stay (EDLOS) for patients managed and discharged only by the emergency department. Secondary outcomes included EDLOS for patients initially seen by the emergency department, and subsequently consulted and admitted, patients reaching government-mandated thresholds, time to initial physician assessment, left-without being seen rate, time to investigation, and measurement of harm. Results The intervention’s median EDLOS for discharged, non-consulted, high acuity patients was 4:05 [95th% CI: 3:58 to 4:15] versus 4:29 [95th% CI: 4:19–4:38] during comparator shifts. The intervention’s median EDLOS for discharged, non-consulted, low acuity patients was 1:55 [95th% CI: 1:48 to 2:05] versus 2:08 [95th% CI: 2:02–2:14]. The intervention’s median physician initial assessment time was 0:55 [95th% CI: 0:53 to 0:58] versus 1:21 [95th% CI: 1:18 to 1:25]. The intervention’s left-without-being-seen rate was 1.5% versus 2.2% for the control (p = 0.06). The MDRNSTAT subgroup analysis resulted in significant decreases in median EDLOS for discharged, non-consulted high (4:01 [95th% CI: 3:43–4:16]) and low acuity patients (1:10 95th% CI: 0:58–1:19]), as well as physician initial assessment time (0:25 [95th% CI: 0:23–0:26]). No patients returned to the emergency department after being discharged by the

  7. V-TIME: a treadmill training program augmented by virtual reality to decrease fall risk in older adults: study design of a randomized controlled trial

    PubMed Central

    2013-01-01

    Background Recent work has demonstrated that fall risk can be attributed to cognitive as well as motor deficits. Indeed, everyday walking in complex environments utilizes executive function, dual tasking, planning and scanning, all while walking forward. Pilot studies suggest that a multi-modal intervention that combines treadmill training to target motor function and a virtual reality obstacle course to address the cognitive components of fall risk may be used to successfully address the motor-cognitive interactions that are fundamental for fall risk reduction. The proposed randomized controlled trial will evaluate the effects of treadmill training augmented with virtual reality on fall risk. Methods/Design Three hundred older adults with a history of falls will be recruited to participate in this study. This will include older adults (n=100), patients with mild cognitive impairment (n=100), and patients with Parkinson’s disease (n=100). These three sub-groups will be recruited in order to evaluate the effects of the intervention in people with a range of motor and cognitive deficits. Subjects will be randomly assigned to the intervention group (treadmill training with virtual reality) or to the active-control group (treadmill training without virtual reality). Each person will participate in a training program set in an outpatient setting 3 times per week for 6 weeks. Assessments will take place before, after, and 1 month and 6 months after the completion of the training. A falls calendar will be kept by each participant for 6 months after completing the training to assess fall incidence (i.e., the number of falls, multiple falls and falls rate). In addition, we will measure gait under usual and dual task conditions, balance, community mobility, health related quality of life, user satisfaction and cognitive function. Discussion This randomized controlled trial will demonstrate the extent to which an intervention that combines treadmill training augmented

  8. Effect of oxandrolone and timing of pubertal induction on final height in Turner’s syndrome: randomised, double blind, placebo controlled trial

    PubMed Central

    Gault, Emma Jane; Perry, Rebecca J; Cole, Tim J; Casey, Sarah; Paterson, Wendy F; Hindmarsh, Peter C; Betts, Peter; Dunger, David B

    2011-01-01

    Objective To examine the effect of oxandrolone and the timing of pubertal induction on final height in girls with Turner’s syndrome receiving a standard dose of growth hormone. Design Randomised, double blind, placebo controlled trial. Setting 36 paediatric endocrinology departments in UK hospitals. Participants Girls with Turner’s syndrome aged 7-13 years at recruitment, receiving recombinant growth hormone therapy (10 mg/m2/week). Interventions Participants were randomised to oxandrolone (0.05 mg/kg/day, maximum 2.5 mg/day) or placebo from 9 years of age. Those with evidence of ovarian failure at 12 years were further randomised to oral ethinylestradiol (year 1, 2 µg daily; year 2, 4 μg daily; year 3, 4 months each of 6, 8, and 10 μg daily) or placebo; participants who received placebo and those recruited after the age of 12.25 years started ethinylestradiol at age 14. Main outcome measure Final height. Results 106 participants were recruited, of whom 14 withdrew and 82/92 reached final height. Both oxandrolone and late pubertal induction increased final height: by 4.6 (95% confidence interval 1.9 to 7.2) cm (P=0.001, n=82) for oxandrolone and 3.8 (0.0 to 7.5) cm (P=0.05, n=48) for late pubertal induction with ethinylestradiol. In the 48 children who were randomised twice, the effects on final height (compared with placebo and early induction of puberty) of oxandrolone alone, late induction alone, and oxandrolone plus late induction were similar, averaging 7.1 (3.4 to 10.8) cm (P<0.001). No cases of virilisation were reported. Conclusion Oxandrolone had a positive effect on final height in girls with Turner’s syndrome treated with growth hormone, as did late pubertal induction with ethinylestradiol at age 14 years. However, these effects were not additive, so using both had no advantage. Oxandrolone could, therefore, be offered as an alternative to late pubertal induction for increasing final height in Turner’s syndrome. Trial registration Current

  9. Sub-Nyquist field trial using time frequency packed DP-QPSK super-channel within fixed ITU-T grid.

    PubMed

    Potì, L; Meloni, G; Berrettini, G; Fresi, F; Foggi, T; Secondini, M; Giorgi, L; Cavaliere, F; Hackett, S; Petronio, A; Nibbs, P; Forgan, R; Leong, A; Masciulli, R; Pfander, C

    2015-06-15

    Sub-Nyquist time frequency packing technique was demonstrated for the first time in a super-channel field trial transmission over long-haul distances. The technique allows a limited spectral occupancy even with low order modulation formats. The transmission was successfully performed on a deployed Australian link between Sydney and Melbourne which included 995 km of uncompensated SMF with coexistent traffic. 40 and 100 Gb/s co-propagating channels were transmitted together with the super-channel in a 50 GHz ITU-T grid without additional penalty. The super-channel consisted of eight sub-channels with low-level modulation format, i.e. DP-QPSK, guaranteeing better OSNR robustness and reduced complexity with respect to higher order formats. At the receiver side, coherent detection was used together with iterative maximum-a-posteriori (MAP) detection and decoding. A 975 Gb/s DP-QPSK super-channel was successfully transmitted between Sydney and Melbourne within four 50GHz WSS channels (200 GHz). A maximum potential SE of 5.58 bit/s/Hz was achieved with an OSNR = 15.8 dB, comparable to the OSNR of the installed 100 Gb/s channels. The system reliability was proven through long term measurements. In addition, by closing the link in a loop back configuration, a potential SE∙d product of 9254 bit/s/Hz·km was achieved. PMID:26193592

  10. Clinical trials update from European Society of Cardiology meeting 2008: TIME-CHF, BACH, BEAUTIFUL, GISSI-HF, and HOME-HF.

    PubMed

    Coletta, Alison P; Cullington, Damien; Clark, Andrew L; Cleland, John G F

    2008-12-01

    This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure presented at the European Society of Cardiology meeting which was held in Munich, Germany from 30th August to 3rd September 2008. Unpublished reports should be considered as preliminary, as analyses may change in the final publication. The TIME-CHF study failed to show that BNP guided therapy was superior to usual care in patients with heart failure. The BACH study suggested that a new biomarker, MR-proANP, was as good as BNP for the diagnosis of heart failure in patients presenting with breathlessness. Ivabradine failed to reduce the incidence of cardiovascular events in patients with coronary artery disease and left ventricular systolic dysfunction in the BEAUTIFUL study, but patients with higher heart rates might have benefited. In GISSI-HF, n-3 PUFA reduced mortality and cardiovascular hospitalisation by a small amount compared to placebo in patients with chronic heart failure, but rosuvastatin had no effect on clinical outcomes. In the HOME-HF study, telemonitoring support failed to reduce the time to first re-hospitalisation or death, or days alive and out of hospital, compared with usual care. PMID:19008149

  11. Real Time in Situ Gamma Radiation Measurements of the Plume Evolution from the Full-Scale Radiological Dispersal Device Field Trials.

    PubMed

    Korpach, Ed; Berg, Rodney; Erhardt, Lorne; Lebel, Luke; Liu, Chuanlei

    2016-05-01

    During the Full-Scale Radiological Dispersal Device Field Trials carried out in Suffield in 2012, several suites of detection and sampling equipment were used to measure and characterize the explosive dispersal of the short half-life radioactive tracer Lanthanum-140 ((140)La). The equipment deployed included networks of in situ real-time radiation monitoring detectors providing measurements of different sensitivities and characteristics. A dense array of lower sensitivity detectors was established near field, ranging from 10 to 450 m from the detonation location. A sparser array of more sensitive detectors was established in the far field (150 m to 3.5 km from the detonation location). Each was used to collect and report the dose rate data from the radioactive plume passage with a sample time resolution of 1 s. The two systems went through independent calibrations and were compared and shown to be consistent with each other. The in situ gamma radiation measurements have allowed the movement and evolution of the plume to be described and to identify deposition rates and non-uniformities in the temporal shape of the plume. This knowledge could be applied for emergency planning guidance for the case of release of radioactive material by a radiological dispersive device. PMID:27023030

  12. The effect of including a series of isometric conditioning contractions to the rowing warm-up on 1,000-m rowing ergometer time trial performance.

    PubMed

    Feros, Simon A; Young, Warren B; Rice, Anthony J; Talpey, Scott W

    2012-12-01

    Rowing requires strength, power, and strength-endurance for optimal performance. A rowing-based warm-up could be enhanced by exploiting the postactivation potentiation (PAP) phenomenon, acutely enhancing power output at the beginning of a race where it is needed most. Minimal research has investigated the effects of PAP on events of longer duration (i.e. 1,000-m rowing). The purpose of this research was to investigate the effects of PAP on 1,000-m rowing ergometer performance through the use of 2 different warm-up procedures: (a) a rowing warm-up combined with a series of isometric conditioning contractions, known as the potentiated warm-up (PW), and (b) a rowing warm-up only (NW). The isometric conditioning contractions in the PW were performed by "pulling" an immovable handle on the rowing ergometer, consisting of 5 sets of 5 seconds (2 seconds at submaximal intensity, and 3 seconds at maximal intensity), with a 15-second recovery between sets. The 1,000-m rowing ergometer time trial was performed after each warm-up condition, whereby mean power output, mean stroke rate, and split time were assessed every 100 m. Ten Australian national level rowers served as the subjects and performed both conditions in a counterbalanced order on separate days. The PW reduced 1,000-m time by 0.8% (p > 0.05). The PW improved mean power output by 6.6% (p < 0.01) and mean stroke rate by 5.2% (p < 0.01) over the first 500 m; resulting in a reduction of 500-m time by 1.9% (p < 0.01), compared with the NW. It appears that the inclusion of isometric conditioning contractions to the rowing warm-up enhance short-term rowing ergometer performance (especially at the start of a race) to a greater extent than a rowing warm-up alone. PMID:22266645

  13. Early time courses of recurrent thromboembolism and bleeding during apixaban or enoxaparin/warfarin therapy. A sub-analysis of the AMPLIFY trial.

    PubMed

    Raskob, Gary E; Gallus, Alex S; Sanders, Paul; Thompson, John R; Agnelli, Giancarlo; Buller, Harry R; Cohen, Alexander T; Ramacciotti, Eduardo; Weitz, Jeffrey I

    2016-04-01

    Risks of recurrence and bleeding are highest during the first weeks of anticoagulant therapy for venous thromboembolism (VTE). We therefore examined the early time course of recurrence and major bleeding in a pre-specified sub-analysis of the AMPLIFY trial, a randomised, double-blind, six-month comparison of oral apixaban with conventional therapy (enoxaparin followed by warfarin) in 5,395 patients with symptomatic proximal deep-vein thrombosis or pulmonary embolism. Early events were of particular interest because apixaban was given without initial heparin treatment. The primary efficacy and safety outcomes were the incidences of the adjudicated composite of recurrent symptomatic VTE or death related to VTE, and of adjudicated major bleeding, respectively. This analysis reports on recurrence and bleeding after 7, 21, and 90 days of therapy, in addition to the previously reported end-of-study results. These were the times specified before statistical analysis. Recurrent VTE after 7, 21, and 90 days, and six months had occurred in 18 (0.7%), 29 (1.1%), 46 (1.8%), and 59 patients (2.3%), respectively, given apixaban, and in 23 (0.9%), 35 (1.3%), 58 (2.2%), and 71 patients (2.7%), respectively, given conventional therapy. Major bleeding had occurred during these time intervals in 3 (0.1%), 5 (0.2%), 11 (0.4%), and 15 patients (0.6%), respectively, who received apixaban, and in 16 (0.6%), 26 (1.0%), 38 (1.4%), and 49 patients (1.8%), respectively, given conventional therapy. Efficacy of apixaban was non-inferior at each time point, with no excess of early recurrences. The reduced bleeding risk associated with apixaban began early during the course of treatment. PMID:26661288

  14. Evaluation of a real-time virtual intervention to empower persons living with HIV to use therapy self-management: study protocol for an online randomized controlled trial

    PubMed Central

    2012-01-01

    Background Living with HIV makes considerable demands on a person in terms of self-management, especially as regards adherence to treatment and coping with adverse side-effects. The online HIV Treatment, Virtual Nursing Assistance and Education (Virus de I’immunodéficience Humaine–Traitement Assistance Virtuelle Infirmière et Enseignement; VIH-TAVIE™) intervention was developed to provide persons living with HIV (PLHIV) with personalized follow-up and real-time support in managing their medication intake on a daily basis. An online randomized controlled trial (RCT) will be conducted to evaluate the efficacy of this intervention primarily in optimizing adherence to combination anti-retroviral therapy (ART) among PLHIV. Methods/design A convenience sample of 232 PLHIV will be split evenly and randomly between an experimental group that will use the web application, and a control group that will be handed a list of websites of interest. Participants must be aged 18 years or older, have been on ART for at least 6 months, and have internet access. The intervention is composed of four interactive computer sessions of 20 to 30 minutes hosted by a virtual nurse who engages the PLHIV in a skills-learning process aimed at improving self-management of medication intake. Adherence constitutes the principal outcome, and is defined as the intake of at least 95% of the prescribed tablets. The following intermediary measures will be assessed: self-efficacy and attitude towards antiretroviral medication, symptom-related discomfort, and emotional support. There will be three measurement times: baseline (T0), after 3 months (T3) and 6 months (T6) of baseline measurement. The principal analyses will focus on comparing the two groups in terms of treatment adherence at the end of follow-up at T6. An intention-to-treat (ITT) analysis will be carried out to evaluate the true value of the intervention in a real context. Discussion Carrying out this online RCT poses various

  15. Using Ecological Momentary Assessment to Test the Effectiveness of a Web-Based Brief Alcohol Intervention Over Time Among Heavy-Drinking Students: Randomized Controlled Trial

    PubMed Central

    2014-01-01

    Background Web-based brief alcohol interventions are effective in reducing alcohol use among students when measured at limited follow-up time points. To date, no studies have tested Web-based brief alcohol intervention effectiveness over time by using a large number of measurements. Objective Testing whether the What Do You Drink (WDYD) Web-based brief alcohol intervention can sustain a reduction in alcohol use among heavy-drinking students aged 18-24 years at 1-, 3-, and 6-month follow-up intervals. Methods A purely Web-based, 2-arm, parallel-group randomized controlled trial applying an ecological momentary assessment approach with 30 weekly measurements was conducted in the Netherlands (2010-2011). Participants were recruited offline and online. A total of 907 participants were randomized into the experimental condition (n=456) including the single-session and fully automated WDYD intervention, or into the control condition (n=451) including assessment only. Weekly alcohol consumption and frequency of binge drinking were the self-assessed outcome measures. Results Attrition rates of the 907 participants were 110 (12.1%), 130 (14.3%), and 162 (17.9%) at 1-, 3-, and 6-month follow-up intervals, respectively. Latent growth curve analyses according to the intention-to-treat principle revealed that participants in the experimental condition had significantly lower weekly alcohol consumption compared to participants in the control condition that was sustained at 3-month follow-up (intercept=–2.60, P<.001; slope=0.16, P=.08). Additional linear regression analyses indicated that this intercept difference resulted from significantly higher levels of alcohol units per week for participants in the control condition compared to those in the experimental condition at 1-month (beta=–2.56, SE 0.74, Cohen’s d=0.20, P=.001), 3-month (beta=–1.76, SE 0.60, Cohen’s d=0.13, P=.003), and 6-month (beta=–1.21, SE 0.58, Cohen’s d=0.09, P=.04) follow-up intervals. Latent

  16. A Randomized controlled trial of culturally-tailored dance and reducing screen time to prevent weight gain in low-Income African-American girls: Stanford GEMS

    PubMed Central

    Robinson, Thomas N.; Matheson, Donna M.; Kraemer, Helena C.; Wilson, Darrell M.; Obarzanek, Eva; Thompson, Nikko S.; Alhassan, Sofiya; Spencer, Tirzah R.; Haydel, K. Farish; Fujimoto, Michelle; Varady, Ann; Killen, Joel D.

    2013-01-01

    Objective To test a 2-year community- and family-based obesity prevention intervention for low-income African-American girls. Design Randomized controlled trial with follow-up measures scheduled at 6, 12, 18 and 24 months. Setting Low-income areas of Oakland, CA. Participants 261 8–10 year old African-American girls and their parents/caregivers. Interventions Families were randomized to two-year, culturally-tailored interventions: (1) after school Hip-Hop, African and Step dance classes and a home/family-based intervention to reduce screen media use or (2) information-based health education. Main Outcome Measure Body mass index (BMI) change. Results Changes in BMI did not differ between groups (adjusted mean difference [95% confidence interval] = 0.04 [−.18, .27] kg/m2 per year). Among secondary outcomes, fasting total cholesterol (−3.49 [−5.28, −1.70] mg/dL per year), LDL-cholesterol (−3.02 [−4.74, −1.31] mg/dL per year), incidence of hyperinsulinemia (Relative Risk 0.35 [0.13, 0.93]), and depressive symptoms (−0.21 [−0.42, −0.001] per year) fell more among girls in the dance and screen time reduction intervention. In exploratory moderator analysis, the dance and screen time reduction intervention slowed BMI gain more than health education among girls who watched more television at baseline (P=.02) and/or those whose parents/guardians were unmarried (P<.01). Conclusions A culturally-tailored after-school dance and screen time reduction intervention for low-income, preadolescent African-American girls did not significantly reduce BMI gain compared to health education, but produced potentially clinically important reductions in lipids, hyperinsulinemia, and depressive symptoms. There was also evidence for greater effectiveness in high-risk subgroups of girls. PMID:21041592

  17. Response to ecallantide treatment of acute attacks of hereditary angioedema based on time to intervention: results from the EDEMA clinical trials.

    PubMed

    Banta, Erin; Horn, Patrick; Craig, Timothy J

    2011-01-01

    Hereditary Angioedema (HAE) is a rare, debilitating, genetic disorder characterized by acute attacks of edema without urticaria. Ecallantide, a direct plasma kallikrein inhibitor, is approved for treatment of acute HAE attacks. This article addresses the efficacy of ecallantide in the treatment of moderate-to-severe attacks of HAE based on time to treatment. A post hoc integrated analysis of the EDEMA4 and EDEMA3-DB clinical trials was performed based on the time to patient's treatment, defined as the time from initial recognition of moderate-to-severe symptoms to dosing (cohort, 0-2, >2-4, >4-6, >6-8, and >8 hours). Mean symptom complex severity (MSCS) score and treatment outcome score (TOS) were analyzed. Complete or near-complete resolution of symptoms was assessed at 4 and 24 hours. In this analysis, 70 patients received 30 mg of subcutaneous (s.c.) ecallantide and 73 patients received placebo. Change from baseline in MSCS score and TOS at 4 hours revealed significantly better response to ecallantide versus placebo for patients treated >2-4 (n = 46; p = 0.002; p = 0.003) or >4-6 (n = 47; p = 0.044; p = 0.043) hours after symptom onset. Fewer patients were treated within 2 hours of symptom onset; for these patients (n = 10; p = 0.752; p = 0.422) treatment did not achieve statistical significance. For overall response, complete or near-complete resolution was greatest within the 0- to 2-hour cohort (71.4%). As with other therapies for HAE early ecallantide therapy is optimal. Treatment with ecallantide within 6 hours of symptom onset leads to more rapid and sustained improvement of symptoms. PMID:21781409

  18. Real-Time Measurement of Functional Tumor Volume by MRI to Assess Treatment Response in Breast Cancer Neoadjuvant Clinical Trials: Validation of the Aegis SER Software Platform

    PubMed Central

    Newitt, David C; Aliu, Sheye O; Witcomb, Neil; Sela, Gal; Kornak, John; Esserman, Laura; Hylton, Nola M

    2014-01-01

    PURPOSE: To evaluate the Aegis software implementation for real-time calculation of functional tumor volume (FTV) in the neoadjuvant breast cancer treatment trial setting. METHODS: The validation data set consisted of 689 contrast-enhanced magnetic resonance imaging (MRI) examinations from the multicenter American College of Radiology Imaging Network 6657 study. Subjects had stage III tumors ≥3 cm in diameter and underwent MRI before, during, and after receiving anthracycline-cyclophosphamide chemotherapy. Studies were previously analyzed by the University of California San Francisco core laboratory using the three-timepoint signal enhancement ratio (SER) FTV algorithm; FTV measurement was subsequently implemented on the Hologic (formerly Sentinelle Medical Inc) Aegis platform. All cases were processed using predefined volumes of interest with no user interaction. Spearman rank correlation was evaluated for all study sites and visits. Cox proportional hazards analysis was used to compare predictive performance of the platforms for recurrence-free survival (RFS) time. RESULTS: Overall agreement between platforms was good; ρ varied from 0.96 to 0.98 for different study visits. Site-by-site analysis showed considerable variation, from ρ = 0.54 to near perfect agreement (ρ = 1.000) for several sites. Mean absolute difference between platforms ranged from 1.67 cm3 pretreatment to 0.2 cm3 posttreatment. The two platforms showed essentially identical performance for predicting RFS using pretreatment or posttreatment FTV. CONCLUSION: Implementation of the SER FTV algorithm on a commercial platform for real-time MRI volume assessments showed very good agreement with the reference core laboratory system, but variations by site and outlier analysis point out sensitivities to implementation-specific differences. PMID:24772212

  19. Watermelon foliar fungicide timing trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foliar diseases are a persistent threat to watermelon production in Oklahoma. Several diseases that include anthracnose, downy mildew, and powdery mildew can result in yield and fruit quality losses when foliage is damaged. Effective fungicides are available for the control of these diseases. How...

  20. Effect of intermittent hypoxia on muscle and cerebral oxygenation during a 20-km time trial in elite athletes: a preliminary report.

    PubMed

    Hamlin, Michael J; Marshall, Helen C; Hellemans, John; Ainslie, Philip N

    2010-08-01

    The effects of intermittent hypoxic exposure (IHE) on cerebral and muscle oxygenation, arterial oxygen saturation (SaO2), and respiratory gas exchange during a 20-km cycle time trial (20TT) were examined (n=9) in a placebo-controlled randomized design. IHE (7:3 min hypoxia to normoxia) involved 90-min sessions for 10 days, with SaO2 clamped at ~80%. Prior to, and 2 days after the intervention, a 20TT was performed. During the final minute of the 20TT, in the IHE group only, muscle oxyhemoglobin (oxy-Hb) was elevated (mean+/-95% confidence interval 1.3+/-1.2 ΔmicroM, p=0.04), whereas cerebral oxy-Hb was reduced (-1.9%+/-1.0%, p<0.01) post intervention compared with baseline. The 20TT performance was unchanged between groups (p=0.7). In the IHE group, SaO2 was higher (1.0+/-0.7Δ%, p=0.006) and end-tidal PCO2 was lower (-1.2+/-0.1 mm Hg, p=0.01) during the final stage of the 20TT post intervention compared with baseline. In summary, reductions in muscle oxy-Hb and systemic SaO2 occurring at exercise intensities close to maximal at the end of a 20TT were offset by IHE, although this was not translated into improved performance. PMID:20725123

  1. fatalityCMR: capture-recapture software to correct raw counts of wildlife fatalities using trial experiments for carcass detection probability and persistence time

    USGS Publications Warehouse

    Peron, Guillaume; Hines, James E.

    2014-01-01

    Many industrial and agricultural activities involve wildlife fatalities by collision, poisoning or other involuntary harvest: wind turbines, highway network, utility network, tall structures, pesticides, etc. Impacted wildlife may benefit from official protection, including the requirement to monitor the impact. Carcass counts can often be conducted to quantify the number of fatalities, but they need to be corrected for carcass persistence time (removal by scavengers and decay) and detection probability (searcher efficiency). In this article we introduce a new piece of software that fits a superpopulation capture-recapture model to raw count data. It uses trial data to estimate detection and daily persistence probabilities. A recurrent issue is that fatalities of rare, protected species are infrequent, in which case the software offers the option to switch to an ‘evidence of absence’ mode, i.e., estimate the number of carcasses that may have been missed by field crews. The software allows distinguishing between different turbine types (e.g. different vegetation cover under turbines, or different technical properties), as well between two carcass age-classes or states, with transition between those classes (e.g, fresh and dry). There is a data simulation capacity that may be used at the planning stage to optimize sampling design. Resulting mortality estimates can be used 1) to quantify the required amount of compensation, 2) inform mortality projections for proposed development sites, and 3) inform decisions about management of existing sites.

  2. Shuffling Adaptive Clinical Trials.

    PubMed

    Gokhale, Sanjay G; Gokhale, Sankalp

    2016-01-01

    Clinical trials are interventional studies on human beings, designed to test the hypothesis for diagnostic techniques, treatments, and disease preventions. Any novel medical technology should be evaluated for its efficacy and safety by clinical trials. The costs associated with developing drugs have increased dramatically over the past decade, and fewer drugs are obtaining regulatory approval. Because of this, the pharmaceutical industry is continually exploring new ways of improving drug developments, and one area of focus is adaptive clinical trial designs. Adaptive designs, which allow for some types of prospectively planned mid-study changes, can improve the efficiency of a trial and maximize the chance of success without undermining validity and integrity of the trial. However it is felt that in adaptive trials; perhaps by using accrued data the actual patient population after the adaptations could deviate from the originally target patient population and so to overcome this drawback; special methods like Bayesian Statistics, predicted probability are used to deduce data-analysis. Here, in this study, mathematical model of a new adaptive design (shuffling adaptive trial) is suggested which uses real-time data, and because there is no gap between expected and observed data, statistical modifications are not needed. Results are obviously clinically relevant. PMID:23751329

  3. Trial Watch

    PubMed Central

    Pol, Jonathan; Bloy, Norma; Obrist, Florine; Eggermont, Alexander; Galon, Jérôme; Hervé Fridman, Wolf; Cremer, Isabelle; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2014-01-01

    During the past 2 decades, the possibility that preparations capable of eliciting tumor-specific immune responses would mediate robust therapeutic effects in cancer patients has received renovated interest. In this context, several approaches to vaccinate cancer patients against their own malignancies have been conceived, including the administration of DNA constructs coding for one or more tumor-associated antigens (TAAs). Such DNA-based vaccines conceptually differ from other types of gene therapy in that they are not devised to directly kill cancer cells or sensitize them to the cytotoxic activity of a drug, but rather to elicit a tumor-specific immune response. In spite of an intense wave of preclinical development, the introduction of this immunotherapeutic paradigm into the clinical practice is facing difficulties. Indeed, while most DNA-based anticancer vaccines are well tolerated by cancer patients, they often fail to generate therapeutically relevant clinical responses. In this Trial Watch, we discuss the latest advances on the use of DNA-based vaccines in cancer therapy, discussing the literature that has been produced around this topic during the last 13 months as well as clinical studies that have been launched in the same time frame to assess the actual therapeutic potential of this intervention. PMID:24800178

  4. Pre-Exercise Hyperhydration-Induced Bodyweight Gain Does Not Alter Prolonged Treadmill Running Time-Trial Performance in Warm Ambient Conditions

    PubMed Central

    Gigou, Pierre-Yves; Dion, Tommy; Asselin, Audrey; Berrigan, Felix; Goulet, Eric D. B.

    2012-01-01

    This study compared the effect of pre-exercise hyperhydration (PEH) and pre-exercise euhydration (PEE) upon treadmill running time-trial (TT) performance in the heat. Six highly trained runners or triathletes underwent two 18 km TT runs (~28 °C, 25%–30% RH) on a motorized treadmill, in a randomized, crossover fashion, while being euhydrated or after hyperhydration with 26 mL/kg bodyweight (BW) of a 130 mmol/L sodium solution. Subjects then ran four successive 4.5 km blocks alternating between 2.5 km at 1% and 2 km at 6% gradient, while drinking a total of 7 mL/kg BW of a 6% sports drink solution (Gatorade, USA). PEH increased BW by 1.00 ± 0.34 kg (P < 0.01) and, compared with PEE, reduced BW loss from 3.1% ± 0.3% (EUH) to 1.4% ± 0.4% (HYP) (P < 0.01) during exercise. Running TT time did not differ between groups (PEH: 85.6 ± 11.6 min; PEE: 85.3 ± 9.6 min, P = 0.82). Heart rate (5 ± 1 beats/min) and rectal (0.3 ± 0.1 °C) and body (0.2 ± 0.1 °C) temperatures of PEE were higher than those of PEH (P < 0.05). There was no significant difference in abdominal discomfort and perceived exertion or heat stress between groups. Our results suggest that pre-exercise sodium-induced hyperhydration of a magnitude of 1 L does not alter 80–90 min running TT performance under warm conditions in highly-trained runners drinking ~500 mL sports drink during exercise. PMID:23016126

  5. Pre-exercise hyperhydration-induced bodyweight gain does not alter prolonged treadmill running time-trial performance in warm ambient conditions.

    PubMed

    Gigou, Pierre-Yves; Dion, Tommy; Asselin, Audrey; Berrigan, Felix; Goulet, Eric D B

    2012-08-01

    This study compared the effect of pre-exercise hyperhydration (PEH) and pre-exercise euhydration (PEE) upon treadmill running time-trial (TT) performance in the heat. Six highly trained runners or triathletes underwent two 18 km TT runs (~28 °C, 25%-30% RH) on a motorized treadmill, in a randomized, crossover fashion, while being euhydrated or after hyperhydration with 26 mL/kg bodyweight (BW) of a 130 mmol/L sodium solution. Subjects then ran four successive 4.5 km blocks alternating between 2.5 km at 1% and 2 km at 6% gradient, while drinking a total of 7 mL/kg BW of a 6% sports drink solution (Gatorade, USA). PEH increased BW by 1.00 ± 0.34 kg (P < 0.01) and, compared with PEE, reduced BW loss from 3.1% ± 0.3% (EUH) to 1.4% ± 0.4% (HYP) (P < 0.01) during exercise. Running TT time did not differ between groups (PEH: 85.6 ± 11.6 min; PEE: 85.3 ± 9.6 min, P = 0.82). Heart rate (5 ± 1 beats/min) and rectal (0.3 ± 0.1 °C) and body (0.2 ± 0.1 °C) temperatures of PEE were higher than those of PEH (P < 0.05). There was no significant difference in abdominal discomfort and perceived exertion or heat stress between groups. Our results suggest that pre-exercise sodium-induced hyperhydration of a magnitude of 1 L does not alter 80-90 min running TT performance under warm conditions in highly-trained runners drinking ~500 mL sports drink during exercise. PMID:23016126

  6. Impact of instruction in the Creighton Model FertilityCare System on time to pregnancy in couples of proven fecundity: results of a randomised trial

    PubMed Central

    Stanford, Joseph B.; Smith, Ken R.; Varner, Michael W.

    2016-01-01

    Background The Creighton Model FertilityCare System (CrMS) teaches women to identify days when intercourse is likely to result in pregnancy. We sought to assess the impact of the CrMS on time to clinically identified pregnancy (TTP), via per-cycle pregnancy rates (fecundability). Methods We conducted a parallel randomised trial at the University of Utah School of Medicine, 2003–2006. Women ages 18–35, in a relationship of proven fertility, who desired to conceive, were block-randomised, stratified for age, with allocation concealment by opaque sequentially numbered sealed envelopes. The control group received the advice to have intercourse 2–3 times per week, and the intervention group received CrMS instruction. All women were asked to begin trying to conceive starting the second cycle in the study and were followed actively up to 7 cycles, without blinding of research personnel. We calculated descriptive statistics and fecundability, and estimated Cox models for TTP. Registration: Clinicaltrials.gov NCT00161395 Results There were 143 women randomised: 71 to the control group (all analysed) and 72 to the CrMS group (69 analysed). The adjusted hazard ratio for the influence of CrMS on TTP was 0.86 (95% CI: 0.53, 1.38). Fecundability in cycles with intent to conceive was 31% in controls and 36% with CrMS (p=0.32). By the first cycle, fecundability was 17% in controls, and 4% with CrMS (p=0.02). No adverse events were reported. Conclusions We found no significant impact of CrMS on TTP or fecundability, but fewer of the women receiving CrMS conceived by the first cycle. PMID:25225008

  7. The Perfect Clinical Trial.

    PubMed

    Bril, V

    2016-01-01

    Multiple phase III clinical trials have failed to show disease-modifying benefits for diabetic sensorimotor polyneuropathy (DSP) and this may be due to the design of the clinical trials. The perfect clinical trial in DSP would enroll sufficiently large numbers of patients having early or minimal disease, as demonstrated by nerve conduction studies (NCS). These patients would be treated with an intervention given at an effective and well-tolerated dose for a sufficient duration of time to show change in the end points selected. For objective or surrogate measures such as NCS and for some small fiber measures, the duration needed to show positive change may be as brief as 6-12 months, but subsequently, trials lasting 5-8 years will be required to demonstrate clinical benefits. PMID:27133143

  8. Clinical Trials

    MedlinePlus

    ... of visits, and any adjustments to treatment. (back) Requirements for Participation Admission into a clinical trial is based on a rigid set of requirements. You must be diagnosed with the illness that ...

