From Medscape Medical News
Yael Waknine
June 22, 2010 — The US Food and Drug Administration (FDA) has approved, under expedited review, the first assay to detect the HIV p24 antigen as well as antibodies to HIV types 1 and 2 (Architect HIV Ag/Ab Combo Assay; Abbott Diagnostics), potentially allowing patients to be diagnosed days earlier than with antibody-only tests.
The p24 HIV antigen is a protein produced by the virus immediately after infection, before the emergence of antibodies. Early detection is critical for controlling viral spread — the company revealed that every 9.5 minutes, someone in the United States is infected with HIV, and 1 in every 5 of these infected individuals does not know it.
"Since individuals are most infectious to others shortly after infection, detecting HIV earlier is critical and life saving," said Peter Leone, MD, medical director, North Carolina HIV/STD Prevention and Control Branch, University of North Carolina, Chapel Hill, in a company news release. "A significant percentage of new HIV infections are transmitted by someone with an undetected acute infection, so identifying more people earlier offers a significant opportunity for counseling, which can reduce high-risk behaviors and also initiate antiretroviral treatment for early-stage infection, if appropriate."
Most tests currently used in the United States detect HIV antibodies only. Although HIV infection can be directly detected via nucleic acid testing, this method is not widely used.
"The approval of this assay represents an advancement in our ability to better diagnose HIV infection in diagnostic settings where nucleic acid testing to detect the virus itself is not routinely used," said Karen Midthun, MD, acting director of FDA's Center for Biologics Evaluation and Research in an agency news release. "It provides for more sensitive detection of recent HIV infections compared with antibody tests alone."
In a behavioral intervention study conducted by Johns Hopkins University and Abbott, 217 blood samples were collected from men who have sex with men. Using 2 different HIV RNA tests as a control, researchers found that the combination antigen/antibody assay detected nearly two thirds (61.9%; 13/21) of acute infections, whereas only 14.3% (3/21) of acute infections were identified by third-generation antibody tests.
The chemiluminescent microparticle immunoassay is indicated as an aid in the diagnosis of HIV-1/HIV-2 infection in adults, including pregnant women, and children as young as 2 years of age. The new assay will run on the company's automated Architect ci8200 system and is expected to be available later this year.
The FDA notes that although the HIV antigen/antibody assay is not intended for routine screening of blood donors, it may be used in urgent situations when licensed blood donor screening tests are unavailable or impractical.
The combination test previously was approved for European use in 2004, with HIV antigen-antibody combination testing being routine in European public health settings and indicated for first-line use in the United Kingdom.
Wednesday, June 23, 2010
Tai Chi Boosts Efficacy of Antidepressant Therapy in Older Adults
From Medscape Medical News
Fran Lowry
June 21, 2010 (Boca Raton, Florida) — Adding an abbreviated version of Tai Chi to antidepressant therapy with escitalopram improved resilience, quality of life, and cognitive function in adults with major depression 60 years and older, according to new research presented here at the New Clinical Drug Evaluation Unit (NCDEU) 50th Anniversary Meeting.
"Fewer than half of elderly depressed patients respond to first-line antidepressant pharmacotherapy," Helen Lavretsky, MD, from the David Geffen School of Medicine at the University of California, Los Angeles, said in her poster presentation here. "There is some information in the literature about the benefits of tai chi in older adults, but this relates to their balance and their physical functioning. We wanted to see whether tai chi would be helpful in improving depression."
The study recruited 112 adults with major depression and treated them with 10 mg of escitalopram daily for 6 weeks. The 70 subjects who partially responded to escitalopram continued to receive 10 mg of escitalopram per day. In addition, they were randomly assigned to receive either 10 weeks of tai chi chih for 2 hours a week or to a lecture on health education for 2 hours a week.
"Tai chi chih is a shortened form of tai chi that has only 20 movements and is easier to remember over the course of 10 weeks," Dr. Lavretsky explained.
Most of the patients (62%) were women, and their mean age was 70 years.
The patients were evaluated for depression, anxiety, resilience, health-related quality of life, psychomotor speed, and cognition.
Both tai chi and health education patients showed similar improvement in the severity of depression, with mean Hamilton Rating Scale for Depression scores of 6.0 in both groups, Dr. Lavretsky reported. However, subjects in the tai chi group showed significantly greater improvement in resilience than did subjects in the health education group (70.2% vs 65.0%; P < .05).
The tai chi group also had better health-related quality of life, with mean well-being scale scores of 80 on the 36-Item Short Form Health Survey vs 66 for the health education group (P < .05), and measures of executive cognitive function, as shown by Stroop mean error scores of 0.03 vs 0.4 errors in the health education group (P < .05).
"Patients who were in the Tai Chi arm had a greater resilience to stress, and I thought the improvement in cognitive measures, such as memory and executive function measures, with tai chi was particularly impressive," Dr. Lavretsky said in an interview.
"I'm in Los Angeles, so people tend to like alternative medicine interventions," she added. "The limiting measure was the degree of arthritis that patients had. The patients who were in the education group liked that intervention, too, but it was very interesting to me to see that this gentle form of exercise had these superior results. Even C-reactive protein levels in the tai chi group were improved."
Commenting on this poster for Medscape Medical News, Craig Nelson, MD, division chief of the Department of Geriatric Medicine at University of California, San Francisco, noted, "The interesting thing about this study was that it showed that the effect of tai chi was greater than that of the education program. That is impressive, because older depressed patients tend to have more of a benefit from a group effect, which an educational program would provide."
He suggested that tai chi may be different in its effects than other exercise. "Looking at such a comparison might be the subject of another study," he said.
This study was funded by the National Center for Complementary and Alternative Medicine. Dr. Lavretsky and Dr. Nelson have disclosed no relevant financial relationships.
New Clinical Drug Evaluation Unit (NCDEU) 50th Anniversary Meeting: Abstract 5, Session II. Presented June 16, 2010.
Fran Lowry
June 21, 2010 (Boca Raton, Florida) — Adding an abbreviated version of Tai Chi to antidepressant therapy with escitalopram improved resilience, quality of life, and cognitive function in adults with major depression 60 years and older, according to new research presented here at the New Clinical Drug Evaluation Unit (NCDEU) 50th Anniversary Meeting.
"Fewer than half of elderly depressed patients respond to first-line antidepressant pharmacotherapy," Helen Lavretsky, MD, from the David Geffen School of Medicine at the University of California, Los Angeles, said in her poster presentation here. "There is some information in the literature about the benefits of tai chi in older adults, but this relates to their balance and their physical functioning. We wanted to see whether tai chi would be helpful in improving depression."
