Diana Mahoney

BOSTON – The recent identification of two gene mutations in a cohort of African Americans with nondiabetic kidney disease helps explain the disproportionately higher rates of kidney disease in this population and represents a disease-mechanism pathway that could lead to new treatments and possibly a cure, Dr. David J. Friedman said at the annual meeting of the International Society on Hypertension in Blacks.

Dr. Friedman of Beth-Israel Deaconess Medical Center, Boston, and his colleagues recently reported the association between two independent variants in the apolipoprotein L1 (APOL1) gene on chromosome 22 and focal segmental glomerulosclerosis (FSGS) and hypertension-attributed end-stage kidney disease in blacks (Science 2010;329:841-5). Not only do the investigators believe that APOL1 is very important to the understanding of nondiabetic renal disease in blacks, "we think the variants in the gene are among the most powerful that have been discovered to date," Dr. Friedman stressed.

The disparity between the rates of end-stage renal disease (ESRD) in blacks and whites in the United States is "incredible," Dr. Friedman stated, noting that the incidence rate is four to five times higher in blacks, according to the 2010 United States Renal Data System annual report. "People have been debating for decades whether the major cause of this disparity is genes or environment. No doubt both are important, but given how strongly this phenotype travels in families, I think we can say with certainty that genes play an important role."

The APOL1 discovery came on the heels of an earlier association linking FSGS, nondiabetic ESRD, and HIV nephropathy in blacks with the MYH9 gene located on the same chromosome, Dr. Friedman explained. "This was quite striking, because we used to think of the three conditions as entirely different diseases, yet each one had exactly the same locus."

Despite the strong association and several years spent looking for causal mutations using fine mapping sequences, the causal variants remained elusive until Dr. Friedman and his colleagues approached the problem from a different perspective.

"We asked, ‘How could any disease gene that’s this deleterious become so common in a population?’ We assumed there was something in this [genetic region] that was beneficial once upon a time to human evolution in Africa," he said. Using mathematical techniques, "we realized that because of the effects of natural selection, the disease gene interval was much larger than anyone thought and probably contained at least five genes." Consequently, the investigators tested new variants in other genes for association with renal disease in African Americans, looking specifically for variants that had not yet been documented, he said.

In a cohort of 205 African Americans with biopsy-proven FSGS and no family history of the disease and 180 African American control subjects, "we saw that variants in the neighboring APOL1 gene were much more strongly associated with renal disease, and unlike the MYH9 variants, which were located in regions of the gene that did not encode for protein, the APOL1 variants were protein-coding sequences."

The investigators determined that the top two variants almost always co-occurred on the same chromosome and each changed an amino acid somewhere on the protein. "We called this the g1 risk allele, and when we controlled for it, a new variant popped up, which we called the g2 allele," he said. Controlling for both the g1 and g2 alleles, "the entire association of this region disappeared and there was no signal left for MYH9."

The investigators also tested the genetic variants in hypertension-associated ESRD in a larger cohort of 1,030 African Americans with the disease and 1,025 geographically matched control subjects and found that the same two variants had a tremendous impact on the development of the disease.

"When combined together, the P value was on the order of 10 to the minus 60, or 35 orders of magnitude greater than the very best MYH9 [result]," Dr. Friedman said. Surprisingly, he noted, we found that these disease variants follow a recessive pattern and together the odds ratio was on the order of 7-10, while the very largest effect sizes of the common variants that affect hypertension or diabetes will confer odds ratios of about 1.4-1.5."

The APOL1 gene and these variants "tend to fall into a different category that we’ve all been familiar with in the past," Dr. Friedman explained. "Most disease variants are either very rare with powerful effects or common with relatively modest effects. The APOL1 variants have a surprising combination of effect size and frequency such that 50%-60% of African Americans carry g1 and/or g2 risk alleles, and 50% are risk homozygous, meaning they are in the highest risk for kidney disease: That translates into about 3.5 million individuals."

Further, while the odds ratios for the more common forms of nondiabetic kidney disease in this population range from 7 to 10, "we’re starting to see odds ratios in the range of 30 for diseases like HIV nephropathy."

Comparing Kidney Disease Rates Between Races

To determine how much of nondiabetic kidney disease can be explained by the genetic variants, the investigators reviewed data from the prospective population-based Dallas Heart Study and compared the outcomes of European American and Caucasian patients, in whom the renal risk alleles are essentially nonexistent, with those of African Americans with zero or one risk allele and those with both risk alleles. Looking at urine protein levels, an indicator of renal microvascular disease, "we found that black individuals with zero or one copy of the risk allele had rates more similar to whites than to blacks with two alleles," Dr. Friedman reported.

