42 results on '"Ghosn, L."'
Search Results
2. Separating the Influence of Environment from Stress Relaxation Effects on Dwell Fatigue Crack Growth in a Nickel-Base Disk Alloy
- Author
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Telesman, J, Gabb, T. P, and Ghosn, L. J
- Subjects
Metals And Metallic Materials - Abstract
Both environmental embrittlement and crack tip visco-plastic stress relaxation play a significant role in determining the dwell fatigue crack growth (DFCG) resistance of nickel-based disk superalloys. In the current study performed on the Low Solvus High Refractory (LSHR) disk alloy, the influence of these two mechanisms were separated so that the effects of each could be quantified and modeled. Seven different microstructural variations of LSHR were produced by controlling the cooling rate and the subsequent aging and thermal exposure heat treatments. Through cyclic fatigue crack growth testing performed both in air and vacuum, it was established that four out of the seven LSHR heat treatments evaluated, possessed similar intrinsic environmental resistance to cyclic crack growth. For these four heat treatments, it was further shown that the large differences in dwell crack growth behavior which still persisted, were related to their measured stress relaxation behavior. The apparent differences in their dwell crack growth resistance were attributed to the inability of the standard linear elastic fracture mechanics (LEFM) stress intensity parameter to account for visco-plastic behavior. Crack tip stress relaxation controls the magnitude of the remaining local tensile stresses which are directly related to the measured dwell crack growth rates. It was hypothesized that the environmentally weakened grain boundary crack tip regions fail during the dwells when their strength is exceeded by the remaining local crack tip tensile stresses. It was shown that the classical creep crack growth mechanisms such as grain boundary sliding did not contribute to crack growth, but the local visco-plastic behavior still plays a very significant role by determining the crack tip tensile stress field which controls the dwell crack growth behavior. To account for the influence of the visco-plastic behavior on the crack tip stress field, an empirical modification to the LEFM stress intensity parameter, Kmax, was developed by incorporating into the formulation the remaining stress level concept as measured by simple stress relaxation tests. The newly proposed parameter, Ksrf, did an excellent job in correlating the dwell crack growth rates for the four heat treatments which were shown to have similar intrinsic environmental cyclic fatigue crack growth resistance.
- Published
- 2016
3. Burst Testing of Triaxial Braided Composite Tubes
- Author
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Salem, J. A, Bail, J. L, Wilmoth, N. G, Ghosn, L. J, Kohlman, L. W, Roberts, G. D, and Martin, R. E
- Subjects
Structural Mechanics ,Composite Materials - Abstract
Applications using triaxial braided composites are limited by the materials transverse strength which is determined by the delamination capacity of unconstrained, free-edge tows. However, structural applications such as cylindrical tubes can be designed to minimize free edge effects and thus the strength with and without edge stresses is relevant to the design process. The transverse strength of triaxial braided composites without edge effects was determined by internally pressurizing tubes. In the absence of edge effects, the axial and transverse strength were comparable. In addition, notched specimens, which minimize the effect of unconstrained tow ends, were tested in a variety of geometries. Although the commonly tested notch geometries exhibited similar axial and transverse net section failure strength, significant dependence on notch configuration was observed. In the absence of unconstrained tows, failure ensues as a result of bias tow rotation, splitting, and fracture at cross-over regions.
- Published
- 2014
4. Effect of fiber volume fraction on the fracture behavior of Nb-1 wt pct Zr/218W composites at elevated temperatures
- Author
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Raj, S. V. and Ghosn, L. J.
- Published
- 2000
- Full Text
- View/download PDF
5. Dwell Notch Low Cycle Fatigue Behavior of a Powder Metallurgy Nickel Disk Alloy
- Author
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Telesman, J, Gabb, T. P, Yamada, Y, Ghosn, L. J, and Jayaraman, N
- Subjects
Metals And Metallic Materials - Abstract
A study was conducted to determine the processes which govern dwell notch low cycle fatigue (NLCF) behavior of a powder metallurgy (P/M) ME3 disk superalloy. The emphasis was placed on the environmentally driven mechanisms which may embrittle the highly stressed notch surface regions and reduce NLCF life. In conjunction with the environmentally driven notch surface degradation processes, the visco-plastic driven mechanisms which can significantly change the notch root stresses were also considered. Dwell notch low cycle fatigue testing was performed in air and vacuum on a ME3 P/M disk alloy specimens heat treated using either a fast or a slow cooling rate from the solutioning treatment. It was shown that dwells at the minimum stress typically produced a greater life debit than the dwells applied at the maximum stress, especially for the slow cooled heat treatment. Two different environmentally driven failure mechanisms were identified as the root cause of early crack initiation in the min dwell tests. Both of these failure mechanisms produced mostly a transgranular crack initiation failure mode and yet still resulted in low NLCF fatigue lives. The lack of stress relaxation during the min dwell tests produced higher notch root stresses which caused early crack initiation and premature failure when combined with the environmentally driven surface degradation mechanisms. The importance of environmental degradation mechanisms was further highlighted by vacuum dwell NLCF tests which resulted in considerably longer NLCF lives, especially for the min dwell tests.
- Published
- 2012
6. Factors Influencing Dwell Fatigue Cracking in Notches of Powder Metallurgy Superalloys
- Author
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Gabb, T. P, Telesman, J, Ghosn, L, Garg, A, and Gayda, J
- Subjects
Aircraft Propulsion And Power - Abstract
The influences of heat treatment and cyclic dwells on the notch fatigue resistance of powder metallurgy disk superalloys were investigated for low solvus high refractory (LSHR) and ME3 disk alloys. Disks were processed to produce material conditions with varied microstructures and associated mechanical properties. Notched specimens were first subjected to baseline dwell fatigue cycles having a dwell at maximum load, as well as tensile, stress relaxation, creep rupture, and dwell fatigue crack growth tests at 704 C. Several material heat treatments displayed a bimodal distribution of fatigue life with the lives varying by two orders-of-magnitude, while others had more consistent fatigue lives. This response was compared to other mechanical properties, in search of correlations. The wide scatter in baseline dwell fatigue life was observed only for material conditions resistant to stress relaxation. For selected materials and conditions, additional tests were then performed with the dwells shifted in part or in total to minimum tensile load. The tests performed with dwells at minimum load exhibited lower fatigue lives than max dwell tests, and also exhibited early crack initiation and a substantial increase in the number of initiation sites. These results could be explained in part by modeling evolution of peak stresses in the notch with continued dwell fatigue cycling. Fatigue-environment interactions were determined to limit life for the fatigue cycles with dwells.
- Published
- 2011
7. Effect of the Machining Processes on Low Cycle Fatigue Behavior of a Powder Metallurgy Disk
- Author
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Telesman, J, Kantzos, P, Gabb, T. P, and Ghosn, L. J
- Subjects
Metals And Metallic Materials - Abstract
A study has been performed to investigate the effect of various machining processes on fatigue life of configured low cycle fatigue specimens machined out of a NASA developed LSHR P/M nickel based disk alloy. Two types of configured specimen geometries were employed in the study. To evaluate a broach machining processes a double notch geometry was used with both notches machined using broach tooling. EDM machined notched specimens of the same configuration were tested for comparison purposes. Honing finishing process was evaluated by using a center hole specimen geometry. Comparison testing was again done using EDM machined specimens of the same geometry. The effect of these machining processes on the resulting surface roughness, residual stress distribution and microstructural damage were characterized and used in attempt to explain the low cycle fatigue results.
- Published
- 2010
8. Mechanical Properties of 17-4PH Stainless Steel Foam Panels
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Raj, S. V, Ghosn, L. J, Lerch, B. a, Hebsur, M, Cosgriff, L. M, and Fedor, J
- Subjects
Metals And Metallic Materials - Abstract
Rectangular 17-4PH stainless steel sandwiched foam panels were fabricated using a commercial manufacturing technique by brazing two sheets to a foam core. Microstructural observations and ultrasonic nondestructive evaluation of the panels revealed large variations in the quality of the brazed areas from one panel to the next as well as within the same panel. Shear tests conducted on specimens machined from the panels exhibited failures either in the brazed region or in the foam core for the poorly brazed and well-brazed samples, respectively. Compression tests were conducted on the foam cores to evaluate their elastic and plastic deformation behavior. These data were compared with published data on polymeric and metallic foams, and with theoretical deformation models proposed for open cell foams.
- Published
- 2007
9. Failure Maps for Rectangular 17-4PH Stainless Steel Sandwiched Foam Panels
- Author
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Raj, S. V and Ghosn, L. J
- Subjects
Aircraft Design, Testing And Performance - Abstract
A new and innovative concept is proposed for designing lightweight fan blades for aircraft engines using commercially available 17-4PH precipitation hardened stainless steel. Rotating fan blades in aircraft engines experience a complex loading state consisting of combinations of centrifugal, distributed pressure and torsional loads. Theoretical failure plastic collapse maps, showing plots of the foam relative density versus face sheet thickness, t, normalized by the fan blade span length, L, have been generated for rectangular 17-4PH sandwiched foam panels under these three loading modes assuming three failure plastic collapse modes. These maps show that the 17-4PH sandwiched foam panels can fail by either the yielding of the face sheets, yielding of the foam core or wrinkling of the face sheets depending on foam relative density, the magnitude of t/L and the loading mode. The design envelop of a generic fan blade is superimposed on the maps to provide valuable insights on the probable failure modes in a sandwiched foam fan blade.
