Multicenter NIH Clinical Trial Will Study Potential Benefits Of Brain Cooling After A Stroke

Researchers at Cedars-Sinai Medical Center in Los Angeles, the University of California, San Diego School of Medicine, and UTHealth’s Medical School will collaborate on the largest clinical trial of hypothermia (brain cooling) for stroke to date.

The ICTuS 2 study (Intravascular Cooling for Acute Stroke) will be led by overall principal investigator Patrick D. Lyden, M.D., former director of the UC San Diego Stroke Center and currently chairman of the Department of Neurology at Cedars-Sinai. Principal investigators at UC San Diego School of Medicine and The University of Texas Health Science Center at Houston (UTHealth) are Thomas Hemmen, M.D., Ph.D., director of the UCSD Stroke Center, and James C. Grotta, M.D., chairman of the Department of Neurology at UT Health, respectively.

Set to begin later this Spring, the three-and-a-half-year study will enroll 400 patients and is funded by two grants from the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health. A UC San Diego grant includes funding for 18 study sites, while a UTHealth grant will fund eight sites. Most of the sites are in the United States, but some are in Europe.

Brain cooling has been shown to decrease brain swelling and reduce loss of neurologic function after an acute stroke. It has also been proven highly effective in saving lives and preventing neurologic damage after cardiac arrest and after oxygen deprivation in newborns. This trial will look specifically at whether hypothermia can be used safely in elderly stroke patients.

“We know hypothermia works,” said Lyden, “but is it safe when you consider age and other conditions such as diabetes or hypertension?”

In the ICTuS 2 trial, investigators will use an endovascular temperature modulation system from Philips Healthcare. Endovascular cooling provides rapid heat exchange and very fast cooling toward target temperature; in awake patients, endovascular cooling is generally superior to cooling blankets or ice packs in maintaining tight temperature control around the target temperature.

Cooling is achieved by inserting a special catheter into the inferior vena cava – the body’s largest vein. No fluid enters the patient; instead, an internal circulation within the catheter transfers heat out. Study participants are covered with a warming blanket to “trick” the body into feeling warm, and temperature sensors in the skin and a mild sedative help suppress shivering. In this study, body temperature will be cooled to 33 degrees C and maintained at that level for 24 hours.

At the conclusion of the cooling period, participants will be re-warmed over 12 hours.

ICTuS 2 is a single-blind, randomized, placebo-controlled trial. To be included, patients must meet certain age and medical criteria, treatment must begin within three hours of stroke onset, and patients must receive intravenous injection of tissue plasminogen activator (tPA), a “clot-busting” medication.

Cedars-Sinai Medical Center
University of Texas Health Science Center at Houston
UC San Diego Medical Center

William C. Reeves New Investigator Award Won By UC Davis Malaria Researcher Win Surachetpong

Malaria researcher Win Surachetpong, a doctoral candidate at the University of California, Davis, is the 2009 winner of the William C. Reeves New Investigator Award, given to the best scientific paper presented at the annual Mosquito and Vector Control Association of California (MVCAC) meeting.

Surachetpong received $1000 and a plaque at the 77th annual MVCAC meeting, held in Burlingame. His scientific paper focused on regulating the development of malaria parasites.

“Win is a very talented, dedicated student and I have been extremely fortunate to have him in my lab,” said his major professor and malaria researcher Shirley Luckhart, an associate professor of medical microbiology and immunology at the UC Davis School of Medicine, and a faculty member of the Graduate Groups of Biochemistry and Molecular Biology; Microbiology; Immunology; and the Graduate Program in Entomology.

“His work,” she said, “has been the foundation of the development of a completely new area of work for us that will probably keep us busy for years to come.”

The award memorializes a renowned entomologist and professor at UC Berkeley who was widely regarded as the world’s foremost authority on the spread and control of mosquito-borne diseases. Reeves (1916-2004) was a frequent visitor to the UC Davis campus.

Surachetpong said that malaria “remains an enormous public health burden, especially in developing countries.” Malaria, caused by the parasite Plasmodium and transmitted by infected anopheline mosquitoes, strikes some 350 to 500 million people a year, killing more than a million, according to the Centers for Disease Control and Prevention.

“New strategies including integrated vector management in combination with current conventional malaria control efforts such as drug treatment and bednet usage could synergistically reduce malaria transmission,” Surachetpong said.

“However, our current knowledge of vector-host-parasite interactions is limited,” he noted. “For example, how mosquito innate immune responses control malaria parasite development and how blood-derived factors modulate mosquito biology remain interesting topics.”

