Michele G. Sullivan

The days when the dietary supplements industry is allowed to regulate itself may be numbered after release of a new federal report addressing growing concerns about dietary supplement industry.

The report, issued in March by the Government Accountability Office, calls on the Food and Drug Administration to expand adverse event reporting and increase its efforts to educate the public about the safety, efficacy, and labeling of these products. The GAO investigation into supplement safety was made at the request of Congress.

According to the 77-page report, the FDA should be tracking all levels of adverse events related to the use of dietary supplements and herbs, not just severe events. And, the report noted, despite the 2007 requirement for improved manufacturing practices, the FDA still lacks even the most basic ability to track the quality of dietary supplements (www.gao.gov/new.items/d09250.pdf

Companies that manufacture the products are not required to identify themselves as such, or to provide the FDA with information about the products, including the product name and ingredients, the report said. And if a product is found to be dangerous, the agency is hamstrung–it can only ask for a voluntary recall as it did in December, when Star Caps, a popular weight-loss supplement, was found to contain prescription-strength levels of the diuretic bumetanide.

The FDA lost its authority to regulate the ingredients of dietary supplements before marketing with the enactment of the Dietary Supplement Health and Education Act of 1994 (DSHEA) (www.cfsan.fda.gov/∼dms/dietsupp.html

Dietary supplements fall within the definition of complementary and alternative medicine (CAM). An earlier federal report issued by the Centers for Disease Control and Prevention found that use of CAM is widespread. For example, when patients with arthritis become frustrated by lack of pain relief, they often turn to dietary supplements.

The issue of quality control has bothered Dr. Roy Altman for years. Supplements and herbal preparations designed to promote joint health and relieve pain are some of the most popular products on the market, grabbing almost as big a market share as weight-loss products, he said in an interview. “We are looking at probably $40–$60 billion spent on over-the-counter arthritis supplements each year,” he said, but noted that “this is only a fraction of what is spent on prescribed arthritis medications.”

Some of these products probably do have a beneficial effect in patients with rheumatic disorders, said Dr. Altman, professor of rheumatology at the University of California, Los Angeles. The problem is identifying which products actually contain what the label promises, and nothing else. “We, and a group of colleagues from Canada, once tested 10 different glucosamine products sold in the U.S. Four of them didn't even have glucosamine in them, and of the remaining six, four had much less than was stated on the product label.”

Similar quality control problems led Congress to request the investigation about 18 months ago, said Lisa Shames, the GAO's director of Food Safety and Agriculture Issues. “There has been a lot of congressional interest into how FDA was implementing the requirements [for oversight of dietary supplements and herbal products], especially the requirement for reporting adverse events,” she said in an interview.

One of the paper's key findings is that adverse events are probably significantly underreported, she said. In December 2007, the FDA began requiring manufacturers of dietary supplements and herbal preparations to report all serious adverse events related to the use of their products. “Since then, FDA has had a threefold increase in the number of events reported, but the big question is whether this is all the events that are happening,” Ms. Shames said. From January through October 2008, the FDA received 948 reports of adverse events, compared with 298 over the same time frame in 2007. “FDA recently estimated that the true number of adverse events could be well over 50,000 each year. We recommended that the FDA require reporting of all adverse events, regardless of their severity.”

The report also called on the FDA to require more information from manufacturers about the ingredients in their products. “There is a real lack of information that FDA needs,” Ms. Shames said. “Herbal products are not registered by the companies that produce them, and companies are not required to tell FDA what product they sell.”

The agency should also increase its efforts to educate the public about the safety of supplements, the report concluded. “People think all these products are safe and approved by the FDA, and of course, this isn't the case,” Ms. Shames said.

The report didn't even touch on manufacturing issues, which are controlled by a set of laws that until recently left manufacturing oversight to the companies, with little government regulation. In 2007, the FDA finalized its Good Manufacturing Practice regulations, which will require quality control measures for all domestic manufacturers and foreign manufacturers that distribute in the United States. But the law is being phased in by company size, with the smallest companies having until June 2010 to come into full compliance.

Dr. Altman noted that the medical literature contains virtually no data on which brand of supplements or herbal preparations most closely resemble their labeling. Nor is country of manufacture a good guideline, Dr. Altman said.

The unreliability of labeling puts both physicians and patients in a bind, he said. “It does present a real dilemma, because even if it's a safe product, like glucosamine, and you'd like to use it, there is no way of really knowing for certain what you're getting. I try and steer my patients toward brands I have personally investigated and feel comfortable with, but there are no databases that contain this information, so people can't make informed choices.”

'I try and steer my patients toward brands I have personally investigated and feel comfortable with.' DR. ALTMAN

The FDA should be tracking all levels of adverse events related to the use of dietary supplements, the GAO report says. ©

The days when the dietary supplements industry is allowed to regulate itself may be numbered after release of a new federal report addressing growing concerns about dietary supplement industry.

The report, issued in March by the Government Accountability Office, calls on the Food and Drug Administration to expand adverse event reporting and increase its efforts to educate the public about the safety, efficacy, and labeling of these products. The GAO investigation into supplement safety was made at the request of Congress.

According to the 77-page report, the FDA should be tracking all levels of adverse events related to the use of dietary supplements and herbs, not just severe events. And, the report noted, despite the 2007 requirement for improved manufacturing practices, the FDA still lacks even the most basic ability to track the quality of dietary supplements (www.gao.gov/new.items/d09250.pdf

Companies that manufacture the products are not required to identify themselves as such, or to provide the FDA with information about the products, including the product name and ingredients, the report said. And if a product is found to be dangerous, the agency is hamstrung–it can only ask for a voluntary recall as it did in December, when Star Caps, a popular weight-loss supplement, was found to contain prescription-strength levels of the diuretic bumetanide.

The FDA lost its authority to regulate the ingredients of dietary supplements before marketing with the enactment of the Dietary Supplement Health and Education Act of 1994 (DSHEA) (www.cfsan.fda.gov/∼dms/dietsupp.html

Dietary supplements fall within the definition of complementary and alternative medicine (CAM). An earlier federal report issued by the Centers for Disease Control and Prevention found that use of CAM is widespread. For example, when patients with arthritis become frustrated by lack of pain relief, they often turn to dietary supplements.

The issue of quality control has bothered Dr. Roy Altman for years. Supplements and herbal preparations designed to promote joint health and relieve pain are some of the most popular products on the market, grabbing almost as big a market share as weight-loss products, he said in an interview. “We are looking at probably $40–$60 billion spent on over-the-counter arthritis supplements each year,” he said, but noted that “this is only a fraction of what is spent on prescribed arthritis medications.”

Some of these products probably do have a beneficial effect in patients with rheumatic disorders, said Dr. Altman, professor of rheumatology at the University of California, Los Angeles. The problem is identifying which products actually contain what the label promises, and nothing else. “We, and a group of colleagues from Canada, once tested 10 different glucosamine products sold in the U.S. Four of them didn't even have glucosamine in them, and of the remaining six, four had much less than was stated on the product label.”

Similar quality control problems led Congress to request the investigation about 18 months ago, said Lisa Shames, the GAO's director of Food Safety and Agriculture Issues. “There has been a lot of congressional interest into how FDA was implementing the requirements [for oversight of dietary supplements and herbal products], especially the requirement for reporting adverse events,” she said in an interview.

One of the paper's key findings is that adverse events are probably significantly underreported, she said. In December 2007, the FDA began requiring manufacturers of dietary supplements and herbal preparations to report all serious adverse events related to the use of their products. “Since then, FDA has had a threefold increase in the number of events reported, but the big question is whether this is all the events that are happening,” Ms. Shames said. From January through October 2008, the FDA received 948 reports of adverse events, compared with 298 over the same time frame in 2007. “FDA recently estimated that the true number of adverse events could be well over 50,000 each year. We recommended that the FDA require reporting of all adverse events, regardless of their severity.”

The report also called on the FDA to require more information from manufacturers about the ingredients in their products. “There is a real lack of information that FDA needs,” Ms. Shames said. “Herbal products are not registered by the companies that produce them, and companies are not required to tell FDA what product they sell.”

The agency should also increase its efforts to educate the public about the safety of supplements, the report concluded. “People think all these products are safe and approved by the FDA, and of course, this isn't the case,” Ms. Shames said.

The report didn't even touch on manufacturing issues, which are controlled by a set of laws that until recently left manufacturing oversight to the companies, with little government regulation. In 2007, the FDA finalized its Good Manufacturing Practice regulations, which will require quality control measures for all domestic manufacturers and foreign manufacturers that distribute in the United States. But the law is being phased in by company size, with the smallest companies having until June 2010 to come into full compliance.

Dr. Altman noted that the medical literature contains virtually no data on which brand of supplements or herbal preparations most closely resemble their labeling. Nor is country of manufacture a good guideline, Dr. Altman said.

The unreliability of labeling puts both physicians and patients in a bind, he said. “It does present a real dilemma, because even if it's a safe product, like glucosamine, and you'd like to use it, there is no way of really knowing for certain what you're getting. I try and steer my patients toward brands I have personally investigated and feel comfortable with, but there are no databases that contain this information, so people can't make informed choices.”

'I try and steer my patients toward brands I have personally investigated and feel comfortable with.' DR. ALTMAN

The FDA should be tracking all levels of adverse events related to the use of dietary supplements, the GAO report says. ©

The days when the dietary supplements industry is allowed to regulate itself may be numbered after release of a new federal report addressing growing concerns about dietary supplement industry.

The report, issued in March by the Government Accountability Office, calls on the Food and Drug Administration to expand adverse event reporting and increase its efforts to educate the public about the safety, efficacy, and labeling of these products. The GAO investigation into supplement safety was made at the request of Congress.

According to the 77-page report, the FDA should be tracking all levels of adverse events related to the use of dietary supplements and herbs, not just severe events. And, the report noted, despite the 2007 requirement for improved manufacturing practices, the FDA still lacks even the most basic ability to track the quality of dietary supplements (www.gao.gov/new.items/d09250.pdf

Companies that manufacture the products are not required to identify themselves as such, or to provide the FDA with information about the products, including the product name and ingredients, the report said. And if a product is found to be dangerous, the agency is hamstrung–it can only ask for a voluntary recall as it did in December, when Star Caps, a popular weight-loss supplement, was found to contain prescription-strength levels of the diuretic bumetanide.

The FDA lost its authority to regulate the ingredients of dietary supplements before marketing with the enactment of the Dietary Supplement Health and Education Act of 1994 (DSHEA) (www.cfsan.fda.gov/∼dms/dietsupp.html

Dietary supplements fall within the definition of complementary and alternative medicine (CAM). An earlier federal report issued by the Centers for Disease Control and Prevention found that use of CAM is widespread. For example, when patients with arthritis become frustrated by lack of pain relief, they often turn to dietary supplements.