- Published
- 2007
10. Low Pressure Plasma Sprayed Overlay Coatings for GRCop-84 Combustion Chamber Liners for Reusable Launch Vehicles
- Author
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Raj, S. V, Barrett, C, Ghosn, L. J, Lerch, B, Robinson, and Thorn, G
- Subjects
Metals And Metallic Materials - Abstract
An advanced Cu-8(at.%)Cr-4%Nb alloy developed at NASA's Glenn Research Center, and designated as GRCop-84, is currently being considered for use as combustor chamber liners and nozzle ramps in NASA s future generations of reusable launch vehicles (RLVs). However, past experience has shown that unprotected copper alloys undergo an environmental attack called "blanching" in rocket engines using liquid hydrogen as fuel and liquid oxygen as the oxidizer. Potential for sulfidation attack of the liners in hydrocarbon-fueled engines is also of concern. Protective overlay coatings alloys are being developed for GRCop-84. The development of this coatings technology has involved a combination of modeling, coatings development and characterization, and process optimization. Coatings have been low pressure plasma sprayed on GRCop-84 substrates of various geometries and shapes. Microstructural, mechanical property data and thermophysical results on the coated substrates are presented and discussed.
- Published
- 2005
11. Characterization of Cold Sprayed CuCrAl Coated GRCop-84 Substrates for Reusable Launch Vehicles
- Author
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Raj, S . V, Barrett, C. A, Lerch, B. A, Karthikeyan, J, Ghosn, L. J, and Haynes, J
- Subjects
Metals And Metallic Materials - Abstract
An advanced Cu-8(at.%)Cr-4%Nb alloy developed at NASA's Glenn Research Center, and designated as GRCop-84, is currently being considered for use as combustor liners and nozzles in NASA's future generations of reusable launch vehicles (RLVs). Despite the fact that this alloy has superior mechanical and oxidation properties compared to many commercially available copper alloys, it is felt that its high temperature and environmental resistance capabilities can be further enhanced with the development and use of suitable coatings. Several coatings and processes are currently being evaluated for their suitability and future down selection. A newly developed CuCrAl has shown excellent oxidation resistance compared to current generation Cu-Cr coating alloys. Cold spray technology for depositing the CuCrAl coating on a GRCop-84 substrate is currently being developed under NASA's Next Generation Launch Technology (NGLT) Propulsion Research and Technology (PR&T) project. The microstructures, mechanical and thermophysical properties of overlay coated GRCop-84 substrates are discussed.
- Published
- 2005
12. An Assessment of the Residual Stresses in Low Pressure Plasma Sprayed Coatings on an Advanced Copper Alloy
- Author
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Raj, S. V, Ghosn, L. J, Agarwal, A, and Lachtrupp, T. P
- Subjects
Metals And Metallic Materials - Abstract
Modeling studies were conducted on low pressure plasma sprayed (LPPS) NiAl top coat applied to an advanced Cu-8(at.%)Cr-4%Nb alloy (GRCop-84) substrate using Ni as a bond coat. A thermal analysis suggested that the NiAl and Ni top and bond coats, respectively, would provide adequate thermal protection to the GRCop-84 substrate in a rocket engine operating under high heat flux conditions. Residual stress measurements were conducted at different depths from the free surface on coated and uncoated GRCop-84 specimens by x-ray diffraction. These data are compared with theoretically estimated values assessed by a finite element analysis simulating the development of these stresses as the coated substrate cools down from the plasma spraying temperature to room temperature.
- Published
- 2002
13. Simulation of Crack Propagation in Engine Rotating Components Under Variable Amplitude Loading
- Author
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Bonacuse, P. J, Ghosn, L. J, Telesman, J, Calomino, A. M, and Kantzos, P
- Subjects
Aircraft Propulsion And Power - Abstract
The crack propagation life of tested specimens has been repeatedly shown to strongly depend on the loading history. Overloads and extended stress holds at temperature can either retard or accelerate the crack growth rate. Therefore, to accurately predict the crack propagation life of an actual component, it is essential to approximate the true loading history. In military rotorcraft engine applications, the loading profile (stress amplitudes, temperature, and number of excursions) can vary significantly depending on the type of mission flown. To accurately assess the durability of a fleet of engines, the crack propagation life distribution of a specific component should account for the variability in the missions performed (proportion of missions flown and sequence). In this report, analytical and experimental studies are described that calibrate/validate the crack propagation prediction capability for a disk alloy under variable amplitude loading. A crack closure based model was adopted to analytically predict the load interaction effects. Furthermore, a methodology has been developed to realistically simulate the actual mission mix loading on a fleet of engines over their lifetime. A sequence of missions is randomly selected and the number of repeats of each mission in the sequence is determined assuming a Poisson distributed random variable with a given mean occurrence rate. Multiple realizations of random mission histories are generated in this manner and are used to produce stress, temperature, and time points for fracture mechanics calculations. The result is a cumulative distribution of crack propagation lives for a given, life limiting, component location. This information can be used to determine a safe retirement life or inspection interval for the given location.
- Published
- 1999
14. Simulation of Crack Propagation in Engine Rotating Components under Variable Amplitude Loading
- Author
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Bonacuse, P. J, Ghosn, L. J, Telesman, J, Calomino, A. M, and Kantzos, P
- Subjects
Structural Mechanics - Abstract
The crack propagation life of tested specimens has been repeatedly shown to strongly depend on the loading history. Overloads and extended stress holds at temperature can either retard or accelerate the crack growth rate. Therefore, to accurately predict the crack propagation life of an actual component, it is essential to approximate the true loading history. In military rotorcraft engine applications, the loading profile (stress amplitudes, temperature, and number of excursions) can vary significantly depending on the type of mission flown. To accurately assess the durability of a fleet of engines, the crack propagation life distribution of a specific component should account for the variability in the missions performed (proportion of missions flown and sequence). In this report, analytical and experimental studies are described that calibrate/validate the crack propagation prediction capability ]or a disk alloy under variable amplitude loading. A crack closure based model was adopted to analytically predict the load interaction effects. Furthermore, a methodology has been developed to realistically simulate the actual mission mix loading on a fleet of engines over their lifetime. A sequence of missions is randomly selected and the number of repeats of each mission in the sequence is determined assuming a Poisson distributed random variable with a given mean occurrence rate. Multiple realizations of random mission histories are generated in this manner and are used to produce stress, temperature, and time points for fracture mechanics calculations. The result is a cumulative distribution of crack propagation lives for a given, life limiting, component location. This information can be used to determine a safe retirement life or inspection interval for the given location.
- Published
- 1998
15. An Assessment of the Axial and Radial Dilation of a DPIMS Tantalum Cartridge for Space Shuttle Flight Experiments
- Author
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Raj, S.V and Ghosn, L. J
- Subjects
Metallic Materials - Abstract
Ground-based heat treatment tests are planned on an argon gas-filled tantalum cartridge developed as pan of a Diffusion Processes in Molten Semiconductors (DPIMS) experiment conducted on NASA's Space Shuttle. The possibility that the cartridge may creep during testing and touch the furnace walls is of real concern in this program. The present paper discusses the results of calculations performed to evaluate this possibility. Deformation mechanism maps were constructed using literature data in order to identify the creep mechanism dominant under the appropriate stresses and temperatures corresponding to the test conditions. These results showed that power-law creep was dominant when the grain size of the material exceeded 55 gm but Coble creep was the important mechanism below this value of grain size. Finite element analysis was used to analyze the heat treatment tWs assuming a furnace run away condition (which is a worst case scenario) using the appropriate creep parameters corresponding to grain sizes of 1 and 100 gm. Calculations were also conducted to simulate the effect of an initial 3 tilt of the cartridge assembly, the maximum possible tilt angle. The von Mises stress and su-ain distributions were calculated assuming that the cartridge was fixed at one end as it was heated from ambient temperature to 1823 K in 1.42 h, maintained at 1823 K for 9.5 h and then further heated to an over temperature condition of 2028 K in 0.3 h. The inelastic axial and radial displacements of the cartridge walls were evaluated by resolving the von Mises strain along the corresponding directions. These calculations reveal that the maximum axial and radial displacements are expected to be about 2.9 and 0.25 mm, respectively, for both fine and coarse-grained materials at 2028 K. It was determined that these displacements occur during heat-up to temperature and creep of the cartridge is likely to be relatively insignificant irrespective of grain size. Furthermore, with a 3' tilt of the cartridge, the deflection is increased by only 0.39 gm which is negligible. Since the gap between the furnace heating elements and the cartridge is about 7.5 mm and less than the maximum radial dilation of 0.25 mm at 2028 K, it is concluded that the cartridge is unlikely to touch the furnace walls during the experiments.