“In this study, we reveal the role of MEK-ERK (mitogen-activated protein kinase/extracellular signal-regulated kinase) signaling in regulation of malaria parasite development by an ingested blood-derived, mammalian cytokine in the mosquito host.”

The results, the researchers said, “provide new insights into the host-parasite-vector relationship that could be utilized as a foundation for new strategies to reduce malaria transmission.”

Surachetpong titled his paper “MAPK/ERK Signaling Regulates the TGF-Betal Dependent Mosquito Response to Plasmodium falciparum.” TGF-beta is a transforming growth factor beta synthesized by skeletal cells and found in most species.

A native of Thailand, Surachetpong joined the Luckhart lab and the Immunology Graduate Group in 2005. He is seeking his doctorate in immunology, with a designated emphasis in vectorborne diseases. His doctoral thesis is “MAPK Signaling Pathways Regulate Anti-Malarial Response in Anopheles Mosquitoes.”


Last year Surachetpong was awarded a prestigious Bill and Melinda Gates Foundation health travel award to present his research at a Keystone Symposia conference in Bangkok, Thailand. The meeting focused on the pathogenesis and control of emerging infections and drug-resistant organisms.
Surachetpong received his doctorate of veterinary science degree at Chulalongkorn University, Bangkok in 2000, ranking first in his class, and his master of science degree in pathobiology in 2005 from the University of Arizona, with high honors.

Source: Kathy Keatley Garvey

University of California – Davis

Combining Exercise With Hormone Could Prevent Weight Gain

Heralded as a promising obesity treatment, the hormone leptin lost its fat-fighting luster when scientists discovered overweight patients were resistant to its effects. But pairing leptin with just a minor amount of exercise seems to revive the hormone’s ability to fight fat again, University of Florida researchers recently discovered.

The combination of leptin and a modest dose of wheel running prevented obese rats on a belt-busting, high-fat diet from gaining weight, even though neither tactic worked alone, say UF researchers, writing in the journal Diabetes.

“They don’t run enough to use sufficient energy to prevent weight gain,” said Philip Scarpace, Ph.D., a professor of pharmacology and therapeutics in the UF College of Medicine and the senior author of the study. “What the act of running appears to do is allow the leptin to work again. It’s a demonstration that this simple act can reverse leptin resistance.”

More than 34 percent of American adults – about 72 million people – are obese or overweight, according to the Centers for Disease Control and Prevention. Scientists had hoped to wield leptin, a hormone that sends the body chemical signals to stop eating and use stored energy, as a weight-loss weapon. Studies in lean animals were promising, but overweight animals and people don’t respond the same way, likely because their bodies already overproduce leptin, causing them to develop resistance to the hormone, Scarpace said.

“Obese animals and humans don’t respond to leptin at all,” he said. “Our lab is interested in elucidating why this is the case. We know that often single-entity treatments are not successful. The concept was maybe a dual-entity treatment would work.”

To test this, the researchers decided to pair leptin with exercise, comparing the effects on both normal-weight and obese rats kept on high-fat diets, which simulate the type of fast-food-filled fare many Americans eat.

The rats were further separated into three groups to test three approaches. One group received leptin, another group got an exercise wheel and the third group got both leptin and a wheel. In the normal-weight rats, leptin and exercise both worked to prevent weight gain. The normal-weight rats ran significantly more than their bulkier peers, logging in about two and a half miles a day on their wheels, and kept off weight proportionally to how much they ran. The rats were allowed to run as much as they chose.

In the obese rats, which ran six to eight times less, neither running nor leptin alone kept the weight from accruing. Giving the rats leptin actually caused them to gain more weight than eating a high-fat diet alone, the study shows.

“This is a startling finding. Leptin is expected to reduce body weight, not promote weight and fat gain,” Scarpace said.

But the obese rats that ran and took leptin kept the extra weight off, Scarpace said. More research is needed to understand exactly why this combination works, but the scientists speculate that the low level of running triggered a metabolic change in the rats that cleared the way for the leptin signal to get through.

“They should have been gaining weight,” Scarpace said. “They don’t run enough to make any difference.”

Christopher Morrison, Ph.D., an assistant professor at the Pennington Biomedical Research Center at Louisiana State University who wrote a commentary about the UF study in Diabetes, said he thinks the discovery has potential to help combat obesity in humans.

“That’s the hope and the reason for doing this type of work,” he said. “The study raises many questions. If we can improve leptin sensitivity and enhance the ability of the signal to get through, maybe it will lead to weight loss.”

