From Medscape Medical News
Jill Stein
June 22, 2010 (San Diego, California) — Men 70 years and older who have low serum testosterone levels appear to be at increased risk for eventual frailty, according to data released here at ENDO 2010: The Endocrine Society 92nd Annual Meeting.
"While prior studies have reported cross-sectional associations between testosterone levels and frailty, this study is the first longitudinal analysis to demonstrate that free testosterone levels predict frailty," Zoe Hyde, MPH, PhD candidate, from the University of Western Australia in Perth, told Medscape Diabetes & Endocrinology.
"Our findings suggest that testosterone could play a role in the pathogenesis of frailty and, in turn, provide a rationale for clinical studies to explore whether testosterone therapy could prevent or treat frailty."
She was quick to emphasize, however, that much more research is needed before testosterone can be "categorically blamed" for frailty and before testosterone supplementation can be recommended as a remedy. "Nonetheless, the data are intriguing," she said.
Ms. Hyde and her associates used the FRAIL scale to assess frailty in 3616 community-dwelling men between 70 and 88 years of age. The FRAIL scale evaluates functional status in older patients on 5 domains: fatigue, resistance (ability to climb a single flight of stairs), ambulation (ability to walk 1 block), illnesses (more than 5), and loss of weight (more than 5%). The scale was developed by the International Academy of Nutrition, Health, and Aging.
The investigators also measured testosterone levels in the study participants.
Frailty status was reevaluated in 1586 men 4 to 7 years after the initial assessments.
Unanswered Questions Prevent Any Definitive Conclusions
Although there is a broad body of research focusing on frailty, the topic is often fraught with myths and a lack of consensus among both researchers and the lay public, Ms. Hyde noted.
For example, contrary to popular belief, frailty is not an inevitable consequence of the aging process, even though frailty increases with age, she said.
Also, investigators do not agree on the precise definition of frailty. The condition is loosely defined as a decline in multiple organ systems that leads to functional impairments, a reduced ability to cope with stressors, and an increased risk for death and disability.
Ms. Hyde noted that frailty is "perhaps best conceptualized as a state of vulnerability, where modest stressors that the body is usually able to cope with are much more likely to lead to serious illness and hospitalization or perhaps even death."
The physiologic pathways that "set the stage" for frailty have not been clarified, she added. However, there is growing evidence to suggest that testosterone plays an important role by producing a loss of muscle and bone mass, which can increase the risk for frailty.
Earlier cross-sectional studies have explored the relation between testosterone and frailty. However, the results have been contradictory, which might be due to a lack of statistical power, she noted.
Longitudinal Design Strengthens Study Findings
At baseline, 548 men (15.2%) were considered frail, which meant that they had at least 3 deficits on the FRAIL scale. At follow-up, 364 men (23.0%) were deemed frail.
At baseline, each 1 standard deviation (SD) decrease in total or free testosterone level was associated with increased odds of frailty (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.11 - 1.38 for total testosterone and OR, 1.29; 95% CI, 1.15 -1.44 for free testosterone).
One SD of total testosterone was 5.6 nmol/L in this sample; 1 SD of free testosterone was 96.5 pmol/L. For every 97 pmol/L decrease in free testosterone, the odds of a man being frail increased by 29% at baseline and 22% at follow-up.
In contrast, lower luteinizing hormone (LH) levels were associated with reduced odds of frailty at baseline (OR, 0.88; 95% CI, 0.81 - 0.95). For every 5.3 IU/L decrease in LH, men were 12% less likely to be frail, Ms. Hyde reported.
After controlling for age, body mass index, smoking, diabetes, social support, and visual and hearing impairments, the Australian researcher told meeting attendees that only a lower free testosterone level at baseline predicted frailty at follow-up (OR, 1.22; 95% CI, 1.05 - 1.42).
"We need large-scale clinical trials to see if testosterone can prevent or treat frailty, and importantly, to assess the possible risks of therapy before we can recommend testosterone therapy in older men," Ms. Hyde said in an interview.
She added, however, that a healthy lifestyle is probably more important in achieving optimal testosterone levels. "My colleagues and I recently showed that a healthy lifestyle was associated with higher testosterone levels," she said. "Given that a healthy lifestyle will likely also reduce the risk of becoming frail, this is probably the best option for now.
Men should keep physically active, not smoke, eat a nutritious diet, and keep their weight in a healthy range."
Ms. Hyde added that she is now conducting research to determine whether testosterone and related sex hormones can predict healthy aging in older men.
"This study adds to earlier work showing an association between low testosterone and measures of frailty in elderly men," James L. Rosenzweig, MD, an endocrinologist and associate professor of medicine at Boston University School of Medicine in Massachusetts, told Medscape Diabetes & Endocrinology.
He added that although he believes that prospective randomized studies should be conducted to examine whether testosterone replacement in elderly men is beneficial for thwarting frailty, there are safety concerns about supplemental testosterone in older men.
"The incidence of prostate cancer — which is often unrecognized — is dramatically increased in elderly men," he said.
"Supplemental testosterone may, in fact, spur the growth of prostate cancer. So that would be one potential negative side effect of testosterone treatment."
He added, however, that it's well known that testosterone can increase muscle mass and bone density. "So it probably would be of interest to specifically look at how testosterone replacement affects these measures of frailty in an elderly population," he said.
The study was funded by the National Health and Medical Research Council of Australia and the MBF Foundation of Australia. Ms. Hyde and Dr. Rosenzweig have disclosed no relevant financial relationships.
ENDO 2010: The Endocrine Society 92nd Annual Meeting: Abstract OR17-3. Presented June 20, 2010
Thursday, June 24, 2010
No CV Benefit on Reducing Homocysteine
From Heartwire
Sue Hughes
June 22, 2010 (Oxford, United Kingdom) - Substantial long-term reductions in blood homocysteine levels with folic-acid and vitamin-B12 supplementation did not have beneficial effects on vascular outcomes in the large-scale SEARCH trial [1].
But a silver lining of good news from the trial is that the vitamin supplements were not associated with any increase in cancer risk, which had been suggested in a previous study.
The trial, published in the June 23, 2010 issue of the Journal of the American Medical Association, was conducted by a team led by Dr Jane M Armitage (University of Oxford, UK).
Results from SEARCH were first reported by heartwire at the 2008 AHA meeting.
End of an Era
Armitage told heartwire that this large randomized trial "rounds off an era of trials with folic acid, which together suggest no benefit in reducing cardiovascular events."
While there is no doubt about the association between increased homocysteine levels and increased heart disease risk, our results suggest that this is not a causal association.
"This is another example of findings from observational studies leading us up the wrong path. While there is no doubt about the association between increased homocysteine levels and increased heart-disease risk, our results suggest that this is not a causal association.
Lowering homocysteine does not reduce that risk. There is probably a third party involved that increases risk of heart disease and increases homocysteine at the same time. So lowering homocysteine should no longer be the focus of our attention," Armitage commented.
She added: "That is not to say that foods high in folic acid will not be beneficial. Folic acid is found in fruit and vegetables, and these of course are good for you, but not necessarily because they contain folic acid."