The results were even more striking for actual hard measures of renal function, he said. "Rates of chronic kidney disease or impaired renal function, indicated by glomerular filtration rates less than 60 mL/min per 1.73 m2, were essentially the same among blacks with zero or one allele and whites, whereas individuals with a risk genotype had a fourfold increase in impaired renal function." Although the study does not include many individuals with ESRD, the investigators hope to look more closely into such patients in future studies, he said.

In their preliminary review of the data, "we can’t tell any difference between African Americans with zero or one copy of the allele and Caucasians, but African Americans with two renal risk alleles have at least 10-fold increase in kidney failure," Dr. Friedman stated. "To our surprise, this really only applies to nondiabetic kidney disease. The alleles have essentially no effect that we can detect on diabetic renal disease."

This realization led the investigators to revisit the issue of natural selection. It turns out, according to Dr. Friedman, "APOL1 is the genetic source for the immunity factor that protected people from African sleeping sickness, a parasitic infection caused by Trypanosoma brucei gambiense." Similar to selection for the gene variants associated with sickle cell anemia, he explained, "inheriting one copy of the APOL1 gene risk variant provides protection from the parasite, while two copies seems to render individuals increases the risk of kidney disease up to 10-fold." Through natural selection, as more people survived African sleeping sickness, the percentage of the population with kidney disease risk variants increased, he said.

The investigators are currently studying the risk variants intensively to figure out how they work. "We think they may differentially regulate processes such as apoptosis and cell repair may function as a chloride channel in mammalian systems in the same way it doses in lysosomes and may affect biological function," Dr. Friedman hypothesized.

In addition to exploring the underlying mechanisms, the potential clinical value of the genetic discovery is also being considered. "This may help us improve risk stratification," Dr. Friedman said. "It’s one thing to say that African Americans have a fourfold increased risk of kidney disease. It’s better to find the tag SNP [single nucleotide polymorphism] that will tell if an individual might have an increased risk. If you can actually find the causal variant, then you can potentially predict with much higher success who is and is not at risk for kidney failure," he stated. "The problem is that it works pretty well in Western African populations, such as Nigerians, but not as well in East Africans, such as Ethiopians."

One of the main questions that Dr. Friedman and his colleagues currently are pursuing is whether hypertension causes kidney disease in these at-risk individuals or whether hypertension is the result of primary renal vascular disease.

"To us, the fact that the very same genetic variants cause hypertension-associated ESRD and FSGS, a primary renal microvascular disease, suggests that these may be the same disease process that we are either catching at different stages or that have different modifiers, and that hypertension in these patients may just be a symptom and not a cause of kidney failure," Dr. Friedman said. Additionally, the investigators are trying to determine why only some people with two risk alleles develop kidney disease and why APOL1 risk variants have little to no effect on diabetic nephropathy, which may offer some clues to how the molecules work, he said.

A cure for nondiabetic kidney disease, which accounts for more than $8.2 billion annually in dialysis coasts, may directly result from the APOL1 finding, Dr. Friedman said. "It’s that important."

Dr. Friedman reported no financial conflicts of interested related to his presentation.

BOSTON – The recent identification of two gene mutations in a cohort of African Americans with nondiabetic kidney disease helps explain the disproportionately higher rates of kidney disease in this population and represents a disease-mechanism pathway that could lead to new treatments and possibly a cure, Dr. David J. Friedman said at the annual meeting of the International Society on Hypertension in Blacks.

Dr. Friedman of Beth-Israel Deaconess Medical Center, Boston, and his colleagues recently reported the association between two independent variants in the apolipoprotein L1 (APOL1) gene on chromosome 22 and focal segmental glomerulosclerosis (FSGS) and hypertension-attributed end-stage kidney disease in blacks (Science 2010;329:841-5). Not only do the investigators believe that APOL1 is very important to the understanding of nondiabetic renal disease in blacks, "we think the variants in the gene are among the most powerful that have been discovered to date," Dr. Friedman stressed.

