Apr. 25, 2013 ? Liver fibrosis results from an excessive accumulation of tough, fibrous scar tissue and occurs in most types of chronic liver diseases. In industrialized countries, the main causes of liver injury leading to fibrosis include chronic hepatitis virus infection, excess alcohol consumption and, increasingly, nonalcoholic steatohepatitis (NASH).
Now, in a new study published in the journal Cell, scientists at the Salk Institute for Biological Studies have discovered that a synthetic form of vitamin D, calcipotriol (a drug already approved by the FDA for the treatment of psoriasis), deactivates the switch governing the fibrotic response in mouse liver cells, suggesting a potential new therapy for fibrotic diseases in humans.
"Because there are currently no effective drugs for liver fibrosis, we believe our findings would open a new door for treatment," says senior author Ronald M. Evans, a professor in Salk's Gene Expression Laboratory and lead researcher in the Institute's new Helmsley Center for Genomic Medicine.
The Salk study focused on a star-shaped "stellate" cell in the liver that serves as a beacon for damage. When called into action, stellate cells produce fibrotic proteins in an attempt to heal an injury. Under chronic stress, however, localized fibrosis expands, eventually leading to cirrhosis, increased risk of liver cancer, and the need for a liver transplant in advanced cases.
The Evans lab discovered a genetic switch through which vitamin D-related ligands such as calcitriol, a hormonally active form of the vitamin, can put the brakes on fibrosis. "Preclinical results suggest the 'vitamin D brake' is highly efficacious and led us to believe that the time is right to consider a trial in the context of chronic liver disease," says Evans, a Howard Hughes Medical Institute Investigator and holder of the March of Dimes Chair in Molecular and Developmental Biology.
Previous studies have shown a physiologic role for vitamin D in liver function, but "it was our discovery of high levels of vitamin D receptor (VDR) in the stellate cell that led us to consider it as a possible off switch for liver fibrosis," says lead author Ning Ding, a research associate in the Gene Expression Laboratory.
"Current therapeutic approaches, which treat the symptoms of liver disease, don't stop liver fibrosis from progressing," says Michael Downes, a senior staff scientist in the Gene Expression Laboratory and co-corresponding author on the paper. "In liver diseases where the underlying cause cannot be cured, progression to cirrhosis is currently inevitable in some people. What we have discovered is that by acting on the genome, VDR can simultaneously defend against multiple fibrotic activators. This is important because many different pro-fibrotic signaling pathways converge on the genome to affect their fibrotic response."
The Salk discovery that calcipotriol counters the fibrotic response in stellate cells illuminates a potentially safer, more effective strategy capable of neutralizing multiple convergent fibrotic triggers.
The Salk scientists say that clinical trials of the vitamin D analog for the treatment of liver fibrosis are being planned. The synthetic vitamin D analog is better than natural vitamin D, they say, for a couple of reasons. First, natural vitamin D, which is found in small amounts in a few foods and produced in the body by exposure to sunlight, degrades quickly, while synthetic versions of vitamin D are less susceptible to breakdown. Second, too much natural vitamin D can cause hypercalcemia, or elevated calcium in the blood, which can lead to nausea and vomiting, frequent urination, muscle weakness and joint aches and pain. The synthetic vitamin D analog, on the other hand, produces a strong response without adding calcium to the blood.
In addition, the researchers say this new model for treating liver fibrosis may also be helpful in treating other diseases with a fibrotic component, including those of the lung, kidney and pancreas.
Other researchers on the study were Ruth T. Yu, Mara H. Sherman, Mathias Leblanc, Mingxiao He, Annette R. Atkins and Grant D. Barish, from the Salk Institute; Nanthakumar Subramaniam, Caroline Wilson, Renuka Rao, Sally Coulter and Christopher Liddle, of the University of Sydney (Australia); and Sue L. Lau , Christopher Scott and Jenny E. Gunton, of the Garvan Insitute for Medical Research (Australia).
The work was supported by grants from the National Institutes of Health, the Howard Hughes Medical Institute, the National Health and Medical Research Council of Australia, the Genentech Foundation, the Leona M. and Harry B. Helmsley Charitable Trust, the Samuel Waxman Cancer Research Foundation, Stand Up to Cancer and Ipsen/Biomeasure.