On the cancer findings, Armitage said: "Our cancer results are reassuring. Most other trials have also shown no significant risk of cancer with folic-acid supplementation, but there was one trial that suggested a small increase in risk, which has probably received overselective emphasis. But it is important to be sure, as folate is added to food in some countries and is given to pregnant women to prevent neural-tube defects. While we can never say never, our data do provide reassurance on the risk of cancer. But it would still be good to see longer-term data when considering cancer risk. We had seven-year follow-up in this study, but we are going to continue to follow our patients well into the future to provide even longer-term data."
While we can never say never, our data do provide reassurance on the risk of cancer.
In the paper, the researchers explain that observational studies have consistently indicated that patients with vascular disease have higher blood levels of homocysteine than do controls, and these differences precede the onset of disease and are independent of other risk factors.
Daily supplementation with folic acid typically lowers homocysteine levels by about 25%, and the addition of vitamin B12 lowers it by a further 7%, and as these vitamins are inexpensive, there is considerable interest in using them to reduce the incidence of vascular disease.
They add that no definite protective effects of these vitamins have been seen in seven previous large-scale randomized trials, but it has been unclear whether this was due to insufficient numbers of events, too short a duration of treatment, attenuation of any effects by populationwide folic-acid fortification, or lack of real benefit. However, a subgroup analysis of the HOPE-2 trial and a meta-analysis of other trials have suggested a protective effect on stroke. To look at this issue further, they conducted the SEARCH trial, in which 12 064 UK survivors of MI were randomized to 2-mg folic acid plus 1-mg vitamin B12 daily or matching placebo.
28% Reduction in Homocysteine
Results showed that allocation to the study vitamins reduced homocysteine by a mean of 3.8 µmol/L (28%). During 6.7 years of follow-up, there was no difference in the primary end point of first major vascular event (coronary death, MI, any revascularization, or stroke) between the two groups. There was also no difference in other major secondary end points or in the incidence of cancer between the two groups.
The authors note that a meta-analysis of individual patient data from eight homocysteine lowering trials (including SEARCH), which has been submitted for publication and includes data on 37 485 individuals, confirms that folic-acid supplementation has no significant effects on major vascular events (RR 1.01) or any of its separate components.
Armitage commented to heartwire : "This meta-analysis gives an even more definitive answer that there is no benefit on heart disease of folic acid and should be the end of this issue," she said.
On the cancer findings, the researchers explain that there have been concerns that folic acid may play a role in carcinogenesis and suggestions that the introduction of folic-acid fortification in the US was linked to an increase in colorectal-cancer incidence during the late 1990s. While previous trials have shown mixed results in this issue, they state: "By contrast, with more than 1300 incident cancers during up to seven years of treatment with 2-mg folic acid and 1-mg vitamin B12 daily, SEARCH provides no evidence of adverse effects on cancer at any particular site."
The SEARCH trial was funded by Merck, as it was also evaluating two different doses of simvastatin. Armitage and other coauthors from the University of Oxford declare no financial conflicts, but the university does receive grants from Merck and other pharmaceutical companies to conduct independent research. Coauthor Dr Peter Sleight (University of Oxford) reports receiving speaker or data safety monitoring board fees from Abbott, AstraZeneca, Aventis, Bayer, Boehringer Ingelheim, Boehringer Mannheim, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Knoll, Medscape, Menarini, Merck, Monarch, MSD, Novartis, Pfizer, Pharmacia, Sanofi-Aventis, and Servier.
Sue Hughes
June 22, 2010 (Oxford, United Kingdom) - Substantial long-term reductions in blood homocysteine levels with folic-acid and vitamin-B12 supplementation did not have beneficial effects on vascular outcomes in the large-scale SEARCH trial [1].
But a silver lining of good news from the trial is that the vitamin supplements were not associated with any increase in cancer risk, which had been suggested in a previous study.
The trial, published in the June 23, 2010 issue of the Journal of the American Medical Association, was conducted by a team led by Dr Jane M Armitage (University of Oxford, UK).
Results from SEARCH were first reported by heartwire at the 2008 AHA meeting.
End of an Era
Armitage told heartwire that this large randomized trial "rounds off an era of trials with folic acid, which together suggest no benefit in reducing cardiovascular events."
While there is no doubt about the association between increased homocysteine levels and increased heart disease risk, our results suggest that this is not a causal association.
"This is another example of findings from observational studies leading us up the wrong path. While there is no doubt about the association between increased homocysteine levels and increased heart-disease risk, our results suggest that this is not a causal association.
Lowering homocysteine does not reduce that risk. There is probably a third party involved that increases risk of heart disease and increases homocysteine at the same time. So lowering homocysteine should no longer be the focus of our attention," Armitage commented.
She added: "That is not to say that foods high in folic acid will not be beneficial. Folic acid is found in fruit and vegetables, and these of course are good for you, but not necessarily because they contain folic acid."
On the cancer findings, Armitage said: "Our cancer results are reassuring. Most other trials have also shown no significant risk of cancer with folic-acid supplementation, but there was one trial that suggested a small increase in risk, which has probably received overselective emphasis. But it is important to be sure, as folate is added to food in some countries and is given to pregnant women to prevent neural-tube defects. While we can never say never, our data do provide reassurance on the risk of cancer. But it would still be good to see longer-term data when considering cancer risk. We had seven-year follow-up in this study, but we are going to continue to follow our patients well into the future to provide even longer-term data."
While we can never say never, our data do provide reassurance on the risk of cancer.
In the paper, the researchers explain that observational studies have consistently indicated that patients with vascular disease have higher blood levels of homocysteine than do controls, and these differences precede the onset of disease and are independent of other risk factors.
Daily supplementation with folic acid typically lowers homocysteine levels by about 25%, and the addition of vitamin B12 lowers it by a further 7%, and as these vitamins are inexpensive, there is considerable interest in using them to reduce the incidence of vascular disease.
They add that no definite protective effects of these vitamins have been seen in seven previous large-scale randomized trials, but it has been unclear whether this was due to insufficient numbers of events, too short a duration of treatment, attenuation of any effects by populationwide folic-acid fortification, or lack of real benefit. However, a subgroup analysis of the HOPE-2 trial and a meta-analysis of other trials have suggested a protective effect on stroke. To look at this issue further, they conducted the SEARCH trial, in which 12 064 UK survivors of MI were randomized to 2-mg folic acid plus 1-mg vitamin B12 daily or matching placebo.
28% Reduction in Homocysteine
Results showed that allocation to the study vitamins reduced homocysteine by a mean of 3.8 µmol/L (28%). During 6.7 years of follow-up, there was no difference in the primary end point of first major vascular event (coronary death, MI, any revascularization, or stroke) between the two groups. There was also no difference in other major secondary end points or in the incidence of cancer between the two groups.
The authors note that a meta-analysis of individual patient data from eight homocysteine lowering trials (including SEARCH), which has been submitted for publication and includes data on 37 485 individuals, confirms that folic-acid supplementation has no significant effects on major vascular events (RR 1.01) or any of its separate components.
Armitage commented to heartwire : "This meta-analysis gives an even more definitive answer that there is no benefit on heart disease of folic acid and should be the end of this issue," she said.