The issue of quality control has bothered Dr. Roy Altman for years. Supplements and herbal preparations designed to promote joint health and relieve pain are some of the most popular products on the market, grabbing almost as big a market share as weight-loss products, he said in an interview. “We are looking at probably $40–$60 billion spent on over-the-counter arthritis supplements each year,” he said, but noted that “this is only a fraction of what is spent on prescribed arthritis medications.”

Some of these products probably do have a beneficial effect in patients with rheumatic disorders, said Dr. Altman, professor of rheumatology at the University of California, Los Angeles. The problem is identifying which products actually contain what the label promises, and nothing else. “We, and a group of colleagues from Canada, once tested 10 different glucosamine products sold in the U.S. Four of them didn't even have glucosamine in them, and of the remaining six, four had much less than was stated on the product label.”

Similar quality control problems led Congress to request the investigation about 18 months ago, said Lisa Shames, the GAO's director of Food Safety and Agriculture Issues. “There has been a lot of congressional interest into how FDA was implementing the requirements [for oversight of dietary supplements and herbal products], especially the requirement for reporting adverse events,” she said in an interview.

One of the paper's key findings is that adverse events are probably significantly underreported, she said. In December 2007, the FDA began requiring manufacturers of dietary supplements and herbal preparations to report all serious adverse events related to the use of their products. “Since then, FDA has had a threefold increase in the number of events reported, but the big question is whether this is all the events that are happening,” Ms. Shames said. From January through October 2008, the FDA received 948 reports of adverse events, compared with 298 over the same time frame in 2007. “FDA recently estimated that the true number of adverse events could be well over 50,000 each year. We recommended that the FDA require reporting of all adverse events, regardless of their severity.”

The report also called on the FDA to require more information from manufacturers about the ingredients in their products. “There is a real lack of information that FDA needs,” Ms. Shames said. “Herbal products are not registered by the companies that produce them, and companies are not required to tell FDA what product they sell.”

The agency should also increase its efforts to educate the public about the safety of supplements, the report concluded. “People think all these products are safe and approved by the FDA, and of course, this isn't the case,” Ms. Shames said.

The report didn't even touch on manufacturing issues, which are controlled by a set of laws that until recently left manufacturing oversight to the companies, with little government regulation. In 2007, the FDA finalized its Good Manufacturing Practice regulations, which will require quality control measures for all domestic manufacturers and foreign manufacturers that distribute in the United States. But the law is being phased in by company size, with the smallest companies having until June 2010 to come into full compliance.

Dr. Altman noted that the medical literature contains virtually no data on which brand of supplements or herbal preparations most closely resemble their labeling. Nor is country of manufacture a good guideline, Dr. Altman said.

The unreliability of labeling puts both physicians and patients in a bind, he said. “It does present a real dilemma, because even if it's a safe product, like glucosamine, and you'd like to use it, there is no way of really knowing for certain what you're getting. I try and steer my patients toward brands I have personally investigated and feel comfortable with, but there are no databases that contain this information, so people can't make informed choices.”

'I try and steer my patients toward brands I have personally investigated and feel comfortable with.' DR. ALTMAN

The FDA should be tracking all levels of adverse events related to the use of dietary supplements, the GAO report says. ©

Statins appear to cut the risk of developing Alzheimer's disease by up to 56%, even in those with the high-risk apolipoprotein E4 allele.

The link between statin use and risk reduction was consistent for lipophilic and hydrophilic agents, but absent in nonstatin cholesterol-lowering drugs, wrote Dr. M.D.M. Haag and colleagues (J. Neurol. Neurosurg. Psychiatry 2009;80:13–7).

They used data from the Rotterdam Study, a prospective population-based cohort study of age-related disorders that included 7,000 Dutch citizens who were free of dementia at baseline (1990–1993). Follow-up exams were conducted through 2004. Average follow-up was 9 years, with nearly 63,000 person-years of follow-up.

At baseline, the subjects' mean age was 69 years; 26% were known to be positive for the apolipoprotein E4 allele (ApoE4). During the follow-up period, dementias were diagnosed in 739 participants, including 582 with Alzheimer's disease, 81 with vascular dementia, and 76 with other types of dementia.

There were 30,241 filled prescriptions for cholesterol-lowering drugs during the study; 92% were for statins and 8% for nonstatins. Most of the prescribed statins were lipophilic (72%). Simvastatin was the most common (59%), followed by atorvastatin and pravastatin (both 13%).

Overall, the use of any statin was associated with a significantly decreased risk of Alzheimer's, compared with nonuse (hazard ratio, 0.57 after adjustment). Nonstatin agents were not significantly different from never-use (HR, 1.05).

Lipophilic and hydrophilic statins were equally effective in reducing the risk (HR, 0.54 each). The protective effect was seen regardless of the duration of statin use (HR, 0.44 for 2.9 years or less, 0.78 for more than 2.9 years) and remained consistent even when analysis was restricted to those 65 or older at baseline.

ApoE4 allele status did not appear to have a confounding effect on the association between statins and Alzheimer's.

The study was funded by Dutch government and university grants. The authors reported no financial conflicts.

Statins appear to cut the risk of developing Alzheimer's disease by up to 56%, even in those with the high-risk apolipoprotein E4 allele.

The link between statin use and risk reduction was consistent for lipophilic and hydrophilic agents, but absent in nonstatin cholesterol-lowering drugs, wrote Dr. M.D.M. Haag and colleagues (J. Neurol. Neurosurg. Psychiatry 2009;80:13–7).

They used data from the Rotterdam Study, a prospective population-based cohort study of age-related disorders that included 7,000 Dutch citizens who were free of dementia at baseline (1990–1993). Follow-up exams were conducted through 2004. Average follow-up was 9 years, with nearly 63,000 person-years of follow-up.

At baseline, the subjects' mean age was 69 years; 26% were known to be positive for the apolipoprotein E4 allele (ApoE4). During the follow-up period, dementias were diagnosed in 739 participants, including 582 with Alzheimer's disease, 81 with vascular dementia, and 76 with other types of dementia.

There were 30,241 filled prescriptions for cholesterol-lowering drugs during the study; 92% were for statins and 8% for nonstatins. Most of the prescribed statins were lipophilic (72%). Simvastatin was the most common (59%), followed by atorvastatin and pravastatin (both 13%).

Overall, the use of any statin was associated with a significantly decreased risk of Alzheimer's, compared with nonuse (hazard ratio, 0.57 after adjustment). Nonstatin agents were not significantly different from never-use (HR, 1.05).

Lipophilic and hydrophilic statins were equally effective in reducing the risk (HR, 0.54 each). The protective effect was seen regardless of the duration of statin use (HR, 0.44 for 2.9 years or less, 0.78 for more than 2.9 years) and remained consistent even when analysis was restricted to those 65 or older at baseline.

ApoE4 allele status did not appear to have a confounding effect on the association between statins and Alzheimer's.

The study was funded by Dutch government and university grants. The authors reported no financial conflicts.

Statins appear to cut the risk of developing Alzheimer's disease by up to 56%, even in those with the high-risk apolipoprotein E4 allele.

The link between statin use and risk reduction was consistent for lipophilic and hydrophilic agents, but absent in nonstatin cholesterol-lowering drugs, wrote Dr. M.D.M. Haag and colleagues (J. Neurol. Neurosurg. Psychiatry 2009;80:13–7).

They used data from the Rotterdam Study, a prospective population-based cohort study of age-related disorders that included 7,000 Dutch citizens who were free of dementia at baseline (1990–1993). Follow-up exams were conducted through 2004. Average follow-up was 9 years, with nearly 63,000 person-years of follow-up.

At baseline, the subjects' mean age was 69 years; 26% were known to be positive for the apolipoprotein E4 allele (ApoE4). During the follow-up period, dementias were diagnosed in 739 participants, including 582 with Alzheimer's disease, 81 with vascular dementia, and 76 with other types of dementia.

There were 30,241 filled prescriptions for cholesterol-lowering drugs during the study; 92% were for statins and 8% for nonstatins. Most of the prescribed statins were lipophilic (72%). Simvastatin was the most common (59%), followed by atorvastatin and pravastatin (both 13%).

Overall, the use of any statin was associated with a significantly decreased risk of Alzheimer's, compared with nonuse (hazard ratio, 0.57 after adjustment). Nonstatin agents were not significantly different from never-use (HR, 1.05).

Lipophilic and hydrophilic statins were equally effective in reducing the risk (HR, 0.54 each). The protective effect was seen regardless of the duration of statin use (HR, 0.44 for 2.9 years or less, 0.78 for more than 2.9 years) and remained consistent even when analysis was restricted to those 65 or older at baseline.

ApoE4 allele status did not appear to have a confounding effect on the association between statins and Alzheimer's.

The study was funded by Dutch government and university grants. The authors reported no financial conflicts.

NASHVILLE — Almost half of the patients in the intensive care unit received medications for off-label indications, with little or no supporting evidence for that use, according to a retrospective review.

Patients received a mean of six approved and five nonapproved medications. Three drug classes accounted for most of the off-label orders: endocrine/metabolic, respiratory, and gastrointestinal. The most frequently prescribed off-label drugs were regular insulin for hyperglycemia; fentanyl for analgesia in critically ill, mechanically ventilated patients; and esomeprazole for the prophylaxis of stress ulcers.

“The use of off-label medications for critically ill patients is very common, and there appears to be a correlation between how sick the patients are and how many off-label drugs they receive,” Ishaq Lat, Pharm.D., said at the annual congress of the Society of Critical Care Medicine. “We extrapolate a lot of what we do in the ICU from other areas of medical treatment, without a great deal of evidence in this patient population.”

Dr. Lat, a pharmacist at the University of Chicago Medical Center, and his colleagues, reviewed all the medication orders in 37 U.S. intensive care units during the same 24-hour period. The study captured data on 414 patients, for whom 4,535 medications were ordered. Of these, 1,805 (40%) were for an off-label use.

Most medications given off label had little evidence supporting their use, Dr. Lat said in an interview. “When the off-label medication orders were evaluated by level of evidence and strength of recommendation, 829 (46%) had grade C or no evidence, and 718 (40%) had a grade 3 or indeterminate rating.”

The analysis found an association between the increasing severity of illness and the use of off-label medications. Patients who received off-label drugs had significantly higher APACHE II (Acute Physiology and Chronic Health Evaluation II) and SOFA (Sepsis-Related Organ Failure) scores than did those who did not receive these drugs.