The study recruited 112 adults with major depression and treated them with 10 mg of escitalopram daily for 6 weeks. The 70 subjects who partially responded to escitalopram continued to receive 10 mg of escitalopram per day. In addition, they were randomly assigned to receive either 10 weeks of tai chi chih for 2 hours a week or to a lecture on health education for 2 hours a week.
"Tai chi chih is a shortened form of tai chi that has only 20 movements and is easier to remember over the course of 10 weeks," Dr. Lavretsky explained.
Most of the patients (62%) were women, and their mean age was 70 years.
The patients were evaluated for depression, anxiety, resilience, health-related quality of life, psychomotor speed, and cognition.
Both tai chi and health education patients showed similar improvement in the severity of depression, with mean Hamilton Rating Scale for Depression scores of 6.0 in both groups, Dr. Lavretsky reported. However, subjects in the tai chi group showed significantly greater improvement in resilience than did subjects in the health education group (70.2% vs 65.0%; P < .05).
The tai chi group also had better health-related quality of life, with mean well-being scale scores of 80 on the 36-Item Short Form Health Survey vs 66 for the health education group (P < .05), and measures of executive cognitive function, as shown by Stroop mean error scores of 0.03 vs 0.4 errors in the health education group (P < .05).
"Patients who were in the Tai Chi arm had a greater resilience to stress, and I thought the improvement in cognitive measures, such as memory and executive function measures, with tai chi was particularly impressive," Dr. Lavretsky said in an interview.
"I'm in Los Angeles, so people tend to like alternative medicine interventions," she added. "The limiting measure was the degree of arthritis that patients had. The patients who were in the education group liked that intervention, too, but it was very interesting to me to see that this gentle form of exercise had these superior results. Even C-reactive protein levels in the tai chi group were improved."
Commenting on this poster for Medscape Medical News, Craig Nelson, MD, division chief of the Department of Geriatric Medicine at University of California, San Francisco, noted, "The interesting thing about this study was that it showed that the effect of tai chi was greater than that of the education program. That is impressive, because older depressed patients tend to have more of a benefit from a group effect, which an educational program would provide."
He suggested that tai chi may be different in its effects than other exercise. "Looking at such a comparison might be the subject of another study," he said.
This study was funded by the National Center for Complementary and Alternative Medicine. Dr. Lavretsky and Dr. Nelson have disclosed no relevant financial relationships.
New Clinical Drug Evaluation Unit (NCDEU) 50th Anniversary Meeting: Abstract 5, Session II. Presented June 16, 2010.
Experts Targeting Smoking and Secondhand Smoke Worldwide
From Heartwire
Michael O'Riordan
June 21, 2010 (Beijing, China) — Smoking, particularly the effects of secondhand smoke in nonsmokers, took center stage at the World Congress of Cardiology (WCC) 2010 last week, with experts calling on cardiologists to play a pivotal role in getting their patients to quit smoking and to reduce smoking in their communities.
"As a cardiologist who actively sees patients, one of the most important things I can do is tell them to stop smoking," Dr Sidney Smith (University of North Carolina, Chapel Hill) told the media during the WCC meeting last week. "It is arguably the major risk factor in the world right now, and if you wanted to do something to really make things better on this planet, you'd get rid of smoking and tobacco use."
Smith, the president-elect and chair of the World Heart Federation scientific advisory board, said the new National Institutes of Health (NIH) cardiovascular risk-reduction guidelines, of which he is a chair, will stress the importance of smoking cessation. "I want to be very clear where I stand on the importance of smoking cessation and tobacco use and the danger not only to the person who is smoking; [there is] also a very important risk in secondhand smoke."
If you wanted to do something to really make things better on this planet, you'd get rid of smoking and tobacco use.
An estimated 20% of cardiovascular disease worldwide is caused by tobacco, and yet, surprisingly, not everybody is aware of the link between cardiovascular disease, smoking, and secondhand smoke. In China, for example, just 4% of smokers are aware that smoking causes heart disease, said Smith.
And yet there is no shortage of scientific evidence. At the meeting, Dr Lynn Goldman (Johns Hopkins Bloomberg School of Public Health, Baltimore, MD), presented data from the recently published Institute of Medicine (IOM) report that reviewed 11 studies looking at smoking bans in different regions and countries and showed that the bans were associated with consistently observed reductions in the risk of MI [1]. The benefit was observed early, often within a year of the ban being implemented.
"We concluded on the basis of the available literature that there is a causal relationship between smoking bans and decreases in acute coronary events," said Goldman during a WCC session on smoking and acute coronary event risk. "And I should say that this is a very high standard of evidence that the Institute of Medicine uses to actually say that a relationship is causal, and for us to have developed a consensus along that line, we really have very little doubt that there is an enormous benefit [to the bans]."
Banned From Smoking in Your Own Home
An essay in the June 17, 2010 issue of the New England Journal of Medicine suggests that smoke-free policies should extend to low-income public housing in the US, making it illegal for individuals living in these dwellings to smoke even in their own homes. [2]
Smoking bans in these multiunit apartments raises ethical concerns, according to authors Drs Jonathan Winickoff (Harvard Medical School, Boston, MA), Mark Gottlieb (Northeastern University School of Law, Boston), and Michelle Mello (Harvard School of Public Health, Boston), but is justified given harm caused by exposure to tobacco, the lack of other avenues of legal redress for nonsmoking residents of public housing, and the slow pace at which no-smoking policies have been implemented in public housing.
"The same legal, practical, and health issues that have driven successful efforts to make workplaces, private vehicles, and private housing smoke-free militate in favor of extending similar protection to the vulnerable public-housing population," write the authors.
Smoking and Heart Disease Enormous Burdens in Asia
Throughout the WCC conference, numerous sessions highlighted the impact of smoking and secondhand smoke on the global risk of cardiovascular disease. Dr Judith MacKay (University of Hong Kong), a policy advisor to the World Health Organization (WHO), stressed that coronary heart disease is an enormous burden in Asia, particularly in China. As documented throughout the meeting, there has been a large shift in the occurrence of cardiovascular disease in the past 50 years, with approximately 60% of the burden lying in low- and middle-income countries. In China alone, estimates suggest that more than three million people die annually from cardiovascular disease.
In even scarier news, MacKay noted that health professionals, despite knowing better, continue to smoke themselves. In China, home to one-third of the world's smokers, 30% of cardiologists smoke, while nearly 25% of individuals worldwide who are training to be a health professional, such as those in medical and nursing schools, also continue to smoke. "Our objectives are very simple," MacKay told the media. "It is to raise public and cardiologists' awareness of the connection between secondhand smoke and heart disease."