The disparity between the rates of end-stage renal disease (ESRD) in blacks and whites in the United States is "incredible," Dr. Friedman stated, noting that the incidence rate is four to five times higher in blacks, according to the 2010 United States Renal Data System annual report. "People have been debating for decades whether the major cause of this disparity is genes or environment. No doubt both are important, but given how strongly this phenotype travels in families, I think we can say with certainty that genes play an important role."

The APOL1 discovery came on the heels of an earlier association linking FSGS, nondiabetic ESRD, and HIV nephropathy in blacks with the MYH9 gene located on the same chromosome, Dr. Friedman explained. "This was quite striking, because we used to think of the three conditions as entirely different diseases, yet each one had exactly the same locus."

Despite the strong association and several years spent looking for causal mutations using fine mapping sequences, the causal variants remained elusive until Dr. Friedman and his colleagues approached the problem from a different perspective.

"We asked, ‘How could any disease gene that’s this deleterious become so common in a population?’ We assumed there was something in this [genetic region] that was beneficial once upon a time to human evolution in Africa," he said. Using mathematical techniques, "we realized that because of the effects of natural selection, the disease gene interval was much larger than anyone thought and probably contained at least five genes." Consequently, the investigators tested new variants in other genes for association with renal disease in African Americans, looking specifically for variants that had not yet been documented, he said.

In a cohort of 205 African Americans with biopsy-proven FSGS and no family history of the disease and 180 African American control subjects, "we saw that variants in the neighboring APOL1 gene were much more strongly associated with renal disease, and unlike the MYH9 variants, which were located in regions of the gene that did not encode for protein, the APOL1 variants were protein-coding sequences."

The investigators determined that the top two variants almost always co-occurred on the same chromosome and each changed an amino acid somewhere on the protein. "We called this the g1 risk allele, and when we controlled for it, a new variant popped up, which we called the g2 allele," he said. Controlling for both the g1 and g2 alleles, "the entire association of this region disappeared and there was no signal left for MYH9."

The investigators also tested the genetic variants in hypertension-associated ESRD in a larger cohort of 1,030 African Americans with the disease and 1,025 geographically matched control subjects and found that the same two variants had a tremendous impact on the development of the disease.

"When combined together, the P value was on the order of 10 to the minus 60, or 35 orders of magnitude greater than the very best MYH9 [result]," Dr. Friedman said. Surprisingly, he noted, we found that these disease variants follow a recessive pattern and together the odds ratio was on the order of 7-10, while the very largest effect sizes of the common variants that affect hypertension or diabetes will confer odds ratios of about 1.4-1.5."

The APOL1 gene and these variants "tend to fall into a different category that we’ve all been familiar with in the past," Dr. Friedman explained. "Most disease variants are either very rare with powerful effects or common with relatively modest effects. The APOL1 variants have a surprising combination of effect size and frequency such that 50%-60% of African Americans carry g1 and/or g2 risk alleles, and 50% are risk homozygous, meaning they are in the highest risk for kidney disease: That translates into about 3.5 million individuals."

Further, while the odds ratios for the more common forms of nondiabetic kidney disease in this population range from 7 to 10, "we’re starting to see odds ratios in the range of 30 for diseases like HIV nephropathy."

Comparing Kidney Disease Rates Between Races

To determine how much of nondiabetic kidney disease can be explained by the genetic variants, the investigators reviewed data from the prospective population-based Dallas Heart Study and compared the outcomes of European American and Caucasian patients, in whom the renal risk alleles are essentially nonexistent, with those of African Americans with zero or one risk allele and those with both risk alleles. Looking at urine protein levels, an indicator of renal microvascular disease, "we found that black individuals with zero or one copy of the risk allele had rates more similar to whites than to blacks with two alleles," Dr. Friedman reported.

The results were even more striking for actual hard measures of renal function, he said. "Rates of chronic kidney disease or impaired renal function, indicated by glomerular filtration rates less than 60 mL/min per 1.73 m2, were essentially the same among blacks with zero or one allele and whites, whereas individuals with a risk genotype had a fourfold increase in impaired renal function." Although the study does not include many individuals with ESRD, the investigators hope to look more closely into such patients in future studies, he said.

In their preliminary review of the data, "we can’t tell any difference between African Americans with zero or one copy of the allele and Caucasians, but African Americans with two renal risk alleles have at least 10-fold increase in kidney failure," Dr. Friedman stated. "To our surprise, this really only applies to nondiabetic kidney disease. The alleles have essentially no effect that we can detect on diabetic renal disease."