  9. A placebo-controlled, double-blind clinical trial to evaluate the efficacy of Imedeen® Time Perfection® for improving the appearance of photodamaged skin

    PubMed Central

    Stephens, Thomas J; Sigler, Monya L; Herndon, James H; Dispensa, Lisa; Le Moigne, Anne

    2016-01-01

    Objective To assess the efficacy of Imedeen Time Perfection for improving the appearance and condition of photoaged skin in healthy women. Methods This randomized, double-blind, placebo-controlled clinical trial enrolled healthy women, 35–60 years of age, with Fitzpatrick I–III and Glogau II–III skin types and mild-to-moderate facial fine lines/wrinkles. The eligible subjects were randomized to receive two tablets daily of either Imedeen Time Perfection (Imedeen) or a matching placebo for 12 weeks. Efficacy assessments included investigator rating of 16 photoaging parameters (ie, global facial appearance and 15 individual facial parameters and the average of all parameters), instrumentation (ie, ultrasound dermal density, moisture level of the stratum corneum, transepidermal water loss, cutometry), and subjects’ self-assessment. Differences in the mean change from baseline to week 12 values on these outcomes were compared between Imedeen and placebo using analysis of variance or a paired t-test. Results Seventy-four subjects with primarily Fitzpatrick skin type III (78%–79%) and Glogau type III (53%–58%) completed the study (Imedeen: n=36; placebo: n=38). The mean difference in change from baseline to week 12 for global facial assessment significantly favored Imedeen over placebo (−0.52; P=0.0017). Additionally, the mean differences in the average of all facial photoaging parameters (−0.29), mottled hyperpigmentation (−0.25), tactile laxity (−0.24), dullness (−0.47), and tactile roughness (−0.62) significantly favored Imedeen over placebo (P≤0.05). Significantly greater increases in ultrasound dermal density (+11% vs +1%; P≤0.05) and stratum corneum moisturization (+30% vs +6%; P≤0.05) were also observed for Imedeen than for placebo. There were no significant differences on other instrumental outcomes. Conclusion The results of this study suggest that Imedeen Time Perfection can positively affect the appearance of photoaged skin

  10. Physiological and metabolic responses of triathletes to a simulated 30-min time-trial in cycling at self-selected intensity.

    PubMed

    Perrey, S; Grappe, F; Girard, A; Bringard, A; Groslambert, A; Bertucci, W; Rouillon, J D

    2003-02-01

    The aim of this study was to investigate the metabolic and physiological responses to a laboratory-based simulated 30-min individual time-trial (ITT 30 ) in cycling at a self-selected intensity. Twelve experienced triathletes (n = 4 women) performed a progressive incremental exercise test on a cycle ergometer to determine .VO2max (52 +/- 5 ml x min -1 x kg -1), maximum power output (300 +/- 12 W), and the second ventilatory threshold. Then, the subjects completed an ITT30 at self-selected work intensity on a stationary ergometer equipped with the SRM Training System. In all subjects, during the ITT30, heart rate and minute ventilation increased (p < 0.05) progressively whereas oxygen consumption and power output remained unchanged. Triathletes rode at consistent pacing corresponding to their highest steady state of blood lactate concentration that increased by no more than 1.0 mmol x l -1 during the final 20-min of ITT30. The self-selected intensity of triathletes during ITT30 represented 88 +/- 5 % (mean +/- SD) of .VO2max and was not significantly different to the energy demand corresponding to the second ventilatory threshold (84 +/- 5 % of .VO2max). Our data suggest that ITT 30 at a self-selected intensity is a good predictor of individual endurance capacity and may be used to estimate racing pace for training purposes. This performance test for the identification of the exercise intensity that demarcate "steady state" is less troublesome than some of the traditional methods, limiting testing to a single session. PMID:12669261

  11. Manipulating Carbohydrate Availability Between Twice-Daily Sessions of High-Intensity Interval Training Over 2 Weeks Improves Time-Trial Performance.

    PubMed

    Cochran, Andrew J; Myslik, Frank; MacInnis, Martin J; Percival, Michael E; Bishop, David; Tarnopolsky, Mark A; Gibala, Martin J

    2015-10-01

    Commencing some training sessions with reduced carbohydrate (CHO) availability has been shown to enhance skeletal muscle adaptations, but the effect on exercise performance is less clear. We examined whether restricting CHO intake between twice daily sessions of high-intensity interval training (HIIT) augments improvements in exercise performance and mitochondrial content. Eighteen active but not highly trained subjects (peak oxygen uptake [VO2peak] = 44 ± 9 ml/kg/min), matched for age, sex, and fitness, were randomly allocated to two groups. On each of 6 days over 2 weeks, subjects completed two training sessions, each consisting of 5 × 4-min cycling intervals (60% of peak power), interspersed by 2 min of recovery. Subjects ingested either 195 g of CHO (HI-HI group: ~2.3 g/kg) or 17 g of CHO (HI-LO group: ~0.3 g/kg) during the 3-hr period between sessions. The training-induced improvement in 250-kJ time trial performance was greater (p = .02) in the HI-LO group (211 ± 66 W to 244 ± 75 W) compared with the HI-HI group (203 ± 53 W to 219 ± 60 W); however, the increases in mitochondrial content was similar between groups, as reflected by similar increases in citrate synthase maximal activity, citrate synthase protein content and cytochrome c oxidase subunit IV protein content (p > .05 for interaction terms). This is the first study to show that a short-term "train low, compete high" intervention can improve whole-body exercise capacity. Further research is needed to determine whether this type of manipulation can also enhance performance in highly-trained subjects. PMID:25811132

  12. Once daily versus three times daily mesalazine granules in active ulcerative colitis: a double-blind, double-dummy, randomised, non-inferiority trial

    PubMed Central

    Kruis, W; Kiudelis, G; Rácz, I; Gorelov, I A; Pokrotnieks, J; Horynski, M; Batovsky, M; Kykal, J; Boehm, S; Greinwald, R; Mueller, R

    2009-01-01

    Objectives: To determine the therapeutic equivalence and safety of once daily (OD) versus three times daily (TID) dosing of a total daily dose of 3 g Salofalk (mesalazine) granules in patients with active ulcerative colitis. Design: A randomised, double-blind, double-dummy, parallel group, multicentre, international, phase III non-inferiority study. Setting: 54 centres in 13 countries. Patients: 380 patients with confirmed diagnosis of established or first attack of ulcerative colitis (clinical activity index (CAI)>4 and endoscopic index ⩾4 at baseline) were randomised and treated. Interventions: 8-week treatment with either 3 g OD or 1 g TID mesalazine granules. Main outcome measures: Clinical remission (CAI⩽4) at study end. Results: 380 patients were evaluable for efficacy and safety by intention-to-treat (ITT); 345 for per protocol (PP) analysis. In the ITT population, 79.1% in the OD group (n = 191) and 75.7% in the TID group (n = 189) achieved clinical remission (p<0.0001 for non-inferiority). Significantly more patients with proctosigmoiditis achieved clinical remission in the OD group (86%; n = 97) versus the TID group (73%; n = 100; p = 0.0298). About 70% of patients in both treatment groups achieved endoscopic remission, and 35% in the OD group and 41% in the TID group achieved histological remission. About 80% of all patients preferred OD dosing. Similar numbers of adverse events occurred in 55 patients (28.8%) in the OD group and in 61 patients (32.3%) in the TID group, indicating that the two dosing regimens were equally safe and well tolerated. Conclusions: OD 3 g mesalazine granules are as effective and safe as a TID 1 g schedule. With respect to the best possible adherence of patients to the treatment, OD dosing of mesalazine should be the preferred application mode in active ulcerative colitis. ClinicalTrials.gov Identifier: NCT00449722 PMID:18832520

  13. 'Mind the Gap'-The Impact of Variations in the Duration of the Treatment Gap and Overall Treatment Time in the First UK Anal Cancer Trial (ACT I)

    SciTech Connect

    Glynne-Jones, Rob; Sebag-Montefiore, David; Adams, Richard; McDonald, Alec; Gollins, Simon; James, Roger; Northover, John M.A.; Meadows, Helen M.; Jitlal, Mark

    2011-12-01

    Purpose: The United Kingdom Coordinating Committee on Cancer Research anal cancer trial demonstrated the benefit of combined modality treatment (CMT) using radiotherapy (RT), infusional 5-fluorouracil, and mitomycin C over RT alone. The present study retrospectively examines the impact of the recommended 6-week treatment gap and local RT boost on long-term outcome. Methods and Materials: A total of 577 patients were randomly assigned RT alone or CMT. After a 6-week gap responders received a boost using either additional external beam radiotherapy (EBRT) (15 Gy) or iridium-192 implant (25 Gy). The effect of boost, the gap between initial treatment (RT alone or CMT) and boost (Tgap), and overall treatment time (OTT) were examined for their impact on outcome. Results: Among the 490 good responders, 436 (89%) patients received a boost after initial treatment. For boosted patients, the risk of anal cancer death decreased by 38% (hazard ratio [HR]: 0.62, 99% CI 0.35-1.12; p = 0.04), but there was no evidence this was mediated via a reduction in locoregional failure (LRF) (HR: 0.90, 99% CI 0.48-1.68; p = 0.66). The difference in Tgap was only 1.4 days longer for EBRT boost, compared with implant (p = 0.51). OTT was longer by 6.1 days for EBRT (p = 0.006). Tgap and OTT were not associated with LRF. Radionecrosis was reported in 8% of boosted, compared with 0% in unboosted patients (p = 0.03). Conclusions: These results question the benefit of a radiotherapy boost after a 6-week gap. The higher doses of a boost may contribute more to an increased risk of late morbidity, rather than local control.

  14. Fluid therapy LiDCO controlled trial-optimization of volume resuscitation of extensively burned patients through noninvasive continuous real-time hemodynamic monitoring LiDCO.

    PubMed

    Tokarik, Monika; Sjöberg, Folke; Balik, Martin; Pafcuga, Igor; Broz, Ludomir

    2013-01-01

    This pilot trial aims at gaining support for the optimization of acute burn resuscitation through noninvasive continuous real-time hemodynamic monitoring using arterial pulse contour analysis. A group of 21 burned patients meeting preliminary criteria (age range 18-75 years with second- third- degree burns and TBSA ≥10-75%) was randomized during 2010. A hemodynamic monitoring through lithium dilution cardiac output was used in 10 randomized patients (LiDCO group), whereas those without LiDCO monitoring were defined as the control group. The modified Brooke/Parkland formula as a starting resuscitative formula, balanced crystalloids as the initial solutions, urine output of 0.5 ml/kg/hr as a crucial value of adequate intravascular filling were used in both groups. Additionally, the volume and vasopressor/inotropic support were based on dynamic preload parameters in the LiDCO group in the case of circulatory instability and oligouria. Statistical analysis was done using t-tests. Within the first 24 hours postburn, a significantly lower consumption of crystalloids was registered in LiDCO group (P = .04). The fluid balance under LiDCO control in combination with hourly diuresis contributed to reducing the cumulative fluid balance approximately by 10% compared with fluid management based on standard monitoring parameters. The amount of applied solutions in the LiDCO group got closer to Brooke formula whereas the urine output was at the same level in both groups (0.8 ml/kg/hr). The new finding in this study is that when a fluid resuscitation is based on the arterial waveform analysis, the initial fluid volume provided was significantly lower than that delivered on the basis of physician-directed fluid resuscitation (by urine output and mean arterial pressure). PMID:23511280

  15. SU-E-QI-21: Iodinated Contrast Agent Time Course In Human Brain Metastasis: A Study For Stereotactic Synchrotron Radiotherapy Clinical Trials

    SciTech Connect

    Obeid, L; Esteve, F; Adam, J; Tessier, A; Balosso, J

    2014-06-15

    Purpose: Synchrotron stereotactic radiotherapy (SSRT) is an innovative treatment combining the selective accumulation of heavy elements in tumors with stereotactic irradiations using monochromatic medium energy x-rays from a synchrotron source. Phase I/II clinical trials on brain metastasis are underway using venous infusion of iodinated contrast agents. The radiation dose enhancement depends on the amount of iodine in the tumor and its time course. In the present study, the reproducibility of iodine concentrations between the CT planning scan day (Day 0) and the treatment day (Day 10) was assessed in order to predict dose errors. Methods: For each of days 0 and 10, three patients received a biphasic intravenous injection of iodinated contrast agent (40 ml, 4 ml/s, followed by 160 ml, 0.5 ml/s) in order to ensure stable intra-tumoral amounts of iodine during the treatment. Two volumetric CT scans (before and after iodine injection) and a multi-slice dynamic CT of the brain were performed using conventional radiotherapy CT (Day 0) or quantitative synchrotron radiation CT (Day 10). A 3D rigid registration was processed between images. The absolute and relative differences of absolute iodine concentrations and their corresponding dose errors were evaluated in the GTV and PTV used for treatment planning. Results: The differences in iodine concentrations remained within the standard deviation limits. The 3D absolute differences followed a normal distribution centered at zero mg/ml with a variance (∼1 mg/ml) which is related to the image noise. Conclusion: The results suggest that dose errors depend only on the image noise. This study shows that stable amounts of iodine are achievable in brain metastasis for SSRT treatment in a 10 days interval.

  16. Trial Watch

    PubMed Central

    Vacchelli, Erika; Vitale, Ilio; Tartour, Eric; Eggermont, Alexander; Sautès-Fridman, Catherine; Galon, Jérôme; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-01-01

    Radiotherapy has extensively been employed as a curative or palliative intervention against cancer throughout the last century, with a varying degree of success. For a long time, the antineoplastic activity of X- and γ-rays was entirely ascribed to their capacity of damaging macromolecules, in particular DNA, and hence triggering the (apoptotic) demise of malignant cells. However, accumulating evidence indicates that (at least part of) the clinical potential of radiotherapy stems from cancer cell-extrinsic mechanisms, including the normalization of tumor vasculature as well as short- and long-range bystander effects. Local bystander effects involve either the direct transmission of lethal signals between cells connected by gap junctions or the production of diffusible cytotoxic mediators, including reactive oxygen species, nitric oxide and cytokines. Conversely, long-range bystander effects, also known as out-of-field or abscopal effects, presumably reflect the elicitation of tumor-specific adaptive immune responses. Ionizing rays have indeed been shown to promote the immunogenic demise of malignant cells, a process that relies on the spatiotemporally defined emanation of specific damage-associated molecular patterns (DAMPs). Thus, irradiation reportedly improves the clinical efficacy of other treatment modalities such as surgery (both in neo-adjuvant and adjuvant settings) or chemotherapy. Moreover, at least under some circumstances, radiotherapy may potentiate anticancer immune responses as elicited by various immunotherapeutic agents, including (but presumably not limited to) immunomodulatory monoclonal antibodies, cancer-specific vaccines, dendritic cell-based interventions and Toll-like receptor agonists. Here, we review the rationale of using radiotherapy, alone or combined with immunomodulatory agents, as a means to elicit or boost anticancer immune responses, and present recent clinical trials investigating the therapeutic potential of this approach in

  17. B-MOBILE - A Smartphone-Based Intervention to Reduce Sedentary Time in Overweight/Obese Individuals: A Within-Subjects Experimental Trial

    PubMed Central

    Bond, Dale S.; Thomas, J. Graham; Raynor, Hollie A.; Moon, Jon; Sieling, Jared; Trautvetter, Jennifer; Leblond, Tiffany; Wing, Rena R.

    2014-01-01

    Purpose Excessive sedentary time (SED) has been linked to obesity and other adverse health outcomes. However, few sedentary-reducing interventions exist and none have utilized smartphones to automate behavioral strategies to decrease SED. We tested a smartphone-based intervention to monitor and decrease SED in overweight/obese individuals, and compared 3 approaches to prompting physical activity (PA) breaks and delivering feedback on SED. Design and Methods Participants [N = 30; Age  = 47.5(13.5) years; 83% female; Body Mass Index (BMI) = 36.2(7.5) kg/m2] wore the SenseWear Mini Armband (SWA) to objectively measure SED for 7 days at baseline. Participants were then presented with 3 smartphone-based PA break conditions in counterbalanced order: (1) 3-min break after 30 SED min; (2) 6-min break after 60 SED min; and (3) 12-min break after 120 SED min. Participants followed each condition for 7 days and wore the SWA throughout. Results All PA break conditions yielded significant decreases in SED and increases in light (LPA) and moderate-to-vigorous PA (MVPA) (p<0.005). Average % SED at baseline (72.2%) decreased by 5.9%, 5.6%, and 3.3% [i.e. by mean (95% CI) −47.2(−66.3, −28.2), −44.5(−65.2, −23.8), and −26.2(−40.7, −11.6) min/d] in the 3-, 6-, and 12-min conditions, respectively. Conversely, % LPA increased from 22.8% to 26.7%, 26.7%, and 24.7% [i.e. by 31.0(15.8, 46.2), 31.0(13.6, 48.4), and 15.3(3.9, 26.8) min/d], and % MVPA increased from 5.0% to 7.0%, 6.7%, and 6.3% (i.e. by 16.2(8.5, 24.0), 13.5(6.3, 20.6), and 10.8(4.2, 17.5) min/d] in the 3-, 6-, and 12-min conditions, respectively. Planned pairwise comparisons revealed the 3-min condition was superior to the 12-min condition in decreasing SED and increasing LPA (p<0.05). Conclusion The smartphone-based intervention significantly reduced SED. Prompting frequent short activity breaks may be the most effective way to decrease SED and increase PA in overweight/obese individuals

  18. Effectiveness of a nurse-led intensive home-visitation programme for first-time teenage mothers (Building Blocks): a pragmatic randomised controlled trial

    PubMed Central

    Robling, Michael; Bekkers, Marie-Jet; Bell, Kerry; Butler, Christopher C; Cannings-John, Rebecca; Channon, Sue; Martin, Belen Corbacho; Gregory, John W; Hood, Kerry; Kemp, Alison; Kenkre, Joyce; Montgomery, Alan A; Moody, Gwenllian; Owen-Jones, Eleri; Pickett, Kate; Richardson, Gerry; Roberts, Zoë E S; Ronaldson, Sarah; Sanders, Julia; Stamuli, Eugena; Torgerson, David

    2016-01-01

    Summary Background Many countries now offer support to teenage mothers to help them to achieve long-term socioeconomic stability and to give a successful start to their children. The Family Nurse Partnership (FNP) is a licensed intensive home-visiting intervention developed in the USA and introduced into practice in England that involves up to 64 structured home visits from early pregnancy until the child's second birthday by specially recruited and trained family nurses. We aimed to assess the effectiveness of giving the programme to teenage first-time mothers on infant and maternal outcomes up to 24 months after birth. Methods We did a pragmatic, non-blinded, randomised controlled, parallel-group trial in community midwifery settings at 18 partnerships between local authorities and primary and secondary care organisations in England. Eligible participants were nulliparous and aged 19 years or younger, and were recruited at less than 25 weeks' gestation. Field-based researchers randomly allocated mothers (1:1) via remote randomisation (telephone and web) to FNP plus usual care (publicly funded health and social care) or to usual care alone. Allocation was stratified by site and minimised by gestation (<16 weeks vs ≥16 weeks), smoking status (yes vs no), and preferred language of data collection (English vs non-English). Mothers and assessors (local researchers at baseline and 24 months' follow-up) were not masked to group allocation, but telephone interviewers were blinded. Primary endpoints were biomarker-calibrated self-reported tobacco use by the mother at late pregnancy, birthweight of the baby, the proportion of women with a second pregnancy within 24 months post-partum, and emergency attendances and hospital admissions for the child within 24 months post-partum. Analyses were by intention to treat. This trial is registered with ISRCTN, number ISRCTN23019866. Findings Between June 16, 2009, and July 28, 2010, we screened 3251 women. After enrolment, 823

  19. The Importance of Doing Trials Right While Doing The Right Trials

    PubMed Central

    Dilts, David M.; Cheng, Steven K.

    2015-01-01

    Effort is being expended in investigating efficiency measures (i.e., doing trials right) through achievement of accrual and endpoint goals for clinical trials. It is time to address the question of impact of such trials in addressing cancer critical needs through effectiveness measures (i.e., doing the right trials?) PMID:22072734

  20. Time?

    NASA Astrophysics Data System (ADS)

    Amoroso, Richard L.

    2013-09-01

    The concept of time in the `clockwork' Newtonian world was irrelevant; and has generally been ignored until recently by several generations of physicists since the implementation of quantum mechanics. We will set aside the utility of time as a property relating to physical calculations of events relating to a metrics line element or as an aspect of the transformation of a particles motion/interaction in a coordinate system or in relation to thermodynamics etc., i.e. we will discard all the usual uses of time as a concept used to circularly define physical parameters in terms of other physical parameters; concentrating instead on time as an aspect of the fundamental cosmic topology of our virtual reality especially as it inseparably relates to the nature and role of the observer in natural science.

  1. Social Problem Solving and Depressive Symptoms over Time: A Randomized Clinical Trial of Cognitive-Behavioral Analysis System of Psychotherapy, Brief Supportive Psychotherapy, and Pharmacotherapy

    ERIC Educational Resources Information Center

    Klein, Daniel N.; Leon, Andrew C.; Li, Chunshan; D'Zurilla, Thomas J.; Black, Sarah R.; Vivian, Dina; Dowling, Frank; Arnow, Bruce A.; Manber, Rachel; Markowitz, John C.; Kocsis, James H.

    2011-01-01

    Objective: Depression is associated with poor social problem solving, and psychotherapies that focus on problem-solving skills are efficacious in treating depression. We examined the associations between treatment, social problem solving, and depression in a randomized clinical trial testing the efficacy of psychotherapy augmentation for…

  2. Assessing sex-differences and the effect of timing of vaccination on immunogenicity, reactogenicity and efficacy of vaccines in young children: study protocol for an individual participant data meta-analysis of randomised controlled trials

    PubMed Central

    Voysey, Merryn; Pollard, Andrew J; Perera, Rafael; Fanshawe, Thomas R

    2016-01-01

    Introduction Disease incidence differs between males and females for some infectious or inflammatory diseases. Sex-differences in immune responses to some vaccines have also been observed, mostly to viral vaccines in adults. Little evidence is available on whether sex-differences occur in response to immunisation in infancy even though this is the age group in which most vaccines are administered. Factors other than sex, such as timing or coadministration of other vaccines, can also influence the immune response to vaccination. Methods and analysis Individual participant data meta-analysis of randomised controlled trials of vaccines in healthy infants and young children will be conducted. Fully anonymised data from ∼170 randomised controlled trials of vaccines for diphtheria, tetanus, Bordetella pertussis, polio, Haemophilus influenzae type B, hepatitis B, Streptococcus pneumoniae, Neisseria meningitidis, measles, mumps, rubella, varicella and rotavirus will be combined for analysis. Outcomes include measures of immunogenicity (immunoglobulins), reactogenicity, safety and disease-specific clinical efficacy. Data from trials of vaccines containing similar components will be combined in hierarchical models and the effect of sex and timing of vaccinations estimated for each outcome separately. Ethics and dissemination Systematic reviews of published estimates of sex-differences cannot adequately answer questions in this field since such comparisons are never the main purpose of a clinical trial, thus a large degree of reporting bias exists in the published literature. Recent improvements in the widespread availability of individual participant data from randomised controlled trials makes it feasible to conduct extensive individual participant data meta-analyses which were previously impossible, thereby reducing the effect of publication or reporting bias on the understanding of the infant immune response. Preliminary results will be available in 2016 with final

  3. The Trial

    ERIC Educational Resources Information Center

    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.

  4. Timing of High-Dose Rate Brachytherapy With External Beam Radiotherapy in Intermediate and High-Risk Localized Prostate CAncer (THEPCA) Patients and Its Effects on Toxicity and Quality of Life: Protocol of a Randomized Feasibility Trial

    PubMed Central

    Palvai, Sreekanth; Harrison, Michael; Shibu Thomas, Sharon; Hayden, Karen; Green, James; Anderson, Oliver; Romero, Lavinia; Lodge, Richard; Burns, Patricia

    2015-01-01

    Background Prostate cancer is the most common cancer in males in the UK and affects around 105 men for every 100,000. The role of radiotherapy in the management of prostate cancer significantly changed over the last few decades with developments in brachytherapy, external beam radiotherapy (EBRT), intensity-modulated radiotherapy (IMRT), and image-guided radiotherapy (IGRT). One of the challenging factors of radiotherapy treatment of localized prostate cancer is the development of acute and late genitourinary and gastrointestinal toxicities. The recent European guidelines suggest that there is no consensus regarding the timing of high-dose rate (HDR) brachytherapy and EBRT. The schedules vary in different institutions where an HDR boost can be given either before or after EBRT. Few centers deliver HDR in between the fractions of EBRT. Objective Assessment of acute genitourinary and gastrointestinal toxicities at various time points to better understand if the order in which treatment modality is delivered (ie, HDR brachytherapy or EBRT first) has an effect on the toxicity profile. Methods Timing of HDR brachytherapy with EBRT in Prostate CAncer (THEPCA) is a single-center, open, randomized controlled feasibility trial in patients with intermediate and high-risk localized prostate cancer. A group of 50 patients aged 18 years old and over with histological diagnosis of prostate cancer (stages T1b-T3BNOMO), will be randomized to one of two treatment arms (ratio 1:1), following explanation of the study and informed consent. Patients in both arms of the study will be treated with HDR brachytherapy and EBRT, however, the order in which they receive the treatments will vary. In Arm A, patients will receive HDR brachytherapy before EBRT. In Arm B (control arm), patients will receive EBRT before HDR brachytherapy. Study outcomes will look at prospective assessment of genitourinary and gastrointestinal toxicities. The primary endpoint will be grade 3 genitourinary toxicity

  5. Protocol for economic evaluation alongside a cluster-randomised controlled trial of a psychoeducational intervention for the primary prevention of postnatal mental health problems in first-time mothers

    PubMed Central

    Ride, Jemimah; Rowe, Heather; Wynter, Karen; Fisher, Jane; Lorgelly, Paula

    2014-01-01

    Introduction Postnatal mental health problems, which are an international public health priority, are a suitable target for preventive approaches. The financial burden of these disorders is borne across sectors in society, including health, early childhood, education, justice and the workforce. This paper describes the planned economic evaluation of What Were We Thinking, a psychoeducational intervention for the prevention of postnatal mental health problems in first-time mothers. Methods and analysis The evaluation will be conducted alongside a cluster-randomised controlled trial of its clinical effectiveness. Cost-effectiveness and costs-utility analyses will be conducted, resulting in estimates of cost per percentage point reduction in combined 30-day prevalence of depression, anxiety and adjustment disorders and cost per quality-adjusted life year gained. Uncertainty surrounding these estimates will be addressed using non-parametric bootstrapping and represented using cost-effectiveness acceptability curves. Additional cost analyses relevant for implementation will also be conducted. Modelling will be employed to estimate longer term cost-effectiveness if the intervention is found to be clinically effective during the period of the trial. Ethics and dissemination Approval to conduct the study was granted by the Southern Health (now Monash Health) Human Research Ethics Committee (24 April 2013; 11388B). The study was registered with the Monash University Human Research Ethics Committee (30 April 2013; CF12/1022-2012000474). The Education and Policy Research Committee, Victorian Government Department of Education and Early Childhood Development approved the study (22 March 2012; 2012_001472). Use of the EuroQol was registered with the EuroQol Group; 16 August 2012. Trial registration number The trial was registered with the Australian New Zealand Clinical Trials Registry on 7 May 2012 (registration number ACTRN12613000506796). PMID:25280810

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

  7. Single-trial estimation of stimulus and spike-history effects on time-varying ensemble spiking activity of multiple neurons: a simulation study

    NASA Astrophysics Data System (ADS)

    Shimazaki, Hideaki

    2013-12-01

    Neurons in cortical circuits exhibit coordinated spiking activity, and can produce correlated synchronous spikes during behavior and cognition. We recently developed a method for estimating the dynamics of correlated ensemble activity by combining a model of simultaneous neuronal interactions (e.g., a spin-glass model) with a state-space method (Shimazaki et al. 2012 PLoS Comput Biol 8 e1002385). This method allows us to estimate stimulus-evoked dynamics of neuronal interactions which is reproducible in repeated trials under identical experimental conditions. However, the method may not be suitable for detecting stimulus responses if the neuronal dynamics exhibits significant variability across trials. In addition, the previous model does not include effects of past spiking activity of the neurons on the current state of ensemble activity. In this study, we develop a parametric method for simultaneously estimating the stimulus and spike-history effects on the ensemble activity from single-trial data even if the neurons exhibit dynamics that is largely unrelated to these effects. For this goal, we model ensemble neuronal activity as a latent process and include the stimulus and spike-history effects as exogenous inputs to the latent process. We develop an expectation-maximization algorithm that simultaneously achieves estimation of the latent process, stimulus responses, and spike-history effects. The proposed method is useful to analyze an interaction of internal cortical states and sensory evoked activity.

  8. Redesigning TRACER trial after TRITON.

    PubMed

    Serebruany, Victor L

    2015-10-15

    Designing of smart clinical trials is critical for regulatory approval and future drug utilization. Importantly, trial design should be reconsidered if the interim analyses suggest unexpected harm, or conflicting results were yielded from the other trials within the same therapeutic area. With regard to antiplatelet agents, the perfect example is redesigning of the ongoing PRoFESS trial by eliminating aspirin from clopidogrel arm after the earlier MATCH trial results became available. The goal was to aseess the unchanged TRACER trial design in light of the evidence yielded from the earlier completed TRITON trial. TRACER was designed as a triple versus dual antiplatelet trial in NSTEMI patients with no previous long-term outcome data supporting such aggressive strategy. TRITON data represented dual versus dual antiplatelet therapy, and became available before TRACER enrollment starts revealing prasugrel front-loaded early vascular benefit predominantly in STEMI patients with the growing over time bleeding and cancer risks. Moreover, large prasugrel NSTEMI TRITON cohort exhibited trend towards excess mortality in experimental arm warning against aggressive TRACER design. The long-term TRITON results in general, and especially in the NSTEMI patients challenge unchanged TRACER trial design. Applying dual, rather than triple antiplatelet therapy protocol modification should be considered in TRACER to minimize bleeding, cancer, and non-cardiovascular death risks. PMID:26126053

  9. Geographic Differences in Time to Culture Conversion in Liquid Media: Tuberculosis Trials Consortium Study 28. Culture Conversion Is Delayed in Africa

    PubMed Central

    Mac Kenzie, William R.; Heilig, Charles M.; Bozeman, Lorna; Johnson, John L.; Muzanye, Grace; Dunbar, Denise; Jost, Kenneth C.; Diem, Lois; Metchock, Beverly; Eisenach, Kathleen; Dorman, Susan; Goldberg, Stefan

    2011-01-01

    Background Tuberculosis Trials Consortium Study 28, was a double blind, randomized, placebo-controlled, phase 2 clinical trial examining smear positive pulmonary Mycobacterium tuberculosis. Over the course of intensive phase therapy, patients from African sites had substantially delayed and lower rates of culture conversion to negative in liquid media compared to non-African patients. We explored potential explanations of this finding. Methods In TBTC Study 28, protocol-correct patients (n = 328) provided spot sputum specimens for M. tuberculosis culture in liquid media, at baseline and weeks 2, 4, 6 and 8 of study therapy. We compared sputum culture conversion for African and non-African patients stratified by four baseline measures of disease severity: AFB smear quantification, extent of disease on chest radiograph, cavity size and the number of days to detection of M. tuberculosis in liquid media using the Kaplan-Meier product-limit method. We evaluated specimen processing and culture procedures used at 29 study laboratories serving 27 sites. Results African TB patients had more extensive disease at enrollment than non-African patients. However, African patients with the least disease by the 4 measures of disease severity had conversion rates on liquid media that were substantially lower than conversion rates in non-African patients with the greatest extent of disease. HIV infection, smoking and diabetes did not explain delayed conversion in Africa. Some inter-site variation in laboratory processing and culture procedures within accepted practice for clinical diagnostic laboratories was found. Conclusions Compared with patients from non-African sites, African patients being treated for TB had delayed sputum culture conversion and lower sputum conversion rates in liquid media that were not explained by baseline severity of disease, HIV status, age, smoking, diabetes or race. Further investigation is warranted into whether modest variation in laboratory

  10. Trial watch

    PubMed Central

    Vacchelli, Erika; Galluzzi, Lorenzo; Fridman, Wolf Hervé; Galon, Jerome; Sautès-Fridman, Catherine; Tartour, Eric; Kroemer, Guido

    2012-01-01

    The long-established notion that apoptosis would be immunologically silent, and hence it would go unnoticed by the immune system, if not tolerogenic, and hence it would actively suppress immune responses, has recently been revisited. In some instances, indeed, cancer cells undergo apoptosis while emitting a spatiotemporally-defined combination of signals that renders them capable of eliciting a long-term protective antitumor immune response. Importantly, only a few anticancer agents can stimulate such an immunogenic cell death. These include cyclophosphamide, doxorubicin and oxaliplatin, which are currently approved by FDA for the treatment of multiple hematologic and solid malignancies, as well as mitoxantrone, which is being used in cancer therapy and against multiple sclerosis. In this Trial Watch, we will review and discuss the progress of recent (initiated after January 2008) clinical trials evaluating the off-label use of cyclophosphamide, doxorubicin, oxaliplatin and mitoxantrone. PMID:22720239

  11. Trial Watch

    PubMed Central

    Galluzzi, Lorenzo; Vacchelli, Erika; Fridman, Wolf Hervé; Galon, Jerome; Sautès-Fridman, Catherine; Tartour, Eric; Zucman-Rossi, Jessica; Zitvogel, Laurence; Kroemer, Guido

    2012-01-01

    Since the advent of hybridoma technology, dating back to 1975, monoclonal antibodies have become an irreplaceable diagnostic and therapeutic tool for a wide array of human diseases. During the last 15 years, several monoclonal antibodies (mAbs) have been approved by FDA for cancer therapy. These mAbs are designed to (1) activate the immune system against tumor cells, (2) inhibit cancer cell-intrinsic signaling pathways, (3) bring toxins in the close proximity of cancer cells, or (4) interfere with the tumor-stroma interaction. More recently, major efforts have been made for the development of immunostimulatory mAbs that either enhance cancer-directed immune responses or limit tumor- (or therapy-) driven immunosuppression. Some of these antibodies, which are thought to facilitate tumor eradication by initiating or sustaining a tumor-specific immune response, have already entered clinical trials. In this Trial Watch, we will review and discuss the clinical progress of the most important mAbs that are have entered clinical trials after January 2008. PMID:22720209

  12. Real-Time Pretreatment Review Limits Unacceptable Deviations on a Cooperative Group Radiation Therapy Technique Trial: Quality Assurance Results of RTOG 0933

    SciTech Connect

    Gondi, Vinai; Cui, Yunfeng; Mehta, Minesh P.; Manfredi, Denise; Xiao, Ying; Galvin, James M.; Rowley, Howard; Tome, Wolfgang A.