Those objectives are part of the efforts of several organizations, including the World Heart Federation, the Centers for Disease Control and Prevention (CDC), the World Lung Foundation, and Roswell Park Cancer Institute, to raise awareness about the cardiovascular risks of smoking and secondhand smoke. The group recently launched a campaign, one that includes the creation of a DVD--Warning: Secondhand Smoke is Hazardous to your Heart--exploring the link between cardiovascular problems and secondhand-smoke exposure. The new report includes many of the studies reported previously by heartwire and highlights a 2009 meta-analysis showing a 17% reduction in acute MI following the implementation of smoke-free laws.
Despite the sobering statistics, there was some good news presented at the WCC meeting. Dr David Wong (University of Hong Kong) presented data showing that the introduction of smoke-free legislation in Hong Kong led to a 28% spike in calls to a youth hotline set up to help adolescents quit smoking, as well as a 28% increase in the number of people who came in for counseling to quit. The data showed, however, that hitting teenagers in the pocketbook is the best way to compel them to quit smoking. After a significant 50% tax hike in 2009 on the cost of cigarettes, the number of calls to the "Youth Quitline" increased 144%, while 111% more teenagers came in for counseling to quit smoking.
The Need for Enforcement and Better Compliance
Most vital, however, in the global campaign against smoking is article 8 of the WHO Framework Convention on Tobacco Control (FCTC), which "commits governments to protecting their citizens from exposure to secondhand smoke in indoor public places and workplaces and public transport." The FCTC came into effect in 2005 and now has 169 parties that cover more than 80% of the world's population.
Presenting during a WCC session on the need to enhance the impact of smoke-free policies to reduce cardiovascular disease, Dr Armando Peruga (World Health Organization) pointed out that 43% of teenagers 13 years old to 15 years old are still living at home with smokers. Europe is the worst offender in this regard, said Peruga, with nearly 78% of 13- to 15-year-olds living at home with a smoker, while 51% of kids in Asia lived with a smoker.
During his presentation, Peruga noted that while 169 countries are parties to article 8, just 17 countries had policies in 2008 that provided universal, comprehensive, and effective protection from secondhand smoke, and only 5% of the population lives in a country with comprehensive, 100% smoke-free policies. The "gold-standard" smoke-free law, one where smoking is prohibited in all enclosed public places and workplaces, including bars, restaurants, and public transport, is rare, he noted, with compliance varying by sector. Hospitals and public transportation tend to most stringently adhere to the smoke-free policy, while bars and restaurants tend be more lax.
"Compliance is still an issue, and as we have been saying, passing a law, even a good law, a comprehensive law, is not enough," said Peruga. "We have always pointed out that enforcement requires small but critical resources. Anyone who forgets this is doomed to have these types of results, with relatively good laws on the books, but with low compliance."
Michael O'Riordan
June 21, 2010 (Beijing, China) — Smoking, particularly the effects of secondhand smoke in nonsmokers, took center stage at the World Congress of Cardiology (WCC) 2010 last week, with experts calling on cardiologists to play a pivotal role in getting their patients to quit smoking and to reduce smoking in their communities.
"As a cardiologist who actively sees patients, one of the most important things I can do is tell them to stop smoking," Dr Sidney Smith (University of North Carolina, Chapel Hill) told the media during the WCC meeting last week. "It is arguably the major risk factor in the world right now, and if you wanted to do something to really make things better on this planet, you'd get rid of smoking and tobacco use."
Smith, the president-elect and chair of the World Heart Federation scientific advisory board, said the new National Institutes of Health (NIH) cardiovascular risk-reduction guidelines, of which he is a chair, will stress the importance of smoking cessation. "I want to be very clear where I stand on the importance of smoking cessation and tobacco use and the danger not only to the person who is smoking; [there is] also a very important risk in secondhand smoke."
If you wanted to do something to really make things better on this planet, you'd get rid of smoking and tobacco use.
An estimated 20% of cardiovascular disease worldwide is caused by tobacco, and yet, surprisingly, not everybody is aware of the link between cardiovascular disease, smoking, and secondhand smoke. In China, for example, just 4% of smokers are aware that smoking causes heart disease, said Smith.
And yet there is no shortage of scientific evidence. At the meeting, Dr Lynn Goldman (Johns Hopkins Bloomberg School of Public Health, Baltimore, MD), presented data from the recently published Institute of Medicine (IOM) report that reviewed 11 studies looking at smoking bans in different regions and countries and showed that the bans were associated with consistently observed reductions in the risk of MI [1]. The benefit was observed early, often within a year of the ban being implemented.
"We concluded on the basis of the available literature that there is a causal relationship between smoking bans and decreases in acute coronary events," said Goldman during a WCC session on smoking and acute coronary event risk. "And I should say that this is a very high standard of evidence that the Institute of Medicine uses to actually say that a relationship is causal, and for us to have developed a consensus along that line, we really have very little doubt that there is an enormous benefit [to the bans]."
Banned From Smoking in Your Own Home
An essay in the June 17, 2010 issue of the New England Journal of Medicine suggests that smoke-free policies should extend to low-income public housing in the US, making it illegal for individuals living in these dwellings to smoke even in their own homes. [2]
Smoking bans in these multiunit apartments raises ethical concerns, according to authors Drs Jonathan Winickoff (Harvard Medical School, Boston, MA), Mark Gottlieb (Northeastern University School of Law, Boston), and Michelle Mello (Harvard School of Public Health, Boston), but is justified given harm caused by exposure to tobacco, the lack of other avenues of legal redress for nonsmoking residents of public housing, and the slow pace at which no-smoking policies have been implemented in public housing.
"The same legal, practical, and health issues that have driven successful efforts to make workplaces, private vehicles, and private housing smoke-free militate in favor of extending similar protection to the vulnerable public-housing population," write the authors.
Smoking and Heart Disease Enormous Burdens in Asia
Throughout the WCC conference, numerous sessions highlighted the impact of smoking and secondhand smoke on the global risk of cardiovascular disease. Dr Judith MacKay (University of Hong Kong), a policy advisor to the World Health Organization (WHO), stressed that coronary heart disease is an enormous burden in Asia, particularly in China. As documented throughout the meeting, there has been a large shift in the occurrence of cardiovascular disease in the past 50 years, with approximately 60% of the burden lying in low- and middle-income countries. In China alone, estimates suggest that more than three million people die annually from cardiovascular disease.
In even scarier news, MacKay noted that health professionals, despite knowing better, continue to smoke themselves. In China, home to one-third of the world's smokers, 30% of cardiologists smoke, while nearly 25% of individuals worldwide who are training to be a health professional, such as those in medical and nursing schools, also continue to smoke. "Our objectives are very simple," MacKay told the media. "It is to raise public and cardiologists' awareness of the connection between secondhand smoke and heart disease."