Off-label use varied significantly with the type of ICU, Dr. Lat noted. Cardiothoracic, surgical, trauma, and bone marrow transplant units had more off-label than on-label medication usages. Medical, coronary, and neurologic ICUs used more on-label medications, he added.

The high rate of off-label prescribing in ICUs may reflect a lack of adequate pharmaceutical research in critically ill patients, Dr. Lat said. “It's very difficult to perform drug studies on patients who are this sick, and there is not much funding available for these studies. So, we're applying what we know from other areas of medicine… without much good evidence.”

A follow-up study will explore the possible relationship between off-label prescribing in the ICU and patient outcomes, he added.

NASHVILLE — Almost half of the patients in the intensive care unit received medications for off-label indications, with little or no supporting evidence for that use, according to a retrospective review.

Patients received a mean of six approved and five nonapproved medications. Three drug classes accounted for most of the off-label orders: endocrine/metabolic, respiratory, and gastrointestinal. The most frequently prescribed off-label drugs were regular insulin for hyperglycemia; fentanyl for analgesia in critically ill, mechanically ventilated patients; and esomeprazole for the prophylaxis of stress ulcers.

“The use of off-label medications for critically ill patients is very common, and there appears to be a correlation between how sick the patients are and how many off-label drugs they receive,” Ishaq Lat, Pharm.D., said at the annual congress of the Society of Critical Care Medicine. “We extrapolate a lot of what we do in the ICU from other areas of medical treatment, without a great deal of evidence in this patient population.”

Dr. Lat, a pharmacist at the University of Chicago Medical Center, and his colleagues, reviewed all the medication orders in 37 U.S. intensive care units during the same 24-hour period. The study captured data on 414 patients, for whom 4,535 medications were ordered. Of these, 1,805 (40%) were for an off-label use.

Most medications given off label had little evidence supporting their use, Dr. Lat said in an interview. “When the off-label medication orders were evaluated by level of evidence and strength of recommendation, 829 (46%) had grade C or no evidence, and 718 (40%) had a grade 3 or indeterminate rating.”

The analysis found an association between the increasing severity of illness and the use of off-label medications. Patients who received off-label drugs had significantly higher APACHE II (Acute Physiology and Chronic Health Evaluation II) and SOFA (Sepsis-Related Organ Failure) scores than did those who did not receive these drugs.

Off-label use varied significantly with the type of ICU, Dr. Lat noted. Cardiothoracic, surgical, trauma, and bone marrow transplant units had more off-label than on-label medication usages. Medical, coronary, and neurologic ICUs used more on-label medications, he added.

The high rate of off-label prescribing in ICUs may reflect a lack of adequate pharmaceutical research in critically ill patients, Dr. Lat said. “It's very difficult to perform drug studies on patients who are this sick, and there is not much funding available for these studies. So, we're applying what we know from other areas of medicine… without much good evidence.”

A follow-up study will explore the possible relationship between off-label prescribing in the ICU and patient outcomes, he added.

NASHVILLE — Almost half of the patients in the intensive care unit received medications for off-label indications, with little or no supporting evidence for that use, according to a retrospective review.

Patients received a mean of six approved and five nonapproved medications. Three drug classes accounted for most of the off-label orders: endocrine/metabolic, respiratory, and gastrointestinal. The most frequently prescribed off-label drugs were regular insulin for hyperglycemia; fentanyl for analgesia in critically ill, mechanically ventilated patients; and esomeprazole for the prophylaxis of stress ulcers.

“The use of off-label medications for critically ill patients is very common, and there appears to be a correlation between how sick the patients are and how many off-label drugs they receive,” Ishaq Lat, Pharm.D., said at the annual congress of the Society of Critical Care Medicine. “We extrapolate a lot of what we do in the ICU from other areas of medical treatment, without a great deal of evidence in this patient population.”

Dr. Lat, a pharmacist at the University of Chicago Medical Center, and his colleagues, reviewed all the medication orders in 37 U.S. intensive care units during the same 24-hour period. The study captured data on 414 patients, for whom 4,535 medications were ordered. Of these, 1,805 (40%) were for an off-label use.

Most medications given off label had little evidence supporting their use, Dr. Lat said in an interview. “When the off-label medication orders were evaluated by level of evidence and strength of recommendation, 829 (46%) had grade C or no evidence, and 718 (40%) had a grade 3 or indeterminate rating.”

The analysis found an association between the increasing severity of illness and the use of off-label medications. Patients who received off-label drugs had significantly higher APACHE II (Acute Physiology and Chronic Health Evaluation II) and SOFA (Sepsis-Related Organ Failure) scores than did those who did not receive these drugs.

Off-label use varied significantly with the type of ICU, Dr. Lat noted. Cardiothoracic, surgical, trauma, and bone marrow transplant units had more off-label than on-label medication usages. Medical, coronary, and neurologic ICUs used more on-label medications, he added.

The high rate of off-label prescribing in ICUs may reflect a lack of adequate pharmaceutical research in critically ill patients, Dr. Lat said. “It's very difficult to perform drug studies on patients who are this sick, and there is not much funding available for these studies. So, we're applying what we know from other areas of medicine… without much good evidence.”

A follow-up study will explore the possible relationship between off-label prescribing in the ICU and patient outcomes, he added.

A genetic variant known to affect height and osteoarthritis risk has now been shown to increase the risk of nonvertebral fracture in older women, possibly because of the increased hip axis length seen in those with two copies of the gene.

“Our results suggest that the GDF5 variants target the long bones, since we find an association with hip axis length,” lead investigator Dr. Joyce van Meurs said in an interview. “This difference in hip axis length could cause a difference in fracture risk.”

Findings from the Rotterdam Study, a prospective population-based cohort of 6,114 individuals aged 55 years and over, showed that women who carried two copies of the gene were 32% more likely to experience nonvertebral fracture during the follow-up period than were noncarriers. Women with one copy of the gene had no increased risk; nor did men, regardless of their genotype, wrote Dr. van Meurs of the Erasmus Medical Centre, Rotterdam, the Netherlands, and her colleagues (Ann. Rheum. Dis. 2008 Nov. 24 [doi:10.1136/ard.2008.099655]).

The Rotterdam Study is an ongoing prospective cohort study that is examining the risks for cardiovascular, neurologic, ophthalmologic, and endocrine diseases in 15,000 subjects aged 45 years and older.

All of those in the genetic study were genotyped for rs143383. The polymorphism lies near the GDF5 gene. Mutations in this area have been linked with skeletal dysplasias, including shortening of the digits, and chondrodysplasias involving joint ankylosis.

In addition to genotyping, the subjects in the Rotterdam study underwent bone mineral density testing and radiologic assessment for osteoarthritis, and were measured for hip axis length and C-telopeptide levels. Fractures were assessed over a 10-year period.

Sixteen percent of the women and 14% of the men were homozygous carriers of rs143383; 48% of both sexes were heterozygous for the variant.

In the men there were no associations between the genotype and osteoarthritis at the hip, knee, or hand; fracture risk; or C-telopeptide levels. However, there were some significant associations among women.

Heterozygous women were 32% less likely to have osteoarthritis of the knee and hand than were noncarriers. Homozygous women were 34% less likely to have knee osteroarthritis and 48% less likely to have hand osteoarthritis than were noncarriers. Women with two copies of the gene also had significantly lower C-telopeptide levels than did noncarriers.

Among women, each copy of the gene was associated with a height increase of 0.55 cm; there was a similar, but nonsignificant, trend in men. The gene was not associated with weight or body mass index in either gender.

Nonvertebral fracture risk also was associated with rs143383 in women, but not in men. Women with two copies of the gene were 32% more likely than were noncarriers to experience a nonvertebral fracture over the follow-up period—a significant difference.

“Neither adjustment nor stratification for height and presence of osteoarthritis had an effect on the association with fracture risk,” the authors noted. “This implies that the association is not driven by any of the other observed associations, and genetic variation in the GDF5 gene seems to contribute independently to an increased fracture risk.”

The hip axis length in female homozygotes was significantly larger than that of either heterozygotes or noncarriers.

The Rotterdam Study is being funded by the European Union and national grants from the Netherlands. None of the authors declared a financial conflict with regard to the study.

A genetic variant known to affect height and osteoarthritis risk has now been shown to increase the risk of nonvertebral fracture in older women, possibly because of the increased hip axis length seen in those with two copies of the gene.

“Our results suggest that the GDF5 variants target the long bones, since we find an association with hip axis length,” lead investigator Dr. Joyce van Meurs said in an interview. “This difference in hip axis length could cause a difference in fracture risk.”

Findings from the Rotterdam Study, a prospective population-based cohort of 6,114 individuals aged 55 years and over, showed that women who carried two copies of the gene were 32% more likely to experience nonvertebral fracture during the follow-up period than were noncarriers. Women with one copy of the gene had no increased risk; nor did men, regardless of their genotype, wrote Dr. van Meurs of the Erasmus Medical Centre, Rotterdam, the Netherlands, and her colleagues (Ann. Rheum. Dis. 2008 Nov. 24 [doi:10.1136/ard.2008.099655]).

The Rotterdam Study is an ongoing prospective cohort study that is examining the risks for cardiovascular, neurologic, ophthalmologic, and endocrine diseases in 15,000 subjects aged 45 years and older.

All of those in the genetic study were genotyped for rs143383. The polymorphism lies near the GDF5 gene. Mutations in this area have been linked with skeletal dysplasias, including shortening of the digits, and chondrodysplasias involving joint ankylosis.

In addition to genotyping, the subjects in the Rotterdam study underwent bone mineral density testing and radiologic assessment for osteoarthritis, and were measured for hip axis length and C-telopeptide levels. Fractures were assessed over a 10-year period.

Sixteen percent of the women and 14% of the men were homozygous carriers of rs143383; 48% of both sexes were heterozygous for the variant.

In the men there were no associations between the genotype and osteoarthritis at the hip, knee, or hand; fracture risk; or C-telopeptide levels. However, there were some significant associations among women.

Heterozygous women were 32% less likely to have osteoarthritis of the knee and hand than were noncarriers. Homozygous women were 34% less likely to have knee osteroarthritis and 48% less likely to have hand osteoarthritis than were noncarriers. Women with two copies of the gene also had significantly lower C-telopeptide levels than did noncarriers.

Among women, each copy of the gene was associated with a height increase of 0.55 cm; there was a similar, but nonsignificant, trend in men. The gene was not associated with weight or body mass index in either gender.

Nonvertebral fracture risk also was associated with rs143383 in women, but not in men. Women with two copies of the gene were 32% more likely than were noncarriers to experience a nonvertebral fracture over the follow-up period—a significant difference.