- Published
- 1998
16. Fatigue crack growth in unidirectional metal matrix composite
- Author
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Ghosn, L. J, Telesman, J, and Kantzos, P
- Subjects
Composite Materials - Abstract
The weight function method was used to determine the effective stress intensity factor and the crack opening profile for a fatigue tested composite which exhibited fiber bridging. The bridging mechanism was modeled using two approaches; the crack closure approach and the shear lag approach. The numerically determined stress intensity factor values from both methods were compared and correlated with the experimentally obtained crack growth rates for SiC/Ti-15-3 (0) (sub 8) oriented composites. The near crack tip opening profile was also determined for both methods and compared with the experimentally obtained measurements.
- Published
- 1990
17. Analysis of Mixed-Mode Crack Propagation Using the Boundary Integral Method
- Author
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Mendelson, A., Ghosn, L., Yagawa, Genki, editor, and Atluri, Satya N., editor
- Published
- 1986
- Full Text
- View/download PDF
18. Separating the Influence of Environment from Stress Relaxation Effects on Dwell Fatigue Crack Growth in a Nickel-Base Disk Alloy
- Author
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Gabb, T., primary, Ghosn, L., additional, and Telesman, J., additional
- Published
- 2016
- Full Text
- View/download PDF
19. Fatigue Crack Growth in a Unidirectional SCS-6/Ti-15-3 Composite
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Kantzos, P, primary, Telesman, J, additional, and Ghosn, L, additional
- Full Text
- View/download PDF
20. Dwell Notch Low Cycle Fatigue Behavior of a Powder Metallurgy Nickel Disk Alloy
- Author
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Telesman, J., primary, Gabb, T., additional, Yamada, Y., additional, Ghosn, L., additional, Hornbach, D., additional, and Jayaraman, N., additional
- Published
- 2012
- Full Text
- View/download PDF
21. Burst pressure failure of titanium tanks damaged by secondary plumes from hypervelocity impacts on aluminum shields
- Author
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Nahra, Henry, primary, Ghosn, L., additional, Christiansen, E., additional, Davis, B. A., additional, Keddy, C., additional, Rodriguez, K., additional, Miller, J., additional, and Bohl, W., additional
- Published
- 2012
- Full Text
- View/download PDF
22. Analysis of crack propagation in roller bearings using the boundary integral equation method - A mixed-mode loading problem
- Author
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Ghosn, L. J
- Subjects
Mechanical Engineering - Abstract
Crack propagation in a rotating inner raceway of a high-speed roller bearing is analyzed using the boundary integral method. The model consists of an edge plate under plane strain condition upon which varying Hertzian stress fields are superimposed. A multidomain boundary integral equation using quadratic elements was written to determine the stress intensity factors KI and KII at the crack tip for various roller positions. The multidomain formulation allows the two faces of the crack to be modeled in two different subregions, making it possible to analyze crack closure when the roller is positioned on or close to the crack line. KI and KII stress intensity factors along any direction were computed. These calculations permit determination of crack growth direction along which the average KI times the alternating KI is maximum.
- Published
- 1988
23. Analysis of mixed-mode crack propagation using the boundary integral method
- Author
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Mendelson, A and Ghosn, L. J
- Subjects
Structural Mechanics - Abstract
Crack propagation in a rotating inner raceway of a high speed roller bearing is analyzed using the boundary integral equation method. The method consists of an edge crack in a plate under tension, upon which varying Hertzian stress fields are superimposed. A computer program for the boundary integral equation method was written using quadratic elements to determine the stress and displacement fields for discrete roller positions. Mode I and Mode II stress intensity factors and crack extension forces G sub 00 (energy release rate due to tensile opening mode) and G sub r0 (energy release rate due to shear displacement mode) were computed. These calculations permit determination of that crack growth angle for which the change in the crack extension forces is maximum. The crack driving force was found to be the alternating mixed-mode loading that occurs with each passage of the most heavily loaded roller. The crack is predicted to propagate in a step-like fashion alternating between radial and inclined segments, and this pattern was observed experimentally. The maximum changes DeltaG sub 00 and DeltaG sub r0 of the crack extension forces are found to be good measures of the crack propagation rate and direction.
- Published
- 1986
24. Three-dimensional analysis of chevron-notched specimens by boundary integral method
- Author
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Mendelson, A and Ghosn, L
- Subjects
Structural Mechanics - Abstract
The chevron-notched short bar and short rod specimens was analyzed by the boundary integral equations method. This method makes use of boundary surface elements in obtaining the solution. The boundary integral models were composed of linear triangular and rectangular surface segments. Results were obtained for two specimens with width to thickness ratios of 1.45 and 2.00 and for different crack length to width ratios ranging from 0.4 to 0.7. Crack opening displacement and stress intensity factors determined from displacement calculations along the crack front and compliance calculations were compared with experimental values and with finite element analysis.
- Published
- 1983
25. Simulation of Crack Propagation in Engine Rotating Components Under Variable Amplitude Loading
- Author
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NATIONAL AERONAUTICS AND SPACE ADMINISTRATION CLEVELAND OH LEWIS RESEARCH CENTER, Bonacuse, P. J., Ghosn, L. J., Telesman, J., Calomino, A. M., Kantzos, P., NATIONAL AERONAUTICS AND SPACE ADMINISTRATION CLEVELAND OH LEWIS RESEARCH CENTER, Bonacuse, P. J., Ghosn, L. J., Telesman, J., Calomino, A. M., and Kantzos, P.
- Abstract
The crack propagation life of tested specimens has been repeatedly shown to strongly depend on the loading history. Overloads and extended stress holds at temperature can either retard or accelerate the crack growth rate. Therefore, to accurately predict the crack propagation life of an actual component, it is essential to approximate the time loading history. In military rotorcraft engine applications, the loading profile (stress amplitudes, temperature, and number of excursions) can vary significantly depending on the type of mission flown. To accurately assess the durability of a fleet of engines, the crack propagation life distribution of a specific component should account for the variability in the missions performed (proportion of missions flown and sequence). In this report, analytical and experimental studies are described that calibrate/validate the crack propagation prediction capability for a disk alloy under variable amplitude loading. A crack closure based model was adopted to analytically predict the load interaction effects. Furthermore. a methodology has been developed to realistically simulate the actual mission mix loading on a fleet of engines over their lifetime. A sequence of missions is randomly selected and the number of repeats of each mission in the sequence is determined assuming a Poisson distributed random variable with a given mean occurrence rate. Multiple realizations of random mission histories are generated in this manner and are used to produce stress, temperature, and time points for fracture mechanics calculations. The result is a cumulative distribution of crack propagation lives for a given, life limiting, component location. This information can be used to determine a safe retirement life or inspection interval for the given location., Prepared in collaboration with Case Western Reserve Univ., Cleveland, OH., and Ohio Aerospace Inst., Cleveland, OH.
- Published
- 1998
26. BURST PRESSURE FAILURE OF TITANIUM TANKS DAMAGED BY SECONDARY PLUMES FROM HYPERVELOCITY IMPACTS ON ALUMINUM SHIELDS.
- Author
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Nahra, H., Ghosn, L., Christiansen, E., Davis, B. A., Keddy, C., Rodriguez, K., Miller, J., and Bohl, W.
- Subjects
- *
FAILURE analysis , *TITANIUM , *ALUMINUM construction , *HYPERVELOCITY , *SPACE vehicle design & construction - Abstract
Metallic pressure tanks used in space missions are inherently vulnerable to hypervelocity impacts from micrometeoroids and orbital debris; thereby knowledge of impact damage and its effect on the tank integrity is crucial to a spacecraft risk assessment. This paper describes tests that have been performed to assess the effects of hypervelocity impact (HVI) damage on Titanium alloy (Ti-6Al-4V) pressure vessels burst pressure and characteristics. The tests consisted of a pair of HVI impact tests on water-filled Ti-6Al-4V tanks (water being used as a surrogate to the actual propellant) and subsequent burst tests as well as a burst test on an undamaged control tank. The tanks were placed behind Aluminum (Al) shields and then each was impacted with a 7 km/s projectile. The resulting impact debris plumes partially penetrated the Ti-6Al-4V tank surfaces resulting in a distribution of craters. During the burst tests, the tank that failed at a lower burst pressure did appear to have the failure initiating at a crater site with observed spall cracks. A fracture mechanics analysis showed that the tanks failure at the impact location may have been due to a spall crack that formed upon impact of a fragmentation on the Titanium surface. This result was corroborated with a finite element analysis from calculated Von-Mises and hoop stresses. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
27. Fatigue Crack Growth Behavior of PWA 1484 Single Crystal Superalloy at Elevated Temperatures
- Author
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Telesman, J., primary and Ghosn, L. J., additional
- Published
- 1996
- Full Text
- View/download PDF
28. The Effect of Fatigue Loading on the Interfacial Shear Properties of SCS-6/Ti-Based MMCS
- Author
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Kantzos, Pete, primary, Eldridge, J., additional, Koss, D. A., additional, and Ghosn, L. J., additional
- Published
- 1992
- Full Text
- View/download PDF
29. The Effect of Fatigue Loading on the Interfacial Shear Properties of SCS-6/Ti-Based MMCS.
- Author
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Kantzos, Pete, Eldridge, J., Koss, D. A., and Ghosn, L. J.