Those objectives are part of the efforts of several organizations, including the World Heart Federation, the Centers for Disease Control and Prevention (CDC), the World Lung Foundation, and Roswell Park Cancer Institute, to raise awareness about the cardiovascular risks of smoking and secondhand smoke. The group recently launched a campaign, one that includes the creation of a DVD--Warning: Secondhand Smoke is Hazardous to your Heart--exploring the link between cardiovascular problems and secondhand-smoke exposure. The new report includes many of the studies reported previously by heartwire and highlights a 2009 meta-analysis showing a 17% reduction in acute MI following the implementation of smoke-free laws.
Despite the sobering statistics, there was some good news presented at the WCC meeting. Dr David Wong (University of Hong Kong) presented data showing that the introduction of smoke-free legislation in Hong Kong led to a 28% spike in calls to a youth hotline set up to help adolescents quit smoking, as well as a 28% increase in the number of people who came in for counseling to quit. The data showed, however, that hitting teenagers in the pocketbook is the best way to compel them to quit smoking. After a significant 50% tax hike in 2009 on the cost of cigarettes, the number of calls to the "Youth Quitline" increased 144%, while 111% more teenagers came in for counseling to quit smoking.
The Need for Enforcement and Better Compliance
Most vital, however, in the global campaign against smoking is article 8 of the WHO Framework Convention on Tobacco Control (FCTC), which "commits governments to protecting their citizens from exposure to secondhand smoke in indoor public places and workplaces and public transport." The FCTC came into effect in 2005 and now has 169 parties that cover more than 80% of the world's population.
Presenting during a WCC session on the need to enhance the impact of smoke-free policies to reduce cardiovascular disease, Dr Armando Peruga (World Health Organization) pointed out that 43% of teenagers 13 years old to 15 years old are still living at home with smokers. Europe is the worst offender in this regard, said Peruga, with nearly 78% of 13- to 15-year-olds living at home with a smoker, while 51% of kids in Asia lived with a smoker.
During his presentation, Peruga noted that while 169 countries are parties to article 8, just 17 countries had policies in 2008 that provided universal, comprehensive, and effective protection from secondhand smoke, and only 5% of the population lives in a country with comprehensive, 100% smoke-free policies. The "gold-standard" smoke-free law, one where smoking is prohibited in all enclosed public places and workplaces, including bars, restaurants, and public transport, is rare, he noted, with compliance varying by sector. Hospitals and public transportation tend to most stringently adhere to the smoke-free policy, while bars and restaurants tend be more lax.
"Compliance is still an issue, and as we have been saying, passing a law, even a good law, a comprehensive law, is not enough," said Peruga. "We have always pointed out that enforcement requires small but critical resources. Anyone who forgets this is doomed to have these types of results, with relatively good laws on the books, but with low compliance."
Tuesday, June 22, 2010
Modest Tea and Coffee Consumption Cuts CHD Risk
From Heartwire
Lisa Nainggolan
June 18, 2010 (Utrecht, the Netherlands) — The latest look at the effects of tea and coffee consumption on cardiovascular morbidity and mortality suggests that moderate intake of either reduces coronary heart disease risk but has little effect on stroke and no effect on all-cause mortality [1]. Tea, however, does seem to reduce CHD deaths.
Dr J Margot de Koning Gans (University Medical Center, Utrecht, the Netherlands) and colleagues prospectively studied more than 35 000 participants in the Dutch portion of the EPIC study, EPIC-NL. They report their findings online June 18, 2010 in Arteriosclerosis, Thrombosis, and Vascular Biology.
Coauthor Dr Yvonne T van der Schouw (University Medical Center) told heartwire the relationship between CHD morbidity and coffee was U-shaped: "We saw a significant protective effect with around two to four cups of coffee a day," whereas for tea, it was a linear and inverse association, with the lowest hazard ratio seen for more than six cups a day. But three to six cups of tea a day was associated with an almost 50% reduction in CHD deaths, although the number of events was small.
She stressed, however, that the findings are applicable only to filter coffee prepared as it is in the Netherlands and primarily to black tea, which is the type of tea consumed by around 80% of Dutch people. And she warned that the results do not indicate that people who have never drunk coffee or tea should start to do so, "because that is not what we studied."
No Association Between Coffee and Tea Intake and Stroke
The Dutch researchers assessed tea and coffee consumption with a validated food-frequency questionnaire and observed the 37 514 participants for 13 years for the occurrence of CVD morbidity and mortality.
For CHD, the lowest hazard ratio was seen for 2.1 to 3.0 cups of coffee per day (0.79; p=0.01) and for tea this was observed for more than six cups per day (0.64; p=0.02). No associations between coffee or tea and stroke were found.
Tea consumption did significantly reduce CHD mortality, however, with a hazard ratio of 0.55 (p=0.03) for 3.1 to 6.0 cups per day. Coffee also reduced CHD mortality, but the effect was not significant. Neither beverage had an effect on all-cause death.
Discussing possible mechanisms for these observed effects, the investigators point out that coffee contains several biologically active substances that could increase CVD risk by increasing cholesterol and decreasing insulin sensitivity, but it also contains other compounds with antioxidant properties that could reduce risk. Tea contains flavonoids, which are antioxidant, but the underlying mechanisms of their effects are still not entirely clear, they note.
They also mention some limitations of their study. Relatively few patients died of CHD or stroke, so there was limited power to detect associations for these end points. Also, they relied on self-reported data on tea and coffee intake.
Evidence Strengthened on Lower CHD Risk With Tea and Coffee
Previous studies have also shown U-shaped association between coffee consumption and CHD morbidity, the investigators note, and modest benefits on CV mortality. Taken together with this study, the findings overall "suggest a modest risk reduction of CV mortality with moderate coffee consumption," they state.
For tea, only prior studies in continental Europe have suggested a decrease in the rate of CHD with increasing tea consumption, and most previous research on tea intake and CHD mortality has been in specific subgroups, such as hypertensive or postmenopausal subjects, they note.
In conclusion, they say, "With this large prospective study, we showed that tea consumption was associated with a reduced risk of CHD mortality. We strengthen the evidence on the lower risk of CHD associated with coffee and tea consumption; however neither . . . was associated with the risk of stroke or all-cause mortality."
The authors declare that they have no conflicts of interest.
Lisa Nainggolan
June 18, 2010 (Utrecht, the Netherlands) — The latest look at the effects of tea and coffee consumption on cardiovascular morbidity and mortality suggests that moderate intake of either reduces coronary heart disease risk but has little effect on stroke and no effect on all-cause mortality [1]. Tea, however, does seem to reduce CHD deaths.