On the cancer findings, the researchers explain that there have been concerns that folic acid may play a role in carcinogenesis and suggestions that the introduction of folic-acid fortification in the US was linked to an increase in colorectal-cancer incidence during the late 1990s. While previous trials have shown mixed results in this issue, they state: "By contrast, with more than 1300 incident cancers during up to seven years of treatment with 2-mg folic acid and 1-mg vitamin B12 daily, SEARCH provides no evidence of adverse effects on cancer at any particular site."
The SEARCH trial was funded by Merck, as it was also evaluating two different doses of simvastatin. Armitage and other coauthors from the University of Oxford declare no financial conflicts, but the university does receive grants from Merck and other pharmaceutical companies to conduct independent research. Coauthor Dr Peter Sleight (University of Oxford) reports receiving speaker or data safety monitoring board fees from Abbott, AstraZeneca, Aventis, Bayer, Boehringer Ingelheim, Boehringer Mannheim, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Knoll, Medscape, Menarini, Merck, Monarch, MSD, Novartis, Pfizer, Pharmacia, Sanofi-Aventis, and Servier.
Antibiotic Uses and Challenges -- A Comprehensive Review From NRCWF
From Medscape Family Medicine
John H. Powers, MD; Janet A. Phoenix, MD, MPH; Diana M. Zuckerman, PhD
Introduction to Antibiotic Uses and Challenges
This review is intended to help primary care physicians prescribe the appropriate antibiotics for their patients. It provides background information on the origins of antibiotics, the classes of drugs, their mechanisms of action, and the organisms and diseases for which they are used. It includes information on when certain medications should be prescribed and in what order medications should be considered. Available antibiotics are a limited resource, and issues of resistance seem to be emerging faster than new antibiotics can become available. For that reason, prescription decisions by each physician for their patients can influence the effectiveness of antibiotics given to all patients, including patients of other physicians. The goal is to use antibiotics prudently, reserving antibiotics not intended for first-line use for instances when older, more commonly used medications fail. In addition, the adverse event profiles of various antibiotics differ, so administration of these drugs to individual patients should be based on the risk-benefit evaluation for each patient.
Background
Antibiotics are molecules used to treat or prevent disease in humans and animals. Their mechanism of action is to kill microbes or at least stop them from growing. Strictly speaking, the term antibiotics refers to naturally occurring molecules, and the term antimicrobials encompasses both naturally occurring and synthetically derived molecules. However, since the term antibiotic is so widely used, this review refers to all antimicrobials as "antibiotics."
The review concentrates on agents used to treat or prevent bacterial infections, rather than fungal or viral infections.
The term bacteriostatic is used to describe antibiotics that stop bacteria from growing.
The term bactericidal refers to antibiotics that kill bacterial or fungal cells outright.[1]
The clinical significance of bactericidal compared with bacteriostatic drugs is not clear in most infectious diseases. The human immune system also is important in curing infections, and stopping organisms from growing may be sufficient to allow the immune system time to cure the infection.[2]
Of note, antibiotics that appear potent in the test tube are not necessarily more beneficial in people when treating or preventing disease.
That is why data from human clinical trials are so important for understanding the benefits and risks of prescribing these powerful but often misused drugs.
Basic Principles of Prescribing Antibiotics
If used appropriately, antibiotics can help patients live longer and feel better. However, the idea that antibiotics "can’t hurt" is incorrect.
Antibiotics can cause serious and life-threatening adverse reactions, such as anaphylaxis and liver toxicity.
In fact, antibiotics are the second most common cause of anaphylaxis in the United States after food allergies.[3]
Less serious but more common adverse events include nausea, vomiting, diarrhea, and skin rash.
Antibiotics have no efficacy against viral infections, such as the common cold or flu. Therefore, prescribing for a viral infection is not warranted. There is no benefit to potentially exposing the patient to adverse events from the antibiotic. In addition, prescribing antibiotics for conditions when they are not needed contributes to antimicrobial resistance, thereby increasing the risk that these drugs will not be effective when they are needed. Resistance can affect not only the person who takes the drug but others to whom resistant bacteria may spread.
It is important to use these drugs only when the benefits outweigh the risks.
The first principle in prescribing antibiotics is to correctly diagnose a bacterial infection for which specific antibiotics are known to be effective compared with placebo.
Even when a bacterial infection is present, in some cases (eg, skin abscesses or asymptomatic bacteriuria), antibiotics may have no effect, and other therapy (eg, drainage of the abscess) may be indicated.
In other cases, such as ear infections, sinus infections, or bronchitis, the benefit of antibiotics is unclear and may be small, so it is necessary to determine the likely risks and benefits for that individual patient.
The second principle is to choose a drug that has the fewest adverse events for that patient. This maximizes the benefit and minimizes the risk.
Third, clinicians should choose a drug that has efficacy in treating or preventing the disease but leaves other bacteria in the body intact. This minimizes the spread of resistance and leaves intact the body’s own organisms that are a natural defense against other invading organisms.
Finally, the clinician should choose a drug that is convenient and inexpensive. Surprisingly, there is no clear evidence that drugs taken once each day have better adherence rates than twice-daily drugs.
In addition to the cost to the patient, antibiotics are one of the largest expenditures of hospital pharmacies, so cost-effective use of these drugs is important to contain healthcare costs.[4]
Gram Classification of Bacterial Cells
Bacterial cells are often grouped into categories on the basis of characteristics of their cell wall structure.
The terms gram-positive and gram-negative reflect the staining technique used to distinguish these differences.
Gram-positive cells retain crystal violet in an ethanol solution and thus appear purplish-blue when viewed under the microscope. Gram-negative bacteria do not retain crystal violet but do retain a counterstain, safranin, and so appear pinkish-red under the microscope.
One cannot classify all bacteria by using this technique. The differences in staining are due to differences in the structures of the outer surfaces of bacteria. Gram-positive and gram-negative cells both have a peptidoglycan layer as part of their cell wall structure. Gram-negative cells have an intact outer membrane that provides a barrier to the uptake of the stain. The membrane displays proteins and carbohydrates and provides a structural barrier to the force of osmotic pressure that could disrupt the cell. In gram-positive organisms, the peptidoglycan layer itself is usually thicker and multilayered than in gram-negative bacteria and displays proteins and carbohydrates that provide the osmotic structural barrier. These outer membrane proteins can act as binding sites, permitting the bacterial cells to penetrate human tissues.
Mechanisms of Bacteriostatic or Bactericidal Action
Many mechanisms exist by which antibiotics exert their effect on bacterial cells (Table 1). These differ depending on the characteristics of the bacterial organisms. Some antibiotics act by inhibiting the synthesis of the cell wall constituents, and so disrupt peptidoglycan substrates or enzymes involved in peptidoglycan assembly or cross-linking of the cell wall. Others block the synthesis of proteins essential for the functioning of bacterial or fungal cells. This activity generally takes place in the ribosomes at the 30S or 50S subunit sites through blockade of one or more of the biosynthetic steps. Another mechanism of action is the blockade of DNA synthesis or repair. This is generally accomplished through inhibition of the topoisomerases, which are essential for cell viability.