This realization led the investigators to revisit the issue of natural selection. It turns out, according to Dr. Friedman, "APOL1 is the genetic source for the immunity factor that protected people from African sleeping sickness, a parasitic infection caused by Trypanosoma brucei gambiense." Similar to selection for the gene variants associated with sickle cell anemia, he explained, "inheriting one copy of the APOL1 gene risk variant provides protection from the parasite, while two copies seems to render individuals increases the risk of kidney disease up to 10-fold." Through natural selection, as more people survived African sleeping sickness, the percentage of the population with kidney disease risk variants increased, he said.

The investigators are currently studying the risk variants intensively to figure out how they work. "We think they may differentially regulate processes such as apoptosis and cell repair may function as a chloride channel in mammalian systems in the same way it doses in lysosomes and may affect biological function," Dr. Friedman hypothesized.

In addition to exploring the underlying mechanisms, the potential clinical value of the genetic discovery is also being considered. "This may help us improve risk stratification," Dr. Friedman said. "It’s one thing to say that African Americans have a fourfold increased risk of kidney disease. It’s better to find the tag SNP [single nucleotide polymorphism] that will tell if an individual might have an increased risk. If you can actually find the causal variant, then you can potentially predict with much higher success who is and is not at risk for kidney failure," he stated. "The problem is that it works pretty well in Western African populations, such as Nigerians, but not as well in East Africans, such as Ethiopians."

One of the main questions that Dr. Friedman and his colleagues currently are pursuing is whether hypertension causes kidney disease in these at-risk individuals or whether hypertension is the result of primary renal vascular disease.

"To us, the fact that the very same genetic variants cause hypertension-associated ESRD and FSGS, a primary renal microvascular disease, suggests that these may be the same disease process that we are either catching at different stages or that have different modifiers, and that hypertension in these patients may just be a symptom and not a cause of kidney failure," Dr. Friedman said. Additionally, the investigators are trying to determine why only some people with two risk alleles develop kidney disease and why APOL1 risk variants have little to no effect on diabetic nephropathy, which may offer some clues to how the molecules work, he said.

A cure for nondiabetic kidney disease, which accounts for more than $8.2 billion annually in dialysis coasts, may directly result from the APOL1 finding, Dr. Friedman said. "It’s that important."

Dr. Friedman reported no financial conflicts of interested related to his presentation.

BOSTON – The recent identification of two gene mutations in a cohort of African Americans with nondiabetic kidney disease helps explain the disproportionately higher rates of kidney disease in this population and represents a disease-mechanism pathway that could lead to new treatments and possibly a cure, Dr. David J. Friedman said at the annual meeting of the International Society on Hypertension in Blacks.

Dr. Friedman of Beth-Israel Deaconess Medical Center, Boston, and his colleagues recently reported the association between two independent variants in the apolipoprotein L1 (APOL1) gene on chromosome 22 and focal segmental glomerulosclerosis (FSGS) and hypertension-attributed end-stage kidney disease in blacks (Science 2010;329:841-5). Not only do the investigators believe that APOL1 is very important to the understanding of nondiabetic renal disease in blacks, "we think the variants in the gene are among the most powerful that have been discovered to date," Dr. Friedman stressed.

The disparity between the rates of end-stage renal disease (ESRD) in blacks and whites in the United States is "incredible," Dr. Friedman stated, noting that the incidence rate is four to five times higher in blacks, according to the 2010 United States Renal Data System annual report. "People have been debating for decades whether the major cause of this disparity is genes or environment. No doubt both are important, but given how strongly this phenotype travels in families, I think we can say with certainty that genes play an important role."

The APOL1 discovery came on the heels of an earlier association linking FSGS, nondiabetic ESRD, and HIV nephropathy in blacks with the MYH9 gene located on the same chromosome, Dr. Friedman explained. "This was quite striking, because we used to think of the three conditions as entirely different diseases, yet each one had exactly the same locus."

Despite the strong association and several years spent looking for causal mutations using fine mapping sequences, the causal variants remained elusive until Dr. Friedman and his colleagues approached the problem from a different perspective.

"We asked, ‘How could any disease gene that’s this deleterious become so common in a population?’ We assumed there was something in this [genetic region] that was beneficial once upon a time to human evolution in Africa," he said. Using mathematical techniques, "we realized that because of the effects of natural selection, the disease gene interval was much larger than anyone thought and probably contained at least five genes." Consequently, the investigators tested new variants in other genes for association with renal disease in African Americans, looking specifically for variants that had not yet been documented, he said.