- Published
- 1992
- Full Text
- View/download PDF
30. Fatigue crack growth in a unidirectional SCS-6/Ti-15-3 composite
- Author
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Ghosn, L
- Published
- 1989
31. Interleukin-6 blocking agents for treating COVID-19: a living systematic review.
- Author
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Ghosn L, Assi R, Evrenoglou T, Buckley BS, Henschke N, Probyn K, Riveros C, Davidson M, Graña C, Bonnet H, Jarde A, Ávila C, Nejstgaard CH, Menon S, Ferrand G, Kapp P, Breuer C, Schmucker C, Sguassero Y, Nguyen TV, Devane D, Meerpohl JJ, Rada G, Hróbjartsson A, Grasselli G, Tovey D, Ravaud P, Chaimani A, and Boutron I
- Subjects
- Aged, Female, Humans, Male, Middle Aged, Bias, Cytokines, COVID-19, Interleukin-6 antagonists & inhibitors, COVID-19 Drug Treatment
- Abstract
Background: It has been reported that people with COVID-19 and pre-existing autoantibodies against type I interferons are likely to develop an inflammatory cytokine storm responsible for severe respiratory symptoms. Since interleukin 6 (IL-6) is one of the cytokines released during this inflammatory process, IL-6 blocking agents have been used for treating people with severe COVID-19., Objectives: To update the evidence on the effectiveness and safety of IL-6 blocking agents compared to standard care alone or to a placebo for people with COVID-19., Search Methods: We searched the World Health Organization (WHO) International Clinical Trials Registry Platform, the Living OVerview of Evidence (L·OVE) platform, and the Cochrane COVID-19 Study Register to identify studies on 7 June 2022., Selection Criteria: We included randomized controlled trials (RCTs) evaluating IL-6 blocking agents compared to standard care alone or to placebo for people with COVID-19, regardless of disease severity., Data Collection and Analysis: Pairs of researchers independently conducted study selection, extracted data and assessed risk of bias. We assessed the certainty of evidence using the GRADE approach for all critical and important outcomes. In this update we amended our protocol to update the methods used for grading evidence by establishing minimal important differences for the critical outcomes., Main Results: This update includes 22 additional trials, for a total of 32 trials including 12,160 randomized participants all hospitalized for COVID-19 disease. We identified a further 17 registered RCTs evaluating IL-6 blocking agents without results available as of 7 June 2022. The mean age range varied from 56 to 75 years; 66.2% (8051/12,160) of enrolled participants were men. One-third (11/32) of included trials were placebo-controlled. Twenty-two were published in peer-reviewed journals, three were reported as preprints, two trials had results posted only on registries, and results from five trials were retrieved from another meta-analysis. Eight were funded by pharmaceutical companies. Twenty-six included studies were multicenter trials; four were multinational and 22 took place in single countries. Recruitment of participants occurred between February 2020 and June 2021, with a mean enrollment duration of 21 weeks (range 1 to 54 weeks). Nineteen trials (60%) had a follow-up of 60 days or more. Disease severity ranged from mild to critical disease. The proportion of participants who were intubated at study inclusion also varied from 5% to 95%. Only six trials reported vaccination status; there were no vaccinated participants included in these trials, and 17 trials were conducted before vaccination was rolled out. We assessed a total of six treatments, each compared to placebo or standard care. Twenty trials assessed tocilizumab, nine assessed sarilumab, and two assessed clazakizumab. Only one trial was included for each of the other IL-6 blocking agents (siltuximab, olokizumab, and levilimab). Two trials assessed more than one treatment. Efficacy and safety of tocilizumab and sarilumab compared to standard care or placebo for treating COVID-19 At day (D) 28, tocilizumab and sarilumab probably result in little or no increase in clinical improvement (tocilizumab: risk ratio (RR) 1.05, 95% confidence interval (CI) 1.00 to 1.11; 15 RCTs, 6116 participants; moderate-certainty evidence; sarilumab: RR 0.99, 95% CI 0.94 to 1.05; 7 RCTs, 2425 participants; moderate-certainty evidence). For clinical improvement at ≥ D60, the certainty of evidence is very low for both tocilizumab (RR 1.10, 95% CI 0.81 to 1.48; 1 RCT, 97 participants; very low-certainty evidence) and sarilumab (RR 1.22, 95% CI 0.91 to 1.63; 2 RCTs, 239 participants; very low-certainty evidence). The effect of tocilizumab on the proportion of participants with a WHO Clinical Progression Score (WHO-CPS) of level 7 or above remains uncertain at D28 (RR 0.90, 95% CI 0.72 to 1.12; 13 RCTs, 2117 participants; low-certainty evidence) and that for sarilumab very uncertain (RR 1.10, 95% CI 0.90 to 1.33; 5 RCTs, 886 participants; very low-certainty evidence). Tocilizumab reduces all cause-mortality at D28 compared to standard care/placebo (RR 0.88, 95% CI 0.81 to 0.94; 18 RCTs, 7428 participants; high-certainty evidence). The evidence about the effect of sarilumab on this outcome is very uncertain (RR 1.06, 95% CI 0.86 to 1.30; 9 RCTs, 3305 participants; very low-certainty evidence). The evidence is uncertain for all cause-mortality at ≥ D60 for tocilizumab (RR 0.91, 95% CI 0.80 to 1.04; 9 RCTs, 2775 participants; low-certainty evidence) and very uncertain for sarilumab (RR 0.95, 95% CI 0.84 to 1.07; 6 RCTs, 3379 participants; very low-certainty evidence). Tocilizumab probably results in little to no difference in the risk of adverse events (RR 1.03, 95% CI 0.95 to 1.12; 9 RCTs, 1811 participants; moderate-certainty evidence). The evidence about adverse events for sarilumab is uncertain (RR 1.12, 95% CI 0.97 to 1.28; 4 RCT, 860 participants; low-certainty evidence). The evidence about serious adverse events is very uncertain for tocilizumab (RR 0.93, 95% CI 0.81 to 1.07; 16 RCTs; 2974 participants; very low-certainty evidence) and uncertain for sarilumab (RR 1.09, 95% CI 0.97 to 1.21; 6 RCTs; 2936 participants; low-certainty evidence). Efficacy and safety of clazakizumab, olokizumab, siltuximab and levilimab compared to standard care or placebo for treating COVID-19 The evidence about the effects of clazakizumab, olokizumab, siltuximab, and levilimab comes from only one or two studies for each blocking agent, and is uncertain or very uncertain., Authors' Conclusions: In hospitalized people with COVID-19, results show a beneficial effect of tocilizumab on all-cause mortality in the short term and probably little or no difference in the risk of adverse events compared to standard care alone or placebo. Nevertheless, both tocilizumab and sarilumab probably result in little or no increase in clinical improvement at D28. Evidence for an effect of sarilumab and the other IL-6 blocking agents on critical outcomes is uncertain or very uncertain. Most of the trials included in our review were done before the waves of different variants of concern and before vaccination was rolled out on a large scale. An additional 17 RCTs of IL-6 blocking agents are currently registered with no results yet reported. The number of pending studies and the number of participants planned is low. Consequently, we will not publish further updates of this review., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)
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- 2023
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32. metaCOVID: A web-application for living meta-analyses of COVID-19 trials.
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Evrenoglou T, Boutron I, Seitidis G, Ghosn L, and Chaimani A
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- Humans, Software, COVID-19 Vaccines, COVID-19
- Abstract
Outputs from living evidence syntheses projects have been used widely during the pandemic by guideline developers to form evidence-based recommendations. However, the needs of different stakeholders cannot be accommodated by solely providing pre-defined non amendable numerical summaries. Stakeholders also need to understand the data and perform their own exploratory analyses. This requires resources, time, statistical expertise, software knowledge as well as relevant clinical expertise to avoid spurious conclusions. To assist them, we created the metaCOVID application which, based on automation processes, facilitates the fast exploration of the data and the conduct of sub-analyses tailored to end-users needs. metaCOVID has been created in R and is freely available as an R-Shiny application. Based on the COVID-NMA platform (https://covid-nma.com/) the application conducts living meta-analyses of randomized controlled trials related to COVID-19 treatments and vaccines for several outcomes. Several options are available for subgroup and sensitivity analyses. The results are presented in downloadable forest plots. We illustrate metaCOVID through three examples involving well-known treatments and vaccines for COVID-19. The application is freely available from https://covid-nma.com/metacovid/., (© 2023 The Authors. Research Synthesis Methods published by John Wiley & Sons Ltd.)