Table 1. Examples of Common Antibiotics and Their Mechanism of Action
Mechanisms of Action Antibiotics
Inhibitors of cell wall biosynthesis Penicillins, cephalosporins, vancomycin, bacitracin
Inhibitors of protein synthesis Tetracyclines, macrolides, aminoglycosides, lincosamides, streptogramins, oxazolidinones
Inhibition of DNA replication/repair Ciprofloxacin, rifampin, fluoroquinolones
Data from Walsh.[1]
http://www.medscape.com/viewarticle/723457?src=mp&spon=9&uac=71630FV
John H. Powers, MD; Janet A. Phoenix, MD, MPH; Diana M. Zuckerman, PhD
Introduction to Antibiotic Uses and Challenges
This review is intended to help primary care physicians prescribe the appropriate antibiotics for their patients. It provides background information on the origins of antibiotics, the classes of drugs, their mechanisms of action, and the organisms and diseases for which they are used. It includes information on when certain medications should be prescribed and in what order medications should be considered. Available antibiotics are a limited resource, and issues of resistance seem to be emerging faster than new antibiotics can become available. For that reason, prescription decisions by each physician for their patients can influence the effectiveness of antibiotics given to all patients, including patients of other physicians. The goal is to use antibiotics prudently, reserving antibiotics not intended for first-line use for instances when older, more commonly used medications fail. In addition, the adverse event profiles of various antibiotics differ, so administration of these drugs to individual patients should be based on the risk-benefit evaluation for each patient.
Background
Antibiotics are molecules used to treat or prevent disease in humans and animals. Their mechanism of action is to kill microbes or at least stop them from growing. Strictly speaking, the term antibiotics refers to naturally occurring molecules, and the term antimicrobials encompasses both naturally occurring and synthetically derived molecules. However, since the term antibiotic is so widely used, this review refers to all antimicrobials as "antibiotics."
The review concentrates on agents used to treat or prevent bacterial infections, rather than fungal or viral infections.
The term bacteriostatic is used to describe antibiotics that stop bacteria from growing.
The term bactericidal refers to antibiotics that kill bacterial or fungal cells outright.[1]
The clinical significance of bactericidal compared with bacteriostatic drugs is not clear in most infectious diseases. The human immune system also is important in curing infections, and stopping organisms from growing may be sufficient to allow the immune system time to cure the infection.[2]
Of note, antibiotics that appear potent in the test tube are not necessarily more beneficial in people when treating or preventing disease.
That is why data from human clinical trials are so important for understanding the benefits and risks of prescribing these powerful but often misused drugs.
Basic Principles of Prescribing Antibiotics
If used appropriately, antibiotics can help patients live longer and feel better. However, the idea that antibiotics "can’t hurt" is incorrect.
Antibiotics can cause serious and life-threatening adverse reactions, such as anaphylaxis and liver toxicity.
In fact, antibiotics are the second most common cause of anaphylaxis in the United States after food allergies.[3]
Less serious but more common adverse events include nausea, vomiting, diarrhea, and skin rash.
Antibiotics have no efficacy against viral infections, such as the common cold or flu. Therefore, prescribing for a viral infection is not warranted. There is no benefit to potentially exposing the patient to adverse events from the antibiotic. In addition, prescribing antibiotics for conditions when they are not needed contributes to antimicrobial resistance, thereby increasing the risk that these drugs will not be effective when they are needed. Resistance can affect not only the person who takes the drug but others to whom resistant bacteria may spread.
It is important to use these drugs only when the benefits outweigh the risks.
The first principle in prescribing antibiotics is to correctly diagnose a bacterial infection for which specific antibiotics are known to be effective compared with placebo.
Even when a bacterial infection is present, in some cases (eg, skin abscesses or asymptomatic bacteriuria), antibiotics may have no effect, and other therapy (eg, drainage of the abscess) may be indicated.
In other cases, such as ear infections, sinus infections, or bronchitis, the benefit of antibiotics is unclear and may be small, so it is necessary to determine the likely risks and benefits for that individual patient.
The second principle is to choose a drug that has the fewest adverse events for that patient. This maximizes the benefit and minimizes the risk.
Third, clinicians should choose a drug that has efficacy in treating or preventing the disease but leaves other bacteria in the body intact. This minimizes the spread of resistance and leaves intact the body’s own organisms that are a natural defense against other invading organisms.
Finally, the clinician should choose a drug that is convenient and inexpensive. Surprisingly, there is no clear evidence that drugs taken once each day have better adherence rates than twice-daily drugs.
In addition to the cost to the patient, antibiotics are one of the largest expenditures of hospital pharmacies, so cost-effective use of these drugs is important to contain healthcare costs.[4]
Gram Classification of Bacterial Cells
Bacterial cells are often grouped into categories on the basis of characteristics of their cell wall structure.
The terms gram-positive and gram-negative reflect the staining technique used to distinguish these differences.
Gram-positive cells retain crystal violet in an ethanol solution and thus appear purplish-blue when viewed under the microscope. Gram-negative bacteria do not retain crystal violet but do retain a counterstain, safranin, and so appear pinkish-red under the microscope.
One cannot classify all bacteria by using this technique. The differences in staining are due to differences in the structures of the outer surfaces of bacteria. Gram-positive and gram-negative cells both have a peptidoglycan layer as part of their cell wall structure. Gram-negative cells have an intact outer membrane that provides a barrier to the uptake of the stain. The membrane displays proteins and carbohydrates and provides a structural barrier to the force of osmotic pressure that could disrupt the cell. In gram-positive organisms, the peptidoglycan layer itself is usually thicker and multilayered than in gram-negative bacteria and displays proteins and carbohydrates that provide the osmotic structural barrier. These outer membrane proteins can act as binding sites, permitting the bacterial cells to penetrate human tissues.
Mechanisms of Bacteriostatic or Bactericidal Action
Many mechanisms exist by which antibiotics exert their effect on bacterial cells (Table 1). These differ depending on the characteristics of the bacterial organisms. Some antibiotics act by inhibiting the synthesis of the cell wall constituents, and so disrupt peptidoglycan substrates or enzymes involved in peptidoglycan assembly or cross-linking of the cell wall. Others block the synthesis of proteins essential for the functioning of bacterial or fungal cells. This activity generally takes place in the ribosomes at the 30S or 50S subunit sites through blockade of one or more of the biosynthetic steps. Another mechanism of action is the blockade of DNA synthesis or repair. This is generally accomplished through inhibition of the topoisomerases, which are essential for cell viability.
Table 1. Examples of Common Antibiotics and Their Mechanism of Action
Mechanisms of Action Antibiotics
Inhibitors of cell wall biosynthesis Penicillins, cephalosporins, vancomycin, bacitracin
Inhibitors of protein synthesis Tetracyclines, macrolides, aminoglycosides, lincosamides, streptogramins, oxazolidinones
Inhibition of DNA replication/repair Ciprofloxacin, rifampin, fluoroquinolones
Data from Walsh.[1]
http://www.medscape.com/viewarticle/723457?src=mp&spon=9&uac=71630FV
Wednesday, June 23, 2010
Newly Diagnosed Diabetes May Increase Risk for Liver Disease
From Medscape Medical News
Laurie Barclay, MD
June 21, 2010 — Adults with newly diagnosed diabetes are at increased risk for advanced liver disease, known as diabetic hepatopathy, according to the results of a population-based, matched, retrospective cohort study reported online June 21 in the Canadian Medical Association Journal.