UF researchers are now aiming to team with doctors and test the leptin and exercise combination in humans. They also are working on additional studies to better understand leptin’s effects and its signaling pathway. Scientists still can’t pinpoint exactly why overweight people develop resistance to leptin and what role the hormone really plays in obesity.

“Leptin may be the cause of obesity rather than a cure,” Scarpace said. “Unless you run.”

Collaborating with Scarpace on the study were Alexandra Shapiro, Ph.D., Michael Matheny, Yi Zhang, Ph.D., Nihal TГјmer, Ph.D., Kit-Yan Cheng, Enda Rodrigues and Sergei Zolutukhin, Ph.D.

The University of Florida Health Science Center – the most comprehensive academic health center in the Southeast – is dedicated to high-quality programs of education, research, patient care and public service. The Health Science Center encompasses the colleges of Dentistry, Public Health and Health Professions, Medicine, Nursing, Pharmacy and Veterinary Medicine, as well as the Veterinary Medical Teaching Hospital and an academic campus in Jacksonville offering graduate education programs in dentistry, medicine, nursing and pharmacy. Patient care activities, under the banner UF&Shands, are provided through teaching hospitals and a network of clinics in Gainesville and Jacksonville. The Health Science Center also has a statewide presence through satellite medical, dental and nursing clinics staffed by UF health professionals; and affiliations with community-based health-care facilities stretching from Hialeah and Miami to the Florida Panhandle.

University of Florida Health Science Center

Flu Pandemics May Be Worsened By Short-Term School Closures, Pitt Study Finds

Closing schools for less than two weeks during a flu pandemic may increase infection rates and prolong an epidemic, say University of Pittsburgh researchers in a study published ahead-of-print and online in the Journal of Public Health Management and Practice. The findings, developed from a series of computer simulations based on U.S. census data, indicate that schools may need to be closed for at least eight weeks in order to significantly decrease the spread of infection.

The value of school closures has been debated as a possible strategy to stem or slow the current H1N1 influenza pandemic. Indeed, hundreds of schools across the country have been closed at different periods during 2009 for fear the virus would spread more quickly if they stayed open.

“Although closing schools may seem like a reasonable way to slow the spread of flu, we found that it was not effective unless sustained for at least eight weeks after implementation,” said study lead author, Bruce Lee, M.D., M.B.A., assistant professor or medicine, epidemiology and biomedical informatics, University of Pittsburgh. Closing schools quickly at the start of an outbreak was much less important than keeping them closed continually throughout the epidemic, he added.

According to study authors, short-duration school closures can increase transmission rates by returning susceptible students back to school in the middle of an epidemic when they are most vulnerable to infection.

The study also found that identifying sick students individually and keeping them from attending school had minimal impact on an epidemic. In addition, there were no significant differences between individual school closures and system-wide closures in mitigating an epidemic.

The study was based on an agent-based computer simulation model of Allegheny County, Pa., that represented the county’s population, school systems, workplaces, households and communities. Simulations were based on the movement of residents each weekday from their households to designated workplaces or schools, and included 1.2 million people – 200,000 of whom were school-aged children. The study also included more than 500,000 households and nearly 300 schools.

Co-authors of the study include Shawn T. Brown, Ph.D., Pittsburgh Supercomputing Center; Philip Cooley, M.S., William Wheaton, M.A., and Diane Wagener, Ph.D., RTI International; Ronald Voorhees, M.D., M.P.H., Allegheny County Health Department; and Maggie Potter, J.D., Samuel Stebbins, M.D., M. P.H., John Grefenstette, Ph.D., Shanta Zimmer, M.D., Richard Zimmerman, M.D., M.P.H., Tina-Marie Assi, M.P.H., Rachel Bailey, M.P.H., and Donald S. Burke, M.D., University of Pittsburgh.

The study is part of the University of Pittsburgh Models of Infectious Disease Agents Study (MIDAS) funded by the National Institutes of Health.

Source: Clare Collins

University of Pittsburgh Schools of the Health Sciences

Study Suggests Need For More Aggressive Outpatient Monitoring Of Patients’ Hearts When Cause Of Stroke Is Unclear

In nearly one third of all people who suffer from a stroke, the underlying cause of the injury is not readily evident to doctors. Atrial fibrillation (AF), or an irregular heartbeat, is believed to be a significant factor in many of these cases.

Stroke researchers at Allegheny General Hospital (AGH) in Pittsburgh are reporting in the journal Neurology (neurology/cgi/content/abstract/71/21/1696) that a new diagnostic approach that extends the monitoring of patients’ hearts after hospital discharge greatly improved their ability to detect AF and treat it appropriately.