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- 2023
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33. Efficacy and safety of COVID-19 vaccines.
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Graña C, Ghosn L, Evrenoglou T, Jarde A, Minozzi S, Bergman H, Buckley BS, Probyn K, Villanueva G, Henschke N, Bonnet H, Assi R, Menon S, Marti M, Devane D, Mallon P, Lelievre JD, Askie LM, Kredo T, Ferrand G, Davidson M, Riveros C, Tovey D, Meerpohl JJ, Grasselli G, Rada G, Hróbjartsson A, Ravaud P, Chaimani A, and Boutron I
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- Humans, Middle Aged, Aged, Adolescent, SARS-CoV-2, 2019-nCoV Vaccine mRNA-1273, COVID-19 prevention & control
- Abstract
Background: Different forms of vaccines have been developed to prevent the SARS-CoV-2 virus and subsequent COVID-19 disease. Several are in widespread use globally. OBJECTIVES: To assess the efficacy and safety of COVID-19 vaccines (as a full primary vaccination series or a booster dose) against SARS-CoV-2., Search Methods: We searched the Cochrane COVID-19 Study Register and the COVID-19 L·OVE platform (last search date 5 November 2021). We also searched the WHO International Clinical Trials Registry Platform, regulatory agency websites, and Retraction Watch., Selection Criteria: We included randomized controlled trials (RCTs) comparing COVID-19 vaccines to placebo, no vaccine, other active vaccines, or other vaccine schedules., Data Collection and Analysis: We used standard Cochrane methods. We used GRADE to assess the certainty of evidence for all except immunogenicity outcomes. We synthesized data for each vaccine separately and presented summary effect estimates with 95% confidence intervals (CIs). MAIN RESULTS: We included and analyzed 41 RCTs assessing 12 different vaccines, including homologous and heterologous vaccine schedules and the effect of booster doses. Thirty-two RCTs were multicentre and five were multinational. The sample sizes of RCTs were 60 to 44,325 participants. Participants were aged: 18 years or older in 36 RCTs; 12 years or older in one RCT; 12 to 17 years in two RCTs; and three to 17 years in two RCTs. Twenty-nine RCTs provided results for individuals aged over 60 years, and three RCTs included immunocompromized patients. No trials included pregnant women. Sixteen RCTs had two-month follow-up or less, 20 RCTs had two to six months, and five RCTs had greater than six to 12 months or less. Eighteen reports were based on preplanned interim analyses. Overall risk of bias was low for all outcomes in eight RCTs, while 33 had concerns for at least one outcome. We identified 343 registered RCTs with results not yet available. This abstract reports results for the critical outcomes of confirmed symptomatic COVID-19, severe and critical COVID-19, and serious adverse events only for the 10 WHO-approved vaccines. For remaining outcomes and vaccines, see main text. The evidence for mortality was generally sparse and of low or very low certainty for all WHO-approved vaccines, except AD26.COV2.S (Janssen), which probably reduces the risk of all-cause mortality (risk ratio (RR) 0.25, 95% CI 0.09 to 0.67; 1 RCT, 43,783 participants; high-certainty evidence). Confirmed symptomatic COVID-19 High-certainty evidence found that BNT162b2 (BioNtech/Fosun Pharma/Pfizer), mRNA-1273 (ModernaTx), ChAdOx1 (Oxford/AstraZeneca), Ad26.COV2.S, BBIBP-CorV (Sinopharm-Beijing), and BBV152 (Bharat Biotect) reduce the incidence of symptomatic COVID-19 compared to placebo (vaccine efficacy (VE): BNT162b2: 97.84%, 95% CI 44.25% to 99.92%; 2 RCTs, 44,077 participants; mRNA-1273: 93.20%, 95% CI 91.06% to 94.83%; 2 RCTs, 31,632 participants; ChAdOx1: 70.23%, 95% CI 62.10% to 76.62%; 2 RCTs, 43,390 participants; Ad26.COV2.S: 66.90%, 95% CI 59.10% to 73.40%; 1 RCT, 39,058 participants; BBIBP-CorV: 78.10%, 95% CI 64.80% to 86.30%; 1 RCT, 25,463 participants; BBV152: 77.80%, 95% CI 65.20% to 86.40%; 1 RCT, 16,973 participants). Moderate-certainty evidence found that NVX-CoV2373 (Novavax) probably reduces the incidence of symptomatic COVID-19 compared to placebo (VE 82.91%, 95% CI 50.49% to 94.10%; 3 RCTs, 42,175 participants). There is low-certainty evidence for CoronaVac (Sinovac) for this outcome (VE 69.81%, 95% CI 12.27% to 89.61%; 2 RCTs, 19,852 participants). Severe or critical COVID-19 High-certainty evidence found that BNT162b2, mRNA-1273, Ad26.COV2.S, and BBV152 result in a large reduction in incidence of severe or critical disease due to COVID-19 compared to placebo (VE: BNT162b2: 95.70%, 95% CI 73.90% to 99.90%; 1 RCT, 46,077 participants; mRNA-1273: 98.20%, 95% CI 92.80% to 99.60%; 1 RCT, 28,451 participants; AD26.COV2.S: 76.30%, 95% CI 57.90% to 87.50%; 1 RCT, 39,058 participants; BBV152: 93.40%, 95% CI 57.10% to 99.80%; 1 RCT, 16,976 participants). Moderate-certainty evidence found that NVX-CoV2373 probably reduces the incidence of severe or critical COVID-19 (VE 100.00%, 95% CI 86.99% to 100.00%; 1 RCT, 25,452 participants). Two trials reported high efficacy of CoronaVac for severe or critical disease with wide CIs, but these results could not be pooled. Serious adverse events (SAEs) mRNA-1273, ChAdOx1 (Oxford-AstraZeneca)/SII-ChAdOx1 (Serum Institute of India), Ad26.COV2.S, and BBV152 probably result in little or no difference in SAEs compared to placebo (RR: mRNA-1273: 0.92, 95% CI 0.78 to 1.08; 2 RCTs, 34,072 participants; ChAdOx1/SII-ChAdOx1: 0.88, 95% CI 0.72 to 1.07; 7 RCTs, 58,182 participants; Ad26.COV2.S: 0.92, 95% CI 0.69 to 1.22; 1 RCT, 43,783 participants); BBV152: 0.65, 95% CI 0.43 to 0.97; 1 RCT, 25,928 participants). In each of these, the likely absolute difference in effects was fewer than 5/1000 participants. Evidence for SAEs is uncertain for BNT162b2, CoronaVac, BBIBP-CorV, and NVX-CoV2373 compared to placebo (RR: BNT162b2: 1.30, 95% CI 0.55 to 3.07; 2 RCTs, 46,107 participants; CoronaVac: 0.97, 95% CI 0.62 to 1.51; 4 RCTs, 23,139 participants; BBIBP-CorV: 0.76, 95% CI 0.54 to 1.06; 1 RCT, 26,924 participants; NVX-CoV2373: 0.92, 95% CI 0.74 to 1.14; 4 RCTs, 38,802 participants). For the evaluation of heterologous schedules, booster doses, and efficacy against variants of concern, see main text of review., Authors' Conclusions: Compared to placebo, most vaccines reduce, or likely reduce, the proportion of participants with confirmed symptomatic COVID-19, and for some, there is high-certainty evidence that they reduce severe or critical disease. There is probably little or no difference between most vaccines and placebo for serious adverse events. Over 300 registered RCTs are evaluating the efficacy of COVID-19 vaccines, and this review is updated regularly on the COVID-NMA platform (covid-nma.com). Implications for practice Due to the trial exclusions, these results cannot be generalized to pregnant women, individuals with a history of SARS-CoV-2 infection, or immunocompromized people. Most trials had a short follow-up and were conducted before the emergence of variants of concern. Implications for research Future research should evaluate the long-term effect of vaccines, compare different vaccines and vaccine schedules, assess vaccine efficacy and safety in specific populations, and include outcomes such as preventing long COVID-19. Ongoing evaluation of vaccine efficacy and effectiveness against emerging variants of concern is also vital., (Copyright © 2022 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)
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- 2022
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34. Transparency and reporting characteristics of COVID-19 randomized controlled trials.