"The negative impact of diabetes mellitus is well recognized, yet little is known about the effect of this disease on the liver, an organ susceptible to nonalcoholic fatty liver disease related to insulin resistance," write Liane Porepa, MD, from the University of Toronto in Ontario, Canada, and colleagues. "We evaluated whether adults with newly diagnosed diabetes were at increased risk of serious liver disease."
The investigators used administrative health databases for the province of Ontario from 1994 to 2006 to identify 438,069 adults with newly diagnosed diabetes. A comparison group of 2,059,708 individuals without known diabetes were matched 5:1 to exposed persons by birth year, sex, and local health region. Persons with preexisting liver or alcohol-related disease were excluded. The main study endpoint was incident serious liver disease, defined as cirrhosis, liver failure and its complications, or receipt of a liver transplant.
Among persons with newly diagnosed diabetes, the incidence rate of serious liver disease was 8.19 per 10,000 person-years vs 4.17 per 10,000 person-years among those without diabetes, yielding an unadjusted hazard ratio (HR) of 1.92 (95% confidence interval [CI], 1.83 - 2.01). After adjustment for age, income, urban residence, healthcare utilization, and preexisting comorbid conditions (hypertension, dyslipidemia, obesity, and cardiovascular disease), the HR was 1.77 (95% CI, 1.68 - 1.86).
"Adults with newly diagnosed diabetes appeared to be at higher risk of advanced liver disease, also known as diabetic hepatopathy," the study authors write. "Whether this reflects nonalcoholic fatty liver disease or direct glycemic injury of the liver remains to be determined."
Limitations of this study include possible misclassification of persons with diabetes, inability to distinguish between newly diagnosed type 1 and type 2 diabetes, and the possibility that diabetes developed as a complication of cirrhosis. In addition, the investigators could not rule out subclinical preexisting liver disease, nonalcoholic fatty liver disease, or steatohepatitis.
"[A]lthough diabetic hepatopathy is potentially less common, it may be appropriate for addition to the list of target-organ conditions related to diabetes, such as glomerulopathy, retinopathy and neuropathy," the study authors conclude. "Annual screening for liver disease might be accomplished by means of a simple biochemical analyte such as alanine aminotransferase. However, before screening can be considered, the efficacy of primary and secondary preventive measures, such as weight loss and glycemic and lipid control, must be validated by good evidence akin to that completed for adults and children with isolated fatty liver and no diabetes."
The Banting and Best Diabetes Centre at the University of Toronto supported this study. The study was also supported by the Institute for Clinical Evaluative Sciences (ICES), which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). No endorsement of the study authors' opinions by ICES or the Ontario MOHLTC is intended or should be inferred. The study authors have disclosed no relevant financial relationships.
CMAJ. Published online June 21, 2010.
Laurie Barclay, MD
June 21, 2010 — Adults with newly diagnosed diabetes are at increased risk for advanced liver disease, known as diabetic hepatopathy, according to the results of a population-based, matched, retrospective cohort study reported online June 21 in the Canadian Medical Association Journal.
"The negative impact of diabetes mellitus is well recognized, yet little is known about the effect of this disease on the liver, an organ susceptible to nonalcoholic fatty liver disease related to insulin resistance," write Liane Porepa, MD, from the University of Toronto in Ontario, Canada, and colleagues. "We evaluated whether adults with newly diagnosed diabetes were at increased risk of serious liver disease."
The investigators used administrative health databases for the province of Ontario from 1994 to 2006 to identify 438,069 adults with newly diagnosed diabetes. A comparison group of 2,059,708 individuals without known diabetes were matched 5:1 to exposed persons by birth year, sex, and local health region. Persons with preexisting liver or alcohol-related disease were excluded. The main study endpoint was incident serious liver disease, defined as cirrhosis, liver failure and its complications, or receipt of a liver transplant.
Among persons with newly diagnosed diabetes, the incidence rate of serious liver disease was 8.19 per 10,000 person-years vs 4.17 per 10,000 person-years among those without diabetes, yielding an unadjusted hazard ratio (HR) of 1.92 (95% confidence interval [CI], 1.83 - 2.01). After adjustment for age, income, urban residence, healthcare utilization, and preexisting comorbid conditions (hypertension, dyslipidemia, obesity, and cardiovascular disease), the HR was 1.77 (95% CI, 1.68 - 1.86).
"Adults with newly diagnosed diabetes appeared to be at higher risk of advanced liver disease, also known as diabetic hepatopathy," the study authors write. "Whether this reflects nonalcoholic fatty liver disease or direct glycemic injury of the liver remains to be determined."
Limitations of this study include possible misclassification of persons with diabetes, inability to distinguish between newly diagnosed type 1 and type 2 diabetes, and the possibility that diabetes developed as a complication of cirrhosis. In addition, the investigators could not rule out subclinical preexisting liver disease, nonalcoholic fatty liver disease, or steatohepatitis.
"[A]lthough diabetic hepatopathy is potentially less common, it may be appropriate for addition to the list of target-organ conditions related to diabetes, such as glomerulopathy, retinopathy and neuropathy," the study authors conclude. "Annual screening for liver disease might be accomplished by means of a simple biochemical analyte such as alanine aminotransferase. However, before screening can be considered, the efficacy of primary and secondary preventive measures, such as weight loss and glycemic and lipid control, must be validated by good evidence akin to that completed for adults and children with isolated fatty liver and no diabetes."
The Banting and Best Diabetes Centre at the University of Toronto supported this study. The study was also supported by the Institute for Clinical Evaluative Sciences (ICES), which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). No endorsement of the study authors' opinions by ICES or the Ontario MOHLTC is intended or should be inferred. The study authors have disclosed no relevant financial relationships.
CMAJ. Published online June 21, 2010.
Anxiety Predicts Heart Disease Years Later
From Heartwire
Lisa Nainggolan
June 21, 2010 (Tilburg, the Netherlands and Stockholm, Sweden) - Two new studies firmly establish anxiety as an independent predictor for subsequent coronary heart disease years down the line [1,2]. Doctors, who often neglect to ask patients about their feelings, should pay heed to these findings, say the researchers.
Dr Annelieke M Roest (Tilburg University, the Netherlands) and colleagues performed the first-ever meta-analysis on the association of anxiety with the incidence of CHD in initially healthy people, using data from the US, Europe, and Asia. Even after multivariate adjustment, anxious people had around a 25% greater risk of CHD and an almost 50% higher risk of cardiac death over a mean follow-up period of 11.2 years.
In the second study, almost 50 000 Swedish men who were medically examined for military service and followed for an average of 37 years were assessed by Dr Imre Janszky (Karolinska Institute, Stockholm, Sweden) and coworkers. Depression was not a predictor for subsequent coronary disease, but those with anxiety disorders--as diagnosed by a psychiatrist--were twice as likely to suffer CHD or acute MI, even after adjustment for baseline confounders.
The new papers appear in the June 29, 2010 issue of the Journal of the American College of Cardiology, as does an accompanying editorial [3] by psychiatrist Dr Joel E Dimsdale (University of California, San Diego).
qAnxiety symptoms can be such a strong beacon, lighting the way to future coronary disease decades in advance.