Led by Ashis Tayal, M.D., a stroke neurologist and medical director of AGH’s Comprehensive Stroke Center, the AGH team explored the use of mobile outpatient cardiac telemetry over a period of 2-3 weeks to monitor patients who have experienced a stroke or a transient ischemic attack (TIA) of unknown cause.

Atrial Fibrillation was diagnosed in 23% of the study participants where conventional diagnostic protocols had failed.

“Stroke is an extremely challenging disease to treat and prevent when we know the cause or an individual’s specific risk factors. That so many patients actually leave the hospital without a precise reason for their injury is a very frustrating scenario for physicians and one that has potentially devastating implications for patients and their families,” Dr. Tayal said.

The nation’s third leading cause of death, stroke is the number one cause of serious, long-term disability.

“If we can indeed identify AF more promptly in these cases, our ability to treat patients and perhaps prevent a second, more catastrophic injury would be significantly enhanced,” he said.

Atrial fibrillation is the most common heart rhythm abnormality that people develop. During AF the heart’s two upper chambers (the atria) beat chaotically and irregularly. The condition causes poor blood flow and the development of blood clots within the heart which can subsequently release into the arteries of the brain and cause a stroke.

Dr. Tayal said the conventional approach to evaluating stroke patients is an extensive in-hospital diagnostic work-up that includes neurological imaging such as MRI and angiography and cardiovascular studies, such as telemetry and holter monitoring, that assess the heart’s rhythm.

“Intermittent AF becomes more common as we grow older and as a known risk factor for stroke, the current standard of care when the cause of injury is unclear is to monitor patients with telemetry for several days in the hospital. Unfortunately, our probability of detecting AF in this brief window of time is less than 1%,” Dr. Tayal said.

Using a newer, mobile telemetry system called CardioNet, Dr. Tayal and his AGH colleagues evaluated 56 patients with stroke of unknown etiology and no previous history of AF for a period of three weeks post-discharge. Hospital based telemetry and holter monitoring results for all were normal.

The CardioNet System requires no patient interaction. Via three leads attached to a lightweight sensor worn on a neck strap or belt clip, the monitor analyzes a patient’s heart rhythm in real time during normal daily activities. When the system identifies an abnormal rhythm, the data is automatically transmitted to the medical team.

Over the course of three weeks, thirteen of the 56 patients in AGH’s study were found to have either prolonged or brief episodes of AF. For those with prolonged incidents — a clear indication of stroke cause — the discovery prompted immediate therapeutic intervention with medication designed to better protect the patient from a repeat stroke.

Dr. Tayal said the results are equally important relative to those found to have brief episodes of AF.

“AF of relatively short duration — 10, 15 seconds or so — does not place a patient at imminent risk of a blood clot or stroke, but it may be a maker of those who are prone to a more dangerous, prolonged episode that does. Knowing that someone is predisposed to AF substantially alters our approach to treating them and may ultimately improve outcomes,” Dr. Tayal said.

Allegheny General Hospital

British Forces Clinic Allied Joint Forces Command Headquarters Naples Wins National Award For No Smoking Day, UK

The British Forces Clinic Allied Joint Forces Command Headquarters Naples in Italy wins a national award for organising an event for No Smoking Day 2007. Lt Cdr Lorraine England QARNNS representing the British Forces team won three prestigious awards for newcomer of the year, best community activity and best Armed Forces activity by designing a children’s and young persons workbook for classroom use and, co-ordinating the delivery of a number of stop-smoking activities within the local British Forces community.

Lt Cdr Lorraine England QARNNS who works as the Senior Nursing Officer and stop-smoking co-ordinator within the British Forces Clinic said: “We are very pleased to win an award for our 2007 No Smoking Day activities as it recognises the strength of collaboration and partnership between the military medical services, service education agencies, SSAFA (Soldiers, Sailors, Airmen and Families Association), HIVE (Help, Information, Volunteer, Exchange) and the No Smoking Day campaign team in delivering effective education about the risks associated with smoking.”

Dan Tickle, Chief Executive of the charity No Smoking Day said: “Thanks to the passionate support of our local organisers, No Smoking Day has remained the UK’s leading public health event for a quarter of a century. For their dedication and commitment – as well as their willingness to spend wet Wednesdays in March dressed as a giant cigarette – we’re indebted to each and every one.”
Next year’s No Smoking Day will be on Wednesday 12 March 2008.


No Smoking Day (NSD) is organised by a charity of the same name run by four full time staff. Based in London, the charity is funded by a coalition of governmental and voluntary sector organisations with an interest in health.