In a cohort of 205 African Americans with biopsy-proven FSGS and no family history of the disease and 180 African American control subjects, "we saw that variants in the neighboring APOL1 gene were much more strongly associated with renal disease, and unlike the MYH9 variants, which were located in regions of the gene that did not encode for protein, the APOL1 variants were protein-coding sequences."

The investigators determined that the top two variants almost always co-occurred on the same chromosome and each changed an amino acid somewhere on the protein. "We called this the g1 risk allele, and when we controlled for it, a new variant popped up, which we called the g2 allele," he said. Controlling for both the g1 and g2 alleles, "the entire association of this region disappeared and there was no signal left for MYH9."

The investigators also tested the genetic variants in hypertension-associated ESRD in a larger cohort of 1,030 African Americans with the disease and 1,025 geographically matched control subjects and found that the same two variants had a tremendous impact on the development of the disease.

"When combined together, the P value was on the order of 10 to the minus 60, or 35 orders of magnitude greater than the very best MYH9 [result]," Dr. Friedman said. Surprisingly, he noted, we found that these disease variants follow a recessive pattern and together the odds ratio was on the order of 7-10, while the very largest effect sizes of the common variants that affect hypertension or diabetes will confer odds ratios of about 1.4-1.5."

The APOL1 gene and these variants "tend to fall into a different category that we’ve all been familiar with in the past," Dr. Friedman explained. "Most disease variants are either very rare with powerful effects or common with relatively modest effects. The APOL1 variants have a surprising combination of effect size and frequency such that 50%-60% of African Americans carry g1 and/or g2 risk alleles, and 50% are risk homozygous, meaning they are in the highest risk for kidney disease: That translates into about 3.5 million individuals."

Further, while the odds ratios for the more common forms of nondiabetic kidney disease in this population range from 7 to 10, "we’re starting to see odds ratios in the range of 30 for diseases like HIV nephropathy."

Comparing Kidney Disease Rates Between Races

To determine how much of nondiabetic kidney disease can be explained by the genetic variants, the investigators reviewed data from the prospective population-based Dallas Heart Study and compared the outcomes of European American and Caucasian patients, in whom the renal risk alleles are essentially nonexistent, with those of African Americans with zero or one risk allele and those with both risk alleles. Looking at urine protein levels, an indicator of renal microvascular disease, "we found that black individuals with zero or one copy of the risk allele had rates more similar to whites than to blacks with two alleles," Dr. Friedman reported.

The results were even more striking for actual hard measures of renal function, he said. "Rates of chronic kidney disease or impaired renal function, indicated by glomerular filtration rates less than 60 mL/min per 1.73 m2, were essentially the same among blacks with zero or one allele and whites, whereas individuals with a risk genotype had a fourfold increase in impaired renal function." Although the study does not include many individuals with ESRD, the investigators hope to look more closely into such patients in future studies, he said.

In their preliminary review of the data, "we can’t tell any difference between African Americans with zero or one copy of the allele and Caucasians, but African Americans with two renal risk alleles have at least 10-fold increase in kidney failure," Dr. Friedman stated. "To our surprise, this really only applies to nondiabetic kidney disease. The alleles have essentially no effect that we can detect on diabetic renal disease."

This realization led the investigators to revisit the issue of natural selection. It turns out, according to Dr. Friedman, "APOL1 is the genetic source for the immunity factor that protected people from African sleeping sickness, a parasitic infection caused by Trypanosoma brucei gambiense." Similar to selection for the gene variants associated with sickle cell anemia, he explained, "inheriting one copy of the APOL1 gene risk variant provides protection from the parasite, while two copies seems to render individuals increases the risk of kidney disease up to 10-fold." Through natural selection, as more people survived African sleeping sickness, the percentage of the population with kidney disease risk variants increased, he said.

The investigators are currently studying the risk variants intensively to figure out how they work. "We think they may differentially regulate processes such as apoptosis and cell repair may function as a chloride channel in mammalian systems in the same way it doses in lysosomes and may affect biological function," Dr. Friedman hypothesized.

In addition to exploring the underlying mechanisms, the potential clinical value of the genetic discovery is also being considered. "This may help us improve risk stratification," Dr. Friedman said. "It’s one thing to say that African Americans have a fourfold increased risk of kidney disease. It’s better to find the tag SNP [single nucleotide polymorphism] that will tell if an individual might have an increased risk. If you can actually find the causal variant, then you can potentially predict with much higher success who is and is not at risk for kidney failure," he stated. "The problem is that it works pretty well in Western African populations, such as Nigerians, but not as well in East Africans, such as Ethiopians."