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Kapp P, Esmail L, Ghosn L, Ravaud P, and Boutron I
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- Humans, Information Dissemination, Peer Review, Randomized Controlled Trials as Topic, Research Report, COVID-19
- Abstract
Background: In the context of the COVID-19 pandemic, randomized controlled trials (RCTs) are essential to support clinical decision-making. We aimed (1) to assess and compare the reporting characteristics of RCTs between preprints and peer-reviewed publications and (2) to assess whether reporting improves after the peer review process for all preprints subsequently published in peer-reviewed journals., Methods: We searched the Cochrane COVID-19 Study Register and L·OVE COVID-19 platform to identify all reports of RCTs assessing pharmacological treatments of COVID-19, up to May 2021. We extracted indicators of transparency (e.g., trial registration, data sharing intentions) and assessed the completeness of reporting (i.e., some important CONSORT items, conflict of interest, ethical approval) using a standardized data extraction form. We also identified paired reports published in preprint and peer-reviewed publications., Results: We identified 251 trial reports: 121 (48%) were first published in peer-reviewed journals, and 130 (52%) were first published as preprints. Transparency was poor. About half of trials were prospectively registered (n = 140, 56%); 38% (n = 95) made their full protocols available, and 29% (n = 72) provided access to their statistical analysis plan report. A data sharing statement was reported in 68% (n = 170) of the reports of which 91% stated their willingness to share. Completeness of reporting was low: only 32% (n = 81) of trials completely defined the pre-specified primary outcome measures; 57% (n = 143) reported the process of allocation concealment. Overall, 51% (n = 127) adequately reported the results for the primary outcomes while only 14% (n = 36) of trials adequately described harms. Primary outcome(s) reported in trial registries and published reports were inconsistent in 49% (n = 104) of trials; of them, only 15% (n = 16) disclosed outcome switching in the report. There were no major differences between preprints and peer-reviewed publications. Of the 130 RCTs published as preprints, 78 were subsequently published in a peer-reviewed journal. There was no major improvement after the journal peer review process for most items., Conclusions: Transparency, completeness, and consistency of reporting of COVID-19 clinical trials were insufficient both in preprints and peer-reviewed publications. A comparison of paired reports published in preprint and peer-reviewed publication did not indicate major improvement., (© 2022. The Author(s).)
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- 2022
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35. Interleukin-1 blocking agents for treating COVID-19.
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Davidson M, Menon S, Chaimani A, Evrenoglou T, Ghosn L, Graña C, Henschke N, Cogo E, Villanueva G, Ferrand G, Riveros C, Bonnet H, Kapp P, Moran C, Devane D, Meerpohl JJ, Rada G, Hróbjartsson A, Grasselli G, Tovey D, Ravaud P, and Boutron I
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- Aged, Female, Humans, Male, Middle Aged, Randomized Controlled Trials as Topic, Respiration, Artificial, Interleukin-1 antagonists & inhibitors, COVID-19 Drug Treatment
- Abstract
Background: Interleukin-1 (IL-1) blocking agents have been used for treating severe coronavirus disease 2019 (COVID-19), on the premise that their immunomodulatory effect might be beneficial in people with COVID-19., Objectives: To assess the effects of IL-1 blocking agents compared with standard care alone or with placebo on effectiveness and safety outcomes in people with COVID-19. We will update this assessment regularly., Search Methods: We searched the Cochrane COVID-19 Study Register and the COVID-19 L-OVE Platform (search date 5 November 2021). These sources are maintained through regular searches of MEDLINE, Embase, CENTRAL, trial registers and other sources. We also checked the World Health Organization International Clinical Trials Registry Platform, regulatory agency websites, Retraction Watch (search date 3 November 2021)., Selection Criteria: We included randomised controlled trials (RCTs) evaluating IL-1 blocking agents compared with standard care alone or with placebo for people with COVID-19, regardless of disease severity., Data Collection and Analysis: We followed Cochrane methodology. The protocol was amended to reduce the number of outcomes considered. Two researchers independently screened and extracted data and assessed the risk of bias with the Cochrane Risk of Bias 2 tool. We rated the certainty of evidence using the GRADE approach for the critical outcomes of clinical improvement (Day 28; ≥ D60); WHO Clinical Progression Score of level 7 or above (i.e. the proportion of participants with mechanical ventilation +/- additional organ support OR death) (D28; ≥ D60); all-cause mortality (D28; ≥ D60); incidence of any adverse events; and incidence of serious adverse events., Main Results: We identified four RCTs of anakinra (three published in peer-reviewed journals, one reported as a preprint) and two RCTs of canakinumab (published in peer-reviewed journals). All trials were multicentre (2 to 133 centres). Two trials stopped early (one due to futility and one as the trigger for inferiority was met). The median/mean age range varied from 58 to 68 years; the proportion of men varied from 58% to 77%. All participants were hospitalised; 67% to 100% were on oxygen at baseline but not intubated; between 0% and 33% were intubated at baseline. We identified a further 16 registered trials with no results available, of which 15 assessed anakinra (four completed, four terminated, five ongoing, three not recruiting) and one (completed) trial assessed canakinumab. Effectiveness of anakinra for people with COVID-19 Anakinra probably results in little or no increase in clinical improvement at D28 (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.97 to 1.20; 3 RCTs, 837 participants; absolute effect: 59 more per 1000 (from 22 fewer to 147 more); moderate-certainty evidence. The evidence is uncertain about an effect of anakinra on 1) the proportion of participants with a WHO Clinical Progression Score of level 7 or above at D28 (RR 0.67, 95% CI 0.36 to 1.22; 2 RCTs, 722 participants; absolute effect: 55 fewer per 1000 (from 107 fewer to 37 more); low-certainty evidence) and ≥ D60 (RR 0.54, 95% CI 0.30 to 0.96; 1 RCT, 606 participants; absolute effect: 47 fewer per 1000 (from 72 fewer to 4 fewer) low-certainty evidence); and 2) all-cause mortality at D28 (RR 0.69, 95% CI 0.34 to 1.39; 2 RCTs, 722 participants; absolute effect: 32 fewer per 1000 (from 68 fewer to 40 more); low-certainty evidence). The evidence is very uncertain about an effect of anakinra on 1) the proportion of participants with clinical improvement at ≥ D60 (RR 0.93, 95% CI 0.78 to 1.12; 1 RCT, 115 participants; absolute effect: 59 fewer per 1000 (from 186 fewer to 102 more); very low-certainty evidence); and 2) all-cause mortality at ≥ D60 (RR 1.03, 95% CI 0.68 to 1.56; 4 RCTs, 1633 participants; absolute effect: 8 more per 1000 (from 84 fewer to 147 more); very low-certainty evidence). Safety of anakinra for people with COVID-19 Anakinra probably results in little or no increase in adverse events (RR 1.02, 95% CI 0.94 to 1.11; 2 RCTs, 722 participants; absolute effect: 14 more per 1000 (from 43 fewer to 78 more); moderate-certainty evidence). The evidence is uncertain regarding an effect of anakinra on serious adverse events (RR 0.95, 95% CI 0.58 to 1.56; 2 RCTs, 722 participants; absolute effect: 12 fewer per 1000 (from 104 fewer to 138 more); low-certainty evidence). Effectiveness of canakinumab for people with COVID-19 Canakinumab probably results in little or no increase in clinical improvement at D28 (RR 1.05, 95% CI 0.96 to 1.14; 2 RCTs, 499 participants; absolute effect: 42 more per 1000 (from 33 fewer to 116 more); moderate-certainty evidence). The evidence of an effect of canakinumab is uncertain on 1) the proportion of participants with a WHO Clinical Progression Score of level 7 or above at D28 (RR 0.72, 95% CI 0.44 to 1.20; 2 RCTs, 499 participants; absolute effect: 35 fewer per 1000 (from 69 fewer to 25 more); low-certainty evidence); and 2) all-cause mortality at D28 (RR:0.75; 95% CI 0.39 to 1.42); 2 RCTs, 499 participants; absolute effect: 20 fewer per 1000 (from 48 fewer to 33 more); low-certainty evidence). The evidence is very uncertain about an effect of canakinumab on all-cause mortality at ≥ D60 (RR 0.55, 95% CI 0.16 to 1.91; 1 RCT, 45 participants; absolute effect: 112 fewer per 1000 (from 210 fewer to 227 more); very low-certainty evidence). Safety of canakinumab for people with COVID-19 Canakinumab probably results in little or no increase in adverse events (RR 1.02; 95% CI 0.86 to 1.21; 1 RCT, 454 participants; absolute effect: 11 more per 1000 (from 74 fewer to 111 more); moderate-certainty evidence). The evidence of an effect of canakinumab on serious adverse events is uncertain (RR 0.80, 95% CI 0.57 to 1.13; 2 RCTs, 499 participants; absolute effect: 44 fewer per 1000 (from 94 fewer to 28 more); low-certainty evidence)., Authors' Conclusions: Overall, we did not find evidence for an important beneficial effect of IL-1 blocking agents. The evidence is uncertain or very uncertain for several outcomes. Sixteen trials of anakinra and canakinumab with no results are currently registered, of which four are completed, and four terminated. The findings of this review are updated on the COVID-NMA platform (covid-nma.com)., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)
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- 2022
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36. A classification of methods used to personalize participative interventions revealed inadequate reporting in trial protocols.