Dr J Margot de Koning Gans (University Medical Center, Utrecht, the Netherlands) and colleagues prospectively studied more than 35 000 participants in the Dutch portion of the EPIC study, EPIC-NL. They report their findings online June 18, 2010 in Arteriosclerosis, Thrombosis, and Vascular Biology.
Coauthor Dr Yvonne T van der Schouw (University Medical Center) told heartwire the relationship between CHD morbidity and coffee was U-shaped: "We saw a significant protective effect with around two to four cups of coffee a day," whereas for tea, it was a linear and inverse association, with the lowest hazard ratio seen for more than six cups a day. But three to six cups of tea a day was associated with an almost 50% reduction in CHD deaths, although the number of events was small.
She stressed, however, that the findings are applicable only to filter coffee prepared as it is in the Netherlands and primarily to black tea, which is the type of tea consumed by around 80% of Dutch people. And she warned that the results do not indicate that people who have never drunk coffee or tea should start to do so, "because that is not what we studied."
No Association Between Coffee and Tea Intake and Stroke
The Dutch researchers assessed tea and coffee consumption with a validated food-frequency questionnaire and observed the 37 514 participants for 13 years for the occurrence of CVD morbidity and mortality.
For CHD, the lowest hazard ratio was seen for 2.1 to 3.0 cups of coffee per day (0.79; p=0.01) and for tea this was observed for more than six cups per day (0.64; p=0.02). No associations between coffee or tea and stroke were found.
Tea consumption did significantly reduce CHD mortality, however, with a hazard ratio of 0.55 (p=0.03) for 3.1 to 6.0 cups per day. Coffee also reduced CHD mortality, but the effect was not significant. Neither beverage had an effect on all-cause death.
Discussing possible mechanisms for these observed effects, the investigators point out that coffee contains several biologically active substances that could increase CVD risk by increasing cholesterol and decreasing insulin sensitivity, but it also contains other compounds with antioxidant properties that could reduce risk. Tea contains flavonoids, which are antioxidant, but the underlying mechanisms of their effects are still not entirely clear, they note.
They also mention some limitations of their study. Relatively few patients died of CHD or stroke, so there was limited power to detect associations for these end points. Also, they relied on self-reported data on tea and coffee intake.
Evidence Strengthened on Lower CHD Risk With Tea and Coffee
Previous studies have also shown U-shaped association between coffee consumption and CHD morbidity, the investigators note, and modest benefits on CV mortality. Taken together with this study, the findings overall "suggest a modest risk reduction of CV mortality with moderate coffee consumption," they state.
For tea, only prior studies in continental Europe have suggested a decrease in the rate of CHD with increasing tea consumption, and most previous research on tea intake and CHD mortality has been in specific subgroups, such as hypertensive or postmenopausal subjects, they note.
In conclusion, they say, "With this large prospective study, we showed that tea consumption was associated with a reduced risk of CHD mortality. We strengthen the evidence on the lower risk of CHD associated with coffee and tea consumption; however neither . . . was associated with the risk of stroke or all-cause mortality."
The authors declare that they have no conflicts of interest.
Saturday, June 12, 2010
New Brain Death Guidelines Issued
From Medscape Medical News
Allison Gandey
June 10, 2010 — The American Academy of Neurology has released new guidelines for determining brain death in adults. Updated for the first time in 15 years, the recommendations provide step-by-step instructions to help guide clinical decision making.
"The brain death diagnosis can be made only after a comprehensive clinical evaluation and often involves more than 25 separate assessments," lead author Eelco Wijdicks, MD, from the Mayo Clinic in Rochester, Minnesota, said in a news release.
The guidelines are published in the June 8 issue of Neurology.
The authors report that new data have confirmed the effectiveness of earlier recommendations. They saw no evidence of recovery of neurologic function after a diagnosis of brain death using the criteria from the 1995 practice parameter.
Checklist for determining brain death.
"To correctly diagnose brain death, it is essential clinicians adhere to a uniform framework," coauthor Gary Gronseth, MD, from the University of Kansas, Kansas City, said in an interview.
"We wanted to provide useful tools to help clinicians," Dr. Gronseth said, "but many factors will still need to be based on clinical judgment."
The authors report insufficient evidence to determine the minimally acceptable observation period to ensure that neurologic functions have ceased irreversibly.
"I think some people will be disappointed that we weren't able to nail this down," Dr. Gronseth said, "but this will be highly variable patient to patient, and there is no general rule."
These new guidelines focus on patients 18 years and older. Another group is currently working on new brain death recommendations for children. Those recommendations are expected to be released in a couple of months. Some predict those guidelines will include a prescribed observation period.
"Different groups take different approaches," Dr. Gronseth noted. "We felt the evidence was lacking."
Single Exam Sufficient
Some clinicians may also be surprised to see that more than 1 exam is not required in the new brain death guidelines. "The original guideline did not require this either, but I think it was a common misconception that 2 exams are necessary. This is not the case," Dr. Gronseth said. "Some people may object, but we found that 1 exam was sufficient."
The authors point out that complex-spontaneous motor movements and false-positive triggering of the ventilator may occur in patients who are brain dead.
Oxygenation diffusion to determine apnea is safe, they report, but there is insufficient evidence to determine the comparative benefit of the various techniques used for apnea testing.
There is also insufficient evidence to determine whether newer ancillary tests accurately confirm the cessation of function of the entire brain.
To correctly diagnose brain death, it is essential clinicians adhere to a uniform framework.
Asked by Medscape Neurology to comment on the new guidelines, James Bernat, MD, from Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire, said he hopes these recommendations will help address the often wide variation among hospitals.
In 2008, guideline senior author David Greer, MD, from Massachusetts General Hospital, in Boston, reported substantial differences in approaches to brain death among leading neurological institutions in the United States.
That study, published in Neurology, prompted this guideline update because the authors felt more detail was needed to help physicians (2008;70;284-289).
"The new recommendations are encouraging uniformity and thoroughness among institutions," Dr. Bernat said.
"Moving forward, I'd like to see a national registry to track brain death, so we can get an idea of how we're doing," Dr. Gronseth said. "This registry should be voluntary. A lot of studies are done this way."
The American Academy of Neurology will be hosting an online conference about the new guidelines Monday, June 21. The authors will present at the session and take questions. The registration deadline for continuing medical education credit is June 16. Clinicians wanting to participate will need a computer with Microsoft Office Powerpoint and a telephone. For more information and to access the audio conference, visit the academy's Web site.