“Neither adjustment nor stratification for height and presence of osteoarthritis had an effect on the association with fracture risk,” the authors noted. “This implies that the association is not driven by any of the other observed associations, and genetic variation in the GDF5 gene seems to contribute independently to an increased fracture risk.”

The hip axis length in female homozygotes was significantly larger than that of either heterozygotes or noncarriers.

The Rotterdam Study is being funded by the European Union and national grants from the Netherlands. None of the authors declared a financial conflict with regard to the study.

A genetic variant known to affect height and osteoarthritis risk has now been shown to increase the risk of nonvertebral fracture in older women, possibly because of the increased hip axis length seen in those with two copies of the gene.

“Our results suggest that the GDF5 variants target the long bones, since we find an association with hip axis length,” lead investigator Dr. Joyce van Meurs said in an interview. “This difference in hip axis length could cause a difference in fracture risk.”

Findings from the Rotterdam Study, a prospective population-based cohort of 6,114 individuals aged 55 years and over, showed that women who carried two copies of the gene were 32% more likely to experience nonvertebral fracture during the follow-up period than were noncarriers. Women with one copy of the gene had no increased risk; nor did men, regardless of their genotype, wrote Dr. van Meurs of the Erasmus Medical Centre, Rotterdam, the Netherlands, and her colleagues (Ann. Rheum. Dis. 2008 Nov. 24 [doi:10.1136/ard.2008.099655]).

The Rotterdam Study is an ongoing prospective cohort study that is examining the risks for cardiovascular, neurologic, ophthalmologic, and endocrine diseases in 15,000 subjects aged 45 years and older.

All of those in the genetic study were genotyped for rs143383. The polymorphism lies near the GDF5 gene. Mutations in this area have been linked with skeletal dysplasias, including shortening of the digits, and chondrodysplasias involving joint ankylosis.

In addition to genotyping, the subjects in the Rotterdam study underwent bone mineral density testing and radiologic assessment for osteoarthritis, and were measured for hip axis length and C-telopeptide levels. Fractures were assessed over a 10-year period.

Sixteen percent of the women and 14% of the men were homozygous carriers of rs143383; 48% of both sexes were heterozygous for the variant.

In the men there were no associations between the genotype and osteoarthritis at the hip, knee, or hand; fracture risk; or C-telopeptide levels. However, there were some significant associations among women.

Heterozygous women were 32% less likely to have osteoarthritis of the knee and hand than were noncarriers. Homozygous women were 34% less likely to have knee osteroarthritis and 48% less likely to have hand osteoarthritis than were noncarriers. Women with two copies of the gene also had significantly lower C-telopeptide levels than did noncarriers.

Among women, each copy of the gene was associated with a height increase of 0.55 cm; there was a similar, but nonsignificant, trend in men. The gene was not associated with weight or body mass index in either gender.

Nonvertebral fracture risk also was associated with rs143383 in women, but not in men. Women with two copies of the gene were 32% more likely than were noncarriers to experience a nonvertebral fracture over the follow-up period—a significant difference.

“Neither adjustment nor stratification for height and presence of osteoarthritis had an effect on the association with fracture risk,” the authors noted. “This implies that the association is not driven by any of the other observed associations, and genetic variation in the GDF5 gene seems to contribute independently to an increased fracture risk.”

The hip axis length in female homozygotes was significantly larger than that of either heterozygotes or noncarriers.

The Rotterdam Study is being funded by the European Union and national grants from the Netherlands. None of the authors declared a financial conflict with regard to the study.

Most patients who undergo a total ankle arthroplasty are able to resume their sports activities at presurgical levels, an observational study has found.

Of the 101 patients surveyed, 62% were active in sports before surgery and 66% after surgery; these patients participated in the same number of recreational activities at the same or at a slightly increased activity level, Dr. Florian D. Naal and his colleagues reported in the American Journal of Sports Medicine.

Dr. Naal of the Schulthess Clinic, Zurich, and his coauthors attributed the favorable outcomes to the new generation of three-component, porous-coated, mobile-bearing implants, which have renewed interest in this procedure, especially among younger patients.

The authors surveyed 101 of their patients who underwent total ankle arthroplasty from 2002 to 2005. The patients' mean age at surgery was 59 years (range, 24–87 years). The primary diagnoses were posttraumatic ankle osteoarthritis (46%), primary ankle osteoarthritis (35%), and inflammatory ankle arthritis (19%). The mean follow-up was 44 months.

Ten patients stopped their activities after surgery, while 14 who were inactive beforehand took up a sport afterward. Patients who kept playing sports engaged in the same number of sports before and after surgery (mean of three), and actually devoted somewhat more time after surgery (mean 4.7 hours vs. 4 hours). The 20% difference was not statistically significant, however (Am. J. Sports Med. 2009;37:95–102).

According to the University of California, Los Angeles, activity scale, activity levels increased significantly after surgery, rising from a score of 4 to 6. Patients who had inflammatory osteoarthritis were the least active, while those with primary ankle osteoarthritis were the most active, although this difference was not significant.

When surveyed about surgical satisfaction on a visual analog scale of 1–10, patients rated their surgery as satisfactory, with a mean score of 8. The mean pain level during sports was 3; 63% of the group was satisfied with the level of postsurgical sports activity.

The American Orthopedic Foot and Ankle Score improved significantly after surgery, from a mean of 45 to a mean of 84. Tibial radiolucencies were observed in 35% of patents, and radiolucencies around the talar component in 8%.

The authors declared they had no potential conflicts of interest relevant to the study.

Most patients who undergo a total ankle arthroplasty are able to resume their sports activities at presurgical levels, an observational study has found.

Of the 101 patients surveyed, 62% were active in sports before surgery and 66% after surgery; these patients participated in the same number of recreational activities at the same or at a slightly increased activity level, Dr. Florian D. Naal and his colleagues reported in the American Journal of Sports Medicine.

Dr. Naal of the Schulthess Clinic, Zurich, and his coauthors attributed the favorable outcomes to the new generation of three-component, porous-coated, mobile-bearing implants, which have renewed interest in this procedure, especially among younger patients.

The authors surveyed 101 of their patients who underwent total ankle arthroplasty from 2002 to 2005. The patients' mean age at surgery was 59 years (range, 24–87 years). The primary diagnoses were posttraumatic ankle osteoarthritis (46%), primary ankle osteoarthritis (35%), and inflammatory ankle arthritis (19%). The mean follow-up was 44 months.

Ten patients stopped their activities after surgery, while 14 who were inactive beforehand took up a sport afterward. Patients who kept playing sports engaged in the same number of sports before and after surgery (mean of three), and actually devoted somewhat more time after surgery (mean 4.7 hours vs. 4 hours). The 20% difference was not statistically significant, however (Am. J. Sports Med. 2009;37:95–102).

According to the University of California, Los Angeles, activity scale, activity levels increased significantly after surgery, rising from a score of 4 to 6. Patients who had inflammatory osteoarthritis were the least active, while those with primary ankle osteoarthritis were the most active, although this difference was not significant.

When surveyed about surgical satisfaction on a visual analog scale of 1–10, patients rated their surgery as satisfactory, with a mean score of 8. The mean pain level during sports was 3; 63% of the group was satisfied with the level of postsurgical sports activity.

The American Orthopedic Foot and Ankle Score improved significantly after surgery, from a mean of 45 to a mean of 84. Tibial radiolucencies were observed in 35% of patents, and radiolucencies around the talar component in 8%.

The authors declared they had no potential conflicts of interest relevant to the study.

Most patients who undergo a total ankle arthroplasty are able to resume their sports activities at presurgical levels, an observational study has found.

Of the 101 patients surveyed, 62% were active in sports before surgery and 66% after surgery; these patients participated in the same number of recreational activities at the same or at a slightly increased activity level, Dr. Florian D. Naal and his colleagues reported in the American Journal of Sports Medicine.

Dr. Naal of the Schulthess Clinic, Zurich, and his coauthors attributed the favorable outcomes to the new generation of three-component, porous-coated, mobile-bearing implants, which have renewed interest in this procedure, especially among younger patients.

The authors surveyed 101 of their patients who underwent total ankle arthroplasty from 2002 to 2005. The patients' mean age at surgery was 59 years (range, 24–87 years). The primary diagnoses were posttraumatic ankle osteoarthritis (46%), primary ankle osteoarthritis (35%), and inflammatory ankle arthritis (19%). The mean follow-up was 44 months.

Ten patients stopped their activities after surgery, while 14 who were inactive beforehand took up a sport afterward. Patients who kept playing sports engaged in the same number of sports before and after surgery (mean of three), and actually devoted somewhat more time after surgery (mean 4.7 hours vs. 4 hours). The 20% difference was not statistically significant, however (Am. J. Sports Med. 2009;37:95–102).

According to the University of California, Los Angeles, activity scale, activity levels increased significantly after surgery, rising from a score of 4 to 6. Patients who had inflammatory osteoarthritis were the least active, while those with primary ankle osteoarthritis were the most active, although this difference was not significant.

When surveyed about surgical satisfaction on a visual analog scale of 1–10, patients rated their surgery as satisfactory, with a mean score of 8. The mean pain level during sports was 3; 63% of the group was satisfied with the level of postsurgical sports activity.

The American Orthopedic Foot and Ankle Score improved significantly after surgery, from a mean of 45 to a mean of 84. Tibial radiolucencies were observed in 35% of patents, and radiolucencies around the talar component in 8%.

The authors declared they had no potential conflicts of interest relevant to the study.

NASHVILLE, TENN. — The investigational antibiotic telavancin was equally effective against both methicillin-resistant and methicillin-susceptible Staphylococcus aureus in patients with hospital-acquired pneumonia, Dr. G. Ralph Corey wrote in a poster presented at the annual congress of the Society of Critical Care Medicine.

Telavancin effected high cure rates across a range of minimum inhibitory concentrations, “suggesting that higher minimum inhibitory concentration rates or resistance to beta-lactams did not affect response to telavancin,” wrote Dr. Corey of Duke University Medical Center, Durham, N.C.

Dr. Corey and his colleagues presented a subanalysis of two phase III randomized clinical trials, Comparison of Telavancin and Vancomycin for Hospital-Acquired Pneumonia Due to Methicillin-Resistant Staphylococcus Aureus (ATTAIN) 1 and ATTAIN 2. The studies assigned 1,532 patients with hospital-acquired pneumonia to either telavancin (10 mg/kg intravenously every 24 hours) or vancomycin standard treatment for 7-21 days.

Dr. Corey's analysis focused on 243 patients in the telavancin arm who were microbiologically evaluable. The patients' mean age was 61 years, and 18% had an Acute Physiology and Chronic Health Evaluation (APACHE) II score of 20 or higher.