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Malmartel A, Ravaud P, Ghosn L, and Tran VT
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- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Randomized Controlled Trials as Topic statistics & numerical data, Clinical Trial Protocols as Topic, Patient Participation methods, Patient Participation statistics & numerical data, Randomized Controlled Trials as Topic classification, Randomized Controlled Trials as Topic standards, Self-Management methods, Self-Management statistics & numerical data
- Abstract
Objectives: The objective of the study was to develop a classification of methods used to personalize participative interventions in randomized controlled trials (RCTs)., Study Design and Setting: We conducted a systematic review including protocols of RCTs assessing participative interventions in PubMed and ClinicalTrials.gov between June 2018 and May 2019. Data extraction was performed by two independent reviewers. We developed a precise classification of methods used to personalize interventions. Then, protocols were reviewed to determine whether personalization was sufficiently described to enable replication., Results: We included 109 protocols. The classification used four components and 13 subcomponents accounting for decision points (when interventions were personalized), tailoring variables (on what interventions were personalized), decision rules (how and by whom interventions were personalized), and nature of the subsequent tailoring (what was personalized in the interventions). In 95% of protocols, at least one component or subcomponent of our classification was not adequately reported to enable the replication of the intervention. Components the least well described were tailoring variables (72% of protocols insufficiently described) and the nature of the subsequent tailoring (46% of protocols)., Conclusion: This study provides the first detailed classification of methods used to personalize interventions. This is required to transparently implement personalization and improve reporting in RCTs., (Copyright © 2021 Elsevier Inc. All rights reserved.)
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- 2021
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37. Interleukin-6 blocking agents for treating COVID-19: a living systematic review.
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Ghosn L, Chaimani A, Evrenoglou T, Davidson M, Graña C, Schmucker C, Bollig C, Henschke N, Sguassero Y, Nejstgaard CH, Menon S, Nguyen TV, Ferrand G, Kapp P, Riveros C, Ávila C, Devane D, Meerpohl JJ, Rada G, Hróbjartsson A, Grasselli G, Tovey D, Ravaud P, and Boutron I
- Subjects
- Aged, Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal, Humanized adverse effects, Bias, COVID-19 mortality, Disease Progression, Female, Humans, Male, Middle Aged, Multicenter Studies as Topic, Randomized Controlled Trials as Topic, Antibodies, Monoclonal, Humanized therapeutic use, Interleukin-6 antagonists & inhibitors, COVID-19 Drug Treatment
- Abstract
Background: Interleukin 6 (IL-6) blocking agents have been used for treating severe coronavirus disease 2019 (COVID-19). Their immunosuppressive effect might be valuable in patients with COVID-19 characterised by substantial immune system dysfunction by controlling inflammation and promoting disease tolerance., Objectives: To assess the effect of IL-6 blocking agents compared to standard care alone or with placebo on efficacy and safety outcomes in COVID-19. We will update this assessment regularly., Search Methods: We searched the World Health Organization (WHO) International Clinical Trials Registry Platform (up to 11 February 2021) and the L-OVE platform, and Cochrane COVID-19 Study Register to identify trials up to 26 February 2021., Selection Criteria: We included randomised controlled trials (RCTs) evaluating IL-6 blocking agents compared with standard care alone or with placebo for people with COVID-19, regardless of disease severity., Data Collection and Analysis: We followed standard Cochrane methodology. The protocol was amended to reduce the number of outcomes considered. Two review authors independently collected data and assessed the risk of bias with the Cochrane Risk of Bias 2 tool. We rated the certainty of evidence with the GRADE approach for the critical outcomes such as clinical improvement (defined as hospital discharge or improvement on the scale used by trialists to evaluate clinical progression or recovery) (day (D) 28 / ≥ D60); WHO Clinical Progression Score of level 7 or above (i.e. the proportion of participants with mechanical ventilation +/- additional organ support OR death) (D28 / ≥ D60); all-cause mortality (D28 / ≥ D60); incidence of any adverse events; and incidence of serious adverse events., Main Results: We identified 10 RCTs with available data including one platform trial comparing tocilizumab and sarilumab with standard of care. These trials evaluated tocilizumab (nine RCTs including two platform trials; seven were reported as peer-reviewed articles, two as preprints; 6428 randomised participants); and two sarilumab (one platform trial reported as peer reviewed article, one reported as preprint, 880 randomised participants). All trials included were multicentre trials. They were conducted in Brazil, China, France, Italy, UK, USA, and four were multi-country trials. The mean age range of participants ranged from 56 to 65 years; 4572 (66.3%) of trial participants were male. Disease severity ranged from mild to critical disease. The reported proportion of participants on oxygen at baseline but not intubated varied from 56% to 100% where reported. Five trials reported the inclusion of intubated patients at baseline. We identified a further 20 registered RCTs of tocilizumab compared to placebo/standard care (five completed without available results, five terminated without available results, eight ongoing, two not recruiting); 11 RCTs of sarilumab (two completed without results, three terminated without available results, six ongoing); six RCTs of clazakisumab (five ongoing, one not recruiting); two RCTs of olokizumab (one completed, one not recruiting); one of siltuximab (ongoing) and one RCT of levilimab (completed without available results). Of note, three were cancelled (2 tocilizumab, 1 clazakisumab). One multiple-arm RCT evaluated both tocilizumab and sarilumab compared to standard of care, one three-arm RCT evaluated tocilizumab and siltuximab compared to standard of care and consequently they appear in each respective comparison. Tocilizumab versus standard care alone or with placebo a. Effectiveness of tocilizumab for patients with COVID-19 Tocilizumab probably results in little or no increase in the outcome of clinical improvement at D28 (RR 1.06, 95% CI 1.00 to 1.13; I
2 = 40.9%; 7 RCTs, 5585 participants; absolute effect: 31 more with clinical improvement per 1000 (from 0 fewer to 67 more); moderate-certainty evidence). However, we cannot exclude that some subgroups of patients could benefit from the treatment. We did not obtain data for longer-term follow-up (≥ D60). The effect of tocilizumab on the proportion of participants with a WHO Clinical Progression Score of level of 7 or above is uncertain at D28 (RR 0.99, 95% CI 0.56 to 1.74; I2 = 64.4%; 3 RCTs, 712 participants; low-certainty evidence). We did not obtain data for longer-term follow-up (≥ D60). Tocilizumab reduces all-cause mortality at D28 compared to standard care alone or placebo (RR 0.89, 95% CI 0.82 to 0.97; I2 = 0.0%; 8 RCTs, 6363 participants; absolute effect: 32 fewer deaths per 1000 (from 52 fewer to 9 fewer); high-certainty evidence). The evidence suggests uncertainty around the effect on mortality at ≥ D60 (RR 0.86, 95% CI 0.53 to 1.40; I2 = 0.0%; 2 RCTs, 519 participants; low-certainty evidence). b. Safety of tocilizumab for patients with COVID-19 The evidence is very uncertain about the effect of tocilizumab on adverse events (RR 1.23, 95% CI 0.87 to 1.72; I2 = 86.4%; 7 RCTs, 1534 participants; very low-certainty evidence). Nevertheless, tocilizumab probably results in slightly fewer serious adverse events than standard care alone or placebo (RR 0.89, 95% CI 0.75 to 1.06; I2 = 0.0%; 8 RCTs, 2312 participants; moderate-certainty evidence). Sarilumab versus standard care alone or with placebo The evidence is uncertain about the effect of sarilumab on all-cause mortality at D28 (RR 0.77, 95% CI 0.43 to 1.36; 2 RCTs, 880 participants; low certainty), on all-cause mortality at ≥ D60 (RR 1.00, 95% CI 0.50 to 2.0; 1 RCT, 420 participants; low certainty), and serious adverse events (RR 1.17, 95% CI 0.77 to 1.77; 2 RCTs, 880 participants; low certainty). It is unlikely that sarilumab results in an important increase of adverse events (RR 1.05, 95% CI 0.88 to 1.25; 1 RCT, 420 participants; moderate certainty). However, an increase cannot be excluded No data were available for other critical outcomes., Authors' Conclusions: On average, tocilizumab reduces all-cause mortality at D28 compared to standard care alone or placebo and probably results in slightly fewer serious adverse events than standard care alone or placebo. Nevertheless, tocilizumab probably results in little or no increase in the outcome clinical improvement (defined as hospital discharge or improvement measured by trialist-defined scales) at D28. The impact of tocilizumab on other outcomes is uncertain or very uncertain. With the data available, we were not able to explore heterogeneity. Individual patient data meta-analyses are needed to be able to identify which patients are more likely to benefit from this treatment. Evidence for an effect of sarilumab is uncertain and evidence for other anti-IL6 agents is unavailable. Thirty-nine RCTs of IL-6 blocking agents with no results are currently registered, of which nine are completed and seven trials were terminated with no results available. The findings of this review will be updated as new data are made available on the COVID-NMA platform (covid-nma.com)., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)- Published
- 2021
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38. Use of wearable biometric monitoring devices to measure outcomes in randomized clinical trials: a methodological systematic review.