Neurology. 2010;74:1911-1918. Abstract
Allison Gandey
June 10, 2010 — The American Academy of Neurology has released new guidelines for determining brain death in adults. Updated for the first time in 15 years, the recommendations provide step-by-step instructions to help guide clinical decision making.
"The brain death diagnosis can be made only after a comprehensive clinical evaluation and often involves more than 25 separate assessments," lead author Eelco Wijdicks, MD, from the Mayo Clinic in Rochester, Minnesota, said in a news release.
The guidelines are published in the June 8 issue of Neurology.
The authors report that new data have confirmed the effectiveness of earlier recommendations. They saw no evidence of recovery of neurologic function after a diagnosis of brain death using the criteria from the 1995 practice parameter.
Checklist for determining brain death.
"To correctly diagnose brain death, it is essential clinicians adhere to a uniform framework," coauthor Gary Gronseth, MD, from the University of Kansas, Kansas City, said in an interview.
"We wanted to provide useful tools to help clinicians," Dr. Gronseth said, "but many factors will still need to be based on clinical judgment."
The authors report insufficient evidence to determine the minimally acceptable observation period to ensure that neurologic functions have ceased irreversibly.
"I think some people will be disappointed that we weren't able to nail this down," Dr. Gronseth said, "but this will be highly variable patient to patient, and there is no general rule."
These new guidelines focus on patients 18 years and older. Another group is currently working on new brain death recommendations for children. Those recommendations are expected to be released in a couple of months. Some predict those guidelines will include a prescribed observation period.
"Different groups take different approaches," Dr. Gronseth noted. "We felt the evidence was lacking."
Single Exam Sufficient
Some clinicians may also be surprised to see that more than 1 exam is not required in the new brain death guidelines. "The original guideline did not require this either, but I think it was a common misconception that 2 exams are necessary. This is not the case," Dr. Gronseth said. "Some people may object, but we found that 1 exam was sufficient."
The authors point out that complex-spontaneous motor movements and false-positive triggering of the ventilator may occur in patients who are brain dead.
Oxygenation diffusion to determine apnea is safe, they report, but there is insufficient evidence to determine the comparative benefit of the various techniques used for apnea testing.
There is also insufficient evidence to determine whether newer ancillary tests accurately confirm the cessation of function of the entire brain.
To correctly diagnose brain death, it is essential clinicians adhere to a uniform framework.
Asked by Medscape Neurology to comment on the new guidelines, James Bernat, MD, from Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire, said he hopes these recommendations will help address the often wide variation among hospitals.
In 2008, guideline senior author David Greer, MD, from Massachusetts General Hospital, in Boston, reported substantial differences in approaches to brain death among leading neurological institutions in the United States.
That study, published in Neurology, prompted this guideline update because the authors felt more detail was needed to help physicians (2008;70;284-289).
"The new recommendations are encouraging uniformity and thoroughness among institutions," Dr. Bernat said.
"Moving forward, I'd like to see a national registry to track brain death, so we can get an idea of how we're doing," Dr. Gronseth said. "This registry should be voluntary. A lot of studies are done this way."
The American Academy of Neurology will be hosting an online conference about the new guidelines Monday, June 21. The authors will present at the session and take questions. The registration deadline for continuing medical education credit is June 16. Clinicians wanting to participate will need a computer with Microsoft Office Powerpoint and a telephone. For more information and to access the audio conference, visit the academy's Web site.
Neurology. 2010;74:1911-1918. Abstract
Wednesday, May 19, 2010
Want a Loan? A Sale? A Job?
By Barbara Findlay Schenck
When Brad Newman introduced himself as an actrepreneur, I was hooked. Everything about his title told me he had information I wanted to hear. Over a few additional seconds, I learned that this actor and entrepreneur is the founder of Zentainment, "a socially conscious media company committed to growing brands that encourage you to dream big and live a sustainable life." From there, a longer conversation — and a business relationship — followed, all spurred by an attention-getting introduction that took just moments to deliver.
The elevator pitch rides into the speed-dating era
Today's economic environment has turned job fairs, trade shows, networking events and even sidewalk sales into buyers' markets where only those with quick, compelling pitches survive.
In the 1990s, high-tech entrepreneurs named these short spiels "elevator pitches" because they could be conveyed during an elevator ride. The tech bubble ballooned and burst (and ballooned again), but elevator pitches are here to stay. Everyone — whether seeking employment, sales or profitable business associations — needs one.
Is your introduction ready to roll?
"So, what do you do?"
Those five words are on the minds of everyone you meet, whether in person or online. Brad Newman's introduction helps provide a formula that can assist you in preparing your answer and attracting attention from those you aim to impress:
Describe yourself in five words or less. Use a distinctive title or phrase that makes people think, "This sounds interesting" or "This is what I'm looking for." Consider the difference between "I'm a copywriter" and "I turn browsers into buyers." Or, in Newman's case, between "social media entrepreneur" and "actrepreneur."
Explain what you do in one sentence. After introducing yourself, introduce your offerings. "Our name combines the words Zen and entertainment, which stakes out our media space," Newman says. "We're a media company that focuses on socially conscious content. That definition tells what Zentainment is and rules out what it isn't." Work on a similarly specific description for your business.
Define your target audience. "Our market is comprised of 30- to 49-year-olds who care about socially conscious living," Newman says. "By defining our market in that way, people immediately know whether our business is for them." In other words, Zentainment isn't trying to be all things to all people. It's focused on a specific target audience, which is a key to success in today's crowded business environment.
Communicate your vision. "We're committed to growing brands that encourage you to dream big and live a sustainable life, whether they're our own brands or ones for which we consult and serve as producers," Newman says. "Our vision is clear enough to keep us focused and broad enough to make us adaptive to the opportunities of a changing market and media world." It's also compelling enough to attract a growing contingent of Zentainment consumers and business clients. What does your business stand for? What attracts your customers and their loyalty? Your answers can serve as a magnet for growth.
Practice, practice, practice. Create a script that conveys who you are, what you offer, your market, and the distinctive benefits you provide. Edit until you can introduce yourself and your business in less than a minute, which is how long most prospects will give you to win their interest.
Shrink your introduction even further so you can tell your story in 20 words or less. That's how much space you have in most marketing materials and online presentations, whether on your own site, on social media sites, or on sites that link to your home page. If you're thinking, "Twenty words? You've got to be kidding," scroll back to the start of this column. That's exactly what Brad Newman used to get my interest.
Barbara Findlay Schenck is a small-business strategist, the author of “Small Business Marketing for Dummies” and the co-author of “Branding for Dummies,” “Selling Your Business for Dummies” and “Business Plans Kit for Dummies.”