    2015-03-01

    Purpose: RTOG 0933 was a phase II trial of hippocampal avoidance during whole brain radiation therapy for patients with brain metastases. The results demonstrated improvement in short-term memory decline, as compared with historical control individuals, and preservation of quality of life. Integral to the conduct of this trial were quality assurance processes inclusive of pre-enrollment credentialing and pretreatment centralized review of enrolled patients. Methods and Materials: Before enrolling patients, all treating physicians and sites were required to successfully complete a “dry-run” credentialing test. The treating physicians were credentialed based on accuracy of magnetic resonance imaging–computed tomography image fusion and hippocampal and normal tissue contouring, and the sites were credentialed based on protocol-specified dosimetric criteria. Using the same criteria, pretreatment centralized review of enrolled patients was conducted. Physicians enrolling 3 consecutive patients without unacceptable deviations were permitted to enroll further patients without pretreatment review, although their cases were reviewed after treatment. Results: In all, 113 physicians and 84 sites were credentialed. Eight physicians (6.8%) failed hippocampal contouring on the first attempt; 3 were approved on the second attempt. Eight sites (9.5%) failed intensity modulated radiation therapy planning on the first attempt; all were approved on the second attempt. One hundred thirteen patients were enrolled in RTOG 0933; 100 were analyzable. Eighty-seven cases were reviewed before treatment; 5 (5.7%) violated the eligibility criteria, and 21 (24%) had unacceptable deviations. With feedback, 18 cases were approved on the second attempt and 2 cases on the third attempt. One patient was treated off protocol. Twenty-two cases were reviewed after treatment; 1 (4.5%) violated the eligibility criteria, and 5 (23%) had unacceptable deviations. Conclusions: Although >95% of the

  13. Object detection in real-time

    NASA Astrophysics Data System (ADS)

    Solder, Ulrich; Graefe, Volker

    1991-03-01

    An algorithm working on monocular gray-scale image sequences for object detection combined with a road tracker is presented. This algorithm appropriate for the real-time demands of an autonomous car driving with speeds over 40 km/h may be used for triggering obstacle avoidance maneuvers such as coming to a safe stop automatically in front of an obstacle or following another car. Moving and static objects have been detected in real-world experiments on various types of roads even under unfavorable weather conditions. . Morgenthaler and

  14. Endovascular treatment for Small Core and Anterior circulation Proximal occlusion with Emphasis on minimizing CT to recanalization times (ESCAPE) trial: methodology.

    PubMed

    Demchuk, Andrew M; Goyal, Mayank; Menon, Bijoy K; Eesa, Muneer; Ryckborst, Karla J; Kamal, Noreen; Patil, Shivanand; Mishra, Sachin; Almekhlafi, Mohammed; Randhawa, Privia A; Roy, Daniel; Willinsky, Robert; Montanera, Walter; Silver, Frank L; Shuaib, Ashfaq; Rempel, Jeremy; Jovin, Tudor; Frei, Donald; Sapkota, Biggya; Thornton, J Michael; Poppe, Alexandre; Tampieri, Donatella; Lum, Cheemun; Weill, Alain; Sajobi, Tolulope T; Hill, Michael D

    2015-04-01

    ESCAPE is a prospective, multicenter, randomized clinical trial that will enroll subjects with the following main inclusion criteria: less than 12 h from symptom onset, age > 18, baseline NIHSS >5, ASPECTS score of >5 and CTA evidence of carotid T/L or M1 segment MCA occlusion, and at least moderate collaterals by CTA. The trial will determine if endovascular treatment will result in higher rates of favorable outcome compared with standard medical therapy alone. Patient populations that are eligible include those receiving IV tPA, tPA ineligible and unwitnessed onset or wake up strokes with 12 h of last seen normal. The primary end-point, based on intention-to-treat criteria is the distribution of modified Rankin Scale scores at 90 days assessed using a proportional odds model. The projected maximum sample size is 500 subjects. Randomization is stratified under a minimization process using age, gender, baseline NIHSS, baseline ASPECTS (8-10 vs. 6-7), IV tPA treatment and occlusion location (ICA vs. MCA) as covariates. The study will have one formal interim analysis after 300 subjects have been accrued. Secondary end-points at 90 days include the following: mRS 0-1; mRS 0-2; Barthel 95-100, EuroQOL and a cognitive battery. Safety outcomes are symptomatic ICH, major bleeding, contrast nephropathy, total radiation dose, malignant MCA infarction, hemicraniectomy and mortality at 90 days. PMID:25546514

  15. Identification of potential surrogate end points in randomized clinical trials of aggressive and indolent non-Hodgkin's lymphoma: correlation of complete response, time-to-event and overall survival end points

    PubMed Central

    Lee, L.; Wang, L.; Crump, M.

    2011-01-01

    Background: The correlation between efficacy end points in randomized controlled trials (RCTs) of systemic therapy for non-Hodgkin's lymphoma (NHL) was investigated to identify an appropriate surrogate end point for overall survival (OS). Methods: RCTs of previously untreated NHL published from 1990 to 2009 were identified. Associations between absolute differences in efficacy end points were determined using nonparametric Spearman's rank correlation coefficients (rs). Results: Thirty-eight RCTs representing 85 treatment arms for aggressive NHL and 20 RCTs representing 42 arms for indolent NHL were included. For aggressive NHL, differences in 3-year progression-free survival (PFS)/event-free survival (EFS) were high correlated with differences in 5-year OS {rs of 0.90 [95% confidence interval (CI) 0.73–0.96]} and linear regression determined that a 10% improvement in 3-year EFS or PFS would predict for a 7% ± 1% improvement in 5-year OS. For indolent histology disease, differences in complete response were strongly correlated with differences in 3-year EFS [rs 0.86 (95% CI 0.35–0.97)], but there was no correlation between 3-year time-to-event end points and 5-year OS. Conclusions: Improvements in 3-year EFS/PFS are highly correlated with improvements in 5-year OS in aggressive NHL and should be explored as a candidate surrogate end point. Definition of these relationships may inform future clinical trial design and interpretation of interim trial data. PMID:21266519

  16. Trial Watch

    PubMed Central

    Aranda, Fernando; Vacchelli, Erika; Eggermont, Alexander; Galon, Jerome; Fridman, Wolf Hervé; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2014-01-01

    Immunostimulatory monoclonal antibodies (mAbs) exert antineoplastic effects by eliciting a novel or reinstating a pre-existing antitumor immune response. Most often, immunostimulatory mAbs activate T lymphocytes or natural killer (NK) cells by inhibiting immunosuppressive receptors, such as cytotoxic T lymphocyte-associated protein 4 (CTLA4) or programmed cell death 1 (PDCD1, best known as PD-1), or by engaging co-stimulatory receptors, like CD40, tumor necrosis factor receptor superfamily, member 4 (TNFRSF4, best known as OX40) or TNFRSF18 (best known as GITR). The CTLA4-targeting mAb ipilimumab has been approved by the US Food and Drug Administration for use in patients with unresectable or metastatic melanoma in 2011. The therapeutic profile of ipilimumab other CTLA4-blocking mAbs, such as tremelimumab, is currently being assessed in subjects affected by a large panel of solid neoplasms. In the last few years, promising clinical results have also been obtained with nivolumab, a PD-1-targeting mAb formerly known as BMS-936558. Accordingly, the safety and efficacy of nivolumab and other PD-1-blocking molecules are being actively investigated. Finally, various clinical trials are underway to test the therapeutic potential of OX40- and GITR-activating mAbs. Here, we summarize recent findings on the therapeutic profile of immunostimulatory mAbs and discuss clinical trials that have been launched in the last 14 months to assess the therapeutic profile of these immunotherapeutic agents. PMID:24701370

  17. Trial watch

    PubMed Central

    Vacchelli, Erika; Galluzzi, Lorenzo; Eggermont, Alexander; Fridman, Wolf Hervé; Galon, Jerome; Sautès-Fridman, Catherine; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido

    2012-01-01

    Toll-like receptors (TLRs) have first been characterized for their capacity to detect conserved microbial components like lipopolysaccharide (LPS) and double-stranded RNA, resulting in the elicitation of potent (innate) immune responses against invading pathogens. More recently, TLRs have also been shown to promote the activation of the cognate immune system against cancer cells. Today, only three TLR agonists are approved by FDA for use in humans: the bacillus Calmette-Guérin (BCG), monophosphoryl lipid A (MPL) and imiquimod. BCG (an attenuated strain of Mycobacterium bovis) is mainly used as a vaccine against tuberculosis, but also for the immunotherapy of in situ bladder carcinoma. MPL (derived from the LPS of Salmonella minnesota) is included in the formulation of Cervarix®, a vaccine against human papillomavirus-16 and -18. Imiquimod (a synthetic imidazoquinoline) is routinely employed for actinic keratosis, superficial basal cell carcinoma, and external genital warts (condylomata acuminata). In this Trial Watch, we will summarize the results of recently completed clinical trials and discuss the progress of ongoing studies that have evaluated/are evaluating FDA-approved TLR agonists as off-label medications for cancer therapy. PMID:23162757

  18. Trial watch

    PubMed Central

    Vacchelli, Erika; Senovilla, Laura; Eggermont, Alexander; Fridman, Wolf Hervé; Galon, Jérôme; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-01-01

    It is now clear that the immune system plays a critical role not only during oncogenesis and tumor progression, but also as established neoplastic lesions respond to therapy. Selected cytotoxic chemicals can indeed elicit immunogenic cell death, a functionally peculiar type of apoptosis that stimulates tumor-specific cognate immune responses. Such immunogenic chemotherapeutics include cyclophosphamide, doxorubicin and oxaliplatin (which are approved by FDA for the treatment of various hematological and solid malignancies), mitoxantrone (which is currently employed both as an anticancer agent and against multiple sclerosis) and patupilone (a microtubular poison in clinical development). One year ago, in the second issue of OncoImmunology, we discussed the scientific rationale behind immunogenic chemotherapy and reviewed the status of recent clinical trials investigating the off-label use of cyclophosphamide, doxorubicin, oxaliplatin and mitoxantrone in cancer patients. Here, we summarize the latest developments in this area of clinical research, covering both high-impact studies that have been published during the last 13 months and clinical trials that have been initiated in the same period to assess the antineoplastic profile of immunogenic chemotherapeutics. PMID:23687621

  19. Adaptive clinical trial designs in oncology

    PubMed Central

    Zang, Yong; Lee, J. Jack

    2015-01-01

    Adaptive designs have become popular in clinical trial and drug development. Unlike traditional trial designs, adaptive designs use accumulating data to modify the ongoing trial without undermining the integrity and validity of the trial. As a result, adaptive designs provide a flexible and effective way to conduct clinical trials. The designs have potential advantages of improving the study power, reducing sample size and total cost, treating more patients with more effective treatments, identifying efficacious drugs for specific subgroups of patients based on their biomarker profiles, and shortening the time for drug development. In this article, we review adaptive designs commonly used in clinical trials and investigate several aspects of the designs, including the dose-finding scheme, interim analysis, adaptive randomization, biomarker-guided randomization, and seamless designs. For illustration, we provide examples of real trials conducted with adaptive designs. We also discuss practical issues from the perspective of using adaptive designs in oncology trials. PMID:25811018

  20. How transparent are migraine clinical trials?

    PubMed Central

    Dufka, Faustine L.; Dworkin, Robert H.

    2014-01-01

    Transparency in research requires public access to unbiased information prior to trial initiation and openly available results upon study completion. The Repository of Registered Migraine Trials is a global snapshot of registered migraine clinical trials and scorecard of results availability via the peer-reviewed literature, registry databases, and gray literature. The 295 unique clinical trials identified employed 447 investigational agents, with 30% of 154 acute migraine trials and 11% of 141 migraine prophylaxis trials testing combinations of agents. The most frequently studied categories in acute migraine trials were triptans, nonsteroidal anti-inflammatory drugs, antiemetics, calcitonin gene-related peptide antagonists, and acetaminophen. Migraine prophylaxis trials frequently studied anticonvulsants, β-blockers, complementary/alternative therapies, antidepressants, and botulinum toxin. Overall, 237 trials were eligible for a results search. Of 163 trials completed at least 12 months earlier, 57% had peer-reviewed literature results, and registries/gray literature added another 13%. Using logistic regression analysis, studies with a sample size below the median of 141 subjects were significantly less likely to have results, but the dominant factor associated with availability of results was time since study completion. In unadjusted models, trials registered on ClinicalTrials.gov and trials with industry primary sponsorship were significantly more likely to have results. Recently completed trials rarely have publicly available results; 2 years after completion, the peer-reviewed literature contains results for fewer than 60% of completed migraine trials. To avoid bias, evidence-based therapy algorithms should consider factors affecting results availability. As negative trials are less likely to be published, special caution should be exercised before recommending a therapy with a high proportion of missing trial results. PMID:25194013

  1. How Do Clinical Trials Work?

    MedlinePlus

    ... Trials Clinical Trial Websites How Do 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 ( ...

  2. Trial Watch

    PubMed Central

    Vacchelli, Erika; Eggermont, Alexander; Fridman, Wolf Hervé; Galon, Jérôme; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-01-01

    Adoptive cell transfer (ACT) represents a prominent form of immunotherapy against malignant diseases. ACT is conceptually distinct from dendritic cell-based approaches (which de facto constitute cellular vaccines) and allogeneic transplantation (which can be employed for the therapy of hematopoietic tumors) as it involves the isolation of autologous lymphocytes exhibiting antitumor activity, their expansion/activation ex vivo and their reintroduction into the patient. Re-infusion is most often performed in the context of lymphodepleting regimens (to minimize immunosuppression by host cells) and combined with immunostimulatory interventions, such as the administration of Toll-like receptor agonists. Autologous cells that are suitable for ACT protocols can be isolated from tumor-infiltrating lymphocytes or generated by engineering their circulating counterparts for the expression of transgenic tumor-specific T-cell receptors. Importantly, lymphocytes can be genetically modified prior to re-infusion for increasing their persistence in vivo, boosting antitumor responses and minimizing side effects. Moreover, recent data indicate that exhausted antitumor T lymphocytes may be rejuvenated in vitro by exposing them to specific cytokine cocktails, a strategy that might considerably improve the clinical success of ACT. Following up the Trial Watch that we published on this topic in the third issue of OncoImmunology (May 2012), here we summarize the latest developments in ACT-related research, covering both high-impact studies that have been published during the last 13 months and clinical trials that have been initiated in the same period to assess the antineoplastic profile of this form of cellular immunotherapy. PMID:23762803

  3. Trial watch

    PubMed Central

    Vacchelli, Erika; Eggermont, Alexander; Sautès-Fridman, Catherine; Galon, Jérôme; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-01-01

    Oncolytic virotherapy is emerging as a promising approach for the treatment of several neoplasms. The term “oncolytic viruses” is generally employed to indicate naturally occurring or genetically engineered attenuated viral particles that cause the demise of malignant cells while sparing their non-transformed counterparts. From a conceptual standpoint, oncolytic viruses differ from so-called “oncotropic viruses” in that only the former are able to kill cancer cells, even though both display a preferential tropism for malignant tissues. Of note, such a specificity can originate at several different steps of the viral cycle, including the entry of virions (transductional specificity) as well as their intracellular survival and replication (post-transcriptional and transcriptional specificity). During the past two decades, a large array of replication-competent and replication-incompetent oncolytic viruses has been developed and engineered to express gene products that would specifically promote the death of infected (cancer) cells. However, contrarily to long-standing beliefs, the antineoplastic activity of oncolytic viruses is not a mere consequence of the cytopathic effect, i.e., the lethal outcome of an intense, productive viral infection, but rather involves the elicitation of an antitumor immune response. In line with this notion, oncolytic viruses genetically modified to drive the local production of immunostimulatory cytokines exert more robust therapeutic effects than their non-engineered counterparts. Moreover, the efficacy of oncolytic virotherapy is significantly improved by some extent of initial immunosuppression (facilitating viral replication and spread) followed by the administration of immunostimulatory molecules (boosting antitumor immune responses). In this Trial Watch, we will discuss the results of recent clinical trials that have evaluated/are evaluating the safety and antineoplastic potential of oncolytic virotherapy. PMID:23894720

  4. Trial watch

    PubMed Central

    Senovilla, Laura; Vacchelli, Erika; Garcia, Pauline; Eggermont, Alexander; Fridman, Wolf Hervé; Galon, Jérôme; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-01-01

    The foundation of modern vaccinology dates back to the 1790s, when the English physician Edward Jenner uncovered the tremendous medical potential of prophylactic vaccination. Jenner’s work ignited a wave of nationwide vaccination campaigns abating the incidence of multiple life-threatening infectious diseases and culminating with the eradication of natural smallpox virus, which was definitively certified by the WHO in 1980. The possibility of using vaccines against cancer was first proposed at the end of the 19th century by Paul Ehrlich and William Coley. However, it was not until the 1990s that such a hypothesis began to be intensively investigated, following the realization that the immune system is not completely unresponsive to tumors and that neoplastic cells express immunogenic tumor-associated antigens (TAAs). Nowadays, anticancer vaccines are rapidly moving from the bench to the bedside, and a few prophylactic and therapeutic preparations have already been approved by FDA for use in humans. In this setting, one interesting approach is constituted by DNA vaccines, i.e., TAA-encoding circularized DNA constructs, often of bacterial origin, that are delivered to patients as such or by means of specific vectors, including (but not limited to) liposomal preparations, nanoparticles, bacteria and viruses. The administration of DNA vaccines is most often performed via the intramuscular or subcutaneous route and is expected to cause (1) the endogenous synthesis of the TAA by myocytes and/or resident antigen-presenting cells; (2) the presentation of TAA-derived peptides on the cell surface, in association with MHC class I molecules; and (3) the activation of potentially therapeutic tumor-specific immune responses. In this Trial Watch, we will summarize the results of recent clinical trials that have evaluated/are evaluating DNA vaccines as therapeutic interventions against cancer. PMID:23734328

  5. Liquid vs Solid Culture Medium to Evaluate Proportion and Time to Change in Management of Suspects of Tuberculosis—A Pragmatic Randomized Trial in Secondary and Tertiary Health Care Units in Brazil

    PubMed Central

    Moreira, Adriana da Silva Rezende; Huf, Gisele; Vieira, Maria Armanda Monteiro da Silva; da Costa, Paulo Albuquerque; Aguiar, Fábio; Marsico, Anna Grazia; Fonseca, Leila de Souza; Ricks, Mônica; Oliveira, Martha Maria; Detjen, Anne; Fujiwara, Paula Isono; Squire, Stephen Bertel; Kritski, Afranio Lineu

    2015-01-01

    Background The use of liquid medium (MGIT960) for tuberculosis (TB) diagnosis was recommended by WHO in 2007. However, there has been no evaluation of its effectiveness on clinically important outcomes. Methods and Findings A pragmatic trial was carried out in a tertiary hospital and a secondary health care unit in Rio de Janeiro City, Brazil. Participants were 16 years or older, suspected of having TB. They were excluded if only cerebral spinal fluid or blood specimens were available for analysis. MGIT960 technique was compared with the Lowenstein-Jensen (LJ) method for laboratory diagnosis of active TB. Primary outcome was the proportion of patients who had their initial medical management changed within 2 months after randomisation. Secondary outcomes were: mean time for changing the procedure, patient satisfaction with the overall treatment and adverse events. Data were analysed by intention-to-treat. Between April 2008 and September 2011, 693 patients were enrolled (348 to MGIT, 345 to LJ). Smear and culture results were positive for 10% and 15.7% of participants, respectively. Patients in the MGIT arm had their initial medical management changed more frequently than those in the LJ group (10.1% MGIT vs 3.8% LJ, RR 2.67 95% CI 1.44–.96, p = 0.002, NNT 16, 95% CI 10–39). Mean time for changing the initial procedure was greater in LJ group at both sites: 20.0 and 29.6 days in MGIT group and 52.2 and 64.3 in LJ group (MD 33.5, 95% CI 30.6–36.4, p = 0.0001). No other important differences were observed. Conclusions This study suggests that opting for the MGIT960 system for TB diagnosis provides a promising case management model for improving the quality of care and control of TB. Trial Registration Controlled-Trials.com ISRCTN79888843 PMID:26046532

  6. Stroke Trials Registry

    MedlinePlus

    ... Trials News About Neurology Image Library Search The Internet Stroke Center Trials Registry Clinical Trials Interventions Conditions ... UT Southwestern Medical Center. Copyright © 1997-2011 - The Internet Stroke Center. All rights reserved. The information contained ...

  7. Trial watch

    PubMed Central

    Vacchelli, Erika; Eggermont, Alexander; Galon, Jérôme; Sautès-Fridman, Catherine; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-01-01

    During the past 20 years, dozens—if not hundreds—of monoclonal antibodies have been developed and characterized for their capacity to mediate antineoplastic effects, either as they activate/enhance tumor-specific immune responses, either as they interrupt cancer cell-intrinsic signal transduction cascades, either as they specifically delivery toxins to malignant cells or as they block the tumor-stroma interaction. Such an intense research effort has lead to the approval by FDA of no less than 14 distinct molecules for use in humans affected by hematological or solid malignancies. In the inaugural issue of OncoImmunology, we briefly described the scientific rationale behind the use of monoclonal antibodies in cancer therapy and discussed recent, ongoing clinical studies investigating the safety and efficacy of this approach in patients. Here, we summarize the latest developments in this exciting area of clinical research, focusing on high impact studies that have been published during the last 15 months and clinical trials launched in the same period to investigate the therapeutic profile of promising, yet hitherto investigational, monoclonal antibodies. PMID:23482847

  8. Trial Watch:

    PubMed Central

    Pol, Jonathan; Bloy, Norma; Obrist, Florine; Eggermont, Alexander; Galon, Jérôme; Cremer, Isabelle; Erbs, Philippe; Limacher, Jean-Marc; Preville, Xavier; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2014-01-01

    Oncolytic viruses are natural or genetically modified viral species that selectively infect and kill neoplastic cells. Such an innate or exogenously conferred specificity has generated considerable interest around the possibility to employ oncolytic viruses as highly targeted agents that would mediate cancer cell-autonomous anticancer effects. Accumulating evidence, however, suggests that the therapeutic potential of oncolytic virotherapy is not a simple consequence of the cytopathic effect, but strongly relies on the induction of an endogenous immune response against transformed cells. In line with this notion, superior anticancer effects are being observed when oncolytic viruses are engineered to express (or co-administered with) immunostimulatory molecules. Although multiple studies have shown that oncolytic viruses are well tolerated by cancer patients, the full-blown therapeutic potential of oncolytic virotherapy, especially when implemented in the absence of immunostimulatory interventions, remains unclear. Here, we cover the latest advances in this active area of translational investigation, summarizing high-impact studies that have been published during the last 12 months and discussing clinical trials that have been initiated in the same period to assess the therapeutic potential of oncolytic virotherapy in oncological indications. PMID:25097804

  9. Trial Watch

    PubMed Central

    Semeraro, Michaela; Vacchelli, Erika; Eggermont, Alexander; Galon, Jerome; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-01-01

    Lenalidomide is a synthetic derivative of thalidomide currently approved by the US Food and Drug Administration for use in patients affected by multiple myeloma (in combination with dexamethasone) and low or intermediate-1 risk myelodysplastic syndromes that harbor 5q cytogenetic abnormalities. For illustrative purposes, the mechanism of action of lenalidomide can be subdivided into a cancer cell-intrinsic, a stromal, and an immunological component. Indeed, lenalidomide not only exerts direct cell cycle-arresting and pro-apoptotic effects on malignant cells, but also interferes with their physical and functional interaction with the tumor microenvironment and mediates a robust, pleiotropic immunostimulatory activity. In particular, lenalidomide has been shown to stimulate the cytotoxic functions of T lymphocytes and natural killer cells, to limit the immunosuppressive impact of regulatory T cells, and to modulate the secretion of a wide range of cytokines, including tumor necrosis factor α, interferon γ as well as interleukin (IL)-6, IL-10, and IL-12. Throughout the last decade, the antineoplastic and immunostimulatory potential of lenalidomide has been investigated in patients affected by a wide variety of hematological and solid malignancies. Here, we discuss the results of these studies and review the status of clinical trials currently assessing the safety and efficacy of this potent immunomodulatory drug in oncological indications. PMID:24482747

  10. Trial Watch

    PubMed Central

    Bloy, Norma; Pol, Jonathan; Manic, Gwenola; Vitale, Ilio; Eggermont, Alexander; Galon, Jérôme; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2014-01-01

    During the past two decades, it has become increasingly clear that the antineoplastic effects of radiation therapy do not simply reflect the ability of X-, β- and γ-rays to damage transformed cells and directly cause their permanent proliferative arrest or demise, but also involve cancer cell-extrinsic mechanisms. Indeed, among other activities, radiotherapy has been shown to favor the establishment of tumor-specific immune responses that operate systemically, underpinning the so-called ‘out-of-field’ or ‘abscopal’ effect. Thus, ionizing rays appear to elicit immunogenic cell death, a functionally peculiar variant of apoptosis associated with the emission of a particularly immunostimulatory combination of damage-associated molecular patterns. In line with this notion, radiation therapy fosters, and thus exacerbates, the antineoplastic effects of various treatment modalities, including surgery, chemotherapy and various immunotherapeutic agents. Here, we summarize recent advances in the use of ionizing rays as a means to induce or potentiate therapeutically relevant anticancer immune responses. In addition, we present clinical trials initiated during the past 12 months to test the actual benefit of radioimmunotherapy in cancer patients. PMID:25941606

  11. Temporal variability of CO2 and N2O emissions in an agricultural long-term field trial regarding effects of different management practices and extreme weather effects

    NASA Astrophysics Data System (ADS)

    Koal, Philipp; Schilling, Rolf; Gerl, Georg; Pritsch, Karin; Munch, Jean Charles

    2016-04-01

    In order to achieve a reduction of greenhouse gas emissions, modern agronomic management practices need to be established. Therefore, to assess the effect of different farming practices on greenhouse gas emissions, reliable data are required. The experiment covers and compares main aspects of agricultural management for a better implementation of sustainable land use. The focus lies on the determination and interpretation of greenhouse gas emissions, where the effects of diverse tillage systems and fertilisation practices of an integrated farming system as well as the impacts of extreme weather conditions are observed. In addition, with analysis of the alterable biological, physical and chemical soil properties a link between the impact of different management systems on greenhouse gas emissions and the observed cycle of matter in the soil, especially the nitrogen and carbon cycle, is enabled. Measurements have been carried out on long-term field trials at the Research Farm Scheyern located in a Tertiary hilly landscape approximately 40 km north of Munich (South Germany). The long-term integrated farming system trial was started in 1992. Since then parcels of land (each around 0.2-0.4 ha) with a particular interior plot set-up have been conducted with the same crop rotation, tillage and fertilisation practice referring to integrated farming management. Thus, the management impacts on the soil of more than 20 years have been examined. Fluxes of CH4, N2O and CO2 have been monitored since 2007 for the integrated farming system trial using an automated system which consists of chambers (0.4 m2 area) with a motor-driven lid, an automated gas sampling unit, an on-line gas chromatographic analysis system, and a control and data logging unit. Precipitation and temperature data have been observed for the experimental field to include weather effects. The main outcomes are the analysis of temporal and spatial dynamics of greenhouse gas emissions influenced by management

  12. Improving medication adherence in diabetes type 2 patients through Real Time Medication Monitoring: a Randomised Controlled Trial to evaluate the effect of monitoring patients' medication use combined with short message service (SMS) reminders

    PubMed Central

    2011-01-01

    Background Innovative approaches are needed to support patients' adherence to drug therapy. The Real Time Medication Monitoring (RTMM) system offers real time monitoring of patients' medication use combined with short message service (SMS) reminders if patients forget to take their medication. This combination of monitoring and tailored reminders provides opportunities to improve adherence. This article describes the design of an intervention study aimed at evaluating the effect of RTMM on adherence to oral antidiabetics. Methods/Design Randomised Controlled Trial (RCT) with two intervention arms and one control arm involving diabetes type 2 patients with suboptimal levels of adherence to oral antidiabetics (less than 80% based on pharmacy refill data). Patients in the first intervention arm use RTMM including SMS reminders and a personal webpage where they can monitor their medication use. Patients in the second intervention arm use RTMM without SMS reminders or webpage access. Patients in the control arm are not exposed to any intervention. Patients are randomly assigned to one of the three arms. The intervention lasts for six months. Pharmacy refill data of all patients are available from 11 months before, until 11 months after the start of the intervention. Primary outcome measure is adherence to oral antidiabetics calculated from: 1) data collected with RTMM, as a percentage of medication taken as prescribed, and as percentage of medication taken within the correct time interval, 2) refill data, taking the number of days for which oral antidiabetics are dispensed during the study period divided by the total number of days of the study period. Differences in adherence between the intervention groups and control group are studied using refill data. Differences in adherence between the two intervention groups are studied using RTMM data. Discussion The intervention described in this article consists of providing RTMM to patients with suboptimal adherence levels

  13. Assessment of the Effect of Intestinal Permeability Probes (Lactulose And Mannitol) and Other Liquids on Digesta Residence Times in Various Segments of the Gut Determined by Wireless Motility Capsule: A Randomised Controlled Trial

    PubMed Central

    Sequeira, Ivana R.; Lentle, Roger G.; Kruger, Marlena C.; Hurst, Roger D.

    2015-01-01

    subjects generally precluded the identification of all but gross variation between treatments. The lack of any differences between treatments in either total small or large intestinal transit times indicates that the solutions administered in the lactulose mannitol test of permeability had no consistent influence on the temporal pattern of absorption. The negatively exponential profile and lack of any peaks in the frequency spectra of cyclic variation in gastric intraluminal pressure that were consistent with reported physiological frequencies of contractile activity profile suggests that the principal source of this variation is stochastic likely resulting from the effects of external events occasioned by normal daily activities on intra-abdominal pressure. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12615000596505 PMID:26629926

  14. Trial Watch

    PubMed Central

    Aranda, Fernando; Vacchelli, Erika; Eggermont, Alexander; Galon, Jerome; Sautès-Fridman, Catherine; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-01-01

    Throughout the past 3 decades, along with the recognition that the immune system not only influences oncogenesis and tumor progression, but also determines how established neoplastic lesions respond therapy, renovated enthusiasm has gathered around the possibility of using vaccines as anticancer agents. Such an enthusiasm quickly tempered when it became clear that anticancer vaccines would have to be devised as therapeutic, rather than prophylactic, measures, and that malignant cells often fail to elicit (or actively suppress) innate and adaptive immune responses. Nonetheless, accumulating evidence indicates that a variety of anticancer vaccines, including cell-based, DNA-based, and purified component-based preparations, are capable of circumventing the poorly immunogenic and highly immunosuppressive nature of most tumors and elicit (at least under some circumstances) therapeutically relevant immune responses. Great efforts are currently being devoted to the identification of strategies that may provide anticancer vaccines with the capacity of breaking immunological tolerance and eliciting tumor-associated antigen-specific immunity in a majority of patients. In this sense, promising results have been obtained by combining anticancer vaccines with a relatively varied panels of adjuvants, including multiple immunostimulatory cytokines, Toll-like receptor agonists as well as inhibitors of immune checkpoints. One year ago, in the December issue of OncoImmunology, we discussed the biological mechanisms that underlie the antineoplastic effects of peptide-based vaccines and presented an abundant literature demonstrating the prominent clinical potential of such an approach. Here, we review the latest developments in this exciting area of research, focusing on high-profile studies that have been published during the last 13 mo and clinical trials launched in the same period to evaluate purified peptides or full-length proteins as therapeutic anticancer agents. PMID:24498550

  15. Pharmacokinetics and drying time of testosterone 2% gel in men with hypogonadism: a multicenter, open-label, single-arm trial.