NSD aims to help people who want to stop smoking by creating a supportive environment for them, and by highlighting the many sources of help available to people who want to quit.

Now in its 25th year it is a firm fixture in the UK calendar because of its popularity amongst smokers and continued success. Three quarters of smokers would like to stop and on NSD over a million try. NSD isn’t just about the Day. Stopping smoking requires much planning, encouragement, support and motivation. Helping others to prepare to quit can be done year round, but the Day provides an excellent focus and motivation for many smokers to stop.


Possible Connection Between Marijuana Abuse And Stroke Or Heart Attacks

Long-term harmful effects of marijuana (MJ) include risk for heart attacks and strokes in addition to impaired learning and memory. The active chemical in MJ called delta-9-tetrahyrdocannabinol (THC) is believed to exert these effects by binding to cannabinoid (CB) receptors located on several cell types in various organs. Scientists have found CB receptors in many organs including the brain, heart, liver, kidney, and spleen.

In this study, researchers investigated if persistent heavy MJ use might be associated with changes in different blood proteins in order to check if the abnormalities in the identified proteins might be related to other side-effects of marijuana.

The study was conducted with 18 long term heavy MJ users and 24 non-drug using volunteers. People with major medical and psychiatric illnesses, hypertension, head injury, HIV positive, alcohol dependency and other drug usage, were excluded from the study. Blood proteins were measured in both control volunteers and MJ users using a new method (protein chip) that has the potential to identify several new target proteins. That approach showed that apolipoprotein C-III (apoC-III) showed significant increases in MJ abusers. ApoC-III belongs to a large family of proteins that interact with lipids and helps lipids to move into and out of cells. ApoC-III is involved in transport of triglycerides and delays the breakdown of triglycerides. Increases in apoC-III levels in the blood occur in parallel with increases in triglyceride levels.

Even though we still don’t understand how heavy MJ use might cause increases in apoC-III levels, this protein might be one of the reasons why some MJ users have increased risks of heart attack and strokes.


Citation source:

Heavy Marijuana Users show Increased Serum Apolipoprotein C-III levels: Evidence from proteomic analyses

S Jayanthi1 S Buie1 S Moore3 RI Herning1 W Better1 NM Wilson1 C Contoreggi2 JL Cadet1

1Molecular Neuropsychiatry Branch
2Office of the Clinical Director, National Institute on Drug Abuse-Intramural Research Program, NIH, BRC, 251 Bayview Boulevard, Baltimore, MD, USA
3Ciphergen Biosystems, Freemont, CA, USA

Molecular Psychiatry advance online publication 13 May 2008

Molecular Psychiatry is a peer-reviewed independent journal that publishes groundbreaking research in psychiatry and related fields. The journal’s Impact Factor is 11.804, 2nd of 95 in Psychiatry

Journal Website: nature/mp
Editor: Julio Licinio, M.D.
University of Miami Miller School of Medicine

Source: Dorie Hightower

Molecular Psychiatry

Evotec Reports Results Of Phase II Proof-Of-Concept Study With EVT 302

Evotec AG (Frankfurt Stock Exchange: EVT; NASDAQ: EVTC) announced the results of a Phase II proof-of-concept study investigating the potential of EVT 302, a reversible and highly selective inhibitor of monoamine oxidase B (MAO-B), as an aid to smoking cessation.

EVT 302 failed to demonstrate any significant improvement in the quit rate compared with placebo. The combination of EVT 302 with a nicotine replacement patch also failed to demonstrate any significant benefit over nicotine replacement therapy (NRT) alone. The study was well performed and the placebo quit rate was well within expectations ensuring adequate power to demonstrate any treatment effect. Throughout this study EVT 302 was well tolerated with subjects experiencing very few treatment-related adverse events.

The study reported today was performed double blind in Germany with 414 otherwise healthy smokers who were motivated to quit smoking. The study assessed whether 8 weeks treatment with EVT 302 resulted in an increase in quit rate compared to placebo. The study also included a comparison of EVT 302 added to NRT (21 mg patch once daily) vs NRT alone to see if there was any additive benefit for the two treatments taken together.

Dr Tim Tasker, Executive Vice President Clinical Development at Evotec, commented: “We are disappointed with the results of this proof-of-concept study which has failed to demonstrate any convincing support for the use of EVT 302 as an aid to smoking cessation. Once a full analysis of all the data is completed Evotec will re-assess the future of EVT 302, given the overall potential of MAO-B-inhibitors in a number of indications and the excellent safety profile demonstrated by EVT 302 in this study.”