The researchers examined clinical cure rates at three minimum inhibitory concentration (MIC) values: 0.25 mcg/mL or less, 0.5 mcg/mL, and 1 mcg/mL. Overall, the clinical cure rate exceeded 80% in patients infected with either methicillin-resistant S. aureus (MRSA) or methicillin-susceptible S. aureus (MSSA).

For patients with MRSA, the cure rate was 82% at the lowest MIC, 91% at 0.5 mcg/mL, and 100% at the highest MIC. For patients with MSSA, the clinical cure rate was 88% at the lowest MIC and 91% at 0.5 mcg/mL. There were no data for the highest MIC.

In the clinically evaluable population from ATTAIN 1 and ATTAIN 2 combined, the clinical cure rate with telavancin treatment was 83%, compared with 81% for vancomycin.

The analysis, and the ATTAIN studies, were sponsored by Astellas Pharma Inc. and Theravance Inc. Dr. Corey was the primary investigator on both ATTAIN trials.

NASHVILLE, TENN. — The investigational antibiotic telavancin was equally effective against both methicillin-resistant and methicillin-susceptible Staphylococcus aureus in patients with hospital-acquired pneumonia, Dr. G. Ralph Corey wrote in a poster presented at the annual congress of the Society of Critical Care Medicine.

Telavancin effected high cure rates across a range of minimum inhibitory concentrations, “suggesting that higher minimum inhibitory concentration rates or resistance to beta-lactams did not affect response to telavancin,” wrote Dr. Corey of Duke University Medical Center, Durham, N.C.

Dr. Corey and his colleagues presented a subanalysis of two phase III randomized clinical trials, Comparison of Telavancin and Vancomycin for Hospital-Acquired Pneumonia Due to Methicillin-Resistant Staphylococcus Aureus (ATTAIN) 1 and ATTAIN 2. The studies assigned 1,532 patients with hospital-acquired pneumonia to either telavancin (10 mg/kg intravenously every 24 hours) or vancomycin standard treatment for 7-21 days.

Dr. Corey's analysis focused on 243 patients in the telavancin arm who were microbiologically evaluable. The patients' mean age was 61 years, and 18% had an Acute Physiology and Chronic Health Evaluation (APACHE) II score of 20 or higher.

The researchers examined clinical cure rates at three minimum inhibitory concentration (MIC) values: 0.25 mcg/mL or less, 0.5 mcg/mL, and 1 mcg/mL. Overall, the clinical cure rate exceeded 80% in patients infected with either methicillin-resistant S. aureus (MRSA) or methicillin-susceptible S. aureus (MSSA).

For patients with MRSA, the cure rate was 82% at the lowest MIC, 91% at 0.5 mcg/mL, and 100% at the highest MIC. For patients with MSSA, the clinical cure rate was 88% at the lowest MIC and 91% at 0.5 mcg/mL. There were no data for the highest MIC.

In the clinically evaluable population from ATTAIN 1 and ATTAIN 2 combined, the clinical cure rate with telavancin treatment was 83%, compared with 81% for vancomycin.

The analysis, and the ATTAIN studies, were sponsored by Astellas Pharma Inc. and Theravance Inc. Dr. Corey was the primary investigator on both ATTAIN trials.

NASHVILLE, TENN. — The investigational antibiotic telavancin was equally effective against both methicillin-resistant and methicillin-susceptible Staphylococcus aureus in patients with hospital-acquired pneumonia, Dr. G. Ralph Corey wrote in a poster presented at the annual congress of the Society of Critical Care Medicine.

Telavancin effected high cure rates across a range of minimum inhibitory concentrations, “suggesting that higher minimum inhibitory concentration rates or resistance to beta-lactams did not affect response to telavancin,” wrote Dr. Corey of Duke University Medical Center, Durham, N.C.

Dr. Corey and his colleagues presented a subanalysis of two phase III randomized clinical trials, Comparison of Telavancin and Vancomycin for Hospital-Acquired Pneumonia Due to Methicillin-Resistant Staphylococcus Aureus (ATTAIN) 1 and ATTAIN 2. The studies assigned 1,532 patients with hospital-acquired pneumonia to either telavancin (10 mg/kg intravenously every 24 hours) or vancomycin standard treatment for 7-21 days.

Dr. Corey's analysis focused on 243 patients in the telavancin arm who were microbiologically evaluable. The patients' mean age was 61 years, and 18% had an Acute Physiology and Chronic Health Evaluation (APACHE) II score of 20 or higher.

The researchers examined clinical cure rates at three minimum inhibitory concentration (MIC) values: 0.25 mcg/mL or less, 0.5 mcg/mL, and 1 mcg/mL. Overall, the clinical cure rate exceeded 80% in patients infected with either methicillin-resistant S. aureus (MRSA) or methicillin-susceptible S. aureus (MSSA).

For patients with MRSA, the cure rate was 82% at the lowest MIC, 91% at 0.5 mcg/mL, and 100% at the highest MIC. For patients with MSSA, the clinical cure rate was 88% at the lowest MIC and 91% at 0.5 mcg/mL. There were no data for the highest MIC.

In the clinically evaluable population from ATTAIN 1 and ATTAIN 2 combined, the clinical cure rate with telavancin treatment was 83%, compared with 81% for vancomycin.

The analysis, and the ATTAIN studies, were sponsored by Astellas Pharma Inc. and Theravance Inc. Dr. Corey was the primary investigator on both ATTAIN trials.

Although dermatologists are undoubtedly contributing to the rise of antibiotic-resistant bacteria, there's plenty of blame to go around, said Dr. Theodore Rosen.

Patients play their part by demanding unnecessary antibiotics and failing to comply with the proper dosing regimen. And even commercial livestock—pigs and chickens, for example—are adding to the problem.

"Swine are routinely fed low-dose antibiotics on farms, which has led to the rise of methicillin-resistant [Staphylococcus] aureus in both the pigs and the farmers who care for them," Dr. Rosen said at the at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation, in Maui.

Studies have confirmed that up to 25% of antibiotic-dosed hogs are colonized with MRSA (Vet. Microbiol. 2008; 126:383–9), and a 2007 report linked drug-resistant Escherichia coli to urinary tract infections in women who routinely consume potentially contaminated food (Foodborne Pathog. Dis. 2007;4:419–31).

"Women with resistant E. coli were about four times more likely to eat chicken or pork three or more times per week than women without the resistant strains," he said in an interview.

Patients who don't take their antibiotics properly, even appropriately prescribed antibiotics, encourage resistant bacterial strains in much the same way as the farmer who underdoses his hogs—by exposing the microbes to doses that aren't strong enough to kill, but are strong enough to lead to survival of mutated, adapted bacteria, said Dr. Rosen of Baylor College of Medicine, Houston.

As long ago as 1945, Scottish biologist and pharmacologist Alexander Fleming—who pioneered the use of penicillin—warned of this remarkable adaptive ability: "It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to a concentration not sufficient to kill them."

"Microbes have had 3.5 billion years to learn how to adapt," Dr. Rosen said. "Given sufficient time and drug use, resistance will develop; there are no antibiotics to which resistance has never developed."

Study after study has confirmed the problem and impact of patient noncompliance worldwide. Dr. Rosen cited an 11-country survey of patients who received antibiotics for an acute infection. The average noncompliance rate was 22%, ranging from 10% in the Netherlands to 44% in China (Int. J. Antimicrob. Agents 2007;29:245–53).

But physicians also play an enormous part in fostering resistance by handing out unnecessary antibiotics, dosing improperly, and failing to match the right bug with the right drug, Dr. Rosen noted. Although there are no data indicating the impact dermatologists might be having on the issue, he pointed out that, in the United States alone, dermatologists prescribe up to 9 million systemic and 4 million topical antibiotic treatments each year (Cutis 2007;79 [suppl. 6]:6–8).

"Before you prescribe, it's important to ask yourself, 'Does this patient really need antibiotics?'" he said. "Could you be looking at a viral infection or a foreign body reaction instead of a real bacterial infection?" Some infections are trivial or self-limiting, and really don't require antibiotic treatment, while others respond well to alternative therapies like incision and drainage.

"Rather than relying on broad-spectrum drugs, it's a better idea to use narrow-spectrum antibiotics whenever possible," he said. "And when in doubt, culture a specimen, identify the organism, and determine its actual antibiotic sensitivity."

SDEF and this newspaper are owned by Elsevier.

'Before you prescribe, it's important to ask yourself, "Does this patient really need antibiotics?"' DR. ROSEN

Although dermatologists are undoubtedly contributing to the rise of antibiotic-resistant bacteria, there's plenty of blame to go around, said Dr. Theodore Rosen.

Patients play their part by demanding unnecessary antibiotics and failing to comply with the proper dosing regimen. And even commercial livestock—pigs and chickens, for example—are adding to the problem.

"Swine are routinely fed low-dose antibiotics on farms, which has led to the rise of methicillin-resistant [Staphylococcus] aureus in both the pigs and the farmers who care for them," Dr. Rosen said at the at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation, in Maui.

Studies have confirmed that up to 25% of antibiotic-dosed hogs are colonized with MRSA (Vet. Microbiol. 2008; 126:383–9), and a 2007 report linked drug-resistant Escherichia coli to urinary tract infections in women who routinely consume potentially contaminated food (Foodborne Pathog. Dis. 2007;4:419–31).

"Women with resistant E. coli were about four times more likely to eat chicken or pork three or more times per week than women without the resistant strains," he said in an interview.

Patients who don't take their antibiotics properly, even appropriately prescribed antibiotics, encourage resistant bacterial strains in much the same way as the farmer who underdoses his hogs—by exposing the microbes to doses that aren't strong enough to kill, but are strong enough to lead to survival of mutated, adapted bacteria, said Dr. Rosen of Baylor College of Medicine, Houston.

As long ago as 1945, Scottish biologist and pharmacologist Alexander Fleming—who pioneered the use of penicillin—warned of this remarkable adaptive ability: "It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to a concentration not sufficient to kill them."

"Microbes have had 3.5 billion years to learn how to adapt," Dr. Rosen said. "Given sufficient time and drug use, resistance will develop; there are no antibiotics to which resistance has never developed."

Study after study has confirmed the problem and impact of patient noncompliance worldwide. Dr. Rosen cited an 11-country survey of patients who received antibiotics for an acute infection. The average noncompliance rate was 22%, ranging from 10% in the Netherlands to 44% in China (Int. J. Antimicrob. Agents 2007;29:245–53).

But physicians also play an enormous part in fostering resistance by handing out unnecessary antibiotics, dosing improperly, and failing to match the right bug with the right drug, Dr. Rosen noted. Although there are no data indicating the impact dermatologists might be having on the issue, he pointed out that, in the United States alone, dermatologists prescribe up to 9 million systemic and 4 million topical antibiotic treatments each year (Cutis 2007;79 [suppl. 6]:6–8).

