Sources of variability on the estimate of treatment effect in the PROWESS trial: Implications for the design and conduct of future studies in severe sepsis*

2004 ◽  
Vol 32 (12) ◽  
pp. 2385-2391 ◽  
Author(s):  
William L. Macias ◽  
Benoit Vallet ◽  
Gordon R. Bernard ◽  
Jean-Louis Vincent ◽  
Pierre-Francois Laterre ◽  
...  
Keyword(s):  
Severe Sepsis ◽  
Treatment Effect ◽  
Future Studies ◽  
Prowess Trial

Efficacy and Safety of Recombinant Human Activated Protein C for Severe Sepsis

2018 ◽  
pp. 61-67
Author(s):  
Anna M. Ward ◽  
Richard M. Pino
Keyword(s):  
Severe Sepsis ◽  
Study Design ◽  
Protein C ◽  
Clinical Case ◽  
Activated Protein C ◽  
Efficacy And Safety ◽  
Prowess Trial ◽  
Study Intervention ◽  
Prowess Study

This chapter provides a summary of the landmark study known as the PROWESS Study. Does treatment with DAA reduce the rate of death from any cause among patients with severe sepsis? Starting with that question, it describes the basics of the study, including funding, study location, who was studied, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, discusses implications, and concludes with a relevant clinical case. The PROWESS trial demonstrated a mortality benefit for DAA among patients with severe sepsis. However, the subsequent ADDRESS, RESOLVE, and PROWESS-SHOCK trials did not demonstrate a benefit of the medication, thus calling the results of PROWESS into question.

scholarly journals Implementation of Straw Racks in Commercial Pig Housing—Impact on Straw Availability and Pig Behaviour

Agriculture ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 5
Author(s):  
Torun Wallgren ◽  
Stefan Gunnarson
Keyword(s):  
Spatial Cognition ◽  
Treatment Effect ◽  
Small Difference ◽  
The Other ◽  
Activity Levels ◽  
Future Studies ◽  
Natural Behaviour ◽  
Significant Difference ◽  
Floor Control ◽  
And Control

This study investigated if straw racks, which enable larger straw rations, induced a more straw-directed behaviour in pigs, as a mean to facilitate the provision of manipulable material and natural behaviour. It was conducted on a commercial farm (459 pigs, 42 pens, 30–120 kg) where half of the pens received 25 L of straw on the floor (CONTROL) and the other half of the pens received straw in a rack holding 44 L of straw (RACK). The pig behaviour in five randomly assigned pens per treatment were recorded for 24 h, during three periods of production. Pig activity levels, exploratory behaviour, pen utilization and available clean straw were scan sampled. During period 1, no pigs were observed interacting with the straw racks. During this period, CONTROL pigs conducted more straw-directed behaviour and less pen-directed behaviour compared to pigs in the pens with a rack during period 1. The lack of rack interactions may imply an underdeveloped spatial cognition in the pigs. Apart from period 1, there were no significant difference in behaviour between RACK and CONTROL pigs. The racks did not disturb the use of the pen. The absent treatment effect in periods 2 and 3 may reflect that there was a too small difference in straw ration between the treatments. In order to design and implement straw racks that promote straw interaction, future studies should focus on understanding pigs’ spatial cognition.

scholarly journals Il trattamento di pazienti con sepsi grave mediante drotrecogin alfa: una valutazione economica con riferimento all’Italia

2002 ◽  
Vol 3 (3) ◽  
pp. 171-177 ◽  
Author(s):  
Carlo Lucioni ◽  
Silvio Mazzi ◽  
Chinn Christopher
Keyword(s):  
Severe Sepsis ◽  
Cost Effectiveness ◽  
Drotrecogin Alfa ◽  
Activated Protein C ◽  
Quality Adjusted Life Year ◽  
Phase Iii ◽  
The Us ◽  
Prowess Trial ◽  
Standard Values ◽  
Clinical Conditions

Sepsis can be defined as a spectrum of clinical conditions caused by the immune response of a host to infection or trauma and characterized by systemic inflammation and coagulation. Particularly in elderly, immunocompromised and critically ill patients, sepsis is a major cause of morbidity and mortality in intensive care units (ICUs) worldwide. In the US, sepsis is the leading cause of death in noncoronary ICU patients. Drotrecogin alfa, or recombinant human activated protein C, has antithrombotic, antiinflammatory, and profibrinolytic properties. Recently in a phase III trial (PROWESS), Drotrecogin alfa demonstrated significantly reduced mortality in severe sepsis patients at 28 days. In this trial important value factors for the assessment of costs and outcomes of severe sepsis were also considered. The purpose of the present study is to determine the economic burden of the treatment with Drotrecogin alfa, according to a cost-effectiveness analysis based on the data of the PROWESS trial. The study has been adapted to the italian health environment. As regards to the costs per surviving patient and costs per QALY (Quality Adjusted Life Year), the predicted cost-effectiveness ratio of drotrecogin alfa in severe sepsis patients is much lower than the standard values considered as acceptable in the international litterature.