One of the main questions that Dr. Friedman and his colleagues currently are pursuing is whether hypertension causes kidney disease in these at-risk individuals or whether hypertension is the result of primary renal vascular disease.

"To us, the fact that the very same genetic variants cause hypertension-associated ESRD and FSGS, a primary renal microvascular disease, suggests that these may be the same disease process that we are either catching at different stages or that have different modifiers, and that hypertension in these patients may just be a symptom and not a cause of kidney failure," Dr. Friedman said. Additionally, the investigators are trying to determine why only some people with two risk alleles develop kidney disease and why APOL1 risk variants have little to no effect on diabetic nephropathy, which may offer some clues to how the molecules work, he said.

A cure for nondiabetic kidney disease, which accounts for more than $8.2 billion annually in dialysis coasts, may directly result from the APOL1 finding, Dr. Friedman said. "It’s that important."

Dr. Friedman reported no financial conflicts of interested related to his presentation.

Despite recent improvements in influenza vaccination rates among U.S. health care personnel, their rates for the 2010-2011 flu season still fell short of national health objectives, a new survey has shown.

Similarly, although the record-high influenza vaccination levels among pregnant women during the 2009-2010 influenza season were sustained during the 2010-2011 season, vaccination levels in that group also remained well below the "Healthy People 2020" target of 80% coverage for pregnant women, Dr. Carolyn Bridges said during a telebriefing on the survey results.

Influenza vaccination coverage among all health care personnel for the 2010-2011 season was 63.5%, representing an increase over the 61.9% reported for the previous year. But that rate still fell short of the Healthy People 2020 coverage goal of 90%, said Dr. Bridges of the National Center for Immunization and Respiratory Diseases.

The most recent season’s results come from an Internet-based survey of 1,931 health care personnel, which the Centers for Disease Control and Prevention and the Rand Corp. conducted in April 2011.

"The vaccination rates were highest among physicians, health care personnel working in hospital settings, and those aged 60 years and older," Dr. Bridges reported.

Among the 13% of survey respondents whose workplace required influenza vaccination, the coverage rate was 98%, compared with 58% among the remaining respondents whose employers had no such requirement, she said.

In the absence of mandatory workplace immunization, offering the vaccine onsite at work, free of charge, and on more than 1 day were associated with an increased likelihood of influenza vaccination, Dr. Bridges stated.

Onsite vaccination in particular was a "key strategy," she said, noting that the coverage rate among respondents who had the onsite option was 66%, compared with 38.5% among those who did not.

With respect to influenza vaccine during pregnancy, the CDC and Rand estimated coverage for the 2010-11 season using data from an Internet panel survey, also conducted in April 2011, among 1,457 women who were pregnant any time between October 2010 and January 2011.

In all, 49% of respondents reported receiving the vaccine, including 32% who received it during pregnancy and 17% who received it [before or after] pregnancy," said Dr. Bridges. The rate is comparable to the 50% coverage rate reported for the previous influenza season, in response to the 2009 H1N1 influenza pandemic. And it was significantly higher than the consistently low rates of approximately 15% reported in prior seasons, she said.

Pregnant women whose providers offered them the influenza vaccination were approximately five times more likely to get vaccinated than were those whose providers did not, "which is consistent with other studies," Dr. Bridges said.

Despite the fact that the influenza vaccine given during pregnancy has been shown to decrease illness in mothers and decrease the risk of influenza and hospitalization in newborns younger than 6 months old who themselves are too young to get the vaccine, "4 out of 10 women reported not receiving an offer for vaccination from their providers," she reported.

An assessment of pregnant women’s attitudes and beliefs about vaccination during pregnancy determined that their top two concerns were safety risks to the baby and the possibility of getting influenza from the vaccine, Dr. Bridges stated. "Women who were offered the vaccine by their providers were more likely to have a positive attitude about the vaccine and its safety, she said.

The findings of both studies are reported in this week’s Morbidity and Mortality Weekly Report (2011;60:1073-7; 1078-82).

Although the 2011-2012 influenza vaccine will include the same influenza strains as last year, that’s not an excuse to skip this year’s shot, according to the CDC’s Advisory Committee on Immunization Practices.