"Before you prescribe, it's important to ask yourself, 'Does this patient really need antibiotics?'" he said. "Could you be looking at a viral infection or a foreign body reaction instead of a real bacterial infection?" Some infections are trivial or self-limiting, and really don't require antibiotic treatment, while others respond well to alternative therapies like incision and drainage.

"Rather than relying on broad-spectrum drugs, it's a better idea to use narrow-spectrum antibiotics whenever possible," he said. "And when in doubt, culture a specimen, identify the organism, and determine its actual antibiotic sensitivity."

SDEF and this newspaper are owned by Elsevier.

'Before you prescribe, it's important to ask yourself, "Does this patient really need antibiotics?"' DR. ROSEN

Although dermatologists are undoubtedly contributing to the rise of antibiotic-resistant bacteria, there's plenty of blame to go around, said Dr. Theodore Rosen.

Patients play their part by demanding unnecessary antibiotics and failing to comply with the proper dosing regimen. And even commercial livestock—pigs and chickens, for example—are adding to the problem.

"Swine are routinely fed low-dose antibiotics on farms, which has led to the rise of methicillin-resistant [Staphylococcus] aureus in both the pigs and the farmers who care for them," Dr. Rosen said at the at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation, in Maui.

Studies have confirmed that up to 25% of antibiotic-dosed hogs are colonized with MRSA (Vet. Microbiol. 2008; 126:383–9), and a 2007 report linked drug-resistant Escherichia coli to urinary tract infections in women who routinely consume potentially contaminated food (Foodborne Pathog. Dis. 2007;4:419–31).

"Women with resistant E. coli were about four times more likely to eat chicken or pork three or more times per week than women without the resistant strains," he said in an interview.

Patients who don't take their antibiotics properly, even appropriately prescribed antibiotics, encourage resistant bacterial strains in much the same way as the farmer who underdoses his hogs—by exposing the microbes to doses that aren't strong enough to kill, but are strong enough to lead to survival of mutated, adapted bacteria, said Dr. Rosen of Baylor College of Medicine, Houston.

As long ago as 1945, Scottish biologist and pharmacologist Alexander Fleming—who pioneered the use of penicillin—warned of this remarkable adaptive ability: "It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to a concentration not sufficient to kill them."

"Microbes have had 3.5 billion years to learn how to adapt," Dr. Rosen said. "Given sufficient time and drug use, resistance will develop; there are no antibiotics to which resistance has never developed."

Study after study has confirmed the problem and impact of patient noncompliance worldwide. Dr. Rosen cited an 11-country survey of patients who received antibiotics for an acute infection. The average noncompliance rate was 22%, ranging from 10% in the Netherlands to 44% in China (Int. J. Antimicrob. Agents 2007;29:245–53).

But physicians also play an enormous part in fostering resistance by handing out unnecessary antibiotics, dosing improperly, and failing to match the right bug with the right drug, Dr. Rosen noted. Although there are no data indicating the impact dermatologists might be having on the issue, he pointed out that, in the United States alone, dermatologists prescribe up to 9 million systemic and 4 million topical antibiotic treatments each year (Cutis 2007;79 [suppl. 6]:6–8).

"Before you prescribe, it's important to ask yourself, 'Does this patient really need antibiotics?'" he said. "Could you be looking at a viral infection or a foreign body reaction instead of a real bacterial infection?" Some infections are trivial or self-limiting, and really don't require antibiotic treatment, while others respond well to alternative therapies like incision and drainage.

"Rather than relying on broad-spectrum drugs, it's a better idea to use narrow-spectrum antibiotics whenever possible," he said. "And when in doubt, culture a specimen, identify the organism, and determine its actual antibiotic sensitivity."

SDEF and this newspaper are owned by Elsevier.

'Before you prescribe, it's important to ask yourself, "Does this patient really need antibiotics?"' DR. ROSEN

Despite massive efforts at outreach and education, many sexually transmitted diseases are on the rise throughout the United States and globally, Dr. Theodore Rosen said at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation in Maui.

Studies from 2006 to 2008 confirm that about 500 million new cases of STDs occur annually, with the United States contributing more than 20 million. While about half occur in patients younger than 25 years, age is no protection, said Dr. Rosen, professor of dermatology at the Baylor School of Medicine, Houston.

"The 'geriatric' population is increasingly at risk for STDs," Dr. Rosen said. A 2006 study that was commissioned by AARP tied the STD boom to America's high divorce rate—53% of marriages end in court. About 30% of adults aged 45–60 years are single, and while sexual activity does fall off with age, about 20% of those over the age of 50 years have sex weekly, and 50% indulge at least once a month (Clin. Geriatr. Med. 2003;19:637–55).

As fear of pregnancy diminishes with age, so does the use of condoms, putting sexually active individuals at risk. "More than 60% of the over-50 group does not use condoms," he said.

"There has been a significant rise in AIDS among patients over age 50 [years]—from 16,288 cases reported in 1990 to 114,981 in 2005," according to Dr. Rosen. Dermatologists need to remember to educate not only the young about the risk of STDs and HIV, but also older, single adults.

Herpes remains the most prevalent STD in the United States, and it's on the rise, he said. A recent World Health Organization bulletin put the country's annual new case load at 1 million, with a prevalence of 50 million (2008[doi:10.2471/07.04628

Initial visits to physicians' offices for genital herpes have risen from about 20,000 per year in 1966 to 300,000 per year in 2006, with no sign of a reversal in that trend.

Compliance with the prescribed treatment regimen is crucial to both suppressing recurrent outbreaks and to diminishing transmission, Dr. Rosen said. Acyclovir (400 mg twice daily), valacyclovir (500–1000 mg daily); and famciclovir (250 mg twice daily) are all equally effective methods to establish chronic suppression.

Genital warts have plowed a similar path through the American landscape since the 1960s, with about 70,000 cases diagnosed in 1966 and more than 450,000 in 2006, according to the National Disease and Therapeutic Index. Surgical ablation and imiquimod have similar clearance rates (80% and 70%, respectively), while the combination of both delivers a one-two punch that clears more than 90% of infections and demonstrates a lower recurrence rate.

The combination of trichloroacetic acid and imiquimod is another good option, and more cost effective than either of those treatments used alone. On average, combination therapy clears warts with just two treatments, while using either independently takes longer. Patients prefer combination therapy because it means fewer visits and it takes less time, Dr. Rosen said.

And although syphilis showed a sharp U.S. decline from 1991 to 2001, it's on the upswing again (Am. J. Pub. Health 2007;97:1076–83). "Incidence rates increased by 57% from 2001 to 2007, with 64% of new cases occurring in men who have sex with men," Dr. Rosen said.

SDEF and this newspaper are owned by Elsevier.

Despite massive efforts at outreach and education, many sexually transmitted diseases are on the rise throughout the United States and globally, Dr. Theodore Rosen said at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation in Maui.

Studies from 2006 to 2008 confirm that about 500 million new cases of STDs occur annually, with the United States contributing more than 20 million. While about half occur in patients younger than 25 years, age is no protection, said Dr. Rosen, professor of dermatology at the Baylor School of Medicine, Houston.

"The 'geriatric' population is increasingly at risk for STDs," Dr. Rosen said. A 2006 study that was commissioned by AARP tied the STD boom to America's high divorce rate—53% of marriages end in court. About 30% of adults aged 45–60 years are single, and while sexual activity does fall off with age, about 20% of those over the age of 50 years have sex weekly, and 50% indulge at least once a month (Clin. Geriatr. Med. 2003;19:637–55).

As fear of pregnancy diminishes with age, so does the use of condoms, putting sexually active individuals at risk. "More than 60% of the over-50 group does not use condoms," he said.

"There has been a significant rise in AIDS among patients over age 50 [years]—from 16,288 cases reported in 1990 to 114,981 in 2005," according to Dr. Rosen. Dermatologists need to remember to educate not only the young about the risk of STDs and HIV, but also older, single adults.

Herpes remains the most prevalent STD in the United States, and it's on the rise, he said. A recent World Health Organization bulletin put the country's annual new case load at 1 million, with a prevalence of 50 million (2008[doi:10.2471/07.04628

Initial visits to physicians' offices for genital herpes have risen from about 20,000 per year in 1966 to 300,000 per year in 2006, with no sign of a reversal in that trend.

Compliance with the prescribed treatment regimen is crucial to both suppressing recurrent outbreaks and to diminishing transmission, Dr. Rosen said. Acyclovir (400 mg twice daily), valacyclovir (500–1000 mg daily); and famciclovir (250 mg twice daily) are all equally effective methods to establish chronic suppression.

Genital warts have plowed a similar path through the American landscape since the 1960s, with about 70,000 cases diagnosed in 1966 and more than 450,000 in 2006, according to the National Disease and Therapeutic Index. Surgical ablation and imiquimod have similar clearance rates (80% and 70%, respectively), while the combination of both delivers a one-two punch that clears more than 90% of infections and demonstrates a lower recurrence rate.

The combination of trichloroacetic acid and imiquimod is another good option, and more cost effective than either of those treatments used alone. On average, combination therapy clears warts with just two treatments, while using either independently takes longer. Patients prefer combination therapy because it means fewer visits and it takes less time, Dr. Rosen said.

And although syphilis showed a sharp U.S. decline from 1991 to 2001, it's on the upswing again (Am. J. Pub. Health 2007;97:1076–83). "Incidence rates increased by 57% from 2001 to 2007, with 64% of new cases occurring in men who have sex with men," Dr. Rosen said.

SDEF and this newspaper are owned by Elsevier.

Despite massive efforts at outreach and education, many sexually transmitted diseases are on the rise throughout the United States and globally, Dr. Theodore Rosen said at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation in Maui.

Studies from 2006 to 2008 confirm that about 500 million new cases of STDs occur annually, with the United States contributing more than 20 million. While about half occur in patients younger than 25 years, age is no protection, said Dr. Rosen, professor of dermatology at the Baylor School of Medicine, Houston.

"The 'geriatric' population is increasingly at risk for STDs," Dr. Rosen said. A 2006 study that was commissioned by AARP tied the STD boom to America's high divorce rate—53% of marriages end in court. About 30% of adults aged 45–60 years are single, and while sexual activity does fall off with age, about 20% of those over the age of 50 years have sex weekly, and 50% indulge at least once a month (Clin. Geriatr. Med. 2003;19:637–55).

As fear of pregnancy diminishes with age, so does the use of condoms, putting sexually active individuals at risk. "More than 60% of the over-50 group does not use condoms," he said.