    PubMed

    Morgentaler, A; McGettigan, J; Xiang, Q; Danoff, T M; Gould, E M

    2015-01-01

    The objective of this study was to assess drying time after application of testosterone 2% gel (Fortesta Gel, Endo Pharmaceuticals), time needed for serum total testosterone (TT) to reach the eugonadal range (⩾ 300 ng dl(-1)), and time to steady-state serum TT. Thirty-four men with primary or secondary hypogonadism were enrolled in the study; 31 men were included in the pharmacokinetics (PKs) population. Testosterone 2% gel (40 mg) was applied once daily in the morning to the front and inner thighs for 14 days. Median gel drying time was 2.4 min (95% confidence interval (CI), 1.7-3.4 min; n = 31). Serum TT concentrations reached the target eugonadal range with a median time of 2.9 h (95% CI, 1.9-4.3 h; n = 24). Median time to steady-state serum TT concentration was 1.1 days (95% CI, 0.7-3.4 days; n = 31). Six patients (17.6%; n = 34) reported treatment-related adverse events; all were mild. The results from this 14-day PK study in men with hypogonadism suggest that testosterone 2% gel dries, on average, in <3 min after application and that testosterone 2% gel rapidly reaches the target eugonadal range and attains steady-state serum TT concentrations in about 1 day. PMID:25056809

  16. Congruency sequence effects are driven by previous-trial congruency, not previous-trial response conflict

    PubMed Central

    Weissman, Daniel H.; Carp, Joshua

    2013-01-01

    Congruency effects in distracter interference tasks are often smaller after incongruent trials than after congruent trials. However, the sources of such congruency sequence effects (CSEs) are controversial. The conflict monitoring model of cognitive control links CSEs to the detection and resolution of response conflict. In contrast, competing theories attribute CSEs to attentional or affective processes that vary with previous-trial congruency (incongruent vs. congruent). The present study sought to distinguish between conflict monitoring and congruency-based accounts of CSEs. To this end, we determined whether CSEs are driven by previous-trial reaction time (RT)—a putative measure of response conflict—or by previous-trial congruency. In two experiments using a face-word Stroop task (n = 49), we found that current-trial congruency effects did not vary with previous-trial RT independent of previous-trial congruency. In contrast, current-trial congruency effects were influenced by previous-trial congruency independent of previous-trial RT. These findings appear more consistent with theories that attribute CSEs to non-conflict processes whose recruitment varies with previous-trial congruency than with theories that link CSEs to previous-trial response conflict. PMID:24027550

  17. International Clinical Trial Day and clinical trials in Ethiopia and Africa.

    PubMed

    Fekadu, Abebaw; Teferra, Solomon; Hailu, Asrat; Gebre-Mariam, Tsige; Addissie, Adamu; Deressa, Wakgari; Yimer, Getnet; Reja, Ahmed

    2014-01-01

    Low income countries like Ethiopia are underrepresented in clinical research. As a major public commitment to clinical research, Ethiopia celebrated the International Clinical Trial Day (ICTD) for the first time on 20 May 2014 under the auspices of Addis Ababa University. The motto for the day was 'Clinical Trials for Excellence in Patient Care'. The celebration offered an opportunity to inform academic staff, researchers, students and the leadership about clinical trials being conducted and to discuss the future of clinical trials in the country. Although clear challenges to the conduct of trials abound, clinical trials registered from Ethiopia in trial registration databases is increasing. Cross-country collaborations, international funding support, motivation of academic staff to conduct clinical trials and the commitment and engagement of the leadership in research are all improving. The overall impact of clinical trials is also encouraging. For example, some of the trials conducted in Ethiopia have informed treatment guidelines. However, administrative capacity, research infrastructure as well as financial support remain weak. There is a need for enhanced university-industry linkage and translation of research findings into locally relevant evidence. Ethiopia, as well as the whole of Africa, has an unparalleled opportunity to lead the way in clinical trials, given its prospect of development and the need to have locally relevant evidence for its growing population. In this commentary we reflect on the celebration of ICTD, the status and opportunities for conducting clinical trials and the way forward for facilitating clinical trials in Ethiopia and Africa. PMID:25526797

  18. Mock Trials for Children.

    ERIC Educational Resources Information Center

    Hickey, M. Gail

    1990-01-01

    Demonstrates how role-playing in a mock trial situation allows children to view critically both sides of an issue and introduce them to trial procedure. Offers pre-trial activities, ways to teach students to see both sides of a situation, themes for mock trials, and supporting resources. (GG)

  19. Discrete Trials Teaching

    ERIC Educational Resources Information Center

    Ghezzi, Patrick M.

    2007-01-01

    The advantages of emphasizing discrete trials "teaching" over discrete trials "training" are presented first, followed by a discussion of discrete trials as a method of teaching that emerged historically--and as a matter of necessity for difficult learners such as those with autism--from discrete trials as a method for laboratory research. The…

  20. How transparent are migraine clinical trials? Repository of Registered Migraine Trials (RReMiT).

    PubMed

    Dufka, Faustine L; Dworkin, Robert H; Rowbotham, Michael C

    2014-10-01

    Transparency in research requires public access to unbiased information prior to trial initiation and openly available results upon study completion. The Repository of Registered Migraine Trials is a global snapshot of registered migraine clinical trials and scorecard of results availability via the peer-reviewed literature, registry databases, and gray literature. The 295 unique clinical trials identified employed 447 investigational agents, with 30% of 154 acute migraine trials and 11% of 141 migraine prophylaxis trials testing combinations of agents. The most frequently studied categories in acute migraine trials were triptans, nonsteroidal anti-inflammatory drugs, antiemetics, calcitonin gene-related peptide antagonists, and acetaminophen. Migraine prophylaxis trials frequently studied anticonvulsants, β-blockers, complementary/alternative therapies, antidepressants, and botulinum toxin. Overall, 237 trials were eligible for a results search. Of 163 trials completed at least 12 months earlier, 57% had peer-reviewed literature results, and registries/gray literature added another 13%. Using logistic regression analysis, studies with a sample size below the median of 141 subjects were significantly less likely to have results, but the dominant factor associated with availability of results was time since study completion. In unadjusted models, trials registered on ClinicalTrials.gov and trials with industry primary sponsorship were significantly more likely to have results. Recently completed trials rarely have publicly available results; 2 years after completion, the peer-reviewed literature contains results for fewer than 60% of completed migraine trials. To avoid bias, evidence-based therapy algorithms should consider factors affecting results availability. As negative trials are less likely to be published, special caution should be exercised before recommending a therapy with a high proportion of missing trial results. PMID:25194013

  1. Optimal timing of initiation of oral P2Y12-receptor antagonist therapy in patients with non-ST elevation acute coronary syndromes. Lessons learnt from the ACCOAST-trial.

    PubMed

    Zeymer, Uwe; Montalescot, Gilles; Ardissino, Diego; Bolognese, Leonardo; Clemmensen, Peter; Collet, Jean-Philippe; Lopez-Sendon, Jose; Widimsky, Petr

    2016-06-01

    The optimal time-point of the initiation of P2Y12 antagonist therapy in patients with non-ST elevation acute coronary syndromes (NTSE-ACS) is still a matter of debate. European guidelines recommend P2Y12 as soon as possible after first medical contact. However, the only trial which compared the two strategies did not demonstrate any benefit of pre-treatment with prasugrel before angiography compared to starting therapy after angiography and just prior to percutaneous coronary intervention (PCI). This paper summarizes the results of pharmacodynamic and previous studies, and gives recommendations for the initiation of P2Y12 antagonist therapy in NSTE-ACS in different clinical situations. PMID:25921481

  2. [Quality control in clinical trials].

    PubMed

    Fukushima, M

    1996-01-01

    Quality control (QC) in clinical trials means the procedures which insure protection of human subjects from research risk, reliability of the data, and thereby assures internal consistency. This has been developed since 1970s in the US, by establishing various regulations which are now called GCP. From the viewpoint of total QC, it should be emphasized that rigorous review of protocol by the Institutional Review Board and obtaining Informed Consent are prerequisites for insuring the quality of the given trial at high scientific level. When pursuing a clinical trial, first of all, facilities of the institutions and the ability of investigators must be of high quality. For this reason, at each institution previous data related to trials should be thoroughly reviewed and analyzed prior to developing a protocol. Educational courses in QC in clinical practice are invaluable. QC of diagnosis means, for example, central pathology review and standardization of diagnostic procedures and process. Secondly, at each institution, data managers collect the data and submit them to the central office at the indicated time. In order to evolve clinical trial, continuous education for data managers and expansion of their job are encouraged. Thirdly, at the statistical center independent from the research group office, subject-specific data managers, the biostatistical staff, must check submitted forms for completeness, consistency and accuracy. Finally, at the data analysis, quality evaluation of the research should also be carried out. Throughout the trial, monitoring and audit are particularly important to assure quality. The sponsor has the responsibility of monitoring the trial and make rigorous onsite visits, and the individual study group also have a monitoring program, while the FDA and the NCI audit by themselves. The purpose of audit is not only to assure data reliability but also to check out patient compliance to drug, education as to regulations and rules of clinical

  3. Combining the P300-complex trial-based concealed information test and the reaction time-based autobiographical implicit association test in concealed memory detection.

    PubMed

    Hu, Xiaoqing; Rosenfeld, J Peter

    2012-08-01

    Despite the P300-concealed information test's validity in detecting concealed memory when it is conducted immediately after the mock crime, whether the P300-CIT's detection efficiency is moderated by time delay remains unknown. Here, we conducted a mock crime study in which guilty participants were tested immediately after the mock crime or 1 month later. An innocent group was also tested. Assuming that the autobiographical Implicit Association Test (aIAT) and the P300-CIT rely on nonoverlapping mechanisms for memory detection, participants were tested using both the P300-CIT and the reaction time (RT)-based aIAT. Results suggested that the sensitivity of both tests remains even after the 1-month delay. The indicators from the RT-aIAT and P300-CIT were uncorrelated, thus combining P300-CIT and aIAT data further increased the efficiency of memory detection. PMID:22681260

  4. A Randomized, controlled, crossover trial to investigate times to onset of the perception of soothing and cooling by over-the-counter heartburn treatments.

    PubMed

    Strugala, V; Dettmar, P W; Sarratt, K; Sykes, J; Berry, P; Thomas, E

    2010-01-01

    This was a randomized, controlled, four-way crossover study in 45 subjects with a tendency to suffer from moderate heartburn following some meals. The study was designed to assess the time to onset of the perceived soothing and cooling effects of the alginate raft-forming products, Gaviscon Liquid (peppermint), Gaviscon Double Action Liquid (peppermint) and Gaviscon Powder Formulation (fresh tropical), compared with a non-active sublingual control. All three Gaviscon products provided significantly faster soothing and cooling effects compared with the control. Based on the upper 95% confidence limits for the median, time to onset of soothing was perceived within 3.15 min, 3.08 min and 4.05 min for Gaviscon Liquid, Double Action Liquid and Powder Formulation, respectively. Similarly, time to onset of cooling was perceived within 1.95 min, 1.23 min and 11.22 min for Gaviscon Liquid, Double Action Liquid and Powder Formulation, respectively. The results show that Gaviscon Liquid and Gaviscon Double Action soothe within 3.15 min and cool within 1.95 min. PMID:20515559

  5. Effect of Weight-bearing Therapeutic Exercise on the Q-angle and Muscle Activity Onset Times of Elite Athletes with Patellofemoral Pain Syndrome: A Randomized Controlled Trial

    PubMed Central

    Lee, Jehoon; Lee, Hwangjae; Lee, Wanhee

    2014-01-01

    [Purpose] The purpose of this study was to determine the effect of a weight-bearing therapeutic exercise program for elite athletes diagnosed as having patellofemoral pain syndrome (PFPS). [Subjects] The subjects were 34 elite athletes from the Seoul T Center. They were randomly allocated to three groups: an elastic band exercise group (EBG), a sling exercise group (SEG), or a control group (CG). [Methods] Therapeutic exercises were performed 3 times a week for 8 weeks. The visual analogue scale (VAS) hamstring length, and static and dynamic Q angles were used to test the exercise effect of the exercises, as well as the onset time of electromyographic activity of vastus medialis oblique (VMO) and vastus lateralis (VL). [Results] Decrease of the dynamic Q-angle in EBG was significant and significantly greater than that in CG. The decrease in VAS in SEG was significant and significantly greater than that in CG. There were significant differences in the VL and VMO activity onset times in SEG between pre- and post-test, and their differences between pre- and post-test were also significantly different. [Conclusion] Weight-bearing therapeutic exercise is hoped that clinicians will use this information for better implementation of effective exercise methods for elite athletes with PFPS. PMID:25140080

  6. High-intensity interval training improves VO(2peak), maximal lactate accumulation, time trial and competition performance in 9-11-year-old swimmers.

    PubMed

    Sperlich, Billy; Zinner, Christoph; Heilemann, Ilka; Kjendlie, Per-Ludvik; Holmberg, Hans-Christer; Mester, Joachim

    2010-11-01

    Training volume in swimming is usually very high when compared to the relatively short competition time. High-intensity interval training (HIIT) has been demonstrated to improve performance in a relatively short training period. The main purpose of the present study was to examine the effects of a 5-week HIIT versus high-volume training (HVT) in 9-11-year-old swimmers on competition performance, 100 and 2,000 m time (T(100 m) and T(2,000 m)), VO(2peak) and rate of maximal lactate accumulation (Lac(max)). In a 5-week crossover study, 26 competitive swimmers with a mean (SD) age of 11.5 ± 1.4 years performed a training period of HIIT and HVT. Competition (P < 0.01; effect size = 0.48) and T(2,000 m) (P = 0.04; effect size = 0.21) performance increased following HIIT. No changes were found in T(100 m) (P = 0.20). Lac(max) increased following HIIT (P < 0.01; effect size = 0.43) and decreased after HVT (P < 0.01; effect size = 0.51). VO(2peak) increased following both interventions (P < 0.05; effect sizes = 0.46-0.57). The increases in competition performance, T(2,000 m), Lac(max) and VO(2peak) following HIIT were achieved in significantly less training time (~2 h/week). PMID:20683609

  7. Extended Follow-up Confirms Early Vaccine-Enhanced Risk of HIV Acquisition and Demonstrates Waning Effect Over Time Among Participants in a Randomized Trial of Recombinant Adenovirus HIV Vaccine (Step Study)

    PubMed Central

    Duerr, Ann; Huang, Yunda; Buchbinder, Susan; Coombs, Robert W.; Sanchez, Jorge; del Rio, Carlos; Casapia, Martin; Santiago, Steven; Gilbert, Peter; Corey, Lawrence; Robertson, Michael N.

    2012-01-01

    Background. The Step Study tested whether an adenovirus serotype 5 (Ad5)–vectored human immunodeficiency virus (HIV) vaccine could prevent HIV acquisition and/or reduce viral load set-point after infection. At the first interim analysis, nonefficacy criteria were met. Vaccinations were halted; participants were unblinded. In post hoc analyses, more HIV infections occurred in vaccinees vs placebo recipients in men who had Ad5-neutralizing antibodies and/or were uncircumcised. Follow-up was extended to assess relative risk of HIV acquisition in vaccinees vs placebo recipients over time. Methods. We used Cox proportional hazard models for analyses of vaccine effect on HIV acquisition and vaccine effect modifiers, and nonparametric and semiparametric methods for analysis of constancy of relative risk over time. Results. One hundred seventy-two of 1836 men were infected. The adjusted vaccinees vs placebo recipients hazard ratio (HR) for all follow-up time was 1.40 (95% confidence interval [CI], 1.03–1.92; P = .03). Vaccine effect differed by baseline Ad5 or circumcision status during first 18 months, but neither was significant for all follow-up time. The HR among uncircumcised and/or Ad5-seropositive men waned with time since vaccination. No significant vaccine-associated risk was seen among circumcised, Ad5-negative men (HR, 0.97; P = 1.0) over all follow-up time. Conclusions. The vaccine-associated risk seen in interim analysis was confirmed but waned with time from vaccination. Clinical Trials Registration. NCT00095576. PMID:22561365

  8. Clinical trials of homoeopathy.

    PubMed Central

    Kleijnen, J; Knipschild, P; ter Riet, G

    1991-01-01

    OBJECTIVE--To establish whether there is evidence of the efficacy of homoeopathy from controlled trials in humans. DESIGN--Criteria based meta-analysis. Assessment of the methodological quality of 107 controlled trials in 96 published reports found after an extensive search. Trials were scored using a list of predefined criteria of good methodology, and the outcome of the trials was interpreted in relation to their quality. SETTING--Controlled trials published world wide. MAIN OUTCOME MEASURES--Results of the trials with the best methodological quality. Trials of classical homoeopathy and several modern varieties were considered separately. RESULTS--In 14 trials some form of classical homoeopathy was tested and in 58 trials the same single homoeopathic treatment was given to patients with comparable conventional diagnosis. Combinations of several homoeopathic treatments were tested in 26 trials; isopathy was tested in nine trials. Most trials seemed to be of very low quality, but there were many exceptions. The results showed a positive trend regardless of the quality of the trial or the variety of homeopathy used. Overall, of the 105 trials with interpretable results, 81 trials indicated positive results whereas in 24 trials no positive effects of homoeopathy were found. The results of the review may be complicated by publication bias, especially in such a controversial subject as homoeopathy. CONCLUSIONS--At the moment the evidence of clinical trials is positive but not sufficient to draw definitive conclusions because most trials are of low methodological quality and because of the unknown role of publication bias. This indicates that there is a legitimate case for further evaluation of homoeopathy, but only by means of well performed trials. PMID:1825800

  9. Hands-on time during cardiopulmonary resuscitation is affected by the process of teambuilding: a prospective randomised simulator-based trial

    PubMed Central

    Hunziker, Sabina; Tschan, Franziska; Semmer, Norbert K; Zobrist, Roger; Spychiger, Martin; Breuer, Marc; Hunziker, Patrick R; Marsch, Stephan C

    2009-01-01

    Background Cardiac arrests are handled by teams rather than by individual health-care workers. Recent investigations demonstrate that adherence to CPR guidelines can be less than optimal, that deviations from treatment algorithms are associated with lower survival rates, and that deficits in performance are associated with shortcomings in the process of team-building. The aim of this study was to explore and quantify the effects of ad-hoc team-building on the adherence to the algorithms of CPR among two types of physicians that play an important role as first responders during CPR: general practitioners and hospital physicians. Methods To unmask team-building this prospective randomised study compared the performance of preformed teams, i.e. teams that had undergone their process of team-building prior to the onset of a cardiac arrest, with that of teams that had to form ad-hoc during the cardiac arrest. 50 teams consisting of three general practitioners each and 50 teams consisting of three hospital physicians each, were randomised to two different versions of a simulated witnessed cardiac arrest: the arrest occurred either in the presence of only one physician while the remaining two physicians were summoned to help ("ad-hoc"), or it occurred in the presence of all three physicians ("preformed"). All scenarios were videotaped and performance was analysed post-hoc by two independent observers. Results Compared to preformed teams, ad-hoc forming teams had less hands-on time during the first 180 seconds of the arrest (93 ± 37 vs. 124 ± 33 sec, P < 0.0001), delayed their first defibrillation (67 ± 42 vs. 107 ± 46 sec, P < 0.0001), and made less leadership statements (15 ± 5 vs. 21 ± 6, P < 0.0001). Conclusion Hands-on time and time to defibrillation, two performance markers of CPR with a proven relevance for medical outcome, are negatively affected by shortcomings in the process of ad-hoc team-building and particularly deficits in leadership. Team-building has

  10. A Clinical Trial of Optimal Time Interval Between Ablation and Diagnostic Activity When a Pretherapy RAI Scanning Is Performed on Patients With Differentiated Thyroid Carcinoma

    PubMed Central

    Yin, Yafu; Mao, Qiufen; Chen, Song; Li, Na; Li, Xuena; Li, Yaming

    2015-01-01

    Abstract This article investigates the association of the time interval between the diagnostic dose and ablation with the stunning effect, when a 74 MBq 131I pretherapy scanning was performed on patients with differentiated thyroid carcinoma (DTC); the patients who were diagnosed as DTC and would be performed radioiodine (RAI) ablation of thyroid remnants or metastases were recruited during January 2011 and May 2012 in our hospital. Thirty-seven patients with DTC who had the RAI ablation of thyroid remnants or metastases for the first time were recruited. All the patients received a dose of 1850 to 7400 MBq of 131I for ablation and a diagnostic scan was performed 24 hours after the administration of 74 MBq 131I before ablation. A posttherapy scan was performed 2 to 7 days after the ablation. The patients were broken down into 3 groups (G1, G2, and G3) according to the interval time between the diagnostic dose and therapy (1–3, 4–7, and >7 days). The fractional concentrations of 131I in remnants or functional metastases were quantified and expressed as therapeutic/diagnostic (Rx/Dx). The level of significance was set at 0.05. Sixty-seven foci were found both on pretherapy and posttherapy scans, the mean ratio of Rx/Dx was 0.43 ± 0.29, and the ratio of 49 foci (73.13%) was <0.6. The ratios in G1, G2, and G3 were 0.46 ± 0.29, 0.29 ± 0.18, and 0.55 ± 0.33, respectively. The differences between G1 and G2, and G2 and G3 were statistically significant (t = 2.40, P = 0.021 and t = 3.28, P = 0.002), whereas the difference between G1 and G3 was not significant (t = 1.01, P = 0.319). By a diagnostic scan of 74 MBq 131I, stunning prominently occurs with a time of 4 to 7 days between the diagnostic dose and ablation. We recommend that for less stunning effect, RAI ablation should be performed within 3 days or postponed until 1 week after the diagnostic dose administrated. PMID:26252311

  11. Frequent interruptions of sedentary time modulates contraction- and insulin-stimulated glucose uptake pathways in muscle: Ancillary analysis from randomized clinical trials.

    PubMed

    Bergouignan, Audrey; Latouche, Celine; Heywood, Sarah; Grace, Megan S; Reddy-Luthmoodoo, Medini; Natoli, Alaina K; Owen, Neville; Dunstan, David W; Kingwell, Bronwyn A

    2016-01-01

    Epidemiological studies have observed associations between frequent interruptions of sitting time with physical activity bouts and beneficial metabolic outcomes, even in individuals who regularly exercise. Frequent interruptions to prolonged sitting reduce postprandial plasma glucose. Here we studied potential skeletal muscle mechanisms accounting for this improved control of glycemia in overweight adults under conditions of one day uninterrupted sitting and sitting interrupted with light-intensity or moderate-intensity walking every 20-min (n = 8); and, after three days of either uninterrupted sitting or light-intensity walking interruptions (n = 5). Contraction- and insulin-mediated glucose uptake signaling pathways as well as changes in oxidative phosphorylation proteins were examined. We showed that 1) both interventions reduce postprandial glucose concentration, 2) acute interruptions to sitting over one day stimulate the contraction-mediated glucose uptake pathway, 3) both acute interruptions to sitting with moderate-intensity activity over one day and light-intensity activity over three days induce a transition to modulation of the insulin-signaling pathway, in association with increased capacity for glucose transport. Only the moderate-intensity interruptions resulted in greater capacity for glycogen synthesis and likely for ATP production. These observations contribute to a mechanistic explanation of improved postprandial glucose metabolism with regular interruptions to sitting time, a promising preventive strategy for metabolic diseases. PMID:27554943

  12. Frequent interruptions of sedentary time modulates contraction- and insulin-stimulated glucose uptake pathways in muscle: Ancillary analysis from randomized clinical trials

    PubMed Central

    Bergouignan, Audrey; Latouche, Celine; Heywood, Sarah; Grace, Megan S.; Reddy-Luthmoodoo, Medini; Natoli, Alaina K.; Owen, Neville; Dunstan, David W.; Kingwell, Bronwyn A.

    2016-01-01

    Epidemiological studies have observed associations between frequent interruptions of sitting time with physical activity bouts and beneficial metabolic outcomes, even in individuals who regularly exercise. Frequent interruptions to prolonged sitting reduce postprandial plasma glucose. Here we studied potential skeletal muscle mechanisms accounting for this improved control of glycemia in overweight adults under conditions of one day uninterrupted sitting and sitting interrupted with light-intensity or moderate-intensity walking every 20-min (n = 8); and, after three days of either uninterrupted sitting or light-intensity walking interruptions (n = 5). Contraction- and insulin-mediated glucose uptake signaling pathways as well as changes in oxidative phosphorylation proteins were examined. We showed that 1) both interventions reduce postprandial glucose concentration, 2) acute interruptions to sitting over one day stimulate the contraction-mediated glucose uptake pathway, 3) both acute interruptions to sitting with moderate-intensity activity over one day and light-intensity activity over three days induce a transition to modulation of the insulin-signaling pathway, in association with increased capacity for glucose transport. Only the moderate-intensity interruptions resulted in greater capacity for glycogen synthesis and likely for ATP production. These observations contribute to a mechanistic explanation of improved postprandial glucose metabolism with regular interruptions to sitting time, a promising preventive strategy for metabolic diseases. PMID:27554943

  13. Microphysical Model of the Venus clouds between 40km and 80km

    NASA Astrophysics Data System (ADS)

    McGouldrick, Kevin

    2013-10-01

    I am continuing to adapt the Community Aerosol and Radiation Model for Atmospheres (CARMA) to successfully simulate the multi-layered clouds of Venus. The present version of the one-dimensional model now includes a simple parameterization of the photochemicial production of sulfuric acid around altitudes of 62km, and its thermochemical destruction below cloud base. Photochemical production in the model is limited by the availability of water vapor and insolation. Upper cloud particles are introduced into the model via binary homogeneous nucleation, while the lower and middle cloud particles are created via activation of involatile cloud condensation nuclei. Growth by condensation and coagulation and coalescence are also treated. Mass loadings and particle sizes compare favorably with the in situ observations by the Pioneer Venus Large Probe Particle Size Spectrometer, and mixing ratios of volatiles compare favorably with remotely sensed observations of water vapor and sulfuric acid vapor. This work was supported by the NASA Planetary Atmospheres Program, grant number NNX11AD79G.

  14. Clinic-based training in comparison to home-based training after first-time lumbar disc surgery: a randomised controlled trial.

    PubMed

    Johansson, Ann-Christin; Linton, Steven J; Bergkvist, Leif; Nilsson, Olle; Cornefjord, Michael

    2009-03-01

    The effectiveness of physiotherapy after first-time lumbar disc surgery is still largely unknown. Studies in this field are heterogeneous and behavioural treatment principles have only been evaluated in one earlier study. The aim of this randomised study was to compare clinic-based physiotherapy with a behavioural approach to a home-based training programme regarding back disability, activity level, behavioural aspects, pain and global health measures. A total of 59 lumbar disc patients without any previous spine surgery or comorbidity participated in the study. Clinic-based physiotherapy with a behavioural approach was compared to home-based training 3 and 12 months after surgery. Additionally, the home training group was followed up 3 months after surgery by a structured telephone interview evaluating adherence to the exercise programme. Outcome measures were: Oswestry Disability Index (ODI), physical activity level, kinesiophobia, coping, pain, quality of life and patient satisfaction. Treatment compliance was high in both groups. There were no differences between the two groups regarding back pain disability measured by ODI 3 and 12 months after surgery. However, back pain reduction and increase in quality of life were significantly higher in the home-based training group. The patients in the clinic-based training group had significantly higher activity levels 12 months after surgery and were significantly more satisfied with physiotherapy care 3 months after surgery compared to the home-based training group. Rehabilitation after first-time lumbar disc surgery can be based on home training as long as the patients receive both careful instructions from a physiotherapist and strategies for active pain coping, and have access to the physiotherapist if questions regarding training arise. This might be a convenient treatment arrangement for most patients. PMID:19020904

  15. Towards an international standard for detection and typing botulinum neurotoxin-producing Clostridia types A, B, E and F in food, feed and environmental samples: a European ring trial study to evaluate a real-time PCR assay.

    PubMed

    Fenicia, Lucia; Fach, Patrick; van Rotterdam, Bart J; Anniballi, Fabrizio; Segerman, Bo; Auricchio, Bruna; Delibato, Elisabetta; Hamidjaja, Raditijo A; Wielinga, Peter R; Woudstra, Cedric; Agren, Joakim; De Medici, Dario; Knutsson, Rickard

    2011-03-01

    A real-time PCR method for detection and typing of BoNT-producing Clostridia types A, B, E, and F was developed on the framework of the European Research Project "Biotracer". A primary evaluation was carried out using 104 strains and 17 clinical and food samples linked to botulism cases. Results showed 100% relative accuracy, 100% relative sensitivity, 100% relative specificity, and 100% selectivity (inclusivity on 73 strains and exclusivity on 31 strains) of the real-time PCR against the reference cultural method combined with the standard mouse bioassay. Furthermore, a ring trial study performed at four different European laboratories in Italy, France, the Netherlands, and Sweden was carried out using 47 strains, and 30 clinical and food samples linked to botulism cases. Results showed a concordance of 95.7% among the four laboratories. The reproducibility generated a relative standard deviation in the range of 2.18% to 13.61%. Considering the high level of agreement achieved between the laboratories, this real-time PCR is a suitable method for rapid detection and typing of BoNT-producing Clostridia in clinical, food and environmental samples and thus support the use of it as an international standard method. PMID:21353718

  16. Legislation for trial registration and data transparency.

    PubMed

    Bian, Zhao-Xiang; Wu, Tai-Xiang

    2010-01-01

    Public confidence in clinical trials has been eroded by data suppression, misrepresentation and manipulation. Although various attempts have been made to achieve universal trial registration- e.g., Declaration of Helsinki, WHO clinical Trial Registry Platform (WHO ICTRP), the International Committee of Medical Journal Editors requirement- they have not succeeded, probably because they lack the enough power of enforcement.Legislation appears to be the most efficient and effective means to ensure that all researchers register their trials and disseminate their data accurately and in a timely manner. We propose that a global network be established. This could be accomplished in two steps. The first step is to legislate about trial registration and data transparency, such as USA's FDAAA Act 2007; and the second step to establish a global network to ensure uniform, international consistency in policy and enforcement of trial registration and data transparency. PMID:20504337

  17. Real-Time Continuous Glucose Monitoring Reduces the Duration of Hypoglycemia Episodes: A Randomized Trial in Very Low Birth Weight Neonates

    PubMed Central

    Uettwiller, Florence; Chemin, Aude; Bonnemaison, Elisabeth; Favrais, Géraldine; Saliba, Elie; Labarthe, François

    2015-01-01

    Objectives Hypoglycemia is frequent in very low birth weight (VLBW) neonates and compromises their neurological outcome. The aim of this study was to compare real-time continuous glucose monitoring system (RT-CGMS) to standard methods by intermittent capillary blood glucose testing in detecting and managing hypoglycemia. Study design Forty-eight VLBW neonates were enrolled in this prospective study. During their 3 first days of life, their glucose level was monitored either by RT-CGMS (CGM-group), or by intermittent capillary glucose testing (IGM-group) associated with a blind-CGMS to detect retrospectively missed hypoglycemia. Outcomes were the number and duration of hypoglycemic (≤50mg/dl) episodes per patient detected by CGMS. Results Forty-three monitorings were analyzed (IGM n = 21, CGM n = 22), with a median recording time of 72 hours. In the IGM group, blind-CGMS revealed a significantly higher number of hypoglycemia episodes than capillary blood glucose testing (1.2±0.4 vs 0.4±0.2 episode/patient, p<0.01). In the CGM-group, the use of RT-CGMS made it possible (i) to detect the same number of hypoglycemia episodes as blind-CGMS (1.2±0.4 episode/patient), (ii) to adapt the glucose supply in neonates with hypoglycemia (increased supply during days 1 and 2), and (iii) to significantly reduce the duration of hypoglycemia episodes per patient (CGM 44[10–140] min versus IGM 95[15–520] min, p<0.05). Furthermore, it reduced the number of blood samples (CGM 16.9±1.0 vs IGM 21.9±1.0 blood sample/patient, p<0.001). Conclusion RT-CGMS played a beneficial role in managing hypoglycemia in VLBW neonates by adjusting the carbohydrate supply to the individual needs and by reducing the duration of hypoglycemia episodes. The clinical significance of the biological differences observed in our study need to be explored. PMID:25590334

  18. Initial formal toxicity evaluation of APC-2, a novel fluorescent tracer agent for real-time measurement of glomerular filtration rate in preparation for a first-in-man clinical trial

    NASA Astrophysics Data System (ADS)

    Bugaj, Joseph E.; Dorshow, Richard B.

    2014-03-01

    The fluorescent tracer agent 2,5-bis[N-(1-carboxy-2-hydroxy)]carbamoyl-3,6-diaminopyrazine, designated APC-2, has been developed with properties and attributes necessary for use as a direct measure of glomerular filtration rate (GFR). Comparison to known standard exogenous GFR agents in animal models has demonstrated an excellent correlation. A clinical trial to demonstrate this same correlation in humans is in preparation. A battery of formal toxicity tests necessary for regulatory clearance to proceed with a clinical trial has been recently completed on this new fluorescent tracer agent. These include single dose toxicity studies in rats and dogs to determine overall toxicity and toxicokinetics of the compound. Blood compatibility, mutation assay, chromosomal aberration assay, and several other assays were also completed. Toxicity assessments were based on mortality, clinical signs, body weight, food consumption and anatomical pathology. Blood samples were collected to assess pharmacokinetic parameters including half-life, area under the curve, and clearance. Urine samples were collected to assess distribution. Doses of up to 200-300 times the estimated human dose were administered. No test-article related effects were noted on body weight, food consumption, ophthalmic observations and no abnormal pathology was seen in either macroscopic or microscopic evaluations of any organs or tissues. All animals survived to scheduled sacrifice. Transient discoloration of skin and urine was noted at the higher dose levels in both species as expected from a highly fluorescent compound and was not considered pathological. Thus initial toxicology studies of this new fluorescent tracer agent APC-2 have resulted in no demonstrable pathological test article concerns.

  19. A Comparative Randomized Trial on the Optimal Timing of Dexamethasone for Pain Relief after Endoscopic Submucosal Dissection for Early Gastric Neoplasm

    PubMed Central

    Pyo, Jeung Hui; Lee, Hyuk; Min, Yang Won; Min, Byung-Hoon; Lee, Jun Haeng; Rhee, Poong-Lyul; Kim, Jae J.