Hospital mortality and resource use in subgroups of the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial *

2004 ◽  
Vol 32 (11) ◽  
pp. 2207-2218 ◽  
Author(s):  
Pierre-Francois Laterre ◽  
Howard Levy ◽  
Gilles Clermont ◽  
Daniel E. Ball ◽  
Rekha Garg ◽  
...  
Keyword(s):  
Severe Sepsis ◽  
Hospital Mortality ◽  
Resource Use ◽  
Protein C ◽  
Activated Protein C ◽  
Prowess Trial

Drotrecogin alfa (activated) in the treatment of severe sepsis patients with multiple-organ dysfunction: data from the PROWESS trial

2003 ◽  
Vol 29 (6) ◽  
pp. 894-903 ◽  
Author(s):  
Jean-François Dhainaut ◽  
◽  
Pierre-François Laterre ◽  
Jonathan M. Janes ◽  
Gordon R. Bernard ◽  
...  
Keyword(s):  
Severe Sepsis ◽  
Organ Dysfunction ◽  
Drotrecogin Alfa ◽  
Multiple Organ ◽  
Multiple Organ Dysfunction ◽  
Drotrecogin Alfa Activated ◽  
Prowess Trial

An Early Developmental Marker for Radial Glia in Rat Spinal Cord

1996 ◽  
Vol 54 ◽  
pp. 36-37
Author(s):  
V. Kriho ◽  
H.-Y. Yang ◽  
C.-M. Lue ◽  
N. Lieska ◽  
G. D. Pappas
Keyword(s):  
Spinal Cord ◽  
Intermediate Filament ◽  
Radial Glia ◽  
Rat Spinal Cord ◽  
Future Studies ◽  
Spinal Cord Development ◽  
Median Septum ◽  
Differentiation Marker ◽  
Early Developmental ◽  
Developing Rat

Radial glia have been classically defined as those early glial cells that radially span their thin processes from the ventricular to the pial surfaces in the developing central nervous system. These radial glia constitute a transient cell population, disappearing, for the most part, by the end of the period of neuronal migration. Traditionally, it has been difficult to definitively identify these cells because the principal criteria available were morphologic only.Using immunofluorescence microscopy, we have previously defined a phenotype for radial glia in rat spinal cord based upon the sequential expression of vimentin, glial fibrillary acidic protein and an intermediate filament-associated protein, IFAP-70/280kD. We report here the application of another intermediate filament-associated protein, IFAP-300kD, originally identified in BHK-21 cells, to the immunofluorescence study of radial glia in the developing rat spinal cord.Results showed that IFAP-300kD appeared very early in rat spinal cord development. In fact by embryonic day 13, IFAP-300kD immunoreactivity was already at its peak and was observed in most of the radial glia which span the spinal cord from the ventricular to the subpial surfaces (Fig. 1). Interestingly, from this time, IFAP-300kD immunoreactivity diminished rapidly in a dorsal to ventral manner, so that by embryonic day 16 it was detectable only in the maturing macroglial cells in the marginal zone of the spinal cord and the dorsal median septum (Fig. 2). By birth, the spinal cord was essentially immuno-negative for this IFAP. Thus, IFAP-300kD appears to be another differentiation marker available for future studies of gliogenesis, especially for the early stages of radial glia differentiation.