- Author
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Graña Possamai C, Ravaud P, Ghosn L, and Tran VT
- Subjects
- Female, Humans, Male, Monitoring, Physiologic methods, Randomized Controlled Trials as Topic methods, Reproducibility of Results, Treatment Outcome, Monitoring, Physiologic instrumentation, Randomized Controlled Trials as Topic instrumentation, Wearable Electronic Devices
- Abstract
Background: Wearable biometric monitoring devices (BMDs) have the potential to transform the conduct of randomized controlled trials (RCTs) by shifting the collection of outcome data from single measurements at predefined time points to dense continuous measurements., Methods: Methodological systematic review to understand how recent RCTs used BMDs to measure outcomes and to describe the reporting of these RCTs. Electronic search was performed in the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE and completed a page-by-page hand search in five leading medical journals between January 1, 2018, and December 31, 2018. Three reviewers independently extracted all primary and secondary outcomes collected using BMDs, and assessed (1) the definitions used to summarize BMD outcome data; (2) whether the validity, reliability, and responsiveness of sensors was reported; (3) the discrepancy with outcomes prespecified in public clinical trial registries; and (4) the methods used to manage missing and incomplete BMD outcome data., Results: Of the 4562 records screened, 75 RCTs were eligible. Among them, 24% tested a pharmacological intervention and 57% used an inertial measurement sensor to measure physical activity. Included trials involved 464 outcomes (average of 6 [SD = 8] outcomes per trial). In total, 35 trials used a BMD to measure a primary outcome. Several issues affected the value and transparency of trials using BMDs to measure outcomes. First, the definition of outcomes used in the trials was highly heterogeneous (e.g., 21 diabetes trials had 266 outcomes and 153 had different unique definitions to measure diabetes control), which limited the combination and comparison of results. Second, information on the validity, reliability, and responsiveness of sensors used was lacking in 74% of trials. Third, half (53%) of the outcomes measured with BMDs had not been prespecified, with a high risk of outcome reporting bias. Finally, reporting on the management of incomplete outcome data (e.g., due to suboptimal compliance with the BMD) was absent in 68% of RCTs., Conclusions: Use of BMDs to measure outcomes is becoming the norm rather than the exception in many fields. Yet, trialists need to account for several methodological issues when specifying and conducting RCTs using these novel tools.
- Published
- 2020
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39. Consolidated Standards of Reporting Trials (CONSORT) extensions covered most types of randomized controlled trials, but the potential workload for authors was high.
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Ghosn L, Boutron I, and Ravaud P
- Subjects
- Humans, Publishing statistics & numerical data, Research Design statistics & numerical data, Guideline Adherence statistics & numerical data, Publishing standards, Randomized Controlled Trials as Topic standards, Randomized Controlled Trials as Topic statistics & numerical data, Research Design standards, Research Report standards, Workload statistics & numerical data
- Abstract
Objectives: Our aim was to determine the coverage of randomized controlled trials (RCTs) by the Consolidated Standards of Reporting Trial (CONSORT) Statement and its extensions and to evaluate the potential workload for authors to adhere to the guidelines., Study Design and Setting: We identified CONSORT extensions from the CONSORT Web site. We randomly selected a sample of 1,000 RCTs indexed in PubMed in 2016 and recorded whether they were covered by CONSORT extensions for specific study designs or interventions. We evaluated the potential workload for authors by counting the number of documents and pages they have to consult to have a full understanding of the guidelines., Results: We identified 14 extensions. Only one extension was updated concurrently with the main CONSORT in 2010, three were updated after 2-7 years, and three are still based on CONSORT 2001. Overall, 81% of RCTs are covered by relevant CONSORT guidelines; missing extensions for specific study designs were under development at the time of the search (Nov 2018). However, 6 of 10 extensions covered <2% of the trials. A median [Q1-Q3] of 4 [4-5] documents and 67 [57-78] pages should be consulted., Conclusion: Most RCTs indexed in PubMed are covered by the CONSORT Statement and extensions, but the potential workload for authors could be high., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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40. A scoping review provided a framework for new ways of doing research through mobilizing collective intelligence.
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Nguyen VT, Benchoufi M, Young B, Ghosn L, Ravaud P, and Boutron I
- Subjects
- Databases, Factual, Forecasting, Humans, Intelligence, Biomedical Research methods, Crowdsourcing methods, Quality Control, Research Design trends
- Abstract
Objectives: New forms of research involving collective intelligence (CI) of diverse individuals mobilized through crowdsourcing is successfully emerging in various fields. This scoping review aimed to describe these methods across different fields and propose a framework for implementation., Study Design and Setting: We searched seven electronic databases for reports describing projects that had mobilized CI with crowdsourcing. We used content analysis to develop themes and categories of the methods., Results: We identified 145 reports. CI was mobilized to generate ideas, conduct evaluations, solve problems, and create intellectual outputs. Most projects (n = 110, 76%) were open to the public without restrictions on participants' expertise. Participants contributed to projects by independent contribution (i.e., no interaction with other participants) (n = 50, 34%), collaboration (n = 41, 28%), competitions (n = 33, 23%), and playing games (n = 16, 11%). In total, 61% of articles (n = 89) reported methods to evaluate participants' contribution and decision-making process: 43% used an independent panel of experts and 18% involved end users. We identified challenges in implementation and sustainability of CI and proposed solutions., Conclusion: New research methods based on CI through crowdsourcing could transform clinical research. This framework facilitates the implementation of these methods., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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41. Congenital hepatoblastoma in a growing health economy.
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Ofoegbu BN, Abdel Salam SEE, Diehl WG, and Ghosn L
- Subjects
- Adult, Antineoplastic Combined Chemotherapy Protocols, Female, Gestational Age, Hepatoblastoma diagnostic imaging, Hepatoblastoma pathology, Hepatoblastoma therapy, Humans, Infant, Infant, Newborn, Liver Neoplasms diagnostic imaging, Liver Neoplasms pathology, Liver Neoplasms therapy, Pregnancy, Ultrasonography, Prenatal, United Arab Emirates, Hepatoblastoma congenital, Liver Neoplasms complications
- Abstract
A 43-year-old woman, whose pregnancy was complicated by the presence of a large single solid intra-abdominal fetal mass, was referred from the private sector into our fetal maternal unit at the Corniche Hospital, Abu Dhabi at 36 weeks postmenstrual age.Investigations subsequently confirmed that this mass was a congenital hepatoblastoma, one of the very rare embryonic tumours. The baby had chemotherapy and surgical excision of the tumour. Fifteen months later, the alpha feto-protein levels remain normal and follow-on MRI scans do not show recurrence or any residual disease.To our knowledge, this is the first case of congenital hepatoblastoma in the United Arab Emirates (UAE). In the UAE, the interphase between private health insurance schemes and medical (public and private) care within a growing health economy enhances access to unique services such as cancer treatments within specialised centres., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2019
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42. Factors associated with online media attention to research: a cohort study of articles evaluating cancer treatments.
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Haneef R, Ravaud P, Baron G, Ghosn L, and Boutron I
- Abstract
Background: New metrics have been developed to assess the impact of research and provide an indication of online media attention and data dissemination. We aimed to describe online media attention of articles evaluating cancer treatments and identify the factors associated with high online media attention., Methods: We systematically searched MEDLINE via PubMed on March 1, 2015 for articles published during the first 6 months of 2014 in oncology and medical journals with a diverse range of impact factors, from 3.9 to 54.4, and selected a sample of articles evaluating a cancer treatment regardless of study design. Altmetric Explorer was used to identify online media attention of selected articles. The primary outcome was media attention an article received online as measured by Altmetric score (i.e., number of mentions in online news outlets, science blogs and social media). Regression analysis was performed to investigate the factors associated with high media attention, and regression coefficients represent the logarithm of ratio of mean (RoM) values of Altmetric score per unit change in the covariate., Results: Among 792 articles, 218 (27.5%) received no online media attention (Altmetric score = 0). The median [Q1-Q3] Altmetric score was 2.0 [0.0-8.0], range 0.0-428.0. On multivariate analysis, factors associated with high Altmetric score were presence of a press release (RoM = 10.14, 95%CI [4.91-20.96]), open access to the article (RoM = 1.48, 95%CI [1.02-2.16]), and journal impact factor (RoM = 1.10, 95%CI [1.07-1.12]. As compared with observational studies, systematic reviews were not associated with high Altmetric score (RoM = 1.46, 95%CI [0.74-2.86]; P = 0.27), nor were RCTs (RoM = 0.65, 95%CI [0.41-1.02]; P = 0.059) and phase I/II non-RCTs (RoM = 0.58, 95%CI [0.33-1.05]; P = 0.07). The articles with abstract conclusions favouring study treatments were not associated with high Altmetric score (RoM = 0.97, 95%CI [0.60-1.58]; P = 0.91)., Conclusions: Most important factors associated with high online media attention were the presence of a press release and the journal impact factor. There was no evidence that study design with high level of evidence and type of abstract conclusion were associated with high online media attention.
- Published
- 2017
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