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Stanford study examines cost-effectiveness of helicopter transport of trauma victimsPublic release date: 25-Apr-2013 [ | E-mail | Share ]
Contact: Sara Wykes swykes@stanfordmed.org 650-721-6263 Stanford University Medical Center
STANFORD, Calif. - Researchers at the Stanford University School of Medicine have for the first time determined how often emergency medical helicopters need to help save the lives of seriously injured people to be considered cost-effective compared with ground ambulances.
The researchers found that if an additional 1.6 percent of seriously injured patients survive after being transported by helicopter from the scene of injury to a level-1 or level-2 trauma center, then such transport should be considered cost-effective. In other words, if 90 percent of seriously injured trauma victims survive with the help of ground transport, 91.6 need to survive with the help of helicopter transport for it to be considered cost-effective.
The study, published online this month in the Annals of Emergency Medicine, does not address whether most helicopter transport actually meets the additional 1.6 percent survivorship threshold.
"What we aimed to do is reduce the uncertainty about the factors that drive the cost-effective use of this important critical care resource," said the study's lead author, M. Kit Delgado, MD, MS, an instructor in the Division of Emergency Medicine. "The goal is to continue to save the lives of those who need air transport, but spare flight personnel the additional risks of flying - and patients with minor injuries the additional cost - when helicopter transport is not likely to be cost-effective." (Helicopter medical services generally bill patients' insurance providers directly, but patients may have to pay some of the bill out of pocket, or, if they're uninsured, possibly all of it.)
The study comes at a time when finding ways to cut medical costs has become a national priority, and the overuse of helicopter transport has come under scrutiny. Previous studies have shown that, on average, over half of patients transported by helicopter have only minor, non-life threatening injuries. For these patients, transport by helicopter instead of ground ambulance is not likely to make a difference in outcomes, and the additional risk and cost of helicopter transport outweighs the benefit, Delgado said.
In 2010, there were an estimated 44,700 U.S. helicopter transports from injury scenes to level-1 and level-2 trauma centers, with an average cost of about $6,500 per transport. The total annual cost is around $290 million. (Level-1 and -2 trauma centers are hospitals equipped and staffed to provide the highest levels of surgical care to trauma patients; level-1 centers offer a broader array of readily available specialty care, and also are committed to research and teaching efforts.)
Yet emergency helicopter transport sits in a cost-efficiency conundrum: It is most needed in remote, rural areas where transport by ground can take far longer than by air. These areas also tend to have sparser populations and therefore fewer calls for aid, making it difficult to recoup the overhead costs of maintaining helicopter services, Delgado said.
In some areas of the country, however, helicopters are automatically launched based on the 911 call. "Once ground responders and the helicopter arrive, sometimes they may find patients who are awake, talking and have stable vital signs," Delgado said. "The challenge is getting helicopters to patients who need them in a rapid fashion so the flight team can intervene and make a difference, but also know based on certain criteria who isn't sick enough to require air transport."
Most health economists consider medical interventions that yield a year of healthy life - a measure known as a quality-adjusted life-year - at a cost of between $50,000 and $100,000 to be cost-effective in high-income countries, such as the United States, Delgado said. If society is willing to pay as much as $100,000 toward helicopter transport for each QALY gained by the seriously injured patients, then helicopter transport needs to reduce the mortality rate of these patients by a modest 1.6 percent compared with ground transport to meet this threshold, the study says. Or it needs to improve long-term disability outcomes, the study says.
"If future studies find helicopter transport leads to improved long-term quality of life and disability outcomes, then helicopter transport would be considered cost-effective, even if no additional lives were saved," Delgado said. "Only a handful of studies have examined outcomes other than death, without definitive results."
For severely injured patients, helicopter evacuation to a trauma center is preferable if it is faster than ground transport. However, helicopter transport is more expensive and poses rare, but often fatal, safety risks - specifically, the risk of crashing. Plus, it is often difficult for emergency responders to discern which patients would actually benefit from being flown in a helicopter rather than driven in an ambulance to a high-level trauma center. Until this study, the survival benefit needed to offset these potential drawbacks hasn't been clear.
"More accurately determining which patients have serious injuries and need to be flown is the most promising way to ensure you are getting a good value by using helicopter transport," Delgado said. "To do this, we should promote diligent use of the Centers for Disease Control's field triage guidelines among EMS responders. This would help ensure that injured victims who are transported by helicopter to a trauma center actually require trauma care. Secondly, we need to figure out whether the practice of autolaunching helicopters based on a 911 call makes sense. If the benefit of the faster response time outweighs the expenditure of resources on those patients who may not actually need helicopter transport, then autolaunching makes sense. If not, the practice should be reconsidered."