"There has been a significant rise in AIDS among patients over age 50 [years]—from 16,288 cases reported in 1990 to 114,981 in 2005," according to Dr. Rosen. Dermatologists need to remember to educate not only the young about the risk of STDs and HIV, but also older, single adults.

Herpes remains the most prevalent STD in the United States, and it's on the rise, he said. A recent World Health Organization bulletin put the country's annual new case load at 1 million, with a prevalence of 50 million (2008[doi:10.2471/07.04628

Initial visits to physicians' offices for genital herpes have risen from about 20,000 per year in 1966 to 300,000 per year in 2006, with no sign of a reversal in that trend.

Compliance with the prescribed treatment regimen is crucial to both suppressing recurrent outbreaks and to diminishing transmission, Dr. Rosen said. Acyclovir (400 mg twice daily), valacyclovir (500–1000 mg daily); and famciclovir (250 mg twice daily) are all equally effective methods to establish chronic suppression.

Genital warts have plowed a similar path through the American landscape since the 1960s, with about 70,000 cases diagnosed in 1966 and more than 450,000 in 2006, according to the National Disease and Therapeutic Index. Surgical ablation and imiquimod have similar clearance rates (80% and 70%, respectively), while the combination of both delivers a one-two punch that clears more than 90% of infections and demonstrates a lower recurrence rate.

The combination of trichloroacetic acid and imiquimod is another good option, and more cost effective than either of those treatments used alone. On average, combination therapy clears warts with just two treatments, while using either independently takes longer. Patients prefer combination therapy because it means fewer visits and it takes less time, Dr. Rosen said.

And although syphilis showed a sharp U.S. decline from 1991 to 2001, it's on the upswing again (Am. J. Pub. Health 2007;97:1076–83). "Incidence rates increased by 57% from 2001 to 2007, with 64% of new cases occurring in men who have sex with men," Dr. Rosen said.

SDEF and this newspaper are owned by Elsevier.

Bariatric surgery isn't the only way for obese patients to lose weight and keep it off.

A new observational study has found that patients can lose as much weight through intensive behavioral efforts as they can through surgical methods. Like surgical patients, nonsurgical patients can also keep most of the weight off for up to 2 years—although they have to work significantly harder in terms of diet and exercise, Dale S. Bond, Ph.D., and colleagues wrote.

The study included 315 obese patients who were enrolled in the National Weight Control Registry, a longitudinal study of patients who are successful at long-term weight-loss maintenance. Everyone enrolled in the study had lost at least 13.6 kg and had kept that weight off for at least 1 year.

For Dr. Bond's study, 105 surgical patients were matched with 210 nonsurgical patients and followed for 1 year. The patients' average age was 45 years. Before their intervention, their mean maximum body mass index was 47 kg/m

In the first year after registry entry, most of the patients in both groups (78 surgical; 173 nonsurgical) reported a weight gain, but the gain did not differ significantly between the groups (mean, 2 kg). By the end of the year, 60% of surgical patients and 70% of nonsurgical patients had maintained their weight loss within 5 kg.

There were several significant differences, however, in the dietary and physical activity behaviors between the two groups, wrote Dr. Bond of Brown University, Providence, R.I. Surgical patients reported consuming more calories from fat and fewer from carbohydrates, and eating more fast food and fewer breakfasts every week, than did their nonsurgical counterparts. Nonsurgical patients reported performing significantly more high-intensity physical activity each week than did surgical patients.

The investigators also found some between-group psychological differences. While both groups reported significant increases in depression over baseline, the increase was greater in the surgical group. Although the authors said their findings should be interpreted cautiously, “it is still concerning that 44% of surgical participants reported depressive symptoms that surpassed the minimal threshold for clinical significance, particularly in light of recent findings indicating a higher risk of suicide death in bariatric surgery patients.”

At both baseline and 1 year, surgical patients also reported lower dietary restraint than did nonsurgical patients. A separate analysis revealed that surgical patients exhibited more night eating at both baseline and 1 year. In a multivariate regression analysis, higher levels of disinhibition toward eating at baseline significantly predicted higher weight gain over 1 year.

“These findings are consistent with other studies showing that increased susceptibility to cues that trigger impulsive eating undermines weight loss and long-term weight loss maintenance,” the authors wrote.

The study was funded by the National Institutes of Health. The authors made no financial disclosures.

Bariatric surgery isn't the only way for obese patients to lose weight and keep it off.

A new observational study has found that patients can lose as much weight through intensive behavioral efforts as they can through surgical methods. Like surgical patients, nonsurgical patients can also keep most of the weight off for up to 2 years—although they have to work significantly harder in terms of diet and exercise, Dale S. Bond, Ph.D., and colleagues wrote.

The study included 315 obese patients who were enrolled in the National Weight Control Registry, a longitudinal study of patients who are successful at long-term weight-loss maintenance. Everyone enrolled in the study had lost at least 13.6 kg and had kept that weight off for at least 1 year.

For Dr. Bond's study, 105 surgical patients were matched with 210 nonsurgical patients and followed for 1 year. The patients' average age was 45 years. Before their intervention, their mean maximum body mass index was 47 kg/m

In the first year after registry entry, most of the patients in both groups (78 surgical; 173 nonsurgical) reported a weight gain, but the gain did not differ significantly between the groups (mean, 2 kg). By the end of the year, 60% of surgical patients and 70% of nonsurgical patients had maintained their weight loss within 5 kg.

There were several significant differences, however, in the dietary and physical activity behaviors between the two groups, wrote Dr. Bond of Brown University, Providence, R.I. Surgical patients reported consuming more calories from fat and fewer from carbohydrates, and eating more fast food and fewer breakfasts every week, than did their nonsurgical counterparts. Nonsurgical patients reported performing significantly more high-intensity physical activity each week than did surgical patients.

The investigators also found some between-group psychological differences. While both groups reported significant increases in depression over baseline, the increase was greater in the surgical group. Although the authors said their findings should be interpreted cautiously, “it is still concerning that 44% of surgical participants reported depressive symptoms that surpassed the minimal threshold for clinical significance, particularly in light of recent findings indicating a higher risk of suicide death in bariatric surgery patients.”

At both baseline and 1 year, surgical patients also reported lower dietary restraint than did nonsurgical patients. A separate analysis revealed that surgical patients exhibited more night eating at both baseline and 1 year. In a multivariate regression analysis, higher levels of disinhibition toward eating at baseline significantly predicted higher weight gain over 1 year.

“These findings are consistent with other studies showing that increased susceptibility to cues that trigger impulsive eating undermines weight loss and long-term weight loss maintenance,” the authors wrote.

The study was funded by the National Institutes of Health. The authors made no financial disclosures.

Bariatric surgery isn't the only way for obese patients to lose weight and keep it off.

A new observational study has found that patients can lose as much weight through intensive behavioral efforts as they can through surgical methods. Like surgical patients, nonsurgical patients can also keep most of the weight off for up to 2 years—although they have to work significantly harder in terms of diet and exercise, Dale S. Bond, Ph.D., and colleagues wrote.

The study included 315 obese patients who were enrolled in the National Weight Control Registry, a longitudinal study of patients who are successful at long-term weight-loss maintenance. Everyone enrolled in the study had lost at least 13.6 kg and had kept that weight off for at least 1 year.

For Dr. Bond's study, 105 surgical patients were matched with 210 nonsurgical patients and followed for 1 year. The patients' average age was 45 years. Before their intervention, their mean maximum body mass index was 47 kg/m

In the first year after registry entry, most of the patients in both groups (78 surgical; 173 nonsurgical) reported a weight gain, but the gain did not differ significantly between the groups (mean, 2 kg). By the end of the year, 60% of surgical patients and 70% of nonsurgical patients had maintained their weight loss within 5 kg.

There were several significant differences, however, in the dietary and physical activity behaviors between the two groups, wrote Dr. Bond of Brown University, Providence, R.I. Surgical patients reported consuming more calories from fat and fewer from carbohydrates, and eating more fast food and fewer breakfasts every week, than did their nonsurgical counterparts. Nonsurgical patients reported performing significantly more high-intensity physical activity each week than did surgical patients.

The investigators also found some between-group psychological differences. While both groups reported significant increases in depression over baseline, the increase was greater in the surgical group. Although the authors said their findings should be interpreted cautiously, “it is still concerning that 44% of surgical participants reported depressive symptoms that surpassed the minimal threshold for clinical significance, particularly in light of recent findings indicating a higher risk of suicide death in bariatric surgery patients.”

At both baseline and 1 year, surgical patients also reported lower dietary restraint than did nonsurgical patients. A separate analysis revealed that surgical patients exhibited more night eating at both baseline and 1 year. In a multivariate regression analysis, higher levels of disinhibition toward eating at baseline significantly predicted higher weight gain over 1 year.

“These findings are consistent with other studies showing that increased susceptibility to cues that trigger impulsive eating undermines weight loss and long-term weight loss maintenance,” the authors wrote.

The study was funded by the National Institutes of Health. The authors made no financial disclosures.

Two European medical societies have collaborated on the first treatment guidelines for acute knee swelling that incorporate both rheumatology and orthopedic surgery perspectives.

The European League Against Rheumatism (EULAR) and the European Federation of National Associations of Orthopedics and Traumatology (EFORT) based their 10-point guideline on an extensive literature search, Dr. Robert B.M. Landewe wrote in the Annals of the Rheumatic Diseases (doi:10.1136/ard.2008.104406).

Where data were insufficient, the joint panel relied on expert consensus, said Dr. Landewe of Maastricht (the Netherlands) University Medical Center. Both international societies will start to implement the recommendations by using them as a template for discussions with the stakeholders of the target population [including primary care providers].”

The joint task force comprised 11 rheumatologists and 12 orthopedic surgeons, who met twice under the leadership of a clinical epidemiologist and a research fellow. The treatment guidelines were aimed at both acute and recent-onset (within the past 4–6 weeks) knee swelling, which, the experts reasoned, would encompass both trauma- and disease-related pathology.

The literature search yielded 48 articles upon which the panel based its 10 recommendations.

1. A clinical examination is necessary to confirm acute knee swelling.

Acute knee swelling is a common problem, occurring in up to 54% of the population, the panel noted. However, many self-referred cases do not show an increase in the volume of the knee.

2. Timely referral is necessary when the examination yields a suspicion of septic arthritis, trauma, tumor, or inflammatory arthritis.

Suspected septic arthritis should be considered an emergency that requires an immediate expert examination. Patients with suspected trauma should also be seen immediately. Suspected bone tumors require a semiacute referral of within 1 week to an orthopedic surgeon with a speciality in bone tumors. Patients with possible inflammatory arthritis should be seen by a rheumatologist within 6 weeks.