"The levels of protective antibodies decline over the course of a year, so the ACIP continues to recommend annual immunization to ensure optimal protection, especially among the elderly, people with compromised immune systems, and those susceptible to complications of the flu," said Dr. Carolyn Bridges of the of the National Center for Immunization and Respiratory Disease.

The ACIP issued its updated influenza immunization recommendations for the 2011-2012 in the shortened format, because there were relatively few changes from last year, Dr. Bridges said.

In addition to the continued recommendation that all individuals ages 6 months and older get vaccinated, the updated guidelines include information on the selected influenza strains (an A/California/7/2009 [H1N1]–like virus; an A/Perth/16/2009 [H3N2]–like virus; and a B/Brisbane/60/2008–like virus), recommended schedules for children 6 months up to 8 years, and information about vaccination for individuals with egg allergies, she said.

Specifically, ACIP recommends that children aged 6 months to 8 years of age who were not vaccinated for influenza last year receive two doses of the vaccine this year, given at least 4 weeks apart, based on the data showing that two doses provide significantly greater protection than one.

Because this year’s vaccine covers the same selection of influenza strains, one dose is sufficient for children who were vaccinated last year, according to the committee.

For people with egg allergies, the CDC recommends that those who have experienced only hives should be vaccinated with the trivalent inactivated vaccine, not the live attenuated influenza vaccine. They should also be observed for 30 minutes after receiving the vaccine.

Before considering vaccination of patients with more serious egg allergies, they should be referred to physicians who have expertise in managing serious reactions.

The recommendation also includes information about a new formulation of the inactivated influenza vaccine, Dr. Bridges stated. The Fluzone Intradermal vaccine (Sanofi Pasteur), which uses a single-dose microinjection system for intradermal delivery, received FDA approval earlier this year. Fluzone is recommended for patients 18 years through 64 years.

Dr. Bridges reported no conflicts of interest with respect to the data presented.

Despite recent improvements in influenza vaccination rates among U.S. health care personnel, their rates for the 2010-2011 flu season still fell short of national health objectives, a new survey has shown.

Similarly, although the record-high influenza vaccination levels among pregnant women during the 2009-2010 influenza season were sustained during the 2010-2011 season, vaccination levels in that group also remained well below the "Healthy People 2020" target of 80% coverage for pregnant women, Dr. Carolyn Bridges said during a telebriefing on the survey results.

Influenza vaccination coverage among all health care personnel for the 2010-2011 season was 63.5%, representing an increase over the 61.9% reported for the previous year. But that rate still fell short of the Healthy People 2020 coverage goal of 90%, said Dr. Bridges of the National Center for Immunization and Respiratory Diseases.

The most recent season’s results come from an Internet-based survey of 1,931 health care personnel, which the Centers for Disease Control and Prevention and the Rand Corp. conducted in April 2011.

"The vaccination rates were highest among physicians, health care personnel working in hospital settings, and those aged 60 years and older," Dr. Bridges reported.

Among the 13% of survey respondents whose workplace required influenza vaccination, the coverage rate was 98%, compared with 58% among the remaining respondents whose employers had no such requirement, she said.

In the absence of mandatory workplace immunization, offering the vaccine onsite at work, free of charge, and on more than 1 day were associated with an increased likelihood of influenza vaccination, Dr. Bridges stated.

Onsite vaccination in particular was a "key strategy," she said, noting that the coverage rate among respondents who had the onsite option was 66%, compared with 38.5% among those who did not.

With respect to influenza vaccine during pregnancy, the CDC and Rand estimated coverage for the 2010-11 season using data from an Internet panel survey, also conducted in April 2011, among 1,457 women who were pregnant any time between October 2010 and January 2011.

In all, 49% of respondents reported receiving the vaccine, including 32% who received it during pregnancy and 17% who received it [before or after] pregnancy," said Dr. Bridges. The rate is comparable to the 50% coverage rate reported for the previous influenza season, in response to the 2009 H1N1 influenza pandemic. And it was significantly higher than the consistently low rates of approximately 15% reported in prior seasons, she said.

Pregnant women whose providers offered them the influenza vaccination were approximately five times more likely to get vaccinated than were those whose providers did not, "which is consistent with other studies," Dr. Bridges said.

Despite the fact that the influenza vaccine given during pregnancy has been shown to decrease illness in mothers and decrease the risk of influenza and hospitalization in newborns younger than 6 months old who themselves are too young to get the vaccine, "4 out of 10 women reported not receiving an offer for vaccination from their providers," she reported.