There is mixed evidence in the literature about the degree to which helicopter transport reduces mortality. It is therefore uncertain whether the routine use of helicopter transport is cost-effective for most patients in the United States when ground transport is also feasible. The study found that the cost-effectiveness also depends on regional variation in the costs of air and ground transport and the percentage of patients who are flown that have minor injuries.
"Of course, this study only applies to situations in which both ground and helicopter transport to a trauma center are feasible," Delgado added. "In situations where the only alternative is being taken by ground to a local nontrauma-center hospital or being flown to a trauma center, then clearly we want any patient with a suspicion of a serious injury flown to that trauma center."
###
The senior author of the study is Jeremy Goldhaber-Fiebert, PhD, assistant professor of health care research and policy. Other Stanford co-authors are Kristan Staudenmayer, MD, MS, assistant professor of surgery; N. Ewen Wang, MD, associate professor of emergency medicine; David Spain, MD, professor of surgery; and Douglas Owens, MD, MS, professor health research and policy.
The study was supported by the Agency for Healthcare Research and Quality, the National Institutes of Health (grants K23HD051595-02 and K01AG037593-01A1) and the Department of Veterans Affairs.
Information about Stanford's Division of Emergency Medicine, which also supported the work, is available at http://med.stanford.edu/emed.
The Stanford University School of Medicine consistently ranks among the nation's top medical schools, integrating research, medical education, patient care and community service. For more news about the school, please visit http://mednews.stanford.edu. The medical school is part of Stanford Medicine, which includes Stanford Hospital & Clinics and Lucile Packard Children's Hospital. For information about all three, please visit http://stanfordmedicine.org/about/news.html.
Print media contact:
Sara Wykes 650-721-6263 (swykes@stanfordmed.org)
Broadcast media contact:
M.A. Malone 650-723-6912 (mamalone@stanford.edu)
[ | E-mail | Share ]
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Stanford study examines cost-effectiveness of helicopter transport of trauma victimsPublic release date: 25-Apr-2013 [ | E-mail | Share ]
Contact: Sara Wykes swykes@stanfordmed.org 650-721-6263 Stanford University Medical Center
STANFORD, Calif. - Researchers at the Stanford University School of Medicine have for the first time determined how often emergency medical helicopters need to help save the lives of seriously injured people to be considered cost-effective compared with ground ambulances.
The researchers found that if an additional 1.6 percent of seriously injured patients survive after being transported by helicopter from the scene of injury to a level-1 or level-2 trauma center, then such transport should be considered cost-effective. In other words, if 90 percent of seriously injured trauma victims survive with the help of ground transport, 91.6 need to survive with the help of helicopter transport for it to be considered cost-effective.
The study, published online this month in the Annals of Emergency Medicine, does not address whether most helicopter transport actually meets the additional 1.6 percent survivorship threshold.
"What we aimed to do is reduce the uncertainty about the factors that drive the cost-effective use of this important critical care resource," said the study's lead author, M. Kit Delgado, MD, MS, an instructor in the Division of Emergency Medicine. "The goal is to continue to save the lives of those who need air transport, but spare flight personnel the additional risks of flying - and patients with minor injuries the additional cost - when helicopter transport is not likely to be cost-effective." (Helicopter medical services generally bill patients' insurance providers directly, but patients may have to pay some of the bill out of pocket, or, if they're uninsured, possibly all of it.)
The study comes at a time when finding ways to cut medical costs has become a national priority, and the overuse of helicopter transport has come under scrutiny. Previous studies have shown that, on average, over half of patients transported by helicopter have only minor, non-life threatening injuries. For these patients, transport by helicopter instead of ground ambulance is not likely to make a difference in outcomes, and the additional risk and cost of helicopter transport outweighs the benefit, Delgado said.
In 2010, there were an estimated 44,700 U.S. helicopter transports from injury scenes to level-1 and level-2 trauma centers, with an average cost of about $6,500 per transport. The total annual cost is around $290 million. (Level-1 and -2 trauma centers are hospitals equipped and staffed to provide the highest levels of surgical care to trauma patients; level-1 centers offer a broader array of readily available specialty care, and also are committed to research and teaching efforts.)
Yet emergency helicopter transport sits in a cost-efficiency conundrum: It is most needed in remote, rural areas where transport by ground can take far longer than by air. These areas also tend to have sparser populations and therefore fewer calls for aid, making it difficult to recoup the overhead costs of maintaining helicopter services, Delgado said.