    2016-01-01

    Background/Aims The aim of this study was to compare the clinical effects of preoperative and postoperative dexamethasone on pain after endoscopic submucosal dissection (ESD) for early gastric neoplasm. Methods Forty patients with early gastric neoplasm who were scheduled for ESD were randomized into two groups according to the timing of steroid administration: preoperative (“pre”, n=20) and postoperative (“post”, n=20) steroid administration. The pre group received 0.15 mg/kg dexamethasone before ESD and placebo after, and the post group received pre-ESD placebo and post-ESD dexamethasone. The present pain intensity (PPI) index and the short-form McGill pain (SF-MP) questionnaire were evaluated. Results The primary outcome was PPI score at 6 hours after ESD. There was a greater reduction in 6-hour PPI in the pre group than in the post group (2.1±0.8 vs 3.0±1.1, respectively; p=0.006). The immediate PPI was also significantly lower in the pre group than in the post group (1.6±0.6 vs 2.9±0.6, respectively; p<0.001), and the total SF-MP scores were significantly lower in the pre group than in the post group both immediately and at 6 hours after the operation. Conclusions Preoperative administration of dexamethasone may produce a superior analgesic effect in patients who undergo ESD compared with the postoperative administration of dexamethasone. PMID:27114413

  20. Prediction of the optimal time for insemination using frozen-thawed semen in a multi-sire insemination trial in bitches.

    PubMed

    Steckler, D; Nöthling, J O; Harper, C

    2013-11-30

    The aims of the study were to determine which of Days 5, 6 or 7 after the blood plasma progesterone concentration (PPC) of bitches first reached 6-9 nmol/L (Day 0) yield the highest fertility and whether day of insemination affects the gender ratio of conceptuses. Six bitches were inseminated on Days 5 and 6 and 6 on Days 6 and 7. Ten million progressively motile frozen-thawed sperm from each of 5 dogs were pooled for the first insemination. The same number of sperm from 5 other dogs were pooled for the second insemination. Only one batch of semen from each dog was used on all bitches, which largely prevented any effect of male and semen. Twenty-three autosomal microsatellites and the amelogenin gene were used to determine the paternity and gender of the conceptuses. Pregnancy rate was 100%. Out of 103 ovulations 66 conceptuses were conceived (conception rate: 64%). The proportion of available oocytes fertilised was 0.11, 0.56, and 0.27 for Days 5, 6, and 7, respectively. The odds of fertilisation was 16.7 and 4.2 times higher from insemination on Day 6 compared to Day 5 (P<0.001) and Day 7 (P = 0.013), respectively. The numbers of male- and female conceptuses were equal (33 each) and gender was independent of insemination day (P = 0.18). This study suggests that intrauterine insemination of bitches should best be done 6 days after PPC first reaches a value between 6 and 9 nmol/L with a second insemination one day later. PMID:24128644

  1. Prevalence and risk factors for low bone mineral density in untreated HIV infection: a substudy of the INSIGHT Strategic Timing of AntiRetroviral Treatment trial

    PubMed Central

    Carr, Andrew; Grund, Birgit; Neuhaus, Jacqueline; Schwartz, Ann; Bernardino, Jose I; White, David; Badel-Faesen, Sharlaa; Avihingsanon, Anchalee; Ensrud, Kristine; Hoy, Jennifer

    2014-01-01

    Background HIV infection is associated with a higher prevalence of low bone mineral density (BMD) and fractures than the general population. There are limited data in HIV-positive adults, naïve to antiretroviral therapy (ART), to estimate the relative contribution of untreated HIV to bone loss. Methods The START Bone Mineral Density substudy is a randomised comparison of the effect of immediate versus deferred initial ART on bone. We evaluated traditional, demographic, HIV-related, and immunological factors for their associations with baseline hip and lumbar spine BMD, measured by dual-energy x-ray absorptiometry, using multiple regression. Results A total of 424 ART-naïve participants were enrolled at 33 sites in six continents; mean (SD) age was 34 (10.1) years, 79.0% were nonwhite, 26.0% were women, and 12.5% had a body mass index (BMI) <20 kg/m2. Mean (SD) Z-scores were -0.41 (0.94) at the spine and -0.36 (0.88) for total hip; 1.9% had osteoporosis and 35.1% had low BMD (hip or spine T-score <-1.0). Factors independently associated with lower BMD at the hip and spine were female sex, Latino/Hispanic ethnicity, lower BMI and higher estimated glomerular filtration rate. Longer time since HIV diagnosis was associated with lower hip BMD. Current or nadir CD4 cell counts, and HIV viral load were not associated with BMD. Conclusions In this geographically and racially diverse population of ART-naïve adults with normal CD4 cell counts, low BMD was common, but osteoporosis was rare. Lower BMD was significantly associated with traditional risk factors but not with CD4 cell count or viral load. PMID:25711332

  2. Remune trial will stop; new trials planned.

    PubMed

    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. PMID:11366461

  3. Teaching Drama Via Trials.

    ERIC Educational Resources Information Center

    Mansour, Wisam

    1998-01-01

    Suggests using a court trial as an activity for teaching drama to English-as-a-foreign-language (EFL) students. Describes use of a court trial for teaching Macbeth to EFL students in Jordan. (Author/VWL)

  4. Research Areas: Clinical Trials

    Cancer.gov

    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.

  5. Research Areas - Clinical Trials

    Cancer.gov

    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.

  6. ClinicalTrials.gov

    MedlinePlus

    ... Health ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of ... This Site ClinicalTrials.gov Background About the Results Database History, Policies, and Laws Media/Press Resources Linking ...

  7. Hepatitis C: Clinical Trials

    MedlinePlus

    ... and Public Home » Hepatitis C » Treatment Decisions Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... can I find out about participating in a hepatitis C clinical trial? Many trials are being conducted ...

  8. Effect of Educational Outreach Timing and Duration on Facility Performance for Infectious Disease Care in Uganda: A Trial with Pre-Post and Cluster Randomized Controlled Components

    PubMed Central

    Burnett, Sarah M.; Mbonye, Martin K.; Naikoba, Sarah; Zawedde-Muyanja, Stella; Kinoti, Stephen N.; Ronald, Allan; Rubashembusya, Timothy; Willis, Kelly S.; Colebunders, Robert; Manabe, Yukari C.; Weaver, Marcia R.

    2015-01-01

    Background Classroom-based learning is often insufficient to ensure high quality care and application of health care guidelines. Educational outreach is garnering attention as a supplemental method to enhance health care worker capacity, yet there is little information about the timing and duration required to improve facility performance. We sought to evaluate the effects of an infectious disease training program followed by either immediate or delayed on-site support (OSS), an educational outreach approach, on nine facility performance indicators for emergency triage, assessment, and treatment; malaria; and pneumonia. We also compared the effects of nine monthly OSS visits to extended OSS, with three additional visits over six months. Methods This study was conducted at 36 health facilities in Uganda, covering 1,275,960 outpatient visits over 23 months. From April 2010 to December 2010, 36 sites received infectious disease training; 18 randomly selected sites in arm A received nine monthly OSS visits (immediate OSS) and 18 sites in arm B did not. From March 2011 to September 2011, arm A sites received three additional visits every two months (extended OSS), while the arm B sites received eight monthly OSS visits (delayed OSS). We compared the combined effect of training and delayed OSS to training followed by immediate OSS to determine the effect of delaying OSS implementation by nine months. We also compared facility performance in arm A during the extended OSS to immediate OSS to examine the effect of additional, less frequent OSS. Results Delayed OSS, when combined with training, was associated with significant pre/post improvements in four indicators: outpatients triaged (44% vs. 87%, aRR = 1.54, 99% CI = 1.11, 2.15); emergency and priority patients admitted, detained, or referred (16% vs. 31%, aRR = 1.74, 99% CI = 1.10, 2.75); patients with a negative malaria test result prescribed an antimalarial (53% vs. 34%, aRR = 0.67, 99% CI = 0.55, 0.82); and pneumonia

  9. Does an L-glutamine-containing, Glucose-free, Oral Rehydration Solution Reduce Stool Output and Time to Rehydrate in Children with Acute Diarrhoea? A Double-blind Randomized Clinical Trial

    PubMed Central

    Gutiérrez, Claudia; Villa, Sofía; Mota, Felipe R.; Calva, Juan J.

    2007-01-01

    This study assessed whether an oral rehydration solution (ORS) in which glucose is replaced by L-glutamine (L-glutamine ORS) is more effective than the standard glucose-based rehydration solution recommended by the World Health Organization (WHO-ORS) in reducing the stool volume and time to rehydrate in acute diarrhoea. In a double-blind, randomized controlled trial in a Mexican hospital, 147 dehydrated children, aged 1–60 month(s), were assigned either to the WHO-ORS (74 children), or to the L-glutamine ORS (73 children) and followed until successful rehydration. There were no significant differences between the groups in stool output during the first four hours, time to successful rehydration, volume of ORS required for rehydration, urinary output, and vomiting. This was independent of rotavirus-associated infection. An L-glutamine-containing glucose-free ORS seems not to offer greater clinical benefit than the standard WHO-ORS in mildly-to-moderately-dehydrated children with acute non-cholera diarrhoea. PMID:18330060

  10. Paperless clinical trials: Myth or reality?

    PubMed

    Gupta, Sandeep K

    2015-01-01

    There is an urgent need to expedite the time-to-market for new drugs and to make the approval process simpler. But clinical trials are a complex process and the increased complexity leads to decreased efficiency. Hence, pharmaceutical organizations want to move toward a more technology-driven clinical trial process for recording, analyzing, reporting, archiving, etc., In recent times, the progress has certainly been made in developing paperless systems that improve data capture and management. The adaptation of paperless processes may require major changes to existing procedures. But this is in the best interests of these organizations to remain competitive because a paperless clinical trial would lead to a consistent and streamlined framework. Moreover, all major regulatory authorities also advocate adoption of paperless trial. But challenges still remain toward implementation of paperless clinical trial process. PMID:26288464

  11. Utah Mock Trial Competition.

    ERIC Educational Resources Information Center

    Oswald, Linda, Comp.

    Background materials and guidelines for secondary students and educators in Utah who wish to participate in the state-wide mock trial competition are provided. Many parts of the publication can be used by educators in other states who are using mock trials in their classrooms or who are developing a state-wide mock trial competition. The manual…

  12. Salem Witch Trials.

    ERIC Educational Resources Information Center

    Ray, Benjamin

    2003-01-01

    Presents a lesson plan that focuses on the Salem (Massachusetts) witchcraft trials. Explains that the first section of the lesson has students learn about the trials as described in the court records. The second section asks students to interpret various images of the trials. (CMK)

  13. Publication and non-publication of drug trial results: a 10-year cohort of trials in Norwegian general practice

    PubMed Central

    Brænd, Anja Maria; Straand, Jørund; Jakobsen, Rune Bruhn; Klovning, Atle

    2016-01-01

    Objectives Previously, we identified a 10-year cohort of protocols from applications to the Norwegian Medicines Agency 1998–2007, consisting of 196 drug trials in general practice. The aim of this study was to examine whether trial results were published and whether trial funding and conflicts of interest were reported. Design Cohort study of trials with systematic searches for published results. Setting Clinical drug trials in Norwegian general practice. Methods We performed systematic literature searches of MEDLINE, Embase and CENTRAL to identify publications originating from each trial using characteristics such as test drug, comparator and patient groups as search terms. When no publication was identified, we contacted trial sponsors for information regarding trial completion and reference to any publications. Main outcome measures We determined the frequency of publication of trial results and trial characteristics associated with publication of results. Results Of the 196 trials, 5 were never started. Of the remaining 191 trials, 71% had results published in a journal, 11% had results publicly available elsewhere and 18% of trials had no results available. Publication was more common among trials with an active comparator drug (χ2 test, p=0.040), with a larger number of patients (total sample size≥median, p=0.010) and with a longer trial period (duration≥median, p=0.025). Trial funding was reported in 85% of publications and increased over time, as did reporting of conflicts of interest among authors. Among the 134 main journal articles from the trials, 60% presented statistically significant results for the investigational drug, and the conclusion of the article was favourable towards the test drug in 78% of papers. Conclusions We did not identify any journal publication of results for 29% of the general practice drug trials. Trials with an active comparator, larger and longer trials were more likely to be published. PMID:27067893

  14. Effect of different agronomic management practices on greenhouse gas emissions and nutrient cycling in a long-term field trial

    NASA Astrophysics Data System (ADS)

    Koal, Philipp; Schilling, Rolf; Gerl, Georg; Pritsch, Karin; Munch, Jean Charles

    2015-04-01

    In order to achieve a reduction of greenhouse gas emissions, modern agronomic management practices need to be established. Therefore, to assess the effect of different farming practices on greenhouse gas emissions, reliable data are required. The experiment covers and compares two main aspects of agricultural management for a better implementation of sustainable land use. The focus lies on the determination and interpretation of greenhouse gas emissions, however, regarding in each case a different agricultural management system, namely an organic farming system and an integrated farming system where the effect of diverse tillage systems and fertilisation practices are observed. In addition, with analysis of the alterable biological, physical and chemical soil properties a link between the impact of different management systems on greenhouse gas emissions and the observed cycle of matter in the soil, especially the nitrogen and carbon cycle, will be enabled. Measurements have been carried out on long-term field trials at the Research Farm Scheyern located in a Tertiary hilly landscape approximately 40 km north of Munich (South Germany). The long-term field trials of the organic and integrated farming system were started in 1992. Since then parcels of land (each around 0.2-0.4 ha) with a particular interior plot set-up have been conducted with the same crop rotation, tillage and fertilisation practice referring to organic and integrated farming management. Thus, the management impacts on the soil of more than 20 years are being examined. Fluxes of CH4, N2O and CO2 have been monitored since 2007 for the integrated farming system trial and since 2012 for the organic farming system trial using an automated system which consists of chambers (0.4 m2 area) with a motor-driven lid, an automated gas sampling unit, an on-line gas chromatographic analysis system, and a control and data logging unit. Precipitation and temperature data have been observed for each experimental

  15. Time to Definitive Health-Related Quality of Life Score Deterioration in Patients with Resectable Metastatic Colorectal Cancer Treated with FOLFOX4 versus Sequential Dose-Dense FOLFOX7 followed by FOLFIRI: The MIROX Randomized Phase III Trial

    PubMed Central

    Hamidou, Zeinab; Chibaudel, Benoist; Hebbar, Mohamed; Hug de Larauze, Marine; André, Thierry; Louvet, Christophe; Brusquant, David; Garcia-Larnicol, Marie-Line; de Gramont, Aimery; Bonnetain, Franck

    2016-01-01

    Purpose We previously showed that a sequential chemotherapy with dose-dense oxaliplatin (FOLFOX7) and irinotecan (FOLFIRI; irinotecan plus 5-fluorouracil/leucovorin) is not superior to FOLFOX4 in patients at advanced stage of colorectal cancer with liver metastases. Here we aimed to determine whether time to health-related quality of life (HRQoL) score definitive deterioration (TUDD) differs by study arm. Methods HRQoL was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 at baseline and every 4 cycles until the end of the study or death. Functional scale, symptom scale, global health status, and financial difficulties were analyzed. The TUDD was defined as the time interval between randomization and the first decrease in HRQoL score ≥ 5-point with no further improvement in HRQoL score ≥ 5 points or any further HRQoL data. TUDD was estimated using the Kaplan-Meier method and the long-rank test. Cox regression analyses were used to identify HRQoL items influencing TUDD. Sensitivity analyses were done using a multiple imputation method and different definitions of TUDD. Results Of the 284 patients, 171 (60.2%) completed HRQoL questionnaires. Cox multivariate analysis showed no statistically significant difference in TUDD for most of the QLQ-C30 scales between treatments. Patients with dyspnea and those without symptoms at baseline had a significantly longer TUDD when there was a delay >12 months between diagnosis of the primary tumor and metastases (HR 0.48 [0.26–0.89]) and when there was diarrhea (HR 0.59 [0.36–0.96]), respectively. Conclusion This study shows that TUDD does not differ significantly according to type of treatment. The TUDD method produces meaningful longitudinal HRQoL results that may facilitate effective clinical decision making in patients with mCRC. Trial Registration ClinicalTrials.gov NCT00268398 PMID:27310205

  16. How experimental trial context affects perceptual categorization

    PubMed Central

    Palmeri, Thomas J.; Mack, Michael L.

    2015-01-01

    To understand object categorization, participants are tested in experiments often quite different from how people experience object categories in the real world. Learning and knowledge of categories is measured in discrete experimental trials, those trials may or may not provide feedback, trials appear one after another, after some fixed inter-trial interval, with hundreds of trials in a row, within experimental blocks with some structure dictated by the experimental design. In the real world, outside of certain educational and vocational contexts, opportunities to learn and use categories are intermixed over time with a whole multitude of intervening experiences. It is clear from any elementary understanding of human cognition that sequential effects matter, yet this understanding is often ignored, and categorization trials are often instead treated as independent events, immune to local trial context. In this perspective, we use some of our work to illustrate some of the consequences of the fact that categorization experiments have a particular trial structure. Experimental trial context can affect performance in category learning and categorization experiments in ways that can profoundly affect theoretical conclusions. PMID:25745412

  17. Clinical Trials in Vision Research

    MedlinePlus

    ... Clinical Trials in Vision Research Clinical Trials in Vision Research Clinical studies depend on people who volunteer. ... about the treatment. How are clinical trials in vision different from other clinical trials? Eyes are one ...

  18. AIDS Clinical Trials Group Network

    MedlinePlus

    ... Center Statistical and Data Management Center Glossaries Sites Clinical Trials About the Trial Process Trials Open to Enrollment Recent Study Results Access to Published Data Clinical Trials Resources Committees Executive Scientific Resource Community General Information ...

  19. A Comparison of In-Context and Traditional Instructional Approaches: Total Task, Single Trial versus Backward Chaining, Multiple Trials.

    ERIC Educational Resources Information Center

    Kayser, Joan E.; And Others

    1986-01-01

    Total task (single trial instruction) and backward chaining (multiple trials instruction) were used to teach eight children with severe handicaps. Total task, single trial instruction resulted in superior acquisition of independent steps in the training setting for three students. In all cases, instructional time was substantially less for total…

  20. Time course of soil carbon storage, 15N and radiocarbon signature in top- and subsoil of a 60-years agricultural field trial - indications for compensating effects of carbon input and turnover

    NASA Astrophysics Data System (ADS)

    Leifeld, Jens; Conen, Franz; Oberholzer, Hans Rudolf; Jochen, Mayer

    2014-05-01

    Soil carbon dynamics are controlled by the delicate balance between carbon inputs and outputs which both are co-regulated by land use and management (LUM) as important anthropogenic drivers. Upon land use change to cropland carbon stocks generally tend to decline but often the contribution of two opposing factors, namely changes in input and decomposition rates, to soil carbon stock changes is indistinguishable. Here we report on an ongoing cropland experiment in Zurich, Switzerland, named ZOFE (Zurich Organic Fertilization Experiment), established on former grassland in 1949. ZOFE encompasses a range of mineral and organic fertilization practices and a zero fertilizer treatment as control. The experiment has a block design with five replicates per treatment. We make use of productivity and fertilization gradients in selected treatments of the ZOFE trial to evaluate how low or high inputs (induced by differential yields and organic fertilization) may affect soil organic carbon storage and transformation. For the most recent sampling that also included subsoil down to 0.9 m, all properties were measured for every single replicate. Topsoil carbon storage declined after grassland conversion at rates of c. 0.2 t C ha-1 a-1, particularly in treatments with mineral fertilizer and high yields, and without fertilization and low yields. Organic matter amendments such as manure or compost could partially offset but not fully compensate some of the topsoil carbon loss. Over time the soil's delta 15N signature declined as well, probably due to increased atmospheric nitrogen deposition. It increased from the top- to the subsoil, indicating increasing microbial transformation, particularly with manure added. The soil's radiocarbon signature revealed distinct bomb peak patterns in all treatments but only in the topsoil. The 14C data confirmed that with higher productivity more recent organic matter was incorporated, both in top and subsoil. Because, in contrast to topsoil

  1. Marketing and clinical trials: a case study

    PubMed Central

    Francis, David; Roberts, Ian; Elbourne, Diana R; Shakur, Haleema; Knight, Rosemary C; Garcia, Jo; Snowdon, Claire; Entwistle, Vikki A; McDonald, Alison M; Grant, Adrian M; Campbell, Marion K

    2007-01-01

    Background Publicly funded clinical trials require a substantial commitment of time and money. To ensure that sufficient numbers of patients are recruited it is essential that they address important questions in a rigorous manner and are managed well, adopting effective marketing strategies. Methods Using methods of analysis drawn from management studies, this paper presents a structured assessment framework or reference model, derived from a case analysis of the MRC's CRASH trial, of 12 factors that may affect the success of the marketing and sales activities associated with clinical trials. Results The case study demonstrates that trials need various categories of people to buy in – hence, to be successful, trialists must embrace marketing strategies to some extent. Conclusion The performance of future clinical trials could be enhanced if trialists routinely considered these factors. PMID:18028537

  2. A multicenter prospective trial to asses a new real-time polymerase chain reaction for detection of Treponema pallidum, herpes simplex-1/2 and Haemophilus ducreyi in genital, anal and oropharyngeal ulcers.

    PubMed

    Glatz, M; Juricevic, N; Altwegg, M; Bruisten, S; Komericki, P; Lautenschlager, S; Weber, R; Bosshard, P P

    2014-12-01

    Treponema pallidum, herpes simplex virus types 1 or 2 (HSV-1/2) and Haemophilus ducreyi are sexually transmitted pathogens that can cause genital, anal and oropharyngeal ulcers. Laboratory evaluation of these pathogens in ulcers requires different types of specimens and tests, increasing the risk of improper specimen handling and time lapse until analysis. We sought to develop a new real-time PCR (TP-HD-HSV1/2 PCR) to facilitate the detection of T. pallidum, HSV-1/2 and H. ducreyi in ulcers. The TP-HD-HSV1/2 PCR was tested (i) in a retrospective study on 193 specimens of various clinical origin and (ii) in a prospective study on 36 patients with genital, anal or oropharyngeal ulcers (ClinicalTrials.gov # NCT01688258). The results of the TP-HD-HSV1/2 PCR were compared with standard diagnostic methods (T. pallidum: serology, dark field microscopy; HSV-1/2: PCR; H. ducreyi: cultivation). Sensitivity and specificity of the TP-HD-HSV1/2 PCR for T. pallidum were both 100%, for HSV-1 100% and 98%, and for HSV-2 100% and 98%, respectively. T. pallidum and HSV-1/2 were detected in 53% and 22% of patients in the prospective study; H. ducreyi was not detected. In the prospective study, 5/19 (26%) specimens were true positive for T. pallidum in the TP-HD-HSV1/2 PCR but non-reactive in the VDRL. The TP-HD-HSV1/2 PCR is sensitive and specific for the detection of T. pallidum and HSV-1/2 in routine clinical practice and it appears superior to serology in early T. pallidum infections. PMID:24909546

  3. Design of clinical trials.

    PubMed

    Rollo, David; Machado, Sanjay; Ceschin, Mauro

    2010-09-01

    Clinical trial design for nuclear medicine diagnostic imaging radiopharmaceuticals must include a design for preclinical safety studies. These studies should establish that the investigational product (IP) does not have a toxic effect. As a further requirement, radiopharmaceutical clinical trials include a human study (phase 1) that provides biodistribution, pharmacokinetics, and radiation dosimetry information. These studies demonstrate to the Food and Drug Administration that the IP either meets or exceeds the toxicology and radiation exposure safety limits. Satisfying this requirement can result in the Food and Drug Administration approving the performance of late-phase (phase 2/3) clinical trials that are designed to validate the clinical efficacy of the diagnostic imaging agent in patients who have a confirmed diagnosis for the intended application. Emphasis is placed on the most typical trial design for diagnostic imaging agents that use a comparator to demonstrate that the new IP is similar in efficacy to an established standard comparator. Such trials are called equivalence, or noninferiority, trials that attempt to show that the new IP is not less effective than the comparator by more than a statistically defined amount. Importantly, the trial design must not inappropriately favor one diagnostic imaging agent over the other. Bias is avoided by the use of a core laboratory with expert physicians who are not involved in the trial for interpreting and objectively scoring the image sets obtained at the clinical trial sites. Clinical trial design must also follow Good Clinical Practice (GCP) guidelines. GCP stipulates the clinical trial process, including protocol and Case Report Form design, analyses planning, as well as analyzing and preparing interim and final clinical trial/study reports. PMID:20674592

  4. COMPETING COMMITMENTS in CLINICAL TRIALS

    PubMed Central

    Lidz, Charles W.; Appelbaum, Paul S.; Joffe, Steven; Albert, Karen; Rosenbaum, Jill; Simon, Lorna

    2013-01-01

    Most discussion about clinical care in clinical trials has concerned whether subjects’ care may be compromised by research procedures. The possibility that clinical researchers might give priority to helping their “patients” even if that required deviating from the imperatives of the research protocol largely has been ignored. We conducted an on-line survey with clinical researchers, including physicians, research nurses and other research staff, to assess the ways and frequency with which clinical trials may be at risk for being compromised by clinical researchers’ attempting to address the clinical needs of subjects. The survey covered recruitment, clinical management while in the trial, and termination decisions. It produced a 72.0% response rate. Over 20% of respondents agreed that researchers should deviate from the protocol to improve subjects’ care; 28% reported that medications restricted by the protocol were given; 21% reported that subjects who were not eligible had been recruited; and 9% said subjects had been retained in a trial despite meeting termination criteria. Some respondents reported that these deviations from the protocol happened many times. The ramifications of these findings are discussed. PMID:19873835

  5. Clinical Trials For Cytoprotection In Stroke

    PubMed Central

    Labiche, Lise A.; Grotta, James C.

    2004-01-01

    Summary: To date, many cytoprotective drugs have reached the stage of pivotal phase 3 efficacy trials in acute stroke patients. (Table 1) Unfortunately, throughout the neuroprotective literature, the phrase “failure to demonstrate efficacy” prevails as a common thread among the many neutral or negative trials, despite the largely encouraging results encountered in preclinical studies. The reasons for this discrepancy are multiple, and have been discussed by Dr. Zivin in his review. Many of the recent trials have addressed deficiencies of the previous ones with more rigorous trial design, including more specific patient selection criteria (ensure homogeneity of stroke location and severity), stratified randomization algorithms (time-to-treat), narrowed therapeutic time-window and pharmacokinetic monitoring. Current trials have also incorporated biologic surrogate markers of toxicity and outcome such as drug levels and neuroimaging. Lastly, multi-modal therapies and coupled cytoprotection/reperfusion strategies are being investigated to optimize tissue salvage. This review will focus on individual therapeutic strategies and we will emphasize what we have learned from these trials both in terms of trial design and the biologic effect (or lack thereof) of these agents. PMID:15717007

  6. Does offering HIV testing at the time of blood donation reduce transfusion-transmission risk and increase disclosure counseling? Results of a randomized controlled trial, São Paulo, Brazil

    PubMed Central

    Goncalez, Thelma T.; Blatyta, Paula F.; Santos, Fernanda M.; Montebello, Sandra; Esposti, Sandra P.D.; Hangai, Fatima N.; Salles, Nanci A.; Mendrone, Alfredo; Truong, Hong-Ha M.; Sabino, Ester C.; McFarland, Willi

    2016-01-01

    Background In a randomized controlled trial (RCT) in a blood bank in São Paulo, we tested the hypotheses that offering client-centered HIV counseling and testing to blood donors would: 1) reduce the risk of HIV contamination in the blood supply by diverting higher risk, test-seeking donors away from donation, and 2) increase return for results and referrals to care. Study Design and Methods We randomly selected weeks between August, 2012 and May, 2013 when donors were offered HIV counseling and testing (N=6,298), leaving usual procedure weeks as control (N=5,569). Results Few candidate donors chose HIV testing (N=81, 1.3%). There was no significant difference in HSV-2 prevalence (a marker of sexual risk) among donors during intervention weeks compared to control (10.4% vs 11.1%, p=0.245). No donor choosing testing was HIV-infected, and there was no difference in HSV-2 prevalence between testers and donors (9.9% vs. 10.4%, p=0.887). Returning for positive results did not differ between testers and donors (3 of 3 vs. 58 of 80, p=0.386). A higher proportion of donors acknowledged that HIV testing was a strong motivation to donate during intervention weeks compared to control (2.6% vs. 2.0%, p=0.032). Conclusion The evidence of our RCT is that offering HIV counseling and testing at the time of donation would not change the risk of contamination in the blood supply, nor improve results disclosure and referral to care. PMID:25646883

  7. CLINICAL TRIALS.GOV

    EPA Science Inventory

    ClinicalTrials.gov provides patients, family members, health care professionals, and members of the public easy access to information on clinical trials for a wide range of diseases and conditions. The U.S. National Institutes of Health (NIH), through its National Library of Medi...

  8. Towards the establishment of a consensus real-time qPCR to monitor Trypanosoma cruzi parasitemia in patients with chronic Chagas disease cardiomyopathy: a substudy from the BENEFIT trial.

    PubMed

    Moreira, Otacilio C; Ramírez, Juan David; Velázquez, Elsa; Melo, Myllena F A Dias; Lima-Ferreira, Carolina; Guhl, Felipe; Sosa-Estani, Sergio; Marin-Neto, Jose Antonio; Morillo, Carlos A; Britto, Constança

    2013-01-01

    Quantitative real-time PCR (qPCR) is an accurate method to quantify Trypanosoma cruzi DNA and can be used to follow-up parasitemia in Chagas disease (CD) patients undergoing chemotherapy. The Benznidazole Evaluation for Interrupting Trypanosomiasis (BENEFIT) study is an international, multicenter, randomized, double-blinded and placebo-controlled clinical trial to evaluate the efficacy of benznidazole (BZ) treatment in patients with chronic Chagas cardiomyopathy (CCC). One important question to be addressed concerns the effectiveness of BZ in reducing overall parasite load in CCC patients, even in the absence of parasitological cure. This report describes the evaluation of multiple procedures for DNA extraction and qPCR-based protocols aiming to establish a standardized methodology for the absolute quantification of T. cruzi DNA in Guanidine-EDTA blood (GEB) samples. A panel of five primer sets directed to the T. cruzi nuclear satellite DNA repeats (Sat-DNA) and to the minicircle DNA conserved regions (kDNA) was compared in either SYBR Green or TaqMan systems. Standard curve parameters such as, amplification efficiency, coefficient of determination and intercept were evaluated, as well as different procedures to generate standard samples containing pre-established T. cruzi DNA concentration. Initially, each primer set was assayed in a SYBR Green qPCR to estimate parasite load in GEB samples from chronic Chagas disease patients. The results achieved from Bayesian transmutability analysis elected the primer sets Cruzi1/Cruzi2 (p=0.0031) and Diaz7/Diaz8 (p=0.0023) coupled to the QIAamp DNA Kit extraction protocol (silica gel column), as the most suitable for monitoring parasitemia in these patients. Comparison between the parasite burden of 150 GEB samples of BENEFIT patients from Argentina, Brazil and Colombia, prior to drug/placebo administration, was performed using Cruzi1/Cruzi2 primers in a SYBR Green approach. The median parasitemia found in patients from

  9. The ethics of clinical trials

    PubMed Central

    Nardini, Cecilia

    2014-01-01

    Over the past decades, randomised controlled trials (RCTs) have prevailed over clinical judgement, case reports, and observational studies and became the gold evidential standard in medicine. Furthermore, during the same time frame, RCTs became a crucial part of the regulatory process whereby a new therapeutic can gain access to the drug market. Today, clinical trials are large and tightly regulated enterprises that have to comply with ethical requirements while maintaining high epistemic standards, a balance that becomes increasingly difficult as the research questions become more sophisticated. In this review, the author will discuss some of the most important ethical issues surrounding RCTs, with an eye to the most recent debates and the context of oncological research in particular. PMID:24482672

  10. The Clinical Trials Transformation Initiative (CTTI).

    PubMed

    Grignolo, Alberto

    2011-01-01

    The Clinical Trials Transformation Initiative (CTTI) is a public-private partnership created in 2007 between the United States Food and Drug Administration (FDA) and Duke University for the purpose of identifying practices that will increase the quality and efficiency of clinical trials. The initiative was generated from the realization that the clinical trials system in the United States has been suffering as a result of increasingly longer study start-up times, slowing enrollment of patients into trials, increasing clinical trial costs, and declining investigator interest in participating in clinical trials. Although CTTI was created to address a crisis for US clinical research, it seeks to identify practice improvements that can be applied internationally, and is therefore engaging international collaborators with international efforts that have similar objectives. CTTI's approach is to involve all sectors in the selection, conduct, and interpretation of its projects; to keep the dialogue open across sectors; to provide evidence that can influence regulatory guidance, and to attempt to create a "level playing field" when recommending change. The hope is that a broad and diverse data-driven discussion of the important issues in clinical trials will lead to meaningful change for the benefit of all concerned, and importantly for patients. PMID:21430332

  11. Improving the operational efficiency of Phase 2 and 3 trials.

    PubMed

    Ganju, Jitendra

    2016-01-01

    The period toward the end of patients' participation in late stage blinded clinical trials is highly resource intensive for the sponsor. Consider first a Phase 3 trial. If the trial is a success, the sponsor has to implement the next steps, which might be filing for approval of the drug with the US Food and Drug Administration (FDA). To shorten the time interval between trial completion and submission of the package to the FDA, sponsors front-load as much work as is possible at risk. The approach is efficient if the trial succeeds but is inefficient if it fails. For a failed trial, the sponsor is unlikely to proceed with the plan that assumed success. Phase 2 trials are also at risk of being inefficient. Many activities, such as planning for drug interaction studies, thorough QT studies, or site selection for Phase 3 trials, are set in motion prior to completion of the Phase 2 trial. The work going on in parallel is wasted if the trial fails. The proposal to improve the efficiency is to let an independent entity provide the sponsor critical information at an earlier time necessary to reevaluate activities ongoing in parallel and external to the trial. PMID:27439520

  12. The Dynamo Clinical Trial

    NASA Astrophysics Data System (ADS)

    Ayres, Thomas R.