Dr Werner Lanthaler, Chief Executive Officer of Evotec, added: “Strict cost containment by focusing our pipeline and de-risking our business according to the “Evotec 2012 – Action Plan to Focus and Grow” is the right strategy also in light of this clinical outcome.”

About Evotec AG

Evotec is a leader in the discovery and development of novel small molecule drugs. Both through its own discovery programs and through research collaborations, it is generating the highest quality research results to its partners in the pharmaceutical and biotechnology industries. In proprietary projects, Evotec specializes in finding novel therapies for neuroscience, pain, and inflammation. Evotec’s portfolio comprises five clinical compounds: EVT 101, a subtype selective NMDA receptor antagonist for the treatment of depression in partnership with Roche, EVT 201, a partial positive allosteric modulator (pPAM) of the GABAA receptor complex for the treatment of insomnia, EVT 302, a MAO-B inhibitor in development for smoking cessation, a P2X7 antagonist for the treatment of inflammatory diseases and a vanilloid receptor (VR1) antagonist for the treatment of pain in partnership with Pfizer. In addition, Evotec has a number of proprietary projects in preclinical development.

Forward-Looking Statements

Information set forth in this press release contains forward-looking statements, which involve a number of risks and uncertainties. Such forward-looking statements include, but are not limited to, statements about our expectations and assumptions concerning future reductions in operating expenses and cash burn, regulatory, clinical and business strategies, the progress of our clinical development programs and timing of the results of our clinical trials, strategic collaborations and management’s plans, objectives and strategies. These statements are neither promises nor guarantees, but are subject to a variety of risks and uncertainties, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in these forward-looking statements. In particular, the risks and uncertainties include, among other things: risks that product candidates may fail in the clinic or may not be successfully marketed or manufactured; risks relating to our ability to advance the development of product candidates currently in the pipeline or in clinical trials; our inability to further identify, develop and achieve commercial success for new products and technologies; competing products may be more successful; our inability to interest potential partners in our technologies and products; our inability to achieve commercial success for our products and technologies; our inability to protect our intellectual property and the cost of enforcing or defending our intellectual property rights; our failure to comply with regulations relating to our products and product candidates, including FDA requirements; the risk that the FDA may interpret the results of our studies differently than we have; the risk that clinical trials may not result in marketable products; the risk that we may be unable to successfully secure regulatory approval of and market our drug candidates; and risks of new, changing and competitive technologies and regulations in the U.S. and internationally.

The list of risks above is not exhaustive. Our most recent Annual Report on Form 20-F, filed with the Securities and Exchange Commission, and other documents filed with, or furnished to the Securities and Exchange Commission, contain additional factors that could impact our businesses and financial performance. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any such statements to reflect any change in our expectations or any change in events, conditions or circumstances on which any such statement is based.

Evotec AG

(DH) New Primary Care Approach Boosts Referrals To NHS Stop Smoking Services By 49%, Uk

The Department of Health is rolling out a new systems-based approach to improve stop smoking interventions in primary care. This new approach has increased referrals to local NHS Stop Smoking services by up to 49% in pilot areas.

People who are referred to local NHS Stop Smoking Services are up to four times more likely to quit.

The new approach was developed to ensure stop smoking interventions by healthcare professionals are routine and systematic, providing a tailored and consistent approach to patient referral. It will be rolled out to practices over the next few months by trained local NHS Stop Smoking Service advisers who will support its implementation in local primary care settings.

The approach recognises smoking as a key clinical issue requiring treatment or referral to a specialist, joining standard issues such as hypertension or high cholesterol.

The system ensures that basic advice on stopping smoking is offered to all smokers, which doubles the likelihood of a quit attempt. Practices which have this systems-based approach in place are expected to see improved quit rates in their patients. There are also two stages within the system for practices to earn QOF points, increasing the potential revenue and funding for the practice.

The systems-based approach for delivering stop smoking in primary care comprises:
* a tiered approach to stop smoking support that establishes three different levels of interventions according to time available; a supportive delivery system of 10 components that ensures that quality stop smoking support becomes routine; and a supportive practice environment that demonstrates commitment to support all patients in stopping smoking.

This new approach, which was successfully pioneered by local NHS Stop Smoking Services in the Yorkshire and Humber region, has been put into practice by trained stop smoking service advisers in Rotherham from January 2007 to September 2008. Over this time, referrals to local NHS Stop Smoking Services increased on average by 49% (from 292 to 432) across nine GP practices in Rotherham, with one practice doubling its referrals.