3. A complete medical history is also an important diagnostic tool.

A careful, thorough history should be taken, noting medical comorbidities, medication, malignancy, hemorrhage, and the speed of pain onset. Fever is also an important clue to the possible nature of knee swelling.

4. The physical exam should focus on the affected knee but include the unaffected knee as well as an assessment of other joints.

Joint assessment should include the localization and characteristics of the swelling, the presence of any effusion, joint stability, pain, skin temperature, and appearance. A general physical exam is valuable only if the joint pathology may be part of a systemic illness.

5. Lab tests are advisable in patients with nontraumatic knee swelling.

These may include white blood cell count and acute phase reactants to help exclude septic arthritis. A baseline C-reactive protein level may be useful in patients with suspected inflammatory arthritis. For suspected gout, serum uric acid measurements are indicated.

6. Patients with suspected septic, crystal, or inflammatory arthritis should undergo joint fluid aspiration.

Joint fluid should be examined for leukocytes, crystals, and bacteria. In cases of trauma-related effusion, the panel was split on the usefulness of hemarthros aspiration. “Evacuation … was considered only helpful in cases with major effusion and no acutely scheduled surgical intervention.” The panel agreed that aspiration is contraindicated in cases of suspected tumor, because of the possibility of seeding malignant cells.

7. A plain x-ray in two planes is enough to identify trauma or erosive changes, cartilage calcification, or cartilage thinning. An ultrasound may be helpful in detecting joint effusion and synovial hypertrophy.

Most studies indicate that ultrasound performs just as well, and that MRI could lead to an overestimation of pathology.

8. Diagnostic arthroscopy is indicated only in exceptional cases.

The data do not support the routine use of this procedure in patients with acute knee swelling, unless there is high suspicion of an intra-articular infection, such as by Mycobacterium tuberculosis or yeasts. “In light of the invasiveness of the procedure and the risk of complications, the expert committee felt unanimously that arthroscopy for diagnostic purposes solely cannot be justified and should therefore be abandoned.”

9. Specific therapies can't begin until an appropriate diagnosis is made.

But because making a firm diagnosis may take some time, general measures can be employed to relieve pain and other symptoms.

10. Noninterventionist therapies, like cold packs, splints, and simple analgesics or nonsteroidal anti-inflammatory drugs, can be used to ease symptoms.

A plan radiograph is enough to identify trauma or erosive changes, cartilage calcification or thinning. ©American College of Rheumatology Clinical Slide Collection, 1972–2004

Two European medical societies have collaborated on the first treatment guidelines for acute knee swelling that incorporate both rheumatology and orthopedic surgery perspectives.

The European League Against Rheumatism (EULAR) and the European Federation of National Associations of Orthopedics and Traumatology (EFORT) based their 10-point guideline on an extensive literature search, Dr. Robert B.M. Landewe wrote in the Annals of the Rheumatic Diseases (doi:10.1136/ard.2008.104406).

Where data were insufficient, the joint panel relied on expert consensus, said Dr. Landewe of Maastricht (the Netherlands) University Medical Center. Both international societies will start to implement the recommendations by using them as a template for discussions with the stakeholders of the target population [including primary care providers].”

The joint task force comprised 11 rheumatologists and 12 orthopedic surgeons, who met twice under the leadership of a clinical epidemiologist and a research fellow. The treatment guidelines were aimed at both acute and recent-onset (within the past 4–6 weeks) knee swelling, which, the experts reasoned, would encompass both trauma- and disease-related pathology.

The literature search yielded 48 articles upon which the panel based its 10 recommendations.

1. A clinical examination is necessary to confirm acute knee swelling.

Acute knee swelling is a common problem, occurring in up to 54% of the population, the panel noted. However, many self-referred cases do not show an increase in the volume of the knee.

2. Timely referral is necessary when the examination yields a suspicion of septic arthritis, trauma, tumor, or inflammatory arthritis.

Suspected septic arthritis should be considered an emergency that requires an immediate expert examination. Patients with suspected trauma should also be seen immediately. Suspected bone tumors require a semiacute referral of within 1 week to an orthopedic surgeon with a speciality in bone tumors. Patients with possible inflammatory arthritis should be seen by a rheumatologist within 6 weeks.

3. A complete medical history is also an important diagnostic tool.

A careful, thorough history should be taken, noting medical comorbidities, medication, malignancy, hemorrhage, and the speed of pain onset. Fever is also an important clue to the possible nature of knee swelling.

4. The physical exam should focus on the affected knee but include the unaffected knee as well as an assessment of other joints.

Joint assessment should include the localization and characteristics of the swelling, the presence of any effusion, joint stability, pain, skin temperature, and appearance. A general physical exam is valuable only if the joint pathology may be part of a systemic illness.

5. Lab tests are advisable in patients with nontraumatic knee swelling.

These may include white blood cell count and acute phase reactants to help exclude septic arthritis. A baseline C-reactive protein level may be useful in patients with suspected inflammatory arthritis. For suspected gout, serum uric acid measurements are indicated.

6. Patients with suspected septic, crystal, or inflammatory arthritis should undergo joint fluid aspiration.

Joint fluid should be examined for leukocytes, crystals, and bacteria. In cases of trauma-related effusion, the panel was split on the usefulness of hemarthros aspiration. “Evacuation … was considered only helpful in cases with major effusion and no acutely scheduled surgical intervention.” The panel agreed that aspiration is contraindicated in cases of suspected tumor, because of the possibility of seeding malignant cells.

7. A plain x-ray in two planes is enough to identify trauma or erosive changes, cartilage calcification, or cartilage thinning. An ultrasound may be helpful in detecting joint effusion and synovial hypertrophy.

Most studies indicate that ultrasound performs just as well, and that MRI could lead to an overestimation of pathology.

8. Diagnostic arthroscopy is indicated only in exceptional cases.

The data do not support the routine use of this procedure in patients with acute knee swelling, unless there is high suspicion of an intra-articular infection, such as by Mycobacterium tuberculosis or yeasts. “In light of the invasiveness of the procedure and the risk of complications, the expert committee felt unanimously that arthroscopy for diagnostic purposes solely cannot be justified and should therefore be abandoned.”

9. Specific therapies can't begin until an appropriate diagnosis is made.

But because making a firm diagnosis may take some time, general measures can be employed to relieve pain and other symptoms.

10. Noninterventionist therapies, like cold packs, splints, and simple analgesics or nonsteroidal anti-inflammatory drugs, can be used to ease symptoms.

A plan radiograph is enough to identify trauma or erosive changes, cartilage calcification or thinning. ©American College of Rheumatology Clinical Slide Collection, 1972–2004

Two European medical societies have collaborated on the first treatment guidelines for acute knee swelling that incorporate both rheumatology and orthopedic surgery perspectives.

The European League Against Rheumatism (EULAR) and the European Federation of National Associations of Orthopedics and Traumatology (EFORT) based their 10-point guideline on an extensive literature search, Dr. Robert B.M. Landewe wrote in the Annals of the Rheumatic Diseases (doi:10.1136/ard.2008.104406).

Where data were insufficient, the joint panel relied on expert consensus, said Dr. Landewe of Maastricht (the Netherlands) University Medical Center. Both international societies will start to implement the recommendations by using them as a template for discussions with the stakeholders of the target population [including primary care providers].”

The joint task force comprised 11 rheumatologists and 12 orthopedic surgeons, who met twice under the leadership of a clinical epidemiologist and a research fellow. The treatment guidelines were aimed at both acute and recent-onset (within the past 4–6 weeks) knee swelling, which, the experts reasoned, would encompass both trauma- and disease-related pathology.

The literature search yielded 48 articles upon which the panel based its 10 recommendations.

1. A clinical examination is necessary to confirm acute knee swelling.

Acute knee swelling is a common problem, occurring in up to 54% of the population, the panel noted. However, many self-referred cases do not show an increase in the volume of the knee.

2. Timely referral is necessary when the examination yields a suspicion of septic arthritis, trauma, tumor, or inflammatory arthritis.

Suspected septic arthritis should be considered an emergency that requires an immediate expert examination. Patients with suspected trauma should also be seen immediately. Suspected bone tumors require a semiacute referral of within 1 week to an orthopedic surgeon with a speciality in bone tumors. Patients with possible inflammatory arthritis should be seen by a rheumatologist within 6 weeks.

3. A complete medical history is also an important diagnostic tool.

A careful, thorough history should be taken, noting medical comorbidities, medication, malignancy, hemorrhage, and the speed of pain onset. Fever is also an important clue to the possible nature of knee swelling.

4. The physical exam should focus on the affected knee but include the unaffected knee as well as an assessment of other joints.

Joint assessment should include the localization and characteristics of the swelling, the presence of any effusion, joint stability, pain, skin temperature, and appearance. A general physical exam is valuable only if the joint pathology may be part of a systemic illness.

5. Lab tests are advisable in patients with nontraumatic knee swelling.

These may include white blood cell count and acute phase reactants to help exclude septic arthritis. A baseline C-reactive protein level may be useful in patients with suspected inflammatory arthritis. For suspected gout, serum uric acid measurements are indicated.

6. Patients with suspected septic, crystal, or inflammatory arthritis should undergo joint fluid aspiration.

Joint fluid should be examined for leukocytes, crystals, and bacteria. In cases of trauma-related effusion, the panel was split on the usefulness of hemarthros aspiration. “Evacuation … was considered only helpful in cases with major effusion and no acutely scheduled surgical intervention.” The panel agreed that aspiration is contraindicated in cases of suspected tumor, because of the possibility of seeding malignant cells.

7. A plain x-ray in two planes is enough to identify trauma or erosive changes, cartilage calcification, or cartilage thinning. An ultrasound may be helpful in detecting joint effusion and synovial hypertrophy.

Most studies indicate that ultrasound performs just as well, and that MRI could lead to an overestimation of pathology.

8. Diagnostic arthroscopy is indicated only in exceptional cases.

The data do not support the routine use of this procedure in patients with acute knee swelling, unless there is high suspicion of an intra-articular infection, such as by Mycobacterium tuberculosis or yeasts. “In light of the invasiveness of the procedure and the risk of complications, the expert committee felt unanimously that arthroscopy for diagnostic purposes solely cannot be justified and should therefore be abandoned.”

9. Specific therapies can't begin until an appropriate diagnosis is made.

But because making a firm diagnosis may take some time, general measures can be employed to relieve pain and other symptoms.

10. Noninterventionist therapies, like cold packs, splints, and simple analgesics or nonsteroidal anti-inflammatory drugs, can be used to ease symptoms.

A plan radiograph is enough to identify trauma or erosive changes, cartilage calcification or thinning. ©American College of Rheumatology Clinical Slide Collection, 1972–2004