    2016-04-01

    The Dynamo Clinical Trial evaluates long-term stellar magnetic health through periodic X-ray examinations (by the Chandra Observatory). So far, there are only three subjects enrolled in the DTC: Alpha Centauri A (a solar-like G dwarf), Alpha Cen B (an early K dwarf, more active than the Sun), and Alpha Canis Majoris A (Procyon, a mid-F subgiant similar in activity to the Sun). Of these, Procyon is a new candidate, so it is too early to judge how it will fare. Of the other two, Alpha Cen B has responded well, with a steady magnetic heartbeat of about 8 years duration. The sickest of the bunch, Alpha Cen A, was in magnetic cardiac arrest during 2005-2010, but has begun responding to treatment in recent years, and seems to be successfully cycling again, perhaps achieving a new peak of magnetic health in the 2016 time frame. If this is the case, it has been 20 years since A's last healthful peak, significantly longer than the middle-aged Sun's 11-year magnetic heartbeat, but perhaps in line with Alpha Cen A's more senescent state (in terms of "relative evolutionary age," apparently an important driver of activity). (By the way, don't miss the exciting movie of the Alpha Cen stars' 20-year X-ray dance.)

  13. Accurate Fiber Length Measurement Using Time-of-Flight Technique

    NASA Astrophysics Data System (ADS)

    Terra, Osama; Hussein, Hatem

    2016-06-01

    Fiber artifacts of very well-measured length are required for the calibration of optical time domain reflectometers (OTDR). In this paper accurate length measurement of different fiber lengths using the time-of-flight technique is performed. A setup is proposed to measure accurately lengths from 1 to 40 km at 1,550 and 1,310 nm using high-speed electro-optic modulator and photodetector. This setup offers traceability to the SI unit of time, the second (and hence to meter by definition), by locking the time interval counter to the Global Positioning System (GPS)-disciplined quartz oscillator. Additionally, the length of a recirculating loop artifact is measured and compared with the measurement made for the same fiber by the National Physical Laboratory of United Kingdom (NPL). Finally, a method is proposed to relatively correct the fiber refractive index to allow accurate fiber length measurement.

  14. Ongoing EEG Phase as a Trial-by-Trial Predictor of Perceptual and Attentional Variability

    PubMed Central

    VanRullen, R.; Busch, N. A.; Drewes, J.; Dubois, Julien

    2011-01-01

    Even in well-controlled laboratory environments, apparently identical repetitions of an experimental trial can give rise to highly variable perceptual outcomes and behavioral responses. This variability is generally discarded as a reflection of intrinsic noise in neuronal systems. However, part of this variability may be accounted for by trial-by-trial fluctuations of the phase of ongoing oscillations at the moment of stimulus presentation. For example, the phase of an electro-encephalogram (EEG) oscillation reflecting the rapid waxing and waning of sustained attention can predict the perception of a subsequent visual stimulus at threshold. Similar ongoing periodicities account for a portion of the trial-by-trial variability of visual reaction times. We review the available experimental evidence linking ongoing EEG phase to perceptual and attentional variability, and the corresponding methodology. We propose future tests of this relation, and discuss the theoretical implications for understanding the neuronal dynamics of sensory perception. PMID:21716580

  15. Effect of end-tidal CO2 clamping on cerebrovascular function, oxygenation, and performance during 15-km time trial cycling in severe normobaric hypoxia: the role of cerebral O2 delivery.

    PubMed

    Fan, Jui-Lin; Bourdillon, Nicolas; Kayser, Bengt

    2013-08-01

    During heavy exercise, hyperventilation-induced hypocapnia leads to cerebral vasoconstriction, resulting in a reduction in cerebral blood flow (CBF). A reduction in CBF would impair cerebral O2 delivery and potentially account for reduced exercise performance in hypoxia. We tested the hypothesis that end-tidal Pco2 (PETCO2) clamping in hypoxic exercise would prevent the hypocapnia-induced reduction in CBF during heavy exercise, thus improving exercise performance. We measured PETCO2, middle cerebral artery velocity (MCAv; index of CBF), prefrontal cerebral cortex oxygenation (cerebral O2Hb; index of cerebral oxygenation), cerebral O2 delivery (DO2), and leg muscle oxygenation (muscle O2Hb) in 10 healthy men (age 27 ± 7 years; VO2max 63.3 ± 6.6 mL/kg/min; mean ± SD) during simulated 15-km time trial cycling (TT) in normoxia and hypoxia (FIO2 = 0.10) with and without CO2 clamping. During exercise, hypoxia elevated MCAv and lowered cerebral O2Hb, cerebral DO2, and muscle O2Hb (P < 0.001). CO2 clamping elevated PETCO2 and MCAv during exercise in both normoxic and hypoxic conditions (P < 0.001 and P = 0.024), but had no effect on either cerebral and muscle O2Hb (P = 0.118 and P = 0.124). Nevertheless, CO2 clamping elevated cerebral DO2 during TT in both normoxic and hypoxic conditions (P < 0.001). CO2 clamping restored cerebral DO2 to normoxic values during TT in hypoxia and tended to have a greater effect on TT performance in hypoxia compared to normoxia (P = 0.097). However, post hoc analysis revealed no effect of CO2 clamping on TT performance either in normoxia (P = 0.588) or in hypoxia (P = 0.108). Our findings confirm that the hyperventilation-induced hypocapnia and the subsequent drop in cerebral oxygenation are unlikely to be the cause of the reduced endurance exercise performance in hypoxia. PMID:24303142

  16. Effect of end-tidal CO2 clamping on cerebrovascular function, oxygenation, and performance during 15-km time trial cycling in severe normobaric hypoxia: the role of cerebral O2 delivery

    PubMed Central

    Fan, Jui-Lin; Bourdillon, Nicolas; Kayser, Bengt

    2013-01-01

    During heavy exercise, hyperventilation-induced hypocapnia leads to cerebral vasoconstriction, resulting in a reduction in cerebral blood flow (CBF). A reduction in CBF would impair cerebral O2 delivery and potentially account for reduced exercise performance in hypoxia. We tested the hypothesis that end-tidal Pco2 (PETCO2) clamping in hypoxic exercise would prevent the hypocapnia-induced reduction in CBF during heavy exercise, thus improving exercise performance. We measured PETCO2, middle cerebral artery velocity (MCAv; index of CBF), prefrontal cerebral cortex oxygenation (cerebral O2Hb; index of cerebral oxygenation), cerebral O2 delivery (DO2), and leg muscle oxygenation (muscle O2Hb) in 10 healthy men (age 27 ± 7 years; VO2max 63.3 ± 6.6 mL/kg/min; mean ± SD) during simulated 15-km time trial cycling (TT) in normoxia and hypoxia (FIO2 = 0.10) with and without CO2 clamping. During exercise, hypoxia elevated MCAv and lowered cerebral O2Hb, cerebral DO2, and muscle O2Hb (P < 0.001). CO2 clamping elevated PETCO2 and MCAv during exercise in both normoxic and hypoxic conditions (P < 0.001 and P = 0.024), but had no effect on either cerebral and muscle O2Hb (P = 0.118 and P = 0.124). Nevertheless, CO2 clamping elevated cerebral DO2 during TT in both normoxic and hypoxic conditions (P < 0.001). CO2 clamping restored cerebral DO2 to normoxic values during TT in hypoxia and tended to have a greater effect on TT performance in hypoxia compared to normoxia (P = 0.097). However, post hoc analysis revealed no effect of CO2 clamping on TT performance either in normoxia (P = 0.588) or in hypoxia (P = 0.108). Our findings confirm that the hyperventilation-induced hypocapnia and the subsequent drop in cerebral oxygenation are unlikely to be the cause of the reduced endurance exercise performance in hypoxia. PMID:24303142

  17. Practical Issues when Planning for Field Trials

    NASA Astrophysics Data System (ADS)

    Andersson, Susanne; Andersson, Anna-Lena

    This chapter is written from a test site leader perspective and describes the role of planning and timing of field trials when testing technical solutions, which could enable people with dementia to live a more independent life. The chapter is based on experiences from setting up the first and second field trials in the three test sites of the COGKNOW project. The intention is to point out some key issues that are important in preparation and planning of a field trial. The chapter addresses issues in the preparatory, the actual and the post-test phase of the field trial in order to help achieve a high level of success both from a general perspective and with a special focus on people with dementia.

  18. Inept media trials of clinical trials

    PubMed Central

    Ramamurthy, N. V.

    2012-01-01

    The Indian media in general, with the exception of a few domain expert journalists, have failed to comprehend the complexities involved in the clinical trial process. In the run up to the deadline-based coverage of a story, a majority of them fall short in conveying the right perspective to readers, but nevertheless they have been successful in sensationalizing an event in this arena. Possibly by unintended misrepresentation, or mostly out of ignorance of the nuances involved in the clinical trials process, the media has done more harm than good, and got away with it. On the other side, the industry has been reluctant to engage with the media in a meaningful dialog for too long now. It bears not only the consequences of damage to its professional reputation following such reportage, but also the repercussions of unnecessary clampdowns by the regulators. Science journalism in India has yet to rise as a profession. PMID:22701819

  19. Clinical Trials - Participants

    MedlinePlus

    ... participating in was reviewed by an IRB. Further Reading For more information about research protections, see: Office ... data and decide whether the results have medical importance. Results from clinical trials are often published in ...

  20. Polyp Prevention Trial

    Cancer.gov

    The primary objective of the Polyp Prevention Trial (PPT) is to determine whether a low fat, high fiber, high vegetable and fruit eating plan will decrease the recurrence of adenomatous polyps of the large bowel.

  1. Participating in Clinical Trials

    MedlinePlus Videos and Cool Tools

    ... experimental drug, therapy, medical device, lifestyle change, or test will help treat, find, or prevent a disease. A clinical trial may compare experimental products or tests to those already available or may compare existing ...

  2. Anchor Trial Launch

    Cancer.gov

    NCI has launched a multicenter phase III clinical trial called the ANCHOR Study -- Anal Cancer HSIL (High-grade Squamous Intraepithelial Lesion) Outcomes Research Study -- to determine if treatment of HSIL in HIV-infected individuals can prevent anal canc

  3. Central coordination as an alternative for local coordination in a multicenter randomized controlled trial: the FAITH trial experience

    PubMed Central

    2012-01-01

    Background Surgeons in the Netherlands, Canada and the US participate in the FAITH trial (Fixation using Alternative Implants for the Treatment of Hip fractures). Dutch sites are managed and visited by a financed central trial coordinator, whereas most Canadian and US sites have local study coordinators and receive per patient payment. This study was aimed to assess how these different trial management strategies affected trial performance. Methods Details related to obtaining ethics approval, time to trial start-up, inclusion, and percentage completed follow-ups were collected for each trial site and compared. Pre-trial screening data were compared with actual inclusion rates. Results Median trial start-up ranged from 41 days (P25-P75 10-139) in the Netherlands to 232 days (P25-P75 98-423) in Canada (p = 0.027). The inclusion rate was highest in the Netherlands; median 1.03 patients (P25-P75 0.43-2.21) per site per month, representing 34.4% of the total eligible population. It was lowest in Canada; 0.14 inclusions (P25-P75 0.00-0.28), representing 3.9% of eligible patients (p < 0.001). The percentage completed follow-ups was 83% for Canadian and Dutch sites and 70% for US sites (p = 0.217). Conclusions In this trial, a central financed trial coordinator to manage all trial related tasks in participating sites resulted in better trial progression and a similar follow-up. It is therefore a suitable alternative for appointing these tasks to local research assistants. The central coordinator approach can enable smaller regional hospitals to participate in multicenter randomized controlled trials. Circumstances such as available budget, sample size, and geographical area should however be taken into account when choosing a management strategy. Trial Registration ClinicalTrials.gov: NCT00761813 PMID:22225733

  4. Contraceptive development and clinical trials.

    PubMed

    Fraser, I S

    1986-02-01

    This article provides an overview of the contraceptive development process, with particular emphasis on the importance of clinical trials. Development of a new contraceptive drug begins with chemical synthesis of a large number of substances that may have antifertility effects. Before human trials are considered, drugs must undergo a complex process of animal toxicology testing. Such studies assess acute, subacute, and chronic toxicity. Once a drug has passed the initial screening process, human testing must follow a logical sequence of clinical trials: phase I, pharmacology testing; phase II, initial assessment of efficacy, safety, acceptability, and ease of use; phase III, acurate assessment of efficacy, side effects, and reasons for discontinuation under controlled conditions; and phase IV, evaluation of effectiveness under field conditions. When these have been satisfactorily completed, a detailed marketing application must be submitted to the drug regulatory agency in each country. The process of assessment of the application often takes as long as 2 years. Once marketing approval has been received, there is still a need for postmarketing surveillance of the performance of the new contraceptive method. In many cases, a careful program of training is required. Among the research and recording strategies for postmarketing surveillance are voluntary recording of possible adverse reactions, longterm prospective cohort studies, retrospective case-control studies, and registered release. As controls on the safety and performance of new contraceptive methods are being tightened, the time scale and costs of development are increasing. The time from the 1st synthesis of a drug to marketing approval often takes 13-14 years and costs US$25-50 million. Since the patent life of a new substance is limited to 17 years in most countries, pharmaceutical companies have little time to recoup development costs, which has caused fewer new methods to be developed. PMID:3708511

  5. Association of trial registration with the results and conclusions of published trials of new oncology drugs

    PubMed Central

    2009-01-01

    Background Registration of clinical trials has been introduced largely to reduce bias toward statistically significant results in the trial literature. Doubts remain about whether advance registration alone is an adequate measure to reduce selective publication, selective outcome reporting, and biased design. One of the first areas of medicine in which registration was widely adopted was oncology, although the bulk of registered oncology trials remain unpublished. The net influence of registration on the literature remains untested. This study compares the prevalence of favorable results and conclusions among published reports of registered and unregistered randomized controlled trials of new oncology drugs. Methods We conducted a cross-sectional study of published original research articles reporting clinical trials evaluating the efficacy of drugs newly approved for antimalignancy indications by the United States Food and Drug Administration (FDA) from 2000 through 2005. Drugs receiving first-time approval for indications in oncology were identified using the FDA web site and Thomson Centerwatch. Relevant trial reports were identified using PubMed and the Cochrane Library. Evidence of advance trial registration was obtained by a search of clinicaltrials.gov, WHO, ISRCTN, NCI-PDQ trial databases and corporate trial registries, as well as articles themselves. Data on blinding, results for primary outcomes, and author conclusions were extracted independently by two coders. Univariate and multivariate logistic regression identified associations between favorable results and conclusions and independent variables including advance registration, study design characteristics, and industry sponsorship. Results Of 137 original research reports from 115 distinct randomized trials assessing 25 newly approved drugs for treating cancer, the 54 publications describing data from trials registered prior to publication were as likely to report statistically significant efficacy

  6. 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

    PubMed Central

    2012-01-01

    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, stratified by

  7. Are clinical trials really the answer?

    PubMed

    Block, G

    1995-12-01

    It has been asserted that clinical trials hold the answer to questions about the role of nutrients in preventing chronic diseases. This is not the case. Clinical trials give us rigorous answers to restricted questions. Rarely can more than one or two substances be tested, usually at a single dose. Subjects usually have to be persons with precancerous conditions or an extremely high risk of the disease in question. Rarely can any diseases other than the most common ones be studied. Most important, clinical trials test the efficacy of an agent that is administered for a limited time, beginning fairly late in life. Few trials will tell us anything about whether dietary amounts of nutrients might contribute to prevention of long-term chronic diseases. They also tell us nothing about whether agents at high doses might reduce disease risk if taken throughout the lifetime. Furthermore, they tell us nothing about other antioxidants, other combinations, or other doses. Clinical trials were developed for therapeutic situations to determine which treatment was better for curing a specific disease. However, the questions about prevention that are of interest may involve persons with no unusual risk of disease, lifetimes of exposure, enormously complex interactions among nutrients, and the effects of these nutrients on hundreds of often uncommon disease conditions. Clinical trials simply cannot answer these questions. Only a solid examination of the laboratory and epidemiologic evidence can approximate the answers to most of the questions of interest. PMID:7495253

  8. Finding time.

    PubMed

    Killeen, Peter R

    2014-01-01

    We understand time through our models of it. These are typically models of our physical chronometers, which we then project into our subjects. A few of these models of the nature of time and its effects on the behavior of organisms are reviewed. New models, such as thermodynamics and spectral decomposition, are recommended for the potential insights that they afford. In all cases, associations are essential features of timing. To make them, time must be discretized by stimuli such as hours, minutes, conditioned stimuli, trials, and contexts in general. Any one association is seldom completely dominant, but rather shares control through proximity in a multidimensional space, important dimensions of which may include physical space and time as rendered by Fourier transforms. PMID:23973706

  9. What we have learned: the impact of quality from a clinical trials perspective

    PubMed Central

    FitzGerald, T. J.

    2011-01-01

    In this review article we address the radiation oncology process improvements in clinical trials and review how these changes improve the quality for the next generation of trials. In recent years we have progressed from a time of limited data acquisition to the present in which we have real time influence of clinical trials quality. This enables immediate availability of the important elements including staging, eligibility, response and outcome for all trial investigators. Modern informatics platforms are well designed for future adaptive clinical trials. We review what will be needed in the informatics architecture of current and future clinical trials. PMID:22177875

  10. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2005-11-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (Z)-4-Hydroxytamoxifen, [18F]-FPS; Adalimumab, alefacept, alemtuzumab, alfimeprase, aprepitant, aripiprazole, atomoxetine hydrochloride; Belatacept, bortezomib; C340, caspofungin acetate, clazosentan sodium, Cypher; Darbepoetin alfa, DB-289, decitabine, dronedarone hydrochloride, duloxetine hydrochloride; Eletriptan, entecavir, ertapenem sodium, escitalopram oxalate, eszopiclone, etoricoxib; Gaboxadol, gadofosveset sodium, galiximab, gemifloxacin mesilate, glutamine; Human insulin; I-131 ch-TNT-1/B, indiplon, inhaled insulin, isatoribine; L-Arginine hydrochloride, liposomal doxorubicin, lopinavir/ritonavir, lumiracoxib; Magnesium sulfate; Natalizumab; Olmesartan medoxomil, omapatrilat, OncoVEX (GM-CSF); rDNA insulin, rupatadine fumarate; Sorafenib; Tadalafil, teduglutide, temsirolimus, tenofovir disoproxil fumarate, tiotropium bromide; Valdecoxib, vardenafil hydrochloride hydrate. PMID:16357953

  11. A licence to vape: Is it time to trial of a nicotine licensing scheme to allow Australian adults controlled access to electronic cigarettes devices and refill solutions containing nicotine?

    PubMed

    Gartner, Coral; Hall, Wayne

    2015-06-01

    Australia has some of the most restrictive laws concerning use of nicotine in e-cigarettes. The only current legal option for Australians to legally possess and use nicotine for vaping is with a medical prescription and domestic supply is limited to compounding pharmacies that prepare medicines for specific patients. An alternative regulatory option that could be implemented under current drugs and poisons regulations is a 'nicotine licensing' scheme utilising current provisions for 'dangerous poisons'. This commentary discusses how such a scheme could be used to trial access to nicotine solutions for vaping outside of a 'medicines framework' in Australia. PMID:25817484

  12. AVERT2 (a very early rehabilitation trial, a very effective reproductive trigger): retrospective observational analysis of the number of babies born to trial staff

    PubMed Central

    Lindley, Richard I; Lalor, Erin; Ellery, Fiona; Chamberlain, Jan; Van Holsteyn, John; Collier, Janice M; Dewey, Helen M; Parsons, Brooke; Moodie, Marjory; Lennon, Sheila; Donnan, Geoffrey A; Thrift, Amanda G; Churilov, Leonid; Langhorne, Peter

    2015-01-01

    Objective To report the number of participants needed to recruit per baby born to trial staff during AVERT, a large international trial on acute stroke, and to describe trial management consequences. Design Retrospective observational analysis. Setting 56 acute stroke hospitals in eight countries. Participants 1074 trial physiotherapists, nurses, and other clinicians. Outcome measures Number of babies born during trial recruitment per trial participant recruited. Results With 198 site recruitment years and 2104 patients recruited during AVERT, 120 babies were born to trial staff. Births led to an estimated 10% loss in time to achieve recruitment. Parental leave was linked to six trial site closures. The number of participants needed to recruit per baby born was 17.5 (95% confidence interval 14.7 to 21.0); additional trial costs associated with each birth were estimated at 5736 Australian dollars on average. Conclusion The staff absences registered in AVERT owing to parental leave led to delayed trial recruitment and increased costs, and should be considered by trial investigators when planning research and estimating budgets. However, the celebration of new life became a highlight of the annual AVERT collaborators’ meetings and helped maintain a cohesive collaborative group. Trial registration Australian New Zealand Clinical Trials Registry no 12606000185561. Disclaimer Participation in a rehabilitation trial does not guarantee successful reproductive activity. PMID:26658193

  13. 32 CFR 935.111 - New trial.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE TERRITORIAL AND INSULAR REGULATIONS... motion made within a reasonable time after discovery by the moving party of matters constituting the grounds upon which the motion for new trial or vacation of judgment is made....

  14. 32 CFR 935.111 - New trial.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE TERRITORIAL AND INSULAR REGULATIONS... motion made within a reasonable time after discovery by the moving party of matters constituting the grounds upon which the motion for new trial or vacation of judgment is made....

  15. 32 CFR 935.111 - New trial.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE TERRITORIAL AND INSULAR REGULATIONS... motion made within a reasonable time after discovery by the moving party of matters constituting the grounds upon which the motion for new trial or vacation of judgment is made....

  16. EEG activity represents the correctness of perceptual decisions trial-by-trial

    PubMed Central

    Pardo-Vazquez, Jose L.; Padrón, Isabel; Fernández-Rey, José; Acuña, Carlos

    2014-01-01

    Performance monitoring is an executive function, which we depend on for detecting and evaluating the consequences of our behavior. Although event related potentials (ERPs) have revealed the existence of differences after correct and incorrect decisions, it is not known whether there is a trial-by-trial representation of the accuracy of the decision. We recorded the electroencephalographic activity (EEG) while participants performed a perceptual discrimination task, with two levels of difficulty, in which they received immediate feedback. Receiver Operating Characteristic (ROC) analyses were used to reveal two components that convey trial-by-trial representations of the correctness of the decisions. Firstly, the performance monitoring-related negativity (PM-N), a negative deflection whose amplitude is higher (more negative) after incorrect trials. Secondly, the performance monitoring-related positivity (PM-P), a positive deflection whose amplitude is higher after incorrect trials. During the time periods corresponding to these components, trials can be accurately categorized as correct or incorrect by looking at the EEG activity; this categorization is more accurate when based on the PM-P. We further show that the difficulty of the discrimination task has a different effect on each component: after easy trials the latency of the PM-N is shorter and the amplitude of the PM-P is higher than after difficult trials. Consistent with previous interpretations of performance-related ERPs, these results suggest a functional differentiation between these components. The PM-N could be related to an automatic error detection system, responsible for fast behavioral corrections of ongoing actions, while the PM-P could reflect the difference between expected and actual outcomes and be related to long-term changes in the decision process. PMID:24734012

  17. TRIAL BURNS: METHODS PERSPECTIVE

    EPA Science Inventory

    When conducting a trial burn, it is necessary to make a number of measurements in order to adequately define the performance of the incinerator. n addition to flue gas emissions for particulate matter, HCl, and selected organics, it is also necessary to measure selected organics ...

  18. TrialNet

    MedlinePlus

    ... Canada, Finland, United Kingdom, Italy, Germany, Australia, and New Zealand. This network is dedicated to the study, prevention, and early treatment of type 1 diabetes. Learn More > Visit us on Facebook Follow us on Twitter TrialNet YouTube Channel Department ...

  19. Clinical Trials: CSDRG Overview

    ERIC Educational Resources Information Center

    Logemann, Jeri A.

    2004-01-01

    Recent importance placed upon efficacy research has spawned the development of the Communication Sciences and Disorders Clinical Trials Research Group (CSDRG). This group, funded by the National Institutes of Health (NIH), was organized by the American Speech Language and Hearing Association to address the need for more treatment efficacy research…

  20. Hybrid 10 Clinical Trial

    PubMed Central

    Gantz, Bruce J.; Hansen, Marlan R.; Turner, Christopher W.; Oleson, Jacob J.; Reiss, Lina A.; Parkinson, Aaron J.

    2010-01-01

    Acoustic plus electric (electric-acoustic) speech processing has been successful in highlighting the important role of articulation information in consonant recognition in those adults that have profound high-frequency hearing loss at frequencies greater than 1500 Hz and less than 60% discrimination scores. Eighty-seven subjects were enrolled in an adult Hybrid multicenter Food and Drug Administration clinical trial. Immediate hearing preservation was accomplished in 85/87 subjects. Over time (3 months to 5 years), some hearing preservation was maintained in 91% of the group. Combined electric-acoustic processing enabled most of this group of volunteers to gain improved speech understanding, compared to their preoperative hearing, with bilateral hearing aids. Most have preservation of low-frequency acoustic hearing within 15 dB of their preoperative pure tone levels. Those with greater losses (> 30 dB) also benefited from the combination of electric-acoustic speech processing. Postoperatively, in the electric-acoustic processing condition, loss of low-frequency hearing did not correlate with improvements in speech perception scores in quiet. Sixteen subjects were identified as poor performers in that they did not achieve a significant improvement through electric-acoustic processing. A multiple regression analysis determined that 91% of the variance in the poorly performing group can be explained by the preoperative speech recognition score and duration of deafness. Signal-to-noise ratios for speech understanding in noise improved more than 9 dB in some individuals in the electric-acoustic processing condition. The relation between speech understanding in noise thresholds and residual low-frequency acoustic hearing is significant (r = 0.62; p < 0.05). The data suggest that, in general, the advantages gained for speech recognition in noise by preserving residual hearing exist, unless the hearing loss approaches profound levels. Preservation of residual low

  1. Transparency of Outcome Reporting and Trial Registration of Randomized Controlled Trials Published in the Journal of Consulting and Clinical Psychology

    PubMed Central

    Azar, Marleine; Riehm, Kira E.; McKay, Dean; Thombs, Brett D.

    2015-01-01

    Background Confidence that randomized controlled trial (RCT) results accurately reflect intervention effectiveness depends on proper trial conduct and the accuracy and completeness of published trial reports. The Journal of Consulting and Clinical Psychology (JCCP) is the primary trials journal amongst American Psychological Association (APA) journals. The objectives of this study were to review RCTs recently published in JCCP to evaluate (1) adequacy of primary outcome analysis definitions; (2) registration status; and, (3) among registered trials, adequacy of outcome registrations. Additionally, we compared results from JCCP to findings from a recent study of top psychosomatic and behavioral medicine journals. Methods Eligible RCTs were published in JCCP in 2013–2014. For each RCT, two investigators independently extracted data on (1) adequacy of outcome analysis definitions in the published report, (2) whether the RCT was registered prior to enrolling patients, and (3) adequacy of outcome registration. Results Of 70 RCTs reviewed, 12 (17.1%) adequately defined primary or secondary outcome analyses, whereas 58 (82.3%) had multiple primary outcome analyses without statistical adjustment or undefined outcome analyses. There were 39 (55.7%) registered trials. Only two trials registered prior to patient enrollment with a single primary outcome variable and time point of assessment. However, in one of the two trials, registered and published outcomes were discrepant. No studies were adequately registered as per Standard Protocol Items: Recommendation for Interventional Trials guidelines. Compared to psychosomatic and behavioral medicine journals, the proportion of published trials with adequate outcome analysis declarations was significantly lower in JCCP (17.1% versus 32.9%; p = 0.029). The proportion of registered trials in JCCP (55.7%) was comparable to behavioral medicine journals (52.6%; p = 0.709). Conclusions The quality of published outcome analysis

  2. Single-trial detection for intraoperative somatosensory evoked potentials monitoring.

    PubMed

    Hu, L; Zhang, Z G; Liu, H T; Luk, K D K; Hu, Y

    2015-12-01

    Abnormalities of somatosensory evoked potentials (SEPs) provide effective evidence for impairment of the somatosensory system, so that SEPs have been widely used in both clinical diagnosis and intraoperative neurophysiological monitoring. However, due to their low signal-to-noise ratio (SNR), SEPs are generally measured using ensemble averaging across hundreds of trials, thus unavoidably producing a tardiness of SEPs to the potential damages caused by surgical maneuvers and a loss of dynamical information of cortical processing related to somatosensory inputs. Here, we aimed to enhance the SNR of single-trial SEPs using Kalman filtering and time-frequency multiple linear regression (TF-MLR) and measure their single-trial parameters, both in the time domain and in the time-frequency domain. We first showed that, Kalman filtering and TF-MLR can effectively capture the single-trial SEP responses and provide accurate estimates of single-trial SEP parameters in the time domain and time-frequency domain, respectively. Furthermore, we identified significant correlations between the stimulus intensity and a set of indicative single-trial SEP parameters, including the correlation coefficient (between each single-trial SEPs and their average), P37 amplitude, N45 amplitude, P37-N45 amplitude, and phase value (at the zero-crossing points between P37 and N45). Finally, based on each indicative single-trial SEP parameter, we investigated the minimum number of trials required on a single-trial basis to suggest the existence of SEP responses, thus providing important information for fast SEP extraction in intraoperative monitoring. PMID:26557929

  3. Cooperative Group Trials in the Community Setting.

    PubMed

    Lloyd Wade, James; Petrelli, Nicholas J; McCaskill-Stevens, Worta

    2015-10-01

    Over the last 40 years the National Cancer Institute (NCI) has created a vibrant public-private partnership for the implementation of NCI-sponsored cooperative group (Network) clinical trials throughout the United States and Canada. Over these four decades, the cancer clinical trials process has become more complex more precise and more resource intensive. During this same time period, financial resources to support the NCI community research initiative have become more constrained. The newest manifestation of NCI-sponsored community based cancer clinical trial research, known as the National Community Oncology Research Program (NCORP) began initial operation August 1, 2014. We describe several key strategies that community sites may use to not only be successful but to thrive in this new financially austere research environment. PMID:26433550

  4. Quality of clinical trials: A moving target

    PubMed Central

    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

  5. Bibliography of Mock Trial Materials.

    ERIC Educational Resources Information Center

    National Inst. for Citizen Education in the Law, Washington, DC.

    This catalog lists general articles on mock trials, information for arranging mock trial competitions, mock trial problem sets, and video tapes. The problem sets contain introductory material, applicable law, statements of facts, witness statements, and documents. The cases include issues in family, consumer, criminal, and immigration law. Several…

  6. MindTrial: An Intelligent System for Clinical Trials

    PubMed Central

    Lee, Yugyung; Dinakarpandian, Deendayal; Katakam, Nikhilesh; Owens, Dennis

    2010-01-01

    The recruitment of human subjects for clinical trials research is a critically important step in the discovery of new cures for diseases. However, the current recruitment methodologies are inherently inefficient. Considerable resources are expended in efforts to recruit adequate numbers of patient volunteers who meet the inclusion/exclusion criteria for clinical trials. Recruitment is particularly challenging for trials involving vulnerable, psychiatrically disordered groups. We have developed a prototype system, called MindTrial, that is based on an online model to enhance the efficiency and quality of recruitment of patients with psychiatric disorders for clinical research. The intelligent component of the MindTrial system can facilitate highly specific matches between clinical trial criteria and volunteers for self-enrollment of sufficient numbers of patient volunteers. We believe this system is particularly valuable in optimizing recruitment for clinical trial studies for development of new drugs. PMID:21347017

  7. Monitoring data and safety in the WHO Antenatal Care Trial.

    PubMed

    Bergsjø, P; Bréart, G; Morabia, A

    1998-10-01

    A committee to monitor data and safety in a large clinical trial should have members with expertise in biostatistics, epidemiology and the clinical field relevant to the trial. Its mandate should cover both logistics and the safety of study subjects, issues which to some extent overlap. While a steering committee and field staff members ideally should be blinded to the experimental and control arms of a randomised clinical trial, the data and safety monitoring committee (DSMC) should have full access to interim trial data to fulfil its role as watchdog. One initial question to be resolved concerns if and when to advise stopping a trial because of danger to study subjects, or on the other hand obvious benefits, in one trial arm. The DSMC of the WHO Antenatal Care Trial decided not to establish any definite stopping rules before implementation. After a scrutiny of the adopted procedures for data collection and handling, the DSMC received monthly reports of recruitment, and individual summary reports of three adverse events by site and trial arm: maternal deaths, fetal deaths and cases of eclampsia. At the time of writing (December 1997) recruitment to the trial is almost complete, but data collection will continue throughout most of 1998, until every index pregnancy has ended in birth or miscarriage. So far, the balance of untoward events between the intervention and control arms have not given cause for alarm. PMID:9805728

  8. Evidence and Clinical Trials.

    NASA Astrophysics Data System (ADS)

    Goodman, Steven N.

    1989-11-01

    This dissertation explores the use of a mathematical measure of statistical evidence, the log likelihood ratio, in clinical trials. The methods and thinking behind the use of an evidential measure are contrasted with traditional methods of analyzing data, which depend primarily on a p-value as an estimate of the statistical strength of an observed data pattern. It is contended that neither the behavioral dictates of Neyman-Pearson hypothesis testing methods, nor the coherency dictates of Bayesian methods are realistic models on which to base inference. The use of the likelihood alone is applied to four aspects of trial design or conduct: the calculation of sample size, the monitoring of data, testing for the equivalence of two treatments, and meta-analysis--the combining of results from different trials. Finally, a more general model of statistical inference, using belief functions, is used to see if it is possible to separate the assessment of evidence from our background knowledge. It is shown that traditional and Bayesian methods can be modeled as two ends of a continuum of structured background knowledge, methods which summarize evidence at the point of maximum likelihood assuming no structure, and Bayesian methods assuming complete knowledge. Both schools are seen to be missing a concept of ignorance- -uncommitted belief. This concept provides the key to understanding the problem of sampling to a foregone conclusion and the role of frequency properties in statistical inference. The conclusion is that statistical evidence cannot be defined independently of background knowledge, and that frequency properties of an estimator are an indirect measure of uncommitted belief. Several likelihood summaries need to be used in clinical trials, with the quantitative disparity between summaries being an indirect measure of our ignorance. This conclusion is linked with parallel ideas in the philosophy of science and cognitive psychology.