Paul Aveyard, Senior Lecturer at the Department of Primary Care and General Practice at Birmingham University and senior consultant on the development of the primary care project, said:

“The approach works by offering patients three levels of intervention, from 30 second very brief advice to intensive support. The primary care programme establishes a supportive delivery system of 10 components that ensures quality stop smoking treatment becomes routine in the practice.

“What we are trying to do is to make the treatment of tobacco addiction routine, in a similar way to hypertension. Previously, the primary care system encouraged GPs to give their patients advice in terms of stop smoking. The difference here is that GPs will now be required to actively manage their patients – such as referring them to a specialist stop smoking service.”

The project was pioneered in Yorkshire and Humber from 2007 and data from the regional pilot in Rotherham shows how successful the approach has been in practices there.

Jacqueline Watson, local NHS Stop Smoking Adviser, Rotherham PCT, said:

“The rollout of Stop Smoking Interventions in Primary Care will help us improve the health of patients and save more lives, in addition to helping practices improve their performance by securing extra QOF points and therefore increasing their potential revenue. I have found that getting practice managers engaged and supportive is key, but in those practices I’ve been working with in Rotherham, it has already enabled managers to transform performance and boost QOF scores.”

The Dinnington Group practice in Rotherham worked alongside their local Stop Smoking Service to boost referrals to the local Stop Smoking Service by over 80%. Irene Botham, Clinical Nurse Manager of the practice said: “Our nurses received expert training from the local NHS Stop Smoking Service in smoking interventions. We worked hard to drive forward the initiative in my practice and saw great results – since we implemented the new systems based approach our referral rates have increased by 82%. There are clear clinical benefits to following this approach and health care professionals have a duty of care to help smokers to quit. In addition, our patients can benefit from the assistance of NHS support with which they are up to four times more likely to quit.”

National evaluation of the project’s rollout across England is due to take place in April 2010.

For more information, healthcare professionals should contact their local NHS Stop Smoking Service, which they can find by using the ‘Local Services Search’ at smokefree.nhs/resources


1. The majority of local NHS Stop Smoking Services in England have been trained to introduce primary care practitioners to the new system and its benefits and will be contacting GP practices imminently. A toolkit for local NHS Stop Smoking Services (LSSS) advisers and resources for practices have been developed to support the rollout. Evaluation is taking place in July & October 2009 and a final evaluation in April 2010.

2. Local NHS Stop Smoking Services

Local NHS Stop Smoking Services offer ongoing free support and advice close to people’s homes. There are over 150 throughout the country, offering a range of services including one-to-one or group support sessions with trained stop smoking advisers.

Advisers help smokers understand their addiction to tobacco and work together on a personalised plan to stop smoking. They can also provide information about nicotine replacement products and other stop smoking medicines. These are available on prescription from the NHS.

A total of 680,289 people in England set a quit date through the local NHS Stop Smoking Services in 2007/8 and over half (350,800 people) reported that they were still smokefree at their four-week follow-up.

3. The evidence is clear that local NHS stop smoking interventions are very successful:

* Offering brief advice to stop smoking is the single most cost-effective and clinically proven preventive action that a healthcare professional can undertake: Anczak J, Nogler R. Tobacco cessation in primary care: maximizing intervention strategies. Clinical Medicine & Research 2003; 1(3): 201-216.

* Smokers are up to four times more likely to quit smoking successfully with support from their local NHS Stop Smoking Services: Ferguson J, Bauld L, Chesterman J, Judge K. The English smoking treatment services: one-year outcomes. Addiction 2008; 100 (Suppl. 2): 59-69 and West R, McNeill A, Raw M. Smoking cessation guidelines for health professionals: an update. Thorax 2000; 55(12): 987-99.

* When stop smoking messages are received from trusted practitioners, motivation and the chances of action is likely to be increased. Fiore M, Bailey W, Cohen S et al. Treating Tobacco Use and Dependence. US Department of Health and Human Services, Public Health Service, 2000.

4. Supportive delivery system – the 10 components to success: The healthcare setting needs to establish a support system to ensure that successful smoking advice becomes routine. There are 10 components that work together and these are essential in making sure that the healthcare team can provide quality stop smoking support. In essence they demonstrate the team’s complete commitment to helping patients quit. Smokers are supported at every level, as is the team in the primary care setting. Managers give their team strong incentives to do well, backed up by the right resources, training and facilities. Each component is a link in the chain. If one link is missing, the whole system becomes weakened.