Dimsdale says it is "odd that anxiety symptoms can be such a strong beacon, lighting the way to future coronary disease decades in advance." Cardiologists, he says "are certainly cognizant of anxiety's effects" on transient physiology, such as blood pressure, palpitations, and angina, but this new research suggests that asking about previous early-life anxiety might be relevant in clinical assessment for the diagnosis and prevention of cardiovascular disease.
And although trials are needed to see whether therapies aimed at alleviating anxiety would reduce cardiovascular risk, "until proven otherwise, the wise clinician might 'assume' that treatment of anxiety disorders might have benefits beyond immediate symptomatic and functional improvement," he observes.
Clinicians Should Be Aware of the Risk of Anxiety
In their meta-analysis, Roest and colleagues combined data from 20 studies, including approximately 250 000 initially healthy individuals from the US, Norway, the Netherlands, Sweden, Japan, and the UK. The studies were all prospective in nature and had to have included at baseline at least one self-report or interview-based assessment of anxiety symptoms or anxiety disorder. End points had to include cardiac mortality or MI.
Adjustment for confounding factors was performed in 18 of the 20 studies; the researchers found that anxious people were at higher risk of CHD (hazard ratio 1.26; p<0.0001) and cardiac death (HR 1.48; p=0.003), with a nonsignificant trend for an association between anxiety and nonfatal MI (HR 1.43; p=0.180).
"Our most important finding was that anxiety was associated with the development of incident CHD in initially healthy persons," Roest told heartwire .
"Clinicians should be aware of this; if they have anxious patients, they might be at risk to develop heart disease, and this was in initially healthy patients. But you also see this risk in patients who already have heart disease; there is a relationship with the progression of heart disease," she noted.
Anxiety, But Not Depression, Associated With CHD Risk
In the Swedish conscript study, depression and anxiety were diagnosed by psychiatrists during the medical exam of males aged 18 to 20 in 1969 and 1970. Data on well-established CHD risk factors and potential confounders were also collected. Participants were followed for CHD and AMI for 37 years.
Multivariate-adjusted hazard ratios for depression were 1.04 for CHD and 1.03 for AMI. For anxiety, these were 2.17 and 2.51, respectively.
"We uniquely investigated the long-term relationship between depression and anxiety, diagnosed by experts in men aged 18 to 20 years, and the subsequent long-term CHD outcome in a large sample of men. Anxiety . . . independently predicted CHD events. In contrast, we found no support for such an effect concerning early-onset depression in men," say Janszky et al.
They suggest that one of the reasons why many previous studies have found a link between depression and CHD could be because these often employed self-reporting of such symptoms.
"Anxiety and depression are independent psychopathological conditions, although they share common symptoms and are very often comorbid." Participants in prior studies may have been unable to distinguish one from the other, they propose.
Roest told heartwire it is important that studies look at the interaction of anxiety and depression, "because there is such a large overlap between them."
Anxiety Disorders as Prevalent as Hypertension
In his editorial, Dimsdale says that new risk factors for CHD need to be "carefully scrutinized for clinical utility." Anxiety disorders, he notes, "are as prevalent as hypertension" and are a major affliction of the young, with a lifetime prevalence of around 28%. Their impact on global functioning is roughly akin to that of lower back pain or leg ulcers. And when anxiety coexists with depression, the corresponding impact on quality of life "is even worse," he observes.
But physicians, he notes, "are frequently timid about assessing emotional symptoms. It is odd that we thread catheters, ablate lesions, and give rectal exams but are uncomfortable asking patients about their lives."
Roest agrees, telling heartwire , "There hasn't been a lot of research on anxiety; most has focused on depression, and what we know from depression is that it's very difficult for physicians to recognize it."
But Dimsdale says "assessment tools like the PRIME-MD [4] are readily available, with easy-to-ask questions," opening the door for discussion. These new findings suggest that including information about anxiety disorders in clinical assessments "might be relevant for the diagnosis (and prevention) of CHD," he concludes.
References
Lisa Nainggolan
June 21, 2010 (Tilburg, the Netherlands and Stockholm, Sweden) - Two new studies firmly establish anxiety as an independent predictor for subsequent coronary heart disease years down the line [1,2]. Doctors, who often neglect to ask patients about their feelings, should pay heed to these findings, say the researchers.
Dr Annelieke M Roest (Tilburg University, the Netherlands) and colleagues performed the first-ever meta-analysis on the association of anxiety with the incidence of CHD in initially healthy people, using data from the US, Europe, and Asia. Even after multivariate adjustment, anxious people had around a 25% greater risk of CHD and an almost 50% higher risk of cardiac death over a mean follow-up period of 11.2 years.
In the second study, almost 50 000 Swedish men who were medically examined for military service and followed for an average of 37 years were assessed by Dr Imre Janszky (Karolinska Institute, Stockholm, Sweden) and coworkers. Depression was not a predictor for subsequent coronary disease, but those with anxiety disorders--as diagnosed by a psychiatrist--were twice as likely to suffer CHD or acute MI, even after adjustment for baseline confounders.
The new papers appear in the June 29, 2010 issue of the Journal of the American College of Cardiology, as does an accompanying editorial [3] by psychiatrist Dr Joel E Dimsdale (University of California, San Diego).
qAnxiety symptoms can be such a strong beacon, lighting the way to future coronary disease decades in advance.
Dimsdale says it is "odd that anxiety symptoms can be such a strong beacon, lighting the way to future coronary disease decades in advance." Cardiologists, he says "are certainly cognizant of anxiety's effects" on transient physiology, such as blood pressure, palpitations, and angina, but this new research suggests that asking about previous early-life anxiety might be relevant in clinical assessment for the diagnosis and prevention of cardiovascular disease.
And although trials are needed to see whether therapies aimed at alleviating anxiety would reduce cardiovascular risk, "until proven otherwise, the wise clinician might 'assume' that treatment of anxiety disorders might have benefits beyond immediate symptomatic and functional improvement," he observes.
Clinicians Should Be Aware of the Risk of Anxiety
In their meta-analysis, Roest and colleagues combined data from 20 studies, including approximately 250 000 initially healthy individuals from the US, Norway, the Netherlands, Sweden, Japan, and the UK. The studies were all prospective in nature and had to have included at baseline at least one self-report or interview-based assessment of anxiety symptoms or anxiety disorder. End points had to include cardiac mortality or MI.
Adjustment for confounding factors was performed in 18 of the 20 studies; the researchers found that anxious people were at higher risk of CHD (hazard ratio 1.26; p<0.0001) and cardiac death (HR 1.48; p=0.003), with a nonsignificant trend for an association between anxiety and nonfatal MI (HR 1.43; p=0.180).
"Our most important finding was that anxiety was associated with the development of incident CHD in initially healthy persons," Roest told heartwire .
"Clinicians should be aware of this; if they have anxious patients, they might be at risk to develop heart disease, and this was in initially healthy patients. But you also see this risk in patients who already have heart disease; there is a relationship with the progression of heart disease," she noted.
Anxiety, But Not Depression, Associated With CHD Risk
In the Swedish conscript study, depression and anxiety were diagnosed by psychiatrists during the medical exam of males aged 18 to 20 in 1969 and 1970. Data on well-established CHD risk factors and potential confounders were also collected. Participants were followed for CHD and AMI for 37 years.