  9. Cluster Randomized Controlled Trial

    PubMed Central

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

    2015-01-01

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

  10. 75 FR 45646 - Design of Clinical Trials of Aerosolized Antimicrobials for the Treatment of Cystic Fibrosis...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-03

    ... clinical trial endpoints to establish efficacy is a major challenge in the design of informative clinical.... The workshop will include discussion of clinical trial endpoints to establish efficacy, such as timing... HUMAN SERVICES Food and Drug Administration Design of Clinical Trials of Aerosolized Antimicrobials...

  11. NATO SOCMET trials

    NASA Astrophysics Data System (ADS)

    Jenden, C. M.

    1993-11-01

    During 1993, Canada, France, Germany and the United Kingdom will be participating in the Smoke and Obscurants Countermeasures Materials Evaluation Tests (SOCMET). The tests will be carried out under the auspices of the NATO Army Armaments Group, AC/225, Panel VI, Sub-Panel 7 whose interests include multispectral smoke screening systems. The tests will comprise two sets of trials; one under cold climate conditions in Quebec, Canada, during February/March 1993 and the other in temperate conditions in Bourges, France during September 1993. This paper provides an insight into the management and aims of SOCMET. The evaluations will be seeking to identify candidate materials which create effective obscurant screens in the visible, infrared and millimetric bands of the electromagnetic spectrum. These materials will be disseminated through a range area dispersal. A key element of the trials will be the evaluation of field test instrumentation which may eventually lead to the development of standardized evaluation techniques. Following the trials, a scientific workshop will be held to review the results. A final report will be presented to NATO which will form the basis of future collaborative developments on multispectral screening systems leading towards standard NATO documentation on smoke and obscurant systems.

  12. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-09-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in the current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: AAV-NGFbeta, aprepitant, aripiprazole, atomoxetine hydrochloride; beta-Methyl-6-chloromelatonin, BMS-214662, bortezomib, bosentan; Calcipotriol/betamethasone dipropionate, CEA-TRICOM, cetuximab, ciclesonide, clofarabine, Cypher; Dalbavancin, darbepoetin alfa, darifenacin hydrobromide, desloratadine, Dexamet, drospirenone, drospirenone/ethinylestradiol, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Ecogramostim, efalizumab, ertapenem sodium, escitalopram oxalate, eszopiclone; Fenretinide; Gefitinib, gestodene, ghrelin (human); hMaxi-K, human papillomavirus vaccine; Imatinib mesylate, indiplon, iodine (i131) tositumomab, irofulven, ISS-1018; Lasofoxifene tartrate, levodopa/carbidopa/entacapone, liposomal doxorubicin; Nemifitide ditriflutate, nesiritide; Omalizumab; Pegfilgrastim, peginterferon alfa-2a, peginterferon alfa-2b, phVEGF-A165, pimecrolimus, pramlintide acetate; Rasburicase, rimonabant hydrochloride; Satraplatin, St. John's Wort extract, sunitinib malate; Tadalafil, tanaproget, Taxus, tiotropium bromide, treprostinil sodium; Valdecoxib, vardenafil hydrochloride hydrate; Ximelagatran; Zileuton. PMID:16258596

  13. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-03-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 3-AP, 667-coumate, 9-aminocamptothecin; Ad5CMV-p53, AES-14, alefacept, anecortave acetate, APC-8024, APD-356, asoprisnil; Bevacizumab, bimakalim, bimatoprost, BLP-25, BR-1; Caspofungin acetate, cetuximab, cypher; Darbepoetin alfa, dexanabinol, dextromethorphan/quinidine sulfate, DNA.HIVA; Efaproxiral sodium, ertapenem sodium; Frovatriptan; HuMax-EGFr, HYB-2055, gamma-hydroxybutyrate sodium, Id-KLH vaccine, imatinib mesylate; Lapatinib, lonafarnib, Motexafin lutetium, MVA.HIVA, mycophenolic acid sodium salt; Nesiritide, NS-2330; Olmesartan medoxomil; Peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, perifosine, pimecrolimus, pregabalin; QbG-10; Ralfinamide, rasburicase, rFGF-2, Ro-31-7453; Sitaxsentan sodium, sorafenib; Tadalafil, TC-1734, telmisartan/hydrochlorothiazide, tenofovir disoproxil fumarate, thymus nuclear protein, tipifarnib; Vandetanib, vibriolysin, vildagliptin, voriconazole. PMID:15834466

  14. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-06-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 131-I-chlorotoxin; Ad5CMV-p53, adalimumab, albumin interferon alfa, alemtuzumab, aliskiren fumarate, aminolevulinic acid methyl ester, anakinra, AR-C126532, atomoxetine hydrochloride; Bevacizumab, bosentan, botulinum toxin type B, brimonidine tartrate/timolol maleate; Calcipotriol/betamethasone dipropionate, cangrelor tetrasodium, cetuximab, ciclesonide, cinacalcet hydrochloride, collagen-PVP, Cypher; Darbepoetin alfa, darusentan, dasatinib, denosumab, desloratadine, dexosome vaccine (lung cancer), dexrazoxane, dextromethorphan/quinidine sulfate, duloxetine hydrochloride; ED-71, eel calcitonin, efalizumab, entecavir, etoricoxib; Falciparum merozoite protein-1/AS02A, fenretinide, fondaparinux sodium; gamma-Hydroxybutyrate sodium, gefitinib, ghrelin (human); hLM609; Icatibant acetate, imatinib mesylate, ipsapirone, irofulven; LBH-589, LE-AON, levocetirizine, LY-450139; Malaria vaccine, mapatumumab, motexafin gadolinium, muraglitazar, mycophenolic acid sodium salt; nab-paclitaxel, nelarabine; O6-Benzylguanine, olmesartan medoxomil, orbofiban acetate; Panitumumab, peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed disodium, peptide YY3-36, pleconaril, prasterone, pregabalin; Ranolazine, rebimastat, recombinant malaria vaccine, rosuvastatin calcium; SQN-400; Taxus, tegaserod maleate, tenofovir disoproxil fumarate, teriparatide, troxacitabine; Valganciclovir hydrochloride, Val-Tyr sardine peptidase, VNP-40101M, vorinostat. PMID:16845450

  15. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-12-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity. prous.com. This issue focuses on the following selection of drugs: 131I-chTNT; Abatacept, adalimumab, alemtuzumab, APC-8015, aprepitant, atazanavir sulfate, atomoxetine hydrochloride, azimilide hydrochloride; Bevacizumab, bortezomib, bosentan, buserelin; Caspofungin acetate, CC-4047, ChAGCD3, ciclesonide, clopidogrel, curcumin, Cypher; Dabigatran etexilate, dapoxetine hydrochloride, darbepoetin alfa, darusentan, denosumab, DMXB-Anabaseine, drospirenone, drospirenone/estradiol, duloxetine hydrochloride, dutasteride; Edodekin alfa, efaproxiral sodium, elaidic acid-cytarabine, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, eszopiclone, etonogestrel/testosterone decanoate, exenatide; Fulvestrant; Gefitinib, glycine, GVS-111; Homoharringtonine; ICC-1132, imatinib mesylate, iodine (I131) tositumomab, i.v. gamma-globulin; Levetiracetam, levocetirizine, lintuzumab, liposomal nystatin, lumiracoxib, lurtotecan; Manitimus, mapatumumab, melatonin, micafungin sodium, mycophenolic acid sodium salt; Oblimersen sodium, OGX-011, olmesartan medoxomil, omalizumab, omapatrilat, oral insulin; Parathyroid hormone (human recombinant), pasireotide, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, phVEGF-A165, pimecrolimus, pitavastatin calcium, plerixafor hydrochloride, posaconazole, pramlintide acetate, prasterone, pregabalin, PT-141; Quercetin; Ranolazine, rosuvastatin calcium, rubitecan, rupatadine fumarate; Sardomozide, sunitinib malate; Tadalafil, talactoferrin alfa, tegaserod maleate, telithromycin, testosterone transdermal patch, TH-9507, tigecycline, tiotropium bromide, tipifarnib, tocilizumab, treprostinil sodium; Valdecoxib, vandetanib

  16. Impact on mortality of the timing of renal replacement therapy in patients with severe acute kidney injury in septic shock: the IDEAL-ICU study (initiation of dialysis early versus delayed in the intensive care unit): study protocol for a randomized controlled trial

    PubMed Central

    2014-01-01

    Background One of the most dreaded complications of septic shock is acute kidney injury. It occurs in around 50% of patients, with a mortality rate of about 60% at 3 months. There is no consensus on the optimal time to initiate renal replacement therapy. Retrospective and observational studies suggest that early implementation of renal replacement therapy could improve the prognosis for these patients. Methods/design This protocol summarizes the rationale and design of a randomized, controlled, multicenter trial investigating the effect of early versus delayed renal replacement therapy in patients with severe acute kidney injury in early septic shock. In total, 864 critically ill adults with septic shock and evidence of acute kidney injury, defined as the failure stage of the RIFLE classification, will be enrolled. The primary outcome is mortality at 90 days. Secondary outcomes include safety, number of days free of mechanical ventilation, number of days free of renal replacement therapy, intensive care length of stay, in-hospital length of stay, quality of life as evaluated by the EQ-5D and renal replacement therapy dependence at hospital discharge. The primary analysis will be intention to treat. Recruitment started in March 2012 and will be completed by March 2015. Discussion This protocol for a randomized controlled study investigating the impact of the timing of renal replacement therapy initiation should provide an answer to a key question for the management of patients with acute kidney injury in the context of septic shock, for whom the mortality rate remains close to 60% despite improved understanding of physiopathology and recent therapeutic advances. Trial registration ClinicalTrials.gov identifier NCT01682590, registered on 10 September 2012. PMID:24998258

  17. Average Is Optimal: An Inverted-U Relationship between Trial-to-Trial Brain Activity and Behavioral Performance

    PubMed Central

    He, Biyu J.; Zempel, John M.

    2013-01-01

    It is well known that even under identical task conditions, there is a tremendous amount of trial-to-trial variability in both brain activity and behavioral output. Thus far the vast majority of event-related potential (ERP) studies investigating the relationship between trial-to-trial fluctuations in brain activity and behavioral performance have only tested a monotonic relationship between them. However, it was recently found that across-trial variability can correlate with behavioral performance independent of trial-averaged activity. This finding predicts a U- or inverted-U- shaped relationship between trial-to-trial brain activity and behavioral output, depending on whether larger brain variability is associated with better or worse behavior, respectively. Using a visual stimulus detection task, we provide evidence from human electrocorticography (ECoG) for an inverted-U brain-behavior relationship: When the raw fluctuation in broadband ECoG activity is closer to the across-trial mean, hit rate is higher and reaction times faster. Importantly, we show that this relationship is present not only in the post-stimulus task-evoked brain activity, but also in the pre-stimulus spontaneous brain activity, suggesting anticipatory brain dynamics. Our findings are consistent with the presence of stochastic noise in the brain. They further support attractor network theories, which postulate that the brain settles into a more confined state space under task performance, and proximity to the targeted trajectory is associated with better performance. PMID:24244146

  18. Future vision for the quality assurance of oncology clinical trials.

    PubMed

    Fitzgerald, Thomas J; Bishop-Jodoin, Maryann; Bosch, Walter R; Curran, Walter J; Followill, David S; Galvin, James M; Hanusik, Richard; King, Steven R; Knopp, Michael V; Laurie, Fran; O'Meara, Elizabeth; Michalski, Jeff M; Saltz, Joel H; Schnall, Mitchell D; Schwartz, Lawrence; Ulin, Kenneth; Xiao, Ying; Urie, Marcia

    2013-01-01

    The National Cancer Institute clinical cooperative groups have been instrumental over the past 50 years in developing clinical trials and evidence-based process improvements for clinical oncology patient care. The cooperative groups are undergoing a transformation process as we further integrate molecular biology into personalized patient care and move to incorporate international partners in clinical trials. To support this vision, data acquisition and data management informatics tools must become both nimble and robust to support transformational research at an enterprise level. Information, including imaging, pathology, molecular biology, radiation oncology, surgery, systemic therapy, and patient outcome data needs to be integrated into the clinical trial charter using adaptive clinical trial mechanisms for design of the trial. This information needs to be made available to investigators using digital processes for real-time data analysis. Future clinical trials will need to be designed and completed in a timely manner facilitated by nimble informatics processes for data management. This paper discusses both past experience and future vision for clinical trials as we move to develop data management and quality assurance processes to meet the needs of the modern trial. PMID:23508883

  19. Inadequate reporting of research ethics review and informed consent in cluster randomised trials: review of random sample of published trials

    PubMed Central

    McRae, Andrew D; Weijer, Charles; Bennett, Carol; Dixon, Stephanie; Taleban, Julia; Skea, Zoe; Eccles, Martin P; Brehaut, Jamie C; Donner, Allan; Saginur, Raphael; Boruch, Robert F; Grimshaw, Jeremy M

    2011-01-01

    Objectives To investigate the extent to which authors of cluster randomised trials adhered to two basic requirements of the World Medical Association’s Declaration of Helsinki and the International Committee of Medical Journal Editors’ uniform requirements for manuscripts (namely, reporting of research ethics review and informed consent), to determine whether the adequacy of reporting has improved over time, and to identify characteristics of cluster randomised trials associated with reporting of ethics practices. Design Review of a random sample of published cluster randomised trials from an electronic search in Medline. Setting Cluster randomised trials in health research published in English language journals from 2000 to 2008. Study sample 300 cluster randomised trials published in 150 journals. Results 77 (26%, 95% confidence interval 21% to 31%) trials failed to report ethics review. The proportion reporting ethics review increased significantly over time (P<0.001). Trials with data collection interventions at the individual level were more likely to report ethics review than were trials that used routine data sources only (79% (n=151) v 55% (23); P=0.008). Trials that accounted for clustering in the design and analysis were more likely to report ethics review. The median impact factor of the journal of publication was higher for trials that reported ethics review (3.4 v 2.3; P<0.001). 93 (31%, 26% to 36%) trials failed to report consent. Reporting of consent increased significantly over time (P<0.001). Trials with interventions targeting participants at the individual level were more likely to report consent than were trials with interventions targeting the cluster level (87% (90) v 48% (41); P<0.001). Trials with data collection interventions at the individual level were more likely to report consent than were those that used routine data sources only (78% (146) v 29% (11); P<0.001). Conclusions Reporting of research ethics protections in cluster

  20. Modelling residence-time response to freshwater input in Apalachicola Bay, Florida, USA

    NASA Astrophysics Data System (ADS)

    Huang, Wenrui; Spaulding, M.

    2002-10-01

    Residence time of an estuary can be used to estimate the rate of removal of freshwater and pollutants from river inflow. In this study, a calibrated three-dimensional hydrodynamic model was used to determine residence time in response to the change of freshwater input in Apalachicola Bay. The bay is about 40 km long and 7 km wide, with an average 3 m water depth. Through hydrodynamic model simulations, the spatial and temporal salinity and the total freshwater volume in the bay were calculated. Then the freshwater fraction method was used to estimate the residence time. Results indicate that the residence time in Apalachicola Bay typically ranges between 3 and 10 days for the daily freshwater input ranging from 177 m3/s to 4561 m3/s. Regression analysis of model results shows that an exponential regression equation can be used to correlate the estuarine residence time to changes of freshwater input.

  1. Application of Time Series Landsat Images to Examining Land-use/Land-cover Dynamic Change.

    PubMed

    Lu, Dengsheng; Hetrick, Scott; Moran, Emilio; Li, Guiying

    2012-07-01

    A hierarchical-based classification method was designed to develop time series land-use/land-cover datasets from Landsat images between 1977 and 2008 in Lucas do Rio Verde, Mato Grosso, Brazil. A post-classification comparison approach was used to examine land-use/land-cover change trajectories, which emphasis is on the conversions from vegetation or agropasture to impervious surface area, from vegetation to agropasture, and from agropasture to regenerating vegetation. Results of this research indicated that increase in impervious surface area mainly resulted from the loss of cerrado in the initial decade of the study period and from loss of agricultural lands in the last two decades. Increase in agropasture was mainly at the expense of losing cerrado in the first two decades and relatively evenly from the loss of primary forest and cerrado in the last decade. When impervious surface area was less than approximately 40 km(2) before 1999, impervious surface area was negatively related to cerrado and forest, and positively related to agropasture areas, but after impervious surface area reached 40 km(2) in 1999, no obvious relationship exists between them. PMID:25328256

  2. [Internet use in clinical trials].

    PubMed

    Refolo, P; Sacchini, D; Minacori, R; Spagnolo, A G

    2014-01-01

    Recruiting patients is a critical point of today's clinical research and, along the years, several solutions have been proposed, even if their efficacy seems to be doubtful. On the other hand, nowadays, Internet represents a great opportunity for improving clinical trial recruitments. Nevertheless, on-line recruitment services (e-recruitment) could ensure some advantages (such as facilitating interaction between supply and demand of clinical research, time and money savings/optimizations, data entry errors reduction), but also raise some issues (such as those related to sampling, information, consent, real identity of participants and risks for data breaches). The article debates on the difficulties to recruit patients for clinical research, in general, and e-recruitment particularly, discussing some ethical issues raised by internet enrolment. PMID:24589968

  3. Trends in UK cancer trials: results from the UK Coordinating Committee for Cancer Research National Register of Cancer Trials

    PubMed Central

    Vale, C; Stewart, L; Tierney, J

    2005-01-01

    We aimed to study trends in the design and conduct of randomised controlled trials (RCTs) in cancer in the UK, using the UK Coordinating Committee for Cancer Research (UKCCCR) National Register of Cancer Trials (NRCT). We conducted a descriptive survey of 520 UK RCTs in cancer that were registered on the UKCCCR NRCT. All trials had been initiated between 1971 and 2000. Trials on the NRCT have been conducted in a wide variety of cancer types, but with a third in breast (22%) or lung cancer (11%). They have largely been funded by the UK public and charity sectors. Overall, there has been a sustained rise in the total numbers of patients entering UK cancer trials over time with a trend towards larger, multicentre trials, greater recruitment targets and a marked reduction in the average time taken to complete trials. Trends in the design and conduct of noncommercial cancer RCTs from 1971 to 2000 are encouraging. It will be interesting to see how they develop in light of the implementation of recent national initiatives regarding cancer clinical trials in the UK. PMID:15756251

  4. Controlled Trials in Children: Quantity, Methodological Quality and Descriptive Characteristics of Pediatric Controlled Trials Published 1948-2006

    PubMed Central

    Thomson, Denise; Hartling, Lisa; Cohen, Eyal; Vandermeer, Ben; Tjosvold, Lisa; Klassen, Terry P.

    2010-01-01

    Background The objective of this study was to describe randomized controlled trials (RCTs) and controlled clinical trials (CCTs) in child health published between 1948 and 2006, in terms of quantity, methodological quality, and publication and trial characteristics. We used the Trials Register of the Cochrane Child Health Field for overall trends and a sample from this to explore trial characteristics in more detail. Methodology/Principal Findings We extracted descriptive data on a random sample of 578 trials. Ninety-six percent of the trials were published in English; the percentage of child-only trials was 90.5%. The most frequent diagnostic categories were infectious diseases (13.2%), behavioural and psychiatric disorders (11.6%), neonatal critical care (11.4%), respiratory disorders (8.9%), non-critical neonatology (7.9%), and anaesthesia (6.5%). There were significantly fewer child-only studies (i.e., more mixed child and adult studies) over time (P = 0.0460). The proportion of RCTs to CCTs increased significantly over time (P<0.0001), as did the proportion of multicentre trials (P = 0.002). Significant increases over time were found in methodological quality (Jadad score) (P<0.0001), the proportion of double-blind studies (P<0.0001), and studies with adequate allocation concealment (P<0.0001). Additionally, we found an improvement in reporting over time: adequate description of withdrawals and losses to follow-up (P<0.0001), sample size calculations (P<0.0001), and intention-to-treat analysis (P<0.0001). However, many trials still do not describe their level of blinding, and allocation concealment was inadequately reported in the majority of studies across the entire time period. The proportion of studies with industry funding decreased slightly over time (P = 0.003), and these studies were more likely to report positive conclusions (P = 0.028). Conclusions/Significance The quantity and quality of pediatric controlled trials has increased over

  5. Reducing trial length in force platform posturographic sleep deprivation measurements

    NASA Astrophysics Data System (ADS)

    Forsman, P.; Hæggström, E.; Wallin, A.

    2007-09-01

    Sleepiness correlates with sleep-related accidents, but convenient tests for sleepiness monitoring are scarce. The posturographic test is a method to assess balance, and this paper describes one phase of the development of a posturographic sleepiness monitoring method. We investigated the relationship between trial length and accuracy of the posturographic time-awake (TA) estimate. Twenty-one healthy adults were kept awake for 32 h and their balance was recorded, 16 times with 30 s trials, as a function of TA. The balance was analysed with regards to fractal dimension, most common sway amplitude and time interval for open-loop stance control. While a 30 s trial allows estimating the TA of individual subjects with better than 5 h accuracy, repeating the analysis using shorter trial lengths showed that 18 s sufficed to achieve the targeted 5 h accuracy. Moreover, it was found that with increasing TA, the posturographic parameters estimated the subjects' TA more accurately.

  6. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2007-12-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Intergrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 249553, 2-Methoxyestradiol; Abatacept, Adalimumab, Adefovir dipivoxil, Agalsidase beta, Albinterferon alfa-2b, Aliskiren fumarate, Alovudine, Amdoxovir, Amlodipine besylate/atorvastatin calcium, Amrubicin hydrochloride, Anakinra, AQ-13, Aripiprazole, AS-1404, Asoprisnil, Atacicept, Atrasentan; Belimumab, Bevacizumab, Bortezomib, Bosentan, Botulinum toxin type B, Brivaracetam; Catumaxomab, Cediranib, Cetuximab, cG250, Ciclesonide, Cinacalcet hydrochloride, Curcumin, Cypher; Darbepoetin alfa, Denosumab, Dihydrexidine; Eicosapentaenoic acid/docosahexaenoic acid, Entecavir, Erlotinib hydrochloride, Escitalopram oxalate, Etoricoxib, Everolimus, Ezetimibe; Febuxostat, Fenspiride hydrochloride, Fondaparinux sodium; Gefitinib, Ghrelin (human), GSK-1562902A; HSV-tk/GCV; Iclaprim, Imatinib mesylate, Imexon, Indacaterol, Insulinotropin, ISIS-112989; L-Alanosine, Lapatinib ditosylate, Laropiprant; Methoxy polyethylene glycol-epoetin-beta, Mipomersen sodium, Motexafin gadolinium; Natalizumab, Nimotuzumab; OSC, Ozarelix; PACAP-38, Paclitaxel nanoparticles, Parathyroid Hormone-Related Protein-(1-36), Pasireotide, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pertuzumab, Picoplatin, Pimecrolimus, Pitavastatin calcium, Plitidepsin; Ranelic acid distrontium salt, Ranolazine, Recombinant human relaxin H2, Regadenoson, RFB4(dsFv)-PE38, RO-3300074, Rosuvastatin calcium; SIR-Spheres, Solifenacin succinate, Sorafenib, Sunitinib malate; Tadalafil, Talabostat, Taribavirin hydrochloride, Taxus, Temsirolimus, Teriparatide, Tiotropium bromide, Tipifarnib, Tirapazamine, Tocilizumab; UCN-01, Ularitide

  7. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-11-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Thomson Reuters Integrity(SM), the drug discovery and development portal, http://www.thomsonreutersintegrity.com. This issue focuses on the following selection of drugs: Abatacept, Adalimumab, AdCD40L, Adefovir, Aleglitazar, Aliskiren fumarate, AM-103, Aminolevulinic acid methyl ester, Amlodipine, Anakinra, Aprepitant, Aripiprazole, Atazanavir sulfate, Axitinib; Belimumab, Bevacizumab, Bimatoprost, Bortezomib, Bupropion/naltrexone; Calcipotriol/betamethasone dipropionate, Certolizumab pegol, Ciclesonide, CYT-997; Darbepoetin alfa, Darunavir, Dasatinib, Desvenlafaxine succinate, Dexmethylphenidate hydrochloride cogramostim; Eltrombopag olamine, Emtricitabine, Escitalopram oxalate, Eslicarbazepine acetate, Eszopiclone, Etravirine, Everolimus-eluting coronary stent, Exenatide, Ezetimibe; Fenretinide, Filibuvir, Fludarabine; Golimumab; Hepatitis B hyperimmunoglobulin, HEV-239, HP-802-247, HPV-16/18 AS04, HPV-6/11/16/18, Human albumin, Human gammaglobulin; Imatinib mesylate, Inotuzumab ozogamicin, Invaplex 50 vaccine; Lapatinib ditosylate, Lenalidomide, Liposomal doxorubicin, Lopinavir, Lumiliximab, LY-686017; Maraviroc, Mecasermin rinfabate; Narlaprevir; Ocrelizumab, Oral insulin, Oritavancin, Oxycodone hydrochloride/naloxone; Paclitaxel-eluting stent, Palonosetron hydrochloride, PAN-811, Paroxetine, Pazopanib hydrochloride, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pertuzumab, Pitavastatin calcium, Posaconazole, Pregabalin, Prucalopride succinate; Raltegravir potassium, Ranibizumab, RHAMM R3 peptide, Rosuvastatin calcium; Salclobuzic acid sodium salt, SCY-635, Selenate sodium, Semapimod hydrochloride, Silodosin, Siltuximab, Silybin, Sirolimus-eluting stent, SIR-Spheres, Sunitinib malate; Tapentadol hydrochloride, Tenofovir disoproxil

  8. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2008-10-01

    Gateways to clinical trials is a guide to the most recent trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (+)-Dapoxetine hydrochloride, (S)-Tenatoprazole sodium salt monohydrate 19-28z, Acotiamide hydrochloride hydrate, ADV-TK, AE-37, Aflibercept, Albinterferon alfa-2b, Aliskiren fumarate, Asenapine maleate, Axitinib; Bavituximab, Becatecarin, beta-1,3/1,6-Glucan, Bevacizumab, Bremelanotide; Calcipotriol/betamethasone dipropionate, Casopitant mesylate, Catumaxomab, CDX-110, Cediranib, CMD-193, Cositecan; Darinaparsin, Denosumab, DP-b99, Duloxetine hydrochloride; E75, Ecogramostim, Elacytarabine, EMD-273063, EndoTAG-1, Enzastaurin hydrochloride, Eplerenone, Eribulin mesilate, Esomeprazole magnesium, Etravirine, Everolimus, Ezetimibe; Faropenem daloxate, Febuxostat, Fenretinide; Ghrelin (human); I-131 ch-TNT-1/B, I-131-3F8, Iclaprim, Iguratimod, Iloperidone, Imatinib mesylate, Inalimarev/Falimarev, Indacaterol, Ipilimumab, Iratumumab, Ispinesib mesylate, Ixabepilone; Lapatinib ditosylate, Laquinimod sodium, Larotaxel dehydrate, Linezolid, LOR-2040; Mapatumumab, MKC-1, Motesanib diphosphate, Mycophenolic acid sodium salt; NK-012; Olanzapine pamoate, Oncolytic HSV, Ortataxel; Paclitaxel nanoparticles, Paclitaxel poliglumex, Paliperidone palmitate, Panitumumab, Patupilone, PCV-9, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pertuzumab, Picoplatin, Pimavanserin tartrate, Pimecrolimus, Plerixafor hydrochloride, PM-02734, Poly I:CLC, PR1, Prasugrel, Pregabalin, Progesterone caproate, Prucalopride, Pumosetrag hydrochloride; RAV-12, RB-006, RB-007, Recombinant human erythropoietin alfa, Rimonabant, Romidepsin; SAR-109659, Satraplatin, Sodium butyrate; Tadalafil, Talampanel, Tanespimycin, Tarenflurbil, Tariquidar

  9. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2006-05-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com/. This issue focuses on the following selection of drugs: Adalimumab, adenosine triphosphate, alemtuzumab, alendronate sodium/cholecalciferol, aliskiren fumarate, AMGN-0007, aminolevulinic acid methyl ester, anakinra, anidulafungin, aripiprazole, atomoxetine hydrochloride; Bevacizumab, bosentan; Calcipotriol/beta methasone dipropionate, caldaret hydrate, caspofungin acetate, cetuximab, cinacalcet hydrochloride, clopidogrel, cocaine-BSA conjugate, conivaptan hydrochloride, Cypher; Darbepoetin alfa, delmitide, desloratadine, desmoteplase, desoxyepothilone B, disufenton sodium, DU-176b, duloxetine hydrochloride, dutasteride; EBV-specific CTLs, ecogramostim, edodekin alfa, efalizumab, eletriptan, emtricitabine, entecavir, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, etoricoxib, everolimus, ezetimibe; Fanapanel, fondaparinux sodium; Gefitinib, GTI-2040, GW-501516; Her2 E75-peptide vaccine, human insulin; Ibogaine, icatibant acetate, Id-KLH vaccine, imatinib mesylate, immune globulin subcutaneous [human], indacaterol, inolimomab, ipilimumab, i.v. gamma-globulin, ivabradine hydrochloride, ixabepilone; Lacosamide, lanthanum carbonate, lenalidomide, levocetirizine, levodopa methyl ester hydrochloride/carbidopa, levodopa/carbidopa/entacapone, lidocaine/prilocaine; Maraviroc, mecasermin, melevodopa hydrochloride, mepolizumab, mitumomab; Nesiritide; Omalizumab, oral insulin; Parathyroid hormone (human recombinant), patupilone, pegaptanib sodium, PEG-filgrastim, pemetrexed disodium, photochlor, pimecrolimus, posaconazole, prasterone, prasugrel, pregabalin, prilocaine, PRX-00023; QS-21; Ranibizumab, ranirestat, rhodamine 123, rotigaptide; Sarcosine, sirolimus

  10. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2006-01-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: ABT-510, adalimumab, alefacept, ambrisentan, aminolevulinic acid methyl ester, armodafinil, aselizumab, asenapine maleate, azelnidipine; Bevacizumab, bexarotene, bimosiamose, biphasic insulin aspart, bortezomib, bosentan, BQ-123; C340, cannabidiol, caspofungin acetate, CC-4047, certolizumab pegol, cetuximab, ciclesonide, cilansetron, Cypher; Dabigatran etexilate, darbepoetin alfa, darifenacin hydrobromide, desloratadine, dexosome vaccine (melanoma), dimethyl fumarate, dronabinol/cannabidiol, drospirenone, drospirenone/estradiol, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Efalizumab, eglumetad hydrate, emoxipin hydrochloride, eplerenone, erlotinib hydrochloride, escitalopram oxalate, etonogestrel/ethinylestradiol; Garenoxacin mesilate, gamma-hydroxybutyrate sodium, gefitinib; H5N1 pandemic influenza vaccine, human growth hormone-(177-191), human insulin; Indacaterol, INKP-100, INKP-102, insulin glargine, i.v. gamma-globulin; KLH; Lapatinib, L-arginine hydrochloride, lasofoxifene tartrate, levocetirizine, licochalcone A, LMI vaccine, lomefloxacin, lubiprostone, lumiracoxib; Miglustat, mycograb; Natalizumab, NCX-4016, nortopixantrone hydrochloride; Olmesartan medoxomil, omalizumab, oral insulin, OrM3; Parathyroid hormone (human recombinant), parecoxib sodium, PCK-3145, PEG-filgrastim, peginterferon alfa-2a, pemetrexed disodium, pexelizumab, photochlor, pimecrolimus, pneumococcal 7-valent conjugate vaccine, polyphenon E; R-126638, R-411, resveratrol, roflumilast, RS-86, ruboxistaurin mesilate hydrate, rupatadine fumarate; Sipuleucel-T, somatropin, St. John's Wort extract; Tadalafil, Taxus

  11. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-01-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs:(R)-Flurbiprofen, 90Yttrium-DOTA-huJ591; ABT-510, ACP-103, Ad5-FGF4, adalimumab, ademetionine, AG-7352, alemtuzumab, Amb a 1 ISS-DNA, anakinra, apaziquone, aprepitant, aripiprazole, atazanavir sulfate; BAL-8557, bevacizumab, BMS-188797, bortezomib, bosentan, brivudine; Calcipotriol/betamethasone dipropionate, cannabidiol, caspofungin acetate, catumaxomab, CERE-120, cetuximab, ciclesonide, cilomilast, cizolirtine citrate, Cypher, cystemustine; Dalbavancin, darifenacin hydrobromide, dasatinib, deferasirox, denosumab, desmoteplase, dihydrexidine, dimethyl fumarate, dutasteride, DW-166HC; Eculizumab, enfuvirtide, entecavir, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, eszopiclone, etoricoxib, everolimus; Fallypride, febuxostat, fenretinide, fesoterodine, fingolimod hydrochloride; Gabapentin enacarbil, gefitinib; hMaxi-K, human papillomavirus vaccine, HYAL-CT1101; Imatinib mesylate, indiplon, inolimomab, ISAtx-247; J591; Lacosamide, landiolol, lasofoxifene tartrate, lestaurtinib, lidocaine/prilocaine, linezolid, lixivaptan, lonafarnib, lopinavir, lopinavir/ritonavir, lumiracoxib; Natalizumab, nesiritide; OC-108, omalizumab, onercept, OSC; Palifermin, palonosetron hydrochloride, parathyroid hormone (human recombinant), parecoxib sodium, PD-MAGE-3 vaccine, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, pegsunercept, pelitinib, pitavastatin calcium, plerixafor hydrochloride, posaconazole, prasterone sulfate, pregabalin; Ramelteon, ranelic acid distrontium salt, rasburicase, rosuvastatin calcium, rotigotine, RSD-1235, rufinamide, rupatadine fumarate; Sarizotan hydrochloride, SHL-749