When Brad Newman introduced himself as an actrepreneur, I was hooked. Everything about his title told me he had information I wanted to hear. Over a few additional seconds, I learned that this actor and entrepreneur is the founder of Zentainment, "a socially conscious media company committed to growing brands that encourage you to dream big and live a sustainable life." From there, a longer conversation — and a business relationship — followed, all spurred by an attention-getting introduction that took just moments to deliver.
The elevator pitch rides into the speed-dating era
Today's economic environment has turned job fairs, trade shows, networking events and even sidewalk sales into buyers' markets where only those with quick, compelling pitches survive.
In the 1990s, high-tech entrepreneurs named these short spiels "elevator pitches" because they could be conveyed during an elevator ride. The tech bubble ballooned and burst (and ballooned again), but elevator pitches are here to stay. Everyone — whether seeking employment, sales or profitable business associations — needs one.
Is your introduction ready to roll?
"So, what do you do?"
Those five words are on the minds of everyone you meet, whether in person or online. Brad Newman's introduction helps provide a formula that can assist you in preparing your answer and attracting attention from those you aim to impress:
Describe yourself in five words or less. Use a distinctive title or phrase that makes people think, "This sounds interesting" or "This is what I'm looking for." Consider the difference between "I'm a copywriter" and "I turn browsers into buyers." Or, in Newman's case, between "social media entrepreneur" and "actrepreneur."
Explain what you do in one sentence. After introducing yourself, introduce your offerings. "Our name combines the words Zen and entertainment, which stakes out our media space," Newman says. "We're a media company that focuses on socially conscious content. That definition tells what Zentainment is and rules out what it isn't." Work on a similarly specific description for your business.
Define your target audience. "Our market is comprised of 30- to 49-year-olds who care about socially conscious living," Newman says. "By defining our market in that way, people immediately know whether our business is for them." In other words, Zentainment isn't trying to be all things to all people. It's focused on a specific target audience, which is a key to success in today's crowded business environment.
Communicate your vision. "We're committed to growing brands that encourage you to dream big and live a sustainable life, whether they're our own brands or ones for which we consult and serve as producers," Newman says. "Our vision is clear enough to keep us focused and broad enough to make us adaptive to the opportunities of a changing market and media world." It's also compelling enough to attract a growing contingent of Zentainment consumers and business clients. What does your business stand for? What attracts your customers and their loyalty? Your answers can serve as a magnet for growth.
Practice, practice, practice. Create a script that conveys who you are, what you offer, your market, and the distinctive benefits you provide. Edit until you can introduce yourself and your business in less than a minute, which is how long most prospects will give you to win their interest.
Shrink your introduction even further so you can tell your story in 20 words or less. That's how much space you have in most marketing materials and online presentations, whether on your own site, on social media sites, or on sites that link to your home page. If you're thinking, "Twenty words? You've got to be kidding," scroll back to the start of this column. That's exactly what Brad Newman used to get my interest.
Barbara Findlay Schenck is a small-business strategist, the author of “Small Business Marketing for Dummies” and the co-author of “Branding for Dummies,” “Selling Your Business for Dummies” and “Business Plans Kit for Dummies.”
Friday, May 7, 2010
HIV Vaccine Research a Field Apart From Classic Vaccinology
From Medscape Medical News
Bob Roehr
May 7, 2010 (Bethesda, Maryland) — HIV vaccine research is diverging from classic vaccinology and its focus on the adaptive immune response, to a field of its own. There has been a shift from protecting against infection to changing the nature of the infection, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID), in Bethesda, Maryland, said in his keynote address here at the National Foundation for Infectious Diseases 13th Annual Conference on Vaccine Research.
The principles of classic vaccinology are that "the response to natural infection is the guidepost to the vaccine. . . . The proof of concept is already done for us by the natural response to infection. . . . The vast portion of people spontaneously recover," he said.
"The virus is cleared and eradicated and the person is left with a protective immunity that, in most cases, is complete and lifelong."
But beginning with the gp160 trial in 1987, researchers quickly learned that the principles of classic vaccinology "didn't apply particularly well to HIV. . . . I've been taking care of HIV-infected individuals for almost 29 years and I have never seen anybody eradicate the virus or spontaneously recover," Dr. Fauci said.
"And protective immunity against subsequent infection doesn't appear to occur. That is amazing. You are infected with a microbe and, while you are infected, you get reexposed to the microbe and you get reinfected. That is depressing for vaccinologists."
"There is no proof of concept to help us. We really have to start from scratch," he said. Basic research has been able to generate a few antibodies that are broadly neutralizing to laboratory strains of HIV, but not to wild-type virus, Dr. Fauci noted.
Once these facts began to sink in, the field shifted toward developing a vaccine that would not protect against infection but that might shift the course of disease progression to one that is less lethal, perhaps even benign. The public health goal of reducing transmission might be accomplished by lowering the viral load of those who are infected. "Those attempts, thus far, have not been successful," Dr. Fauci said.
STEP Back
The early stopping of the STEP trial, which was testing an HIV vaccine developed by Merck with the support of NIAID, led the field to another reevaluation. The mix of basic and developmentally oriented research was recalibrated back toward the former.
Then came the Thai study (RV144) "using a pox virus vector and an envelope boost, which, when you looked immunologically, had virtually none of the classical parameters that would predict protection. [Cytotoxic T lymphocytes] were nowhere to be found; neutralizing antibody, nowhere to be found," Dr. Fauci said.
But "for the first time we found a modest, weak, but real signal of prevention of acquisition," he said. "There was no doubt that the Kaplan–Meier curves were separated. We now had a weak signal upon which to build."
The fact that the vaccine had no effect on the viral load of those who became infected confounded the expectations of many, but not Dr. Fauci.
"I think it argues for the dichotomy of effect on acquisition vs the control of chronic viral infection. It is telling us something that perhaps we should have realized a long time ago — an immune response that protects against acquisition might be quite different from the immune response that actually controls chronic virus replication."
"What we have now is a whole new way of looking at things. . . . We really know what is going on and what is needed."
He sees the way forward as building on the empiricism of the RV144 trial while, at the same time, pursuing the fundamental issues of basic research.
Dr. Fauci is not sure that it will be possible to isolate correlates of protection from acquisition from the small number of infections in the Thai trial, "but it certainly will tell us what they are not. And what they aren't is 750 ELISPOTS on an assay. What they aren't is broadly cross-reacting neutralizing antibodies. . . . It may be that they are important, but they are not a requirement."
Different Virus
"As scary and dangerous as HIV infection is, it is a very inefficiently transmitted infection. One of the reasons is that there is a bottleneck to transmission." It has become apparent that "the transmitting virus might be quite different from the chronic replicating virus."