The 10 components are:

* Senior level commitment
* Incentives
* Protocol
* Teamwork
* Training
* Environment
* Resources
* Therapies
* NHS Stop Smoking information
* feedback

5. Smoking remains the main cause of preventable morbidity and premature death in England, leading to an estimated 82,900 deaths in 2007 (18 per cent of all deaths of adults aged 35 and over) estimated to be caused by smoking. (Statistics on Smoking, England 2008, Health Information Centre).

NICE (National Institute for Health and Clinical Excellence) recommends that all healthcare practitioners give brief stop smoking messages to all smokers (unless exceptional circumstances make it inappropriate to discuss smoking).

Department of Health, UK

Androgenic Regulation Of Hedgehog Signaling Pathway Components In Prostate Cancer Cells

UroToday – Tumors share many characteristics with developing embryonic tissues including the presence of rapidly dividing cells and cells in multiple states of differentiation. Therefore, it should not be surprising that the cellular signaling processes that govern normal embryonic development play some role in tumor biology. Hedgehog (Hh) is one of the fundamental developmental signaling pathways that is believed to have a role in prostate cancer. Hh signaling is driven by a family of ligands, referred to as “hedgehogs”, that bind to a cell surface receptor protein, Patched, activating a signaling cascade that upregulates gene transcription mediated by Gli transcription factors. For prostate cancer, reports that hedgehog ligands and Gli are overexpressed in the tumor cells supports the idea that these tumor cells might have abnormally activated autocrine Hedgehog signaling. Likewise, experimental evidence that the Hh signaling inhibitor, cyclopamine, or Gli knockdown suppresses prostate cancer cell growth provides pre-clinical evidence to support the use of Hh inhibitors for prostate cancer. However, a recent study from Dr. Wade Bushman’s group at the University of Wisconsin1 failed to find any evidence for autocrine hedgehog signaling in the most commonly utilized human prostate cancer cell lines and this report raises important questions regarding the nature of the molecular pathway through which Hh signaling components become dysregulated in prostate cancer.

Our experimental work, described in this publication, shows that androgen regulates the expression of key components of the Hh signaling pathway, at least in the androgen-sensitive human prostate cancer LNCaP cells and in other derivatives of this cell line. When grown in the presence of androgen, these cells express very little, if any, hedgehog ligand. Yet, when they are switched to an androgen-depleted growth medium, they become virtual “hedgehog factories”, upregulating Sonic, Indian and Desert hedgehog mRNA and protein expression up to 30,000-fold. The burst of hedgehog production was accompanied by the awakening of autocrine hedgehog signaling in the tumor cells as measured by upregulation of endogenous GLI target genes. Moreover, the induced hedgehog ligands were secreted out into the medium of androgen-deprived cells and we showed that they are paracrine-active and able to drive Hh signaling in mouse bone pre-osteoblasts, an activity that is associated with osteoblastic differentiation of these cells. Finally, in contrast to hedgehog ligands that were upregulated by androgen deprivation, GLI1 expression was upregulated by androgen in LNCaP cells. We attribute this novel activity to the potential consequence of the ETS gene fusion in these cells since GLI is known to be a target of the EWS:ETS fusion gene in Ewing Sarcoma cells2. In summary, our experimental work showed that some of the most important components of the Hh signaling pathway are regulated by androgen action in this model prostate cancer cell system. Whereas, the published work was restricted to the use of LNCaP cell derivatives, we have also observed these same results using androgen-sensitive VCaP cells. Moreover, the clinical relevance of our findings is supported by a recent report from a group of French investigators that describes upregulated hedgehog ligand expression in prostate tumors from hormone-treated patients3.

Based upon the cumulative evidence, we believe that the data support consideration of the use of anti-Hh therapy as an adjuvant for hormone therapy in the treatment of advanced or castration-resistant prostate cancer. For these tumors, Hh signaling blockade might supplement hormone therapy by further slowing the proliferative rate of tumor cells as well as by suppressing their potential for further metastatic spread or bone-related co-morbidity. Whereas the common anti-hedgehog agent, cyclopamine, is a difficult drug to work with due to its extreme hydrophobicity, there are other anti-Hh therapeutics currently in development and we would encourage clinical trials to assess effectiveness of these new agents along with hormone therapy.

1 Zhang J, Lipinski R, Shaw A, Gipp J, Bushman W. J Urol, 177: 1179-85, 2007.
2 Zwerner JP, Joo J, Warner KL, Christensen L, et al. Oncogene, 22: 3282-91, 2008.
3 Azouly S, Terry S, Chimingqi M, Sirah N, et al. J Pathol, 216: 460-70, 2008.

Ralph Buttyan, PhD, et al. as part of Beyond the Abstract on UroToday

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