  12. Gateways to clinical trials.

    PubMed

    Moral, M A; Tomillero, A

    2008-03-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 131-I-Chlorotoxin, 423557; Abatacept, Ad.Egr.TNF.11D, Adalimumab, AE-941, Ambrisentan, AMR-001, Anacetrapib, Anakinra, Aripiprazole, Atazanavir sulfate; BAY-639044, Bazedoxifene acetate, Belimumab, Bevacizumab, Bortezomib, Botulinum toxin type B, Brivaracetam, Bucindolol hydrochloride; Carfilzomib, Carisbamate, CCX-282, CD20Bi, Ceftobiprole, Certolizumab pegol, CF-101, Cinacalcet hydrochloride, Cypher; Darifenacin hydrobromide, Degarelix acetate, Denosumab, Desvenlafaxine succinate, Dexlansoprazole, Dexverapamil, Drotrecogin alfa (activated), Duloxetine hydrochloride, Dutasteride; Efalizumab, EPs-7630, Escitalopram oxalate, Etoricoxib; Fluticasone furoate, Fondaparinux sodium, Fospropofol disodium; Hexadecyloxypropyl-cidofovir, HIV gp120/NefTat/AS02A, HPV-6/11/16/18; INCB-18424, Incyclinide, Inhalable human insulin, Insulin detemir; KNS-760704, KW-0761; Lacosamide, Lenalidomide, Levetiracetam, Licofelone, Lidocaine/prilocaine; mAb 216, MEDI-528, Men ACWY, Meningococcal C-CRM197 vaccine, Methylnaltrexone bromide; Nemifitide ditriflutate, Nicotine conjugate vaccine, Nilotinib hydrochloride monohydrate; Octaparin; Parathyroid hormone (human recombinant), Pegaptanib octasodium, Pitrakinra, Prasterone, Pregabalin; Ranelic acid distrontium salt, Rasagiline mesilate, Retigabine, Rimonabant, RTS,S/AS02D; Sarcosine, Sitaxentan sodium, Solifenacin succinate, Sunitinib malate; Taranabant, Taxus, Teduglutide, Teriparatide, Ticagrelor, Travoprost, TRU-015; USlipristal acetate, Urocortin 2; Vardenafil hydrochloride hydrate; YM-155, Yttrium 90 (90Y) ibritumomab tiuxetan; Zanolimumab, Zoledronic acid monohydrate, Zotarolimus

  13. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-09-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com This issue focuses on the following selection of drugs: A-007, A6, adalimumab, adenosine triphosphate, alefacept, alemtuzumab, AllerVax Ragweed, amphora, anakinra, angiotensin-(1-7), anidulafungin, apomine, aripiprazole, atomoxetine hydrochloride, avanafil; BAL-8557, becatecarin, bevacizumab, biphasic insulin aspart, BMS-188797, bortezomib, bosentan, botulinum toxin type B, brivudine; Calcipotriol/betamethasone dipropionate, caspofungin acetate, catumaxomab, certolizumab pegol, cetuximab, CG-0070, ciclesonide, cinacalcet hydrochloride, clindamycin phosphate/benzoyl peroxide, cryptophycin 52, Cypher; Dabigatran etexilate, darapladib, darbepoetin alfa, decitabine, deferasirox, desloratadine, dexanabinol, dextromethorphan/quinidine sulfate, DMF, drotrecogin alfa (activated), duloxetine hydrochloride; E-7010, edaravone, efalizumab, emtricitabine, entecavir, eplerenone, erlotinib hydrochloride, escitalopram oxalate, estradiol valerate/dienogest, eszopiclone, exenatide, ezetimibe; Fondaparinux sodium, fulvestrant; Gefitinib, gestodene, GYKI-16084; Hyaluronic acid, hydralazine hydrochloride/isosorbide dinitrate; Imatinib mesylate, indiplon, insulin glargine; Juzen-taiho-to; Lamivudine/zidovudine/abacavir sulfate, L-arginine hydrochloride, lasofoxifene tartrate, L-BLP-25, lenalidomide, levocetirizine, levodopa/carbidopa/entacapone, lexatumumab, lidocaine/prilocaine, lubiprostone, lumiracoxib; MAb-14.18, mitoquidone; Natalizumab, neridronic acid, neuradiab; Olpadronic acid sodium salt, omalizumab; p53-DC vaccine, parathyroid hormone (human recombinant), peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed disodium, perifosine, pimecrolimus, prasterone, prasugrel, PRO-2000

  14. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Thomson Reuters Integrity(SM), the drug discovery and development portal, http://www.thomsonreutersintegrity.com. This issue focuses on the following selection of drugs: 17-Hydroxyprogesterone caproate; Abacavir sulfate/lamivudine, Aclidinium bromide, Adalimumab, Adefovir, Alemtuzumab, Alkaline phosphatase, Amlodipine, Apilimod mesylate, Aripiprazole, Axitinib, Azacitidine; Belotecan hydrochloride, Berberine iodide, Bevacizumab, Bortezomib, Bosentan, Bryostatin 1; Calcipotriol/hydrocortisone, Carglumic acid, Certolizumab pegol, Cetuximab, Cinacalcet hydrochloride, Cixutumumab, Coumarin, Custirsen sodium; Darbepoetin alfa, Darifenacin hydrobromide, Darunavir, Dasatinib, Denibulin hydrochloride, Denosumab, Diacetylmorphine, Dulanermin, Duloxetine hydrochloride; Ecogramostim, Enfuvirtide, Entecavir, Enzastaurin hydrochloride, Eplerenone, Escitalopram oxalate, Esomeprazole sodium, Etravirine, Everolimus, Ezetimibe; Fenofibrate/pravastatin sodium, Ferric carboxymaltose, Flavangenol, Fondaparinux sodium; Glutamine, GSK-1024850A; Hepatitis B hyperimmunoglobulin, Hib-MenC, HIV-LIPO-5; Immunoglobulin intravenous (human), Indacaterol maleate, Indibulin, Indium 111 (¹¹¹In) ibritumomab tiuxetan, Influenza A (H1N1) 2009 Monovalent vaccine, Inhalable human insulin, Insulin glulisine; Lapatinib ditosylate, Leucovorin/UFT; Maraviroc, Mecasermin, MMR-V, Morphine hydrochloride, Morphine sulfate/naltrexone hydrochloride, Mycophenolic acid sodium salt; Naproxen/esomeprazole magnesium, Natalizumab; Oncolytic HSV; Paliperidone, PAN-811, Paroxetine, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b/ribavirin, Pegvisomant, Pemetrexed disodium, Pimecrolimus, Posaconazole, Pregabalin; Raltegravir potassium, Ranelic acid distrontium salt, Rasburicase, Rilpivirine

  15. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2004-01-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Know- ledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: ABI-007, Ad.Egr.TNF.11D, adefovir dipivoxil, AdPEDF.11, AES-14, albumex, alefacept, alemtuzumab, aliskiren fumarate, alvimopan hydrate, aAminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, anakinra, anti-IL-12 MAb, aprepitant, atazanavir sulfate, atrasentan, avanafil; Banoxantrone, BG-12, bimatoprost, bortezomib, bosentan; Calcipotriol/betamethasone dipropionate, caspofungin acetate, CBT-1, ciclesonide, clofarabine, conivaptan hydrochloride, CpG-7909, C-Vax, Cypher; DA-8159, DAC:GLP-1, darbepoetin alfa, darifenacin, duloxetine hydrochloride; Eculizumab, efalizumab, efaproxiral sodium, EGF vaccine, eletriptan, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, ETC-642, etoricoxib, everolimus, exenatide; Gefitinib, IV gamma-globulin; Human insulin, gamma-hydroxybutyrate sodium; IDN-6556, iguratimod, imatinib mesylate, indiplon, ixabepilone; Laquinimod, LB-80380, lidocaine/prilocaineliraglutide, lopinavir, lopinavir/ritonavir, lucinactant; MAb-14.18, melatonin, MLN-591-DM1; NC-531, neridronic acid, nesiritide, neutrophil-inhibitory factor, niacin/lovastatin; Oblimersen sodium, olcegepant, oral Insulin, ORV-105; Palonosetron hydrochloride, PAmAb, pegaptanib sodium, peginterferon alfa-2a, pegvisomant, perifosine, pexelizumab, phenoxodiol, phenserine tartrate, pimecrolimus, pramlintide acetate, pregabalin, PRO-542, prostate cancer vaccine, PT-141; Ramelteon, rasagiline mesilate, rDNA insulin, reslizumab, rh-Lactoferrin, ribamidine hydrochloride, rosuvastatin calcium; S-8184l, SC-1, sorafenib, St. John's Wort extract, SU-11248; Taxus, telbivudine, tenofovir disoproxil fumarate, teriparatide

  16. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2004-09-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 101M, 166Ho-DOTMP, 3-AP; Abatacept, abetimus sodium, ACR-16, adefovir dipivoxil, alefacept, AMD-070, aminolevulinic acid hexyl ester, anatumomab mafenatox, anti-CTLA-4 MAb, antigastrin therapeutic vaccine, AP-12009, AP-23573, APC-8024, aripiprazole, ATL-962, atomoxetine hydrochloride; Bevacizumab, bimatoprost, bortezomib, bosentan, BR-1; Calcipotriol/betamethasone dipropionate, cinacalcet hydrochloride, clofazimine, colchicine, cold-adapted influenza vaccine trivalent, CRM197; Desloratadine, desoxyepothilone B, diethylhomospermine; Edodekin alfa, efalizumab, elcometrine, eletriptan, enfuvirtide, entecavir, EP-2101, eplerenone, erlotinib hydrochloride, etoricoxib, everolimus, exherin, ezetimibe; Febuxostat, fluorescein lisicol, fosamprenavir calcium, frovatriptan; Hemoglobin raffimer, HSPPC-96, human insulin; Imatinib mesylate, insulin detemir, insulin glargine, IRX-2, istradefylline, IV gamma-globulin, ixabepilone; Kahalalide F; L-759274, levodopa/carbidopa/entacapone, licofelone, lonafarnib, lopinavir, lurtotecan, LY-156735; MAb G250, mecasermin, melatonin, midostaurin, muraglitazar; Nesiritide, nitronaproxen; O6-Benzylguanine, olmesartan medoxomil, olmesartan medoxomil/hydrochlorothiazide, omapatrilat, oral insulin; Parecoxib sodium, PCK-3145, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ ribavirin, pemetrexed disodium, peptide YY3-36, PG-CPT, phenoxodiol, pimecrolimus, posaconazole; Rasagiline mesilate, rDNA insulin, RG228, rimonabant hydrochloride, rosuvastatin calcium, rotigotine hydrochloride; S-3304, safinamide mesilate, salcaprozic acid sodium salt, SDZ-SID-791, SGN-30, soblidotin

  17. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-09-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: AAV1/SERCA2a, Abacavir sulfate/lamivudine, Adalimumab, Aliskiren fumarate, Ambrisentan, Aripiprazole, AT-7519, Atazanavir sulfate, Atomoxetine hydrochloride, Azacitidine, Azelnidipine; Besifloxacin hydrochloride, Bevacizumab, Bioabsorbable everolimus-eluting coronary stent, Bortezomib, Bosentan, Budesonide/formoterol fumarate; CAIV-T, Carisbamate, Casopitant mesylate, Certolizumab pegol, Cetuximab, Ciclesonide, Ciprofloxacin/dexamethasone, CTCE-9908; Dalcetrapib, Darunavir, Deferasirox, Desloratadine, Disitertide, Drotrecogin alfa (activated), DTA-H19, Duloxetine hydrochloride, Dutasteride; Ecogramostim, Efalizumab, Emtricitabine, Eribulin mesilate, Escitalopram oxalate, Eszopiclone, EUR-1008, Everolimus-eluting coronary stent, Exenatide; Fampridine, Fluticasone furoate, Formoterol fumarate/fluticasone propionate, Fosamprenavir calcium, Fulvestrant; Gabapentin enacarbil, GS-7904L; HPV-6/11/16/18, Human Secretin, Hydralazine hydrochloride/isosorbide dinitrate; Imatinib mesylate, Imexon, Inalimarev/Falimarev, Indacaterol, Indacaterol maleate, Inhalable human insulin, Insulin detemir, Insulin glargine, Ixabepilone; L-Alanosine, Lapatinib ditosylate, Lenalidomide, Levocetirizine dihydrochloride, Liraglutide, Lisdexamfetamine mesilate, Lopinavir, Loratadine/montelukast sodium, Lutropin alfa; MeNZB, Mepolizumab, Micafungin sodium, Morphine hydrochloride; Nabiximols, Nikkomycin Z; Olmesartan medoxomil, Omalizumab; Paclitaxel-eluting stent, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Perifosine, PF-489791, Plitidepsin, Posaconazole, Pregabalin; QAX-576; Raltegravir potassium, Ramelteon, Rasagiline

  18. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X

    2008-01-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prouse Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 101M, 3F8; Abatacept, ABT-263, Adalimumab, AG-7352, Agatolimod sodium, Alfimeprase, Aliskiren fumarate, Alvimopan hydrate, Aminolevulinic acid hexyl ester, Ammonium tetrathiomolybdate, Anakinra, Aripiprazole, AS-1404, AT-9283, Atomoxetine hydrochloride, AVE-1642, AVE-9633, Axitinib, AZD-0530; Becocalcidiol, Belotecan hydrochloride, Bevacizumab, BG-9928, BIBF-1120, BMS-275183, Bortezomib, Bosentan; Catumaxomab, Cetuximab, CHR-2797, Ciclesonide, Clevidipine, Cypher, Cytarabine/daunorubicin; Darifenacin hydrobromide, Darunavir, Denosumab, Desvenlafaxine succinate, Disufenton sodium, Duloxetine hydrochloride, Dutasteride; Eculizumab, Efalizumab, Eicosapentaenoic acid/docosahexaenoic acid, Eplerenone, Epratuzumab, Erlotinib hydrochloride, Escitalopram oxalate, Ethynylcytidine, Etravirine, Everolimus, Ezetimibe; Fulvestrant; Garenoxacin mesilate, Gefitinib, Gestodene; HI-164, Hydralazine hydrochloride/isosorbide dinitrate; Icatibant acetate, ICX-RHY, Idraparinux sodium, Indacaterol, Ispronicline, Ivabradine hydrochloride, Ixabepilone; KB-2115, KW-2449; L-791515, Lapatinib ditosylate, LGD-4665, Licofelone, Liposomal doxorubicin, Lisdexamfetamine mesilate, Lumiracoxib; Methoxy polyethylene glycol-epoetin-beta, Miglustat, Mipomersen sodium, Mitumprotimut-T, MK-0822A, MK-0974; Nelarabine; Obatoclax mesylate, Olmesartan medoxomil, Olmesartan medoxomil/hydrochlorothiazide; Paliperidone, Palonosetron hydrochloride, Panitumumab, Pegfilgrastim, Peginterferon alfa-2a, Pemetrexed disodium, Perospirone hydrochloride, Pertuzumab, Pimecrolimus, Pitrakinra, Pixantrone maleate, Posaconazole, Pregabalin; Quercetin; RALGA, Raltegravir

  19. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abiraterone acetate, Ad5CMV-p53, adefovir dipivoxil, AE-941, ambrisentan, aripiprazole, atomoxetine hydrochloride, atrasentan; BCH-10618, bimatoprost, BMS-184476, BMS-275183, BMS-387032, botulinum toxin type B, BR-1, BR96-Doxorubicin; Capravirine, caspofungin acetate, cinacalcet hydrochloride; Darbepoetin alfa, desloratadine, dextrin sulfate, DJ-927, duloxetine hydrochloride; Elacridar, emtricitabine, eplerenone, ertapenem sodium, escitalopram oxalate, ESP-24217, etoricoxib, exenatide, ezetimibe; Ferumoxtran-10, fondaparinux sodium, fosamprenavir calcium; GS-7904L, GW-5634; HMN-214, human insulin; IC-14, imatinib mesylate, indiplon, insulin glargine, insulinotropin, iseganan hydrochloride; Lanthanum carbonate, L-Arginine hydrochloride, LEA29Y, lenalidomide, LE-SN38, lestaurtinib, L-MDAM, lometrexol, lopinavir, lopinavir/ritonavir; Magnesium sulfate, maraviroc, mepolizumab, metreleptin, milataxel, MNA-715, morphine hydrochloride; Nesiritide, neutrophil-inhibitory factor, NK-911; Olanzapine/fluoxetine hydrochloride, olmesartan medoxomil, omalizumab, ortataxel, oxycodone hydrochloride/ibuprofen; Panitumumab, patupilone, PC-515, PD-MAGE-3 Vaccine, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ ribavirin, pemetrexed disodium, pimecrolimus, prasugrel, pregabalin, PRO-2000; Rosuvastatin calcium, RPR-113090; sabarubicin hydrochloride, safinamide mesilate, SB-715992, sitaxsentan sodium, soblidotin, synthadotin; Tadalafil, taltobulin, temsirolimus, tenofovir disoproxil fumarate, tenofovir disoproxil fumarate/emtricitabine, testosterone gel, tigecycline, tipranavir, tirapazamine, trabectedin

  20. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2005-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (-)-Epigallocatechin gallate, (Z)-4-hydroxytamoxifen; Ad.muIFN-beta AD-237, adalimumab, adefovir dipivoxil, agalsidase alfa, alemtuzumab, almotriptan, ALVAC vCP1452, alvimopan hydrate, ambrisentan, anakinra, anti-IFN-gamma MAb; Bimatoprost, BMS-188797, BMS-214662, bortezomib, bosentan, bovine lactoferrin; Caffeine, canertinib dihydrochloride, canfosfamide hydrochloride, cannabidiol, caspofungin acetate, cetuximab, cH36, ChimeriVax-JE, ciclesonide, cilansetron, cinacalcet hydrochloride, clopidogrel, CpG-7909, Cypher; Daptomycin, darbepoetin alfa, darifenacin hydrobromide, decitabine, denufosol tetrasodium, Dexamet, diindolemethane, drotrecogin alfa (activated), duloxetine hydrochloride, DX-9065a; E-7010, edaravone, efalizumab, eicosapentaenoic acid/docosahexaenoic acid, elacridar, eletriptan, emtricitabine, epratuzumab, erlotinib hydrochloride, ertapenem sodium, eszopiclone, everolimus, ezetimibe; Fludarabine, fondaparinux sodium; gamma-Hydroxybutyrate sodium, gavestinel sodium, gefitinib, granisetron-Biochronomer; Human Albumin, human insulin; Imatinib mesylate, indiplon, interleukin-2 XL, isatoribine, ISS-1018, i.v. gamma-globulin, ivabradine hydrochloride, ixabepilone; Lanthanum carbonate, L-arginine hydrochloride, liposomal doxorubicin, LY-450139; Magnesium sulfate, melatonin, motexafin gadolinium, mycophenolic acid sodium salt; Natalizumab, nesiritide, niacin/lovastatin; OGX-011, olmesartan medoxomil, omalizumab, ospemifene; PACAP38, panitumumab, parathyroid hormone (human recombinant), parecoxib sodium, patupilone, pegfilgrastim, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b

  1. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-04-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity. prous.com. This issue focuses on the following selection of drugs: ABX-IL-8, Acclaim, adalimumab, AGI-1067, alagebrium chloride, alemtuzumab, Alequel, Androgel, anti-IL-12 MAb, AOD-9604, aripiprazole, atomoxetine hydrochloride; Biphasic insulin aspart, bosentan, botulinum toxin type B, bovine lactoferrin, brivudine; Cantuzumab mertansine, CB-1954, CDB-4124, CEA-TRICOM, choriogonadotropin alfa, cilansetron, CpG-10101, CpG-7909, CTL-102, CTL-102/CB-1954; DAC:GRF, darbepoetin alfa, davanat-1, decitabine, del-1 Genemedicine, dexanabinol, dextofisopam, dnaJP1, dronedarone hydrochloride, dutasteride; Ecogramostim, eletriptan, emtricitabine, EPI-hNE-4, eplerenone, eplivanserin fumarate, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, esomeprazole magnesium, etoricoxib, ezetimibe; Falecalcitriol, fingolimod hydrochloride; Gepirone hydrochloride; HBV-ISS, HSV-2 theracine, human insulin; Imatinib mesylate, Indiplon, insulin glargine, ISAtx-247; L612 HuMAb, levodopa/carbidopa/entacapone, lidocaine/prilocaine, LL-2113AD, lucinactant, LY-156735; Meclinertant, metelimumab, morphine hydrochloride, morphine-6-glucuronide; Natalizumab, nimotuzumab, NX-1207, NYVAC-HIV C; Omalizumab, onercept, osanetant; PABA, palosuran sulfate, parathyroid hormone (human recombinant), parecoxib sodium, PBI-1402, PCK-3145, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, pimecrolimus, PINC, pregabalin; Ramelteon, rasagiline mesilate, rasburicase, rimonabant hydrochloride, RO-0098557, rofecoxib, rosiglitazone maleate/metformin hydrochloride; Safinamide mesilate, SHL-749, sitaxsentan sodium, sparfosic acid, SprayGel, squalamine, St. John's Wort

  2. Advances in designs for Alzheimer’s disease clinical trials

    PubMed Central

    Cummings, Jeffrey; Gould, Heath; Zhong, Kate

    2012-01-01

    There is an urgent need to identify new treatments for the rapidly growing population of people with Alzheimer’s disease (AD). Innovations in clinical trial designs many help to reduce development time, provide more definitive answers regarding drug efficacy, and facilitate prioritizing compounds to be advanced to Phase III clinical trials. Standard designs compare drug and placebo changes from baseline on a rating scale. Baysian adaptive clinical trials allow the use of data collected in the trial to modify doses, sample size, trial duration, and entry criteria in an ongoing way as the data are collected. Disease-modification is supported by findings on staggered start and delayed withdrawal designs. Futility designs can use historical controls and may shorten trial duration. Combination therapy designs may allow investigation of additive or synergistic treatment effects. Novel trial selection criteria allow investigation of treatment effects in asymptomatic or minimally symptomatic, prodromal AD populations. The Clinical Dementia Rating-Sum of Boxes (CDR-SOB) can be considered as a single trial outcome in early disease populations. Alternate forms of the Alzheimer’s Disease Assessment Scale-Cognitive Portion (ADAS-cog), computerized measures, and pharmacoeconomic scales provide new and relevant information on drug effects. Comparative dose strategies are used in trials of symptomatic agents, and novel methods including withdrawal designs, symptom emergence analyses, and sequential designs are being utilized to assess the efficacy of putative psychotropic agents. The choice of trial design is driven by the question to be answered by the clinical trial; an increasing number of design approaches are available and may be useful in accelerating and refining AD drug development. PMID:23383393

  3. SMARTer Discontinuation Trial Designs for Developing an Adaptive Treatment Strategy

    PubMed Central

    Compton, Scott N.; Rynn, Moira A.; Walkup, John T.; Murphy, Susan A.

    2012-01-01

    Abstract Objective Developing evidenced-based practices for the management of childhood psychiatric disorders requires research studies that address how to treat children during both the acute phase of the disorder and beyond. Given the selection of a medication for acute treatment, discontinuation trials are used to evaluate the effects of treatment duration (e.g., time on medication) and/or maintenance strategies following successful acute-phase treatment. Recently, sequential multiple assignment randomized trials (SMART) have been proposed for use in informing sequences of critical clinical decisions such as those mentioned. The objective of this article is to illustrate how a SMART study is related to the standard discontinuation trial design, while addressing additional clinically important questions with similar trial resources. Method The recently completed Child/Adolescent Anxiety Multimodal Study (CAMS), a randomized trial that examined the relative efficacy of three acute-phase treatments for pediatric anxiety disorders, along with a next logical step, a standard discontinuation trial design, is used to clarify the ideas. This example is used to compare the discontinuation trial design relative to the SMART design. Results We find that the standard discontinuation trial can be modified slightly using a SMART design to yield high-quality data that can be used to address a wider variety of questions in addition to the impact of treatment duration. We discuss how this innovative trial design is ultimately more efficient and less costly than the standard discontinuation trial, and may result in more representative comparisons between treatments. Conclusions Mental health researchers who are interested in addressing questions concerning the effects of continued treatment (for different durations) following successful acute-phase treatment should consider SMART designs in place of discontinuation trial designs in their research. SMART designs can be used to

  4. Likelihood and clinical trials.

    PubMed

    Hill, G; Forbes, W; Kozak, J; MacNeill, I

    2000-03-01

    The history of the application of statistical theory to the analysis of clinical trials is reviewed. The current orthodoxy is a somewhat illogical hybrid of the original theory of significance tests of Edgeworth, Karl Pearson, and Fisher, and the subsequent decision theory approach of Neyman, Egon Pearson, and Wald. This hegemony is under threat from Bayesian statisticians. A third approach is that of likelihood, stemming from the work of Fisher and Barnard. This approach is illustrated using hypothetical data from the Lancet articles by Bradford Hill, which introduced clinicians to statistical theory. PMID:10760630

  5. Methodological challenges in online trials.

    PubMed

    Murray, Elizabeth; Khadjesari, Zarnie; White, Ian R; Kalaitzaki, Eleftheria; Godfrey, Christine; McCambridge, Jim; Thompson, Simon G; Wallace, Paul

    2009-01-01

    Health care and health care services are increasingly being delivered over the Internet. There is a strong argument that interventions delivered online should also be evaluated online to maximize the trial's external validity. Conducting a trial online can help reduce research costs and improve some aspects of internal validity. To date, there are relatively few trials of health interventions that have been conducted entirely online. In this paper we describe the major methodological issues that arise in trials (recruitment, randomization, fidelity of the intervention, retention, and data quality), consider how the online context affects these issues, and use our experience of one online trial evaluating an intervention to help hazardous drinkers drink less (DownYourDrink) to illustrate potential solutions. Further work is needed to develop online trial methodology. PMID:19403465

  6. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2002-11-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abacavir sulfate, abarelix, adalimumab, adefovir dipivoxil, AdGVVEGF121.10, anastrozole, anecortave acetate, aripiprazole, asulacrine isethionate, atazanavir, ATL-962, 16-Aza-epothilone B; Bevacizumab, bicalutamide, blonanserin, BMS-188667, bosentan; Celecoxib, celmoleukin, cetuximab, cilomilast, cinacalcet hydrochloride, CNTF(Ax15), colesevelam hydrochloride; Daclizumab, delavirdine mesilate, desogestrel, desoxyepothilone B, dexmethylphenidate hydrochloride, duloxetine hydrochloride; Ecogramostim, emtricitabine, epalrestat, escitalopram oxalate, examorelin, exendin-4, ezetimibe; Fidarestat, frovatriptan; HIV-1 Immunogen; Iloperidone, insulin detemir, insulin lispro, irinotecan hydrochloride; Keratinocyte growth factor; Lasofoxifene tartrate, levetiracetam, levormeloxifene, levosimendan, lumiracoxib, LY-307161 SR; Memantine hydrochloride, MEN-10755, metformin hydrochloride, metreleptin, motexafin gadolinium; Naratriptan hydrochloride, natalizumab, nesiritide, nicotine, NN-2211, NN-414; Olanzapine, omalizumab; Pegaptanib sodium, peginterferon alfa-2a, peginterferon alfa-2b, pegvisomant, pimecrolimus, pirfenidone, pramlintide acetate prasterone, pregabalin; Quetiapine fumarate; Rabeprazole sodium, raloxifene hydrochloride, raltitrexed, rDNA insulin, rFGF-2, risedronate sodium, rofecoxib, roflumilast, rosiglitazone maleate; SN-22995; Tacrolimus, tadalafil, tegaserod maleate, tiotropium bromide, tomoxetine hydrochloride, trastuzumab, trimegestone; Voglibose, Voriconazole; Ziprasidone hydrochloride. PMID:12616707

  7. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2002-05-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables can be retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abacavir sulfate, abarelix, abciximab, acarbose, alefacept, alteplase, amisulpride, amoxicillin trihydrate, apomorphine hydrochloride, aprepitant, argatroban monohydrate, aspirin, atenolol; Betamethasone dipropionate, betamethasone valerate, bicalutamide, bleomycin sulfate; Calcium carbonate, candesartan cilexetil, celecoxib, cetirizine hydrochloride, cisplatin, clarithromycin, clavulanate potassium, clomethiazole edisilate, clopidogrel hydrogensulfate, cyclophosphamide, chorionic gonadotropin (human); Dalteparin sodium, desloratadine, dexamethasone, doxorubicin, DPC-083; Efalizumab, efavirenz, enoxaparin sodium, eprosartan mesilate, etanercept, etoposide, ezetimibe; Faropenem daloxate, fenofibrate, fluocinolone acetonide, flutamide, fluvastatin sodium, follitropin beta, fondaparinux sodium; Gabapentin, glibenclamide, goserelin, granisetron hydrochloride; Haloperidol, hydrochlorothiazide; Imiquimod, interferon beta-1a, irbesartan, iseganan hydrochloride; L-758298, lamivudine, lanoteplase, leflunomide, leuprorelin acetate, loratadine, losartan potassium; Melagatran, metformin hydrochloride, methotrexate, metronidazole, micafungin sodium, mitoxantrone hydrochloride; Nelfinavir mesilate, neutral insulin injection, nizatidine; Olopatadine hydrochloride, omeprazole, ondansetron hydrochloride; Pamidronate sodium, paracetamol, paroxetine hydrochloride, perindopril, pimecrolimus, pioglitazone hydrochloride, piroxicam, pleconaril, pralmorelin, pravastatin sodium, prednisolone, prednisone, propofol; Raloxifene hydrochloride, ranpirnase, remifentanil hydrochloride, risedronate sodium, risperidone, rofecoxib, ropinirole

  8. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, ademetionine, agalsidase alfa, agalsidase beta, alemtuzumab, alfimeprase, AMG-162, androgel, anidulafungin, antigastrin therapeutic vaccine, aripiprazole, atomoxetine hydrochloride; Bazedoxifene acetate, bevacizumab, bosentan; Caldaret hydrate, canfosfamide hydrochloride, choriogonadotropin alfa, ciclesonide, combretastatin A-4 phosphate, CY-2301; Darbepoetin alfa, darifenacin hydrobromide, decitabine, degarelix acetate, duloxetine hydrochloride; ED-71, enclomiphene citrate, eplerenone, epratuzumab, escitalopram oxalate, eszopiclone, ezetimibe; Fingolimod hydrochloride, FP-1096; HMR-3339A, HSV-TK/GCV gene therapy, human insulin, HuOKT3gamma1(Ala234-Ala235); Idursulfase, imatinib mesylate, indiplon, InnoVax C insulin glargine, insulin glulisine, irofulven; Labetuzumab, lacosamide, lanthanum carbonate, LyphoDerm, Lyprinol; Magnesium sulfate, metelimumab, methylphenidate hydrochloride; Natalizumab, NO-aspirin; OROS(R); PC-515, pegaptanib sodium, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, peptide YY3-36, posaconazole, pregabalin, PT-141, pyridoxamine; R-744, ramelteon, ranelic acid distrontium salt, rebimastat, repinotan hydrochloride, rhC1, rhGAD65, rosiglitazone maleate/metformin hydrochloride; Sardomozide, solifenacin succinate; Tadalafil, taxus, telavancin, telithromycin, tenofovir disoproxil fumarate, teriparatide, testosterone transdermal patch, tetomilast, tirapazamine, torcetrapib; Valspodar, vardenafil hydrochloride hydrate, vildagliptin; Yttrium Y90 epratuzumab; Ziprasidone hydrochloride. PMID:15672123

  9. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2002-01-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses, which has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the world's first drug discovery and development portal, providing information on study design, treatments, conclusions and references. This issue focuses on the following selection of drugs: Abacavir sulfate; abciximab; abetimus sodium; adalimumab; aldesleukin; almotriptan; alteplase; amisulpride; amitriptyline hydrochloride; amoxicillin trihydrate; atenolol; atorvastatin calcium; atrasentan; Beclometasone dipropionate; bosentan; Captopril; ceftriaxone sodium; cerivastatin sodium; cetirizine hydrochloride; cisplatin; citalopram hydrobromide; Dalteparin sodium; darusentan; desirudin; digoxin; Efalizumab; enoxaparin sodium; ertapenem sodium; esomeprazole magnesium; estradiol; ezetimibe; Famotidine; farglitazar; fluorouracil; fluticasone propionate; fosamprenavir sodium; Glibenclamide; glucosamine sulfate; Heparin sodium; HSPPC-96; hydrochlorothiazide; Imatinib mesilate; implitapide; Lamivudine; lansoprazole; lisinopril; losartan potassium; l-Propionylcarnitine; Melagatran; metformin hydrochloride; methotrexate; methylsulfinylwarfarin; Nateglinide; norethisterone; Olmesartan medoxomil; omalizumab; omapatrilat; omeprazole; oseltamivir phosphate; oxatomide; Pantoprazole; piperacillin sodium; pravastatin sodium; Quetiapine hydrochloride; Rabeprazole sodium; raloxifene hydrochloride; ramosetron hydrochloride; ranolazine; rasburicase; reboxetine mesilate; recombinant somatropin; repaglinide; reteplase; rosiglitazone; rosiglitazone maleate; rosuvastatin calcium; Sertraline; simvastatin; sumatriptan succinate; Tazobactam sodium; tenecteplase; tibolone; tinidazole; tolterodine tartrate; troglitazone; Uniprost; Warfarin sodium; Ximelagatran. PMID:11980386

  10. Gatewa