The transmitting virus appears to have a unique hypoglycosylated molecular signature that, surprisingly, appears to be easier to neutralize than variants found later in infection. However, once infection is established, the virus rapidly diversifies with conformational changes and the addition of glycands that can shield antibody binding sites, and the virus evades immune control.
Dr. Fauci pointed to the work of Dennis Burton, showing that "when looking at acquisition, you really need low levels of neutralizing antibody, much lower than you would have predicted" from the study of established infections. "There is a direct correlation between the ease of neutralization of a transmitting virus [and] the virus that has been replicating for years."
He added that "as the quasi-species develops, the virus diverges. The further you are from infection, the more divergent the virus is; the closer you are to the initial infection, the more homogeneous the virus is."
"Once the virus robustly replicates and gets into the lymphoid tissue, for all practical purposes, the ballgame is over for a vaccine. No matter what we do, you don't eradicate the virus. . . . The focus really needs to be on blocking acquisition. That is the end game."
It is why he is focusing on very early events, far earlier than the adaptive immune system is capable of reacting to.
Dr. Fauci indicated that, taken together, the cytotoxic T lymphocyte response will play, at best, a small role in future research toward a preventive vaccine. It might have some role in immunotherapy for HIV disease, but his comments on the effectiveness, tolerability, and cost of available small-molecule drugs create a high bar in moving HIV immunotherapy from basic research into regular clinical practice.
Dr. Fauci has disclosed no relevant financial relationships.
National Foundation for Infectious Diseases (NFID) 13th Annual Conference on Vaccine Research: Session 8. Presented April 27, 2010.
Bob Roehr
May 7, 2010 (Bethesda, Maryland) — HIV vaccine research is diverging from classic vaccinology and its focus on the adaptive immune response, to a field of its own. There has been a shift from protecting against infection to changing the nature of the infection, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID), in Bethesda, Maryland, said in his keynote address here at the National Foundation for Infectious Diseases 13th Annual Conference on Vaccine Research.
The principles of classic vaccinology are that "the response to natural infection is the guidepost to the vaccine. . . . The proof of concept is already done for us by the natural response to infection. . . . The vast portion of people spontaneously recover," he said.
"The virus is cleared and eradicated and the person is left with a protective immunity that, in most cases, is complete and lifelong."
But beginning with the gp160 trial in 1987, researchers quickly learned that the principles of classic vaccinology "didn't apply particularly well to HIV. . . . I've been taking care of HIV-infected individuals for almost 29 years and I have never seen anybody eradicate the virus or spontaneously recover," Dr. Fauci said.
"And protective immunity against subsequent infection doesn't appear to occur. That is amazing. You are infected with a microbe and, while you are infected, you get reexposed to the microbe and you get reinfected. That is depressing for vaccinologists."
"There is no proof of concept to help us. We really have to start from scratch," he said. Basic research has been able to generate a few antibodies that are broadly neutralizing to laboratory strains of HIV, but not to wild-type virus, Dr. Fauci noted.
Once these facts began to sink in, the field shifted toward developing a vaccine that would not protect against infection but that might shift the course of disease progression to one that is less lethal, perhaps even benign. The public health goal of reducing transmission might be accomplished by lowering the viral load of those who are infected. "Those attempts, thus far, have not been successful," Dr. Fauci said.
STEP Back
The early stopping of the STEP trial, which was testing an HIV vaccine developed by Merck with the support of NIAID, led the field to another reevaluation. The mix of basic and developmentally oriented research was recalibrated back toward the former.
Then came the Thai study (RV144) "using a pox virus vector and an envelope boost, which, when you looked immunologically, had virtually none of the classical parameters that would predict protection. [Cytotoxic T lymphocytes] were nowhere to be found; neutralizing antibody, nowhere to be found," Dr. Fauci said.
But "for the first time we found a modest, weak, but real signal of prevention of acquisition," he said. "There was no doubt that the Kaplan–Meier curves were separated. We now had a weak signal upon which to build."
The fact that the vaccine had no effect on the viral load of those who became infected confounded the expectations of many, but not Dr. Fauci.
"I think it argues for the dichotomy of effect on acquisition vs the control of chronic viral infection. It is telling us something that perhaps we should have realized a long time ago — an immune response that protects against acquisition might be quite different from the immune response that actually controls chronic virus replication."
"What we have now is a whole new way of looking at things. . . . We really know what is going on and what is needed."
He sees the way forward as building on the empiricism of the RV144 trial while, at the same time, pursuing the fundamental issues of basic research.
Dr. Fauci is not sure that it will be possible to isolate correlates of protection from acquisition from the small number of infections in the Thai trial, "but it certainly will tell us what they are not. And what they aren't is 750 ELISPOTS on an assay. What they aren't is broadly cross-reacting neutralizing antibodies. . . . It may be that they are important, but they are not a requirement."
Different Virus
"As scary and dangerous as HIV infection is, it is a very inefficiently transmitted infection. One of the reasons is that there is a bottleneck to transmission." It has become apparent that "the transmitting virus might be quite different from the chronic replicating virus."
The transmitting virus appears to have a unique hypoglycosylated molecular signature that, surprisingly, appears to be easier to neutralize than variants found later in infection. However, once infection is established, the virus rapidly diversifies with conformational changes and the addition of glycands that can shield antibody binding sites, and the virus evades immune control.
Dr. Fauci pointed to the work of Dennis Burton, showing that "when looking at acquisition, you really need low levels of neutralizing antibody, much lower than you would have predicted" from the study of established infections. "There is a direct correlation between the ease of neutralization of a transmitting virus [and] the virus that has been replicating for years."
He added that "as the quasi-species develops, the virus diverges. The further you are from infection, the more divergent the virus is; the closer you are to the initial infection, the more homogeneous the virus is."
"Once the virus robustly replicates and gets into the lymphoid tissue, for all practical purposes, the ballgame is over for a vaccine. No matter what we do, you don't eradicate the virus. . . . The focus really needs to be on blocking acquisition. That is the end game."
It is why he is focusing on very early events, far earlier than the adaptive immune system is capable of reacting to.
Dr. Fauci indicated that, taken together, the cytotoxic T lymphocyte response will play, at best, a small role in future research toward a preventive vaccine. It might have some role in immunotherapy for HIV disease, but his comments on the effectiveness, tolerability, and cost of available small-molecule drugs create a high bar in moving HIV immunotherapy from basic research into regular clinical practice.
Dr. Fauci has disclosed no relevant financial relationships.
National Foundation for Infectious Diseases (NFID) 13th Annual Conference on Vaccine Research: Session 8. Presented April 27, 2010.
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