In some areas of the country, however, helicopters are automatically launched based on the 911 call. "Once ground responders and the helicopter arrive, sometimes they may find patients who are awake, talking and have stable vital signs," Delgado said. "The challenge is getting helicopters to patients who need them in a rapid fashion so the flight team can intervene and make a difference, but also know based on certain criteria who isn't sick enough to require air transport."
Most health economists consider medical interventions that yield a year of healthy life - a measure known as a quality-adjusted life-year - at a cost of between $50,000 and $100,000 to be cost-effective in high-income countries, such as the United States, Delgado said. If society is willing to pay as much as $100,000 toward helicopter transport for each QALY gained by the seriously injured patients, then helicopter transport needs to reduce the mortality rate of these patients by a modest 1.6 percent compared with ground transport to meet this threshold, the study says. Or it needs to improve long-term disability outcomes, the study says.
"If future studies find helicopter transport leads to improved long-term quality of life and disability outcomes, then helicopter transport would be considered cost-effective, even if no additional lives were saved," Delgado said. "Only a handful of studies have examined outcomes other than death, without definitive results."
For severely injured patients, helicopter evacuation to a trauma center is preferable if it is faster than ground transport. However, helicopter transport is more expensive and poses rare, but often fatal, safety risks - specifically, the risk of crashing. Plus, it is often difficult for emergency responders to discern which patients would actually benefit from being flown in a helicopter rather than driven in an ambulance to a high-level trauma center. Until this study, the survival benefit needed to offset these potential drawbacks hasn't been clear.
"More accurately determining which patients have serious injuries and need to be flown is the most promising way to ensure you are getting a good value by using helicopter transport," Delgado said. "To do this, we should promote diligent use of the Centers for Disease Control's field triage guidelines among EMS responders. This would help ensure that injured victims who are transported by helicopter to a trauma center actually require trauma care. Secondly, we need to figure out whether the practice of autolaunching helicopters based on a 911 call makes sense. If the benefit of the faster response time outweighs the expenditure of resources on those patients who may not actually need helicopter transport, then autolaunching makes sense. If not, the practice should be reconsidered."
There is mixed evidence in the literature about the degree to which helicopter transport reduces mortality. It is therefore uncertain whether the routine use of helicopter transport is cost-effective for most patients in the United States when ground transport is also feasible. The study found that the cost-effectiveness also depends on regional variation in the costs of air and ground transport and the percentage of patients who are flown that have minor injuries.
"Of course, this study only applies to situations in which both ground and helicopter transport to a trauma center are feasible," Delgado added. "In situations where the only alternative is being taken by ground to a local nontrauma-center hospital or being flown to a trauma center, then clearly we want any patient with a suspicion of a serious injury flown to that trauma center."
###
The senior author of the study is Jeremy Goldhaber-Fiebert, PhD, assistant professor of health care research and policy. Other Stanford co-authors are Kristan Staudenmayer, MD, MS, assistant professor of surgery; N. Ewen Wang, MD, associate professor of emergency medicine; David Spain, MD, professor of surgery; and Douglas Owens, MD, MS, professor health research and policy.
The study was supported by the Agency for Healthcare Research and Quality, the National Institutes of Health (grants K23HD051595-02 and K01AG037593-01A1) and the Department of Veterans Affairs.
Information about Stanford's Division of Emergency Medicine, which also supported the work, is available at http://med.stanford.edu/emed.
The Stanford University School of Medicine consistently ranks among the nation's top medical schools, integrating research, medical education, patient care and community service. For more news about the school, please visit http://mednews.stanford.edu. The medical school is part of Stanford Medicine, which includes Stanford Hospital & Clinics and Lucile Packard Children's Hospital. For information about all three, please visit http://stanfordmedicine.org/about/news.html.
Print media contact:
Sara Wykes 650-721-6263 (swykes@stanfordmed.org)
Broadcast media contact:
M.A. Malone 650-723-6912 (mamalone@stanford.edu)
[ | E-mail | Share ]
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
NEW YORK (AP) ? The longtime feud between late-night hosts Jay Leno and David Letterman is the stuff of legend and, apparently, so yesterday.
The two Jimmys: Jimmy Kimmel and Jimmy Fallon, agree there's no rivalry between them.
Both were among the honorees in New York Tuesday at a gala recognizing Time magazine's annual list of the 100 Most Influential People in the World.
"I feel good about it. We're very friendly. I know people expect us to dislike each other and say bad things about each other but that will never happen," said 45-year-old Kimmel.