Autophagy and ageing: implications for age-related neurodegenerative diseases

2013 ◽  
Vol 55 ◽  
pp. 119-131 ◽  
Author(s):  
Bernadette Carroll ◽  
Graeme Hewitt ◽  
Viktor I. Korolchuk
Keyword(s):  
Neurodegenerative Diseases ◽  
Energy Availability ◽  
Future Studies ◽  
Intracellular Degradation ◽  
Age Related ◽  
Autophagy Induction ◽  
Social Importance ◽  
Cellular Dysfunction ◽  
Autophagy Activity ◽  
Intense Research

Autophagy is a process of lysosome-dependent intracellular degradation that participates in the liberation of resources including amino acids and energy to maintain homoeostasis. Autophagy is particularly important in stress conditions such as nutrient starvation and any perturbation in the ability of the cell to activate or regulate autophagy can lead to cellular dysfunction and disease. An area of intense research interest is the role and indeed the fate of autophagy during cellular and organismal ageing. Age-related disorders are associated with increased cellular stress and assault including DNA damage, reduced energy availability, protein aggregation and accumulation of damaged organelles. A reduction in autophagy activity has been observed in a number of ageing models and its up-regulation via pharmacological and genetic methods can alleviate age-related pathologies. In particular, autophagy induction can enhance clearance of toxic intracellular waste associated with neurodegenerative diseases and has been comprehensively demonstrated to improve lifespan in yeast, worms, flies, rodents and primates. The situation, however, has been complicated by the identification that autophagy up-regulation can also occur during ageing. Indeed, in certain situations, reduced autophagosome induction may actually provide benefits to ageing cells. Future studies will undoubtedly improve our understanding of exactly how the multiple signals that are integrated to control appropriate autophagy activity change during ageing, what affect this has on autophagy and to what extent autophagy contributes to age-associated pathologies. Identification of mechanisms that influence a healthy lifespan is of economic, medical and social importance in our ‘ageing’ world.

Mesophyll conductance: the leaf corridors for photosynthesis

2020 ◽  
Vol 48 (2) ◽  
pp. 429-439 ◽  
Author(s):  
Jorge Gago ◽  
Danilo M. Daloso ◽  
Marc Carriquí ◽  
Miquel Nadal ◽  
Melanie Morales ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Main Role ◽  
Mesophyll Conductance ◽  
Future Studies ◽  
Cell Structures ◽  
Leaf Tissues ◽  
Change Framework ◽  
Chloroplast Stroma

Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cross to be finally assimilated in photosynthesis, known as the mesophyll conductance (gm). Therefore, the gm reflects the pathway through different air, water and biophysical barriers within the leaf tissues and cell structures. Currently, it is known that gm can impose the same level of limitation (or even higher depending of the conditions) to photosynthesis than the wider known stomata or biochemistry. In this mini-review, we are focused on each of the gm determinants to summarize the current knowledge on the mechanisms driving gm from anatomical to metabolic and biochemical perspectives. Special attention deserve the latest studies demonstrating the importance of the molecular mechanisms driving anatomical traits as cell wall and the chloroplast surface exposed to the mesophyll airspaces (Sc/S) that significantly constrain gm. However, even considering these recent discoveries, still is poorly understood the mechanisms about signaling pathways linking the environment a/biotic stressors with gm responses. Thus, considering the main role of gm as a major driver of the CO2 availability at the carboxylation sites, future studies into these aspects will help us to understand photosynthesis responses in a global change framework.

An Overview of Facilities Providing Clinical Services for Persons Who Stutter in Kuwait

2016 ◽  
Vol 1 (4) ◽  
pp. 79-95
Author(s):  
Latifa Alsalmi ◽  
Robert Mayo
Keyword(s):  
Special Education ◽  
Department Heads ◽  
Clinical Services ◽  
Medical Settings ◽  
Non Profit ◽  
Future Studies ◽  
Language Services ◽  
Medical Centers ◽  
Clinical Directors

Presently, no clear picture is available about the facilities providing clinical services for persons who stutter (PWS) in Kuwait. This information is crucial for any awareness program to be established in the future. The purpose of this study was to identify clinical facilities and speech-language personnel that provide services for PWS in Kuwait. Participants consisted of 21 clinical directors of governmental medical centers, non-profit clinics, and private clinics as well as department heads of governmental school clinics where speech-language services were provided. Participants were interviewed regarding the availability of speech-language services within their centers and whether or not PWS receive services. The results revealed that four out of five governmental medical centers with a total of 32 speech-language pathologists (SLPs) provided services for PWS. Additionally, 12 schools of special education were found to have 62 SLPs on their staff providing fluency services for students. Finally, two stand-alone private clinics and one non-profit clinic provided services for PWS. Results indicated an overall shortage of SLPs in the country, especially in medical settings. This study sets the foundation for a series of future studies investigating the type and quality of stuttering services provided by the identified facilities in Kuwait.

Severe Sepsis: Two Drugs Not Better Than One

2012 ◽  
Vol 5 (6) ◽  
pp. 9
Author(s):  
SHERRY BOSCHERT
Keyword(s):  
Severe Sepsis ◽  
Better Than
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