Multivariate-adjusted hazard ratios for depression were 1.04 for CHD and 1.03 for AMI. For anxiety, these were 2.17 and 2.51, respectively.
"We uniquely investigated the long-term relationship between depression and anxiety, diagnosed by experts in men aged 18 to 20 years, and the subsequent long-term CHD outcome in a large sample of men. Anxiety . . . independently predicted CHD events. In contrast, we found no support for such an effect concerning early-onset depression in men," say Janszky et al.
They suggest that one of the reasons why many previous studies have found a link between depression and CHD could be because these often employed self-reporting of such symptoms.
"Anxiety and depression are independent psychopathological conditions, although they share common symptoms and are very often comorbid." Participants in prior studies may have been unable to distinguish one from the other, they propose.
Roest told heartwire it is important that studies look at the interaction of anxiety and depression, "because there is such a large overlap between them."
Anxiety Disorders as Prevalent as Hypertension
In his editorial, Dimsdale says that new risk factors for CHD need to be "carefully scrutinized for clinical utility." Anxiety disorders, he notes, "are as prevalent as hypertension" and are a major affliction of the young, with a lifetime prevalence of around 28%. Their impact on global functioning is roughly akin to that of lower back pain or leg ulcers. And when anxiety coexists with depression, the corresponding impact on quality of life "is even worse," he observes.
But physicians, he notes, "are frequently timid about assessing emotional symptoms. It is odd that we thread catheters, ablate lesions, and give rectal exams but are uncomfortable asking patients about their lives."
Roest agrees, telling heartwire , "There hasn't been a lot of research on anxiety; most has focused on depression, and what we know from depression is that it's very difficult for physicians to recognize it."
But Dimsdale says "assessment tools like the PRIME-MD [4] are readily available, with easy-to-ask questions," opening the door for discussion. These new findings suggest that including information about anxiety disorders in clinical assessments "might be relevant for the diagnosis (and prevention) of CHD," he concludes.
References
Tuesday, June 22, 2010
Adolescent BP Predicts Progression to Hypertension in Young Adulthood
From Medscape Medical News
Laurie Barclay, MD
June 18, 2010 — Adolescent blood pressure (BP) predicts progression to hypertension in young adulthood, with teen-age boys with normal BP 3 to 4 times more likely than girls to have high BP early in adulthood, according to the results of a study reported online June 14 in Hypertension.
"Although prehypertension at adolescence is accepted to indicate increased future risk of hypertension, large-scale/long follow-up studies are required to better understand how adolescent ...BP tracks into young adulthood," write Amir Tirosh, MD, PhD, from Brigham and Women's Hospital in Boston, Massachusetts, and colleagues.
The study cohort consisted of 23,191 male and 3789 female adolescents enrolled in the Metabolic Lifestyle and Nutrition Assessment in Young Adults study. At baseline, mean age was 17.4 years, and BP was less than 140/90 mm Hg or categorized according to current criteria for pediatric BP and body mass index (BMI) values. Incidence of hypertension was determined retrospectively between the ages of 17 and 25 years and prospectively with repeated BP measurements between the ages of 25 and 42 years.
Between the ages of 17 and 42 years, 3810 new cases of hypertension were detected, with a cumulative risk for hypertension 3 to 4 times higher in men vs women, based on survival analyses. Cox regression models adjusted for age and BMI and stratified by baseline BP showed that the hazard ratio (HR) of hypertension increased gradually across BP groups within the normotensive range at age 17 years. There was no apparent threshold effect. In the group with BP 130 to 139/85 to 89 mm Hg, the HR was 2.50 (95% confidence interval [CI], 1.75 - 3.57) for boys and 2.31 (95% CI, 0.71 - 7.60) for girls.
"Blood pressure values well below the hypertensive range already can serve as good predictors for future hypertension," Dr. Tirosh said in a news release. "The rate of progression to hypertension is higher in teen-agers whose systolic blood pressure is 110 versus those whose blood pressure is 100 and is different between boys and girls."
Even after adjustment for BP at age 17 years, BMI at that age was strongly associated with a future risk for hypertension, especially in boys. However, BMI at age 30 years attenuated this association, especially in girls.
"BMI is considered an independent risk factor that interacts with blood pressure to predict future risk of hypertension," Dr. Tirosh said. "Together, these factors provide a simple and useful tool that can serve as a red flag to detect subgroups of teens at high risk of hypertension as adults while in their teens."
Limitations of this study include single-visit measurement of BP at age 17 years in a fairly stressful setting, higher-stress military environment in the study cohort, and database of age 17 years limited to rather basic information.
"It is never too early to start lifestyle modification and intervene to prevent hypertension, heart disease and diabetes," Dr. Tirosh concluded. "Hypertension, heart disease and their prevention have been perceived as more relevant to an older population, but now we know that slight changes in blood pressure and weight should represent an alert for pediatricians to begin prevention as early as possible. It is better to prevent a disease than treat it."
The Talpiot Medical Leadership Program, Chaim Sheba Medical Center, Tel-Hashomer, Israel, and the Israeli Defense Forces Medical Corps funded this study. The study authors have disclosed no relevant financial relationships.
Hypertension. Published online June 14, 2010.
Laurie Barclay, MD
June 18, 2010 — Adolescent blood pressure (BP) predicts progression to hypertension in young adulthood, with teen-age boys with normal BP 3 to 4 times more likely than girls to have high BP early in adulthood, according to the results of a study reported online June 14 in Hypertension.
"Although prehypertension at adolescence is accepted to indicate increased future risk of hypertension, large-scale/long follow-up studies are required to better understand how adolescent ...BP tracks into young adulthood," write Amir Tirosh, MD, PhD, from Brigham and Women's Hospital in Boston, Massachusetts, and colleagues.
The study cohort consisted of 23,191 male and 3789 female adolescents enrolled in the Metabolic Lifestyle and Nutrition Assessment in Young Adults study. At baseline, mean age was 17.4 years, and BP was less than 140/90 mm Hg or categorized according to current criteria for pediatric BP and body mass index (BMI) values. Incidence of hypertension was determined retrospectively between the ages of 17 and 25 years and prospectively with repeated BP measurements between the ages of 25 and 42 years.
Between the ages of 17 and 42 years, 3810 new cases of hypertension were detected, with a cumulative risk for hypertension 3 to 4 times higher in men vs women, based on survival analyses. Cox regression models adjusted for age and BMI and stratified by baseline BP showed that the hazard ratio (HR) of hypertension increased gradually across BP groups within the normotensive range at age 17 years. There was no apparent threshold effect. In the group with BP 130 to 139/85 to 89 mm Hg, the HR was 2.50 (95% confidence interval [CI], 1.75 - 3.57) for boys and 2.31 (95% CI, 0.71 - 7.60) for girls.
"Blood pressure values well below the hypertensive range already can serve as good predictors for future hypertension," Dr. Tirosh said in a news release. "The rate of progression to hypertension is higher in teen-agers whose systolic blood pressure is 110 versus those whose blood pressure is 100 and is different between boys and girls."
Even after adjustment for BP at age 17 years, BMI at that age was strongly associated with a future risk for hypertension, especially in boys. However, BMI at age 30 years attenuated this association, especially in girls.