He agreed that making nice is a good thing.
"It is nice. We're like (vocalist duo) Peaches & Herb. I'm Peaches," he laughed.
They'll face-off in the ratings next year when Fallon leaves NBC's "Late Night with Jimmy Fallon" and replaces Leno as host of "The Tonight Show."
Thirty-eight-year-old Fallon said, as of now, things won't change much when he switches to "The Tonight Show."
"We do a great show now. I think we're ready. I thank Jay Leno for being awesome and still being number one because without him I wouldn't have a job," he laughed. "It's just like they call you up from the minor league so I'm ready to go for the majors and I'm gonna swing for the fences."
In January, ABC's "Jimmy Kimmel Live!" moved to the 11:35 p.m. EST time slot, putting it in direct competition with "The Tonight Show" and "Late Show with David Letterman."
___
Online:
http://www.latenightwithjimmyfallon.com/
http://beta.abc.go.com/shows/jimmy-kimmel-live
___
Alicia Rancilio covers entertainment for The Associated Press. Follow her online at http://www.twitter.com/aliciar
Hundreds of scientists, engineers and space-law experts are gathering this week to discuss the growing problem of space debris, and will propose ways to curb the accumulation of new junk in orbit.
The 6th European Conference on Space Debris is being held April 22-25 at the European Space Operations Center in Darmstadt, Germany. More than 300 representatives, ranging from researchers to policymakers, are expected to attend the four-day event, according to officials at the European Space Agency (ESA).
Conference attendees will discuss the buildup of potentially harmful debris in orbit, and address possible ways to remove defunct satellites and other pieces of errant space hardware.
More than 170 million pieces of space junk are currently orbiting Earth, including 29,000 objects that are larger than 4 inches (10 centimeters), according to ESA estimates. As they speed through space at 17,000 mph (27,000 km/h), these objects pose collision risks to both other satellites in orbit and the International Space Station.
"Any of these objects can harm an operational spacecraft," Heiner Klinkrad, head of ESA's Space Debris Office, said in a statement.
Roughly two-thirds of the known pieces of debris were created by explosions in orbit or collisions, ESA officials said.
In 2009, a U.S. Iridium communications satellite was struck by a defunct Russian Cosmos military satellite in what became a wake-up call for the industry. The crash destroyed the two spacecraft and left a huge cloud of debris.
Then, in 2007, China intentionally destroyed one of its aging weather satellites in a controversial anti-satellite test that littered Earth?s orbit with more than 2,500 scraps of space junk.
Since then, researchers and satellite operators have tried to tackle the issue of sustainability in space.
"Space-debris mitigation measures, if properly implemented by satellite designers and mission operators, can curtail the growth rate of the debris population," Klinkrad said. "Active debris removal, however, has been shown to be necessary to reverse the debris increase."
But finding any solution to the space-debris problem will require a collaborative approach.
"As this is a global task, active removal is a challenge that should be undertaken by joint efforts in cooperation with the world's space agencies and industry," Thomas Reiter, ESA's director of human spaceflight and operations, said in a statement.
Follow Denise Chow on Twitter @denisechow. Follow us?@Spacedotcom,?Facebook?or?Google+. Originally published on?SPACE.com.
Copyright 2013 SPACE.com, a TechMediaNetwork company. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.
Sanitation workers consistently make it onto the list of the top 10 most dangerous occupations as tracked by The Bureau of Labor Statistics. It?s no wonder since they are often working in the dark, carrying heavy loads, working in traffic, handling hazardous materials, maneuvering large trucks in tight spaces and battling fatigue. Communication is a key factor in reinforcing safe behavior, yet reaching workers can be challenging when they spend most of their time on the road.
Increasingly, solid waste companies are installing electronic message boards at their facilities as a way to improve communication. The need for a mobile communications option is also becoming critical with the rapid growth of smart phone and tablet use. Most companies underestimate what?s involved in developing an effective program. There are three components to a successful deployment?
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Jude Carter is Director of Marketing for The Marlin Company (Wallingford, CT). Her expertise includes all aspects of marketing, new business development, sales management and strategic planning. She joined The Marlin Company in 2005. As Director of Marketing, she is responsible for developing and executing the company?s integrated marketing strategy, which includes brand awareness, lead generation, direct marketing, events, PR, business development support and training. Jude can be reached at (800) 344-5901 or visit www.themarlincompany.com.
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Public release date: 25-Apr-2013
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