"BMI is considered an independent risk factor that interacts with blood pressure to predict future risk of hypertension," Dr. Tirosh said. "Together, these factors provide a simple and useful tool that can serve as a red flag to detect subgroups of teens at high risk of hypertension as adults while in their teens."
Limitations of this study include single-visit measurement of BP at age 17 years in a fairly stressful setting, higher-stress military environment in the study cohort, and database of age 17 years limited to rather basic information.
"It is never too early to start lifestyle modification and intervene to prevent hypertension, heart disease and diabetes," Dr. Tirosh concluded. "Hypertension, heart disease and their prevention have been perceived as more relevant to an older population, but now we know that slight changes in blood pressure and weight should represent an alert for pediatricians to begin prevention as early as possible. It is better to prevent a disease than treat it."
The Talpiot Medical Leadership Program, Chaim Sheba Medical Center, Tel-Hashomer, Israel, and the Israeli Defense Forces Medical Corps funded this study. The study authors have disclosed no relevant financial relationships.
Hypertension. Published online June 14, 2010.
H1N1 Virus Enters Pigs in HK, Swaps Genes
From Reuters Health Information
By Tan Ee Lyn
HONG KONG (Reuters) Jun 17 - The H1N1 virus has been spreading quietly in pigs in Hong Kong and swapping genes with other viruses, and researchers said the findings support calls for tighter disease surveillance in pigs before new viruses can emerge and infect people.
Their report, published June 18th in Science, confirms the theory that flu viruses infecting swine can swap genes with other viruses that are in pigs, including more dangerous ones like the H5N1 or H9N2 bird flu viruses.
Dr. Malik Peiris, an influenza expert who worked on the study, said the discovery underlines the importance of disease surveillance in pigs.
"It demonstrates the pandemic virus can easily go back to pigs. Once it does so, it can reassort with other pig viruses and give rise to potentially unexpected consequences," said Dr. Peiris, a microbiology professor at the University of Hong Kong.
Dr. Peiris and colleagues, including Dr. Guan Yi at the University of Hong Kong, have found pandemic H1N1 viruses in nasal swabs taken from apparently healthy pigs at a Hong Kong abattoir during routine checks since October 2009.
"From genetic analysis, what it suggests is each of those viruses we found in pigs all came from humans," Dr. Peiris said in a telephone interview.
"It is not surprising because the pandemic virus emerged from pigs, so it is not surprising that it goes back to pigs."
A sample isolated from Hong Kong pigs in January 2010 carried genes from three viruses - the pandemic H1N1, a European "avian like" H1N1 and a so-called "triple reassortant" virus containing bits of human, pig and bird flu viruses which were first discovered in North America in 1998.
"This suggests that the pig is a place where the pandemic virus might actually change and reassort and get new properties possibly," Dr. Peiris said.
"The pandemic virus in humans has been extremely stable. It hasn't changed at all even though people were concerned it might reassort and mix with human viruses ... but it seems that it can mix with other flu viruses (in a pig)."
Genetic research has suggested that H1N1, first identified in people in April 2009, had in fact been circulating for at least a decade and probably in pigs. Despite tight controls on herd to protect them from people, little checking is done globally to see whether food herds are infected and if so, with what viruses.
Studies in the past year have turned up pigs in Canada and other countries infected with the pandemic H1N1 virus, evidently carried to the animals by people.
"I must emphasize the point that it doesn't mean that pork is dangerous to eat at all (if well cooked). What it means is it is important to carry out systematic surveillance in pigs so we know what is going on in pigs in regard to influenza viruses in general and the pandemic virus in particular," Dr. Peiris said.
Asked if there was a possibility of the H1N1 getting mixed up with the H5N1, Dr. Peiris said: "That is certainly a possibility, that's why we need to keep track.
"If it is quite able to readily reassort and pick up genes from pig viruses, you might have other combinations of genes that can arise. Unless we are alert to it, we potentially could have a virus that is ... more virulent coming back to humans."
Although H5N1 is a mostly avian virus, it causes more severe illness in people than seasonal flu and kills 60% of the people it infects. It has infected 499 people and killed 295 of them since re-emerging in 2003.
http://www.sciencemag.org/cgi/content/abstract/sci;328/5985/1529
Science 2010;328:1529.
By Tan Ee Lyn
HONG KONG (Reuters) Jun 17 - The H1N1 virus has been spreading quietly in pigs in Hong Kong and swapping genes with other viruses, and researchers said the findings support calls for tighter disease surveillance in pigs before new viruses can emerge and infect people.
Their report, published June 18th in Science, confirms the theory that flu viruses infecting swine can swap genes with other viruses that are in pigs, including more dangerous ones like the H5N1 or H9N2 bird flu viruses.
Dr. Malik Peiris, an influenza expert who worked on the study, said the discovery underlines the importance of disease surveillance in pigs.
"It demonstrates the pandemic virus can easily go back to pigs. Once it does so, it can reassort with other pig viruses and give rise to potentially unexpected consequences," said Dr. Peiris, a microbiology professor at the University of Hong Kong.
Dr. Peiris and colleagues, including Dr. Guan Yi at the University of Hong Kong, have found pandemic H1N1 viruses in nasal swabs taken from apparently healthy pigs at a Hong Kong abattoir during routine checks since October 2009.
"From genetic analysis, what it suggests is each of those viruses we found in pigs all came from humans," Dr. Peiris said in a telephone interview.
"It is not surprising because the pandemic virus emerged from pigs, so it is not surprising that it goes back to pigs."
A sample isolated from Hong Kong pigs in January 2010 carried genes from three viruses - the pandemic H1N1, a European "avian like" H1N1 and a so-called "triple reassortant" virus containing bits of human, pig and bird flu viruses which were first discovered in North America in 1998.
"This suggests that the pig is a place where the pandemic virus might actually change and reassort and get new properties possibly," Dr. Peiris said.
"The pandemic virus in humans has been extremely stable. It hasn't changed at all even though people were concerned it might reassort and mix with human viruses ... but it seems that it can mix with other flu viruses (in a pig)."
Genetic research has suggested that H1N1, first identified in people in April 2009, had in fact been circulating for at least a decade and probably in pigs. Despite tight controls on herd to protect them from people, little checking is done globally to see whether food herds are infected and if so, with what viruses.
Studies in the past year have turned up pigs in Canada and other countries infected with the pandemic H1N1 virus, evidently carried to the animals by people.
"I must emphasize the point that it doesn't mean that pork is dangerous to eat at all (if well cooked). What it means is it is important to carry out systematic surveillance in pigs so we know what is going on in pigs in regard to influenza viruses in general and the pandemic virus in particular," Dr. Peiris said.
Asked if there was a possibility of the H1N1 getting mixed up with the H5N1, Dr. Peiris said: "That is certainly a possibility, that's why we need to keep track.
"If it is quite able to readily reassort and pick up genes from pig viruses, you might have other combinations of genes that can arise. Unless we are alert to it, we potentially could have a virus that is ... more virulent coming back to humans."
Although H5N1 is a mostly avian virus, it causes more severe illness in people than seasonal flu and kills 60% of the people it infects. It has infected 499 people and killed 295 of them since re-emerging in 2003.
http://www.sciencemag.org/cgi/content/abstract/sci;328/5985/1529
Science 2010;328:1529.
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