An assessment of pregnant women’s attitudes and beliefs about vaccination during pregnancy determined that their top two concerns were safety risks to the baby and the possibility of getting influenza from the vaccine, Dr. Bridges stated. "Women who were offered the vaccine by their providers were more likely to have a positive attitude about the vaccine and its safety, she said.

The findings of both studies are reported in this week’s Morbidity and Mortality Weekly Report (2011;60:1073-7; 1078-82).

Although the 2011-2012 influenza vaccine will include the same influenza strains as last year, that’s not an excuse to skip this year’s shot, according to the CDC’s Advisory Committee on Immunization Practices.

"The levels of protective antibodies decline over the course of a year, so the ACIP continues to recommend annual immunization to ensure optimal protection, especially among the elderly, people with compromised immune systems, and those susceptible to complications of the flu," said Dr. Carolyn Bridges of the of the National Center for Immunization and Respiratory Disease.

The ACIP issued its updated influenza immunization recommendations for the 2011-2012 in the shortened format, because there were relatively few changes from last year, Dr. Bridges said.

In addition to the continued recommendation that all individuals ages 6 months and older get vaccinated, the updated guidelines include information on the selected influenza strains (an A/California/7/2009 [H1N1]–like virus; an A/Perth/16/2009 [H3N2]–like virus; and a B/Brisbane/60/2008–like virus), recommended schedules for children 6 months up to 8 years, and information about vaccination for individuals with egg allergies, she said.

Specifically, ACIP recommends that children aged 6 months to 8 years of age who were not vaccinated for influenza last year receive two doses of the vaccine this year, given at least 4 weeks apart, based on the data showing that two doses provide significantly greater protection than one.

Because this year’s vaccine covers the same selection of influenza strains, one dose is sufficient for children who were vaccinated last year, according to the committee.

For people with egg allergies, the CDC recommends that those who have experienced only hives should be vaccinated with the trivalent inactivated vaccine, not the live attenuated influenza vaccine. They should also be observed for 30 minutes after receiving the vaccine.

Before considering vaccination of patients with more serious egg allergies, they should be referred to physicians who have expertise in managing serious reactions.

The recommendation also includes information about a new formulation of the inactivated influenza vaccine, Dr. Bridges stated. The Fluzone Intradermal vaccine (Sanofi Pasteur), which uses a single-dose microinjection system for intradermal delivery, received FDA approval earlier this year. Fluzone is recommended for patients 18 years through 64 years.

Dr. Bridges reported no conflicts of interest with respect to the data presented.

Despite recent improvements in influenza vaccination rates among U.S. health care personnel, their rates for the 2010-2011 flu season still fell short of national health objectives, a new survey has shown.

Similarly, although the record-high influenza vaccination levels among pregnant women during the 2009-2010 influenza season were sustained during the 2010-2011 season, vaccination levels in that group also remained well below the "Healthy People 2020" target of 80% coverage for pregnant women, Dr. Carolyn Bridges said during a telebriefing on the survey results.

Influenza vaccination coverage among all health care personnel for the 2010-2011 season was 63.5%, representing an increase over the 61.9% reported for the previous year. But that rate still fell short of the Healthy People 2020 coverage goal of 90%, said Dr. Bridges of the National Center for Immunization and Respiratory Diseases.

The most recent season’s results come from an Internet-based survey of 1,931 health care personnel, which the Centers for Disease Control and Prevention and the Rand Corp. conducted in April 2011.

"The vaccination rates were highest among physicians, health care personnel working in hospital settings, and those aged 60 years and older," Dr. Bridges reported.

Among the 13% of survey respondents whose workplace required influenza vaccination, the coverage rate was 98%, compared with 58% among the remaining respondents whose employers had no such requirement, she said.

In the absence of mandatory workplace immunization, offering the vaccine onsite at work, free of charge, and on more than 1 day were associated with an increased likelihood of influenza vaccination, Dr. Bridges stated.

Onsite vaccination in particular was a "key strategy," she said, noting that the coverage rate among respondents who had the onsite option was 66%, compared with 38.5% among those who did not.

With respect to influenza vaccine during pregnancy, the CDC and Rand estimated coverage for the 2010-11 season using data from an Internet panel survey, also conducted in April 2011, among 1,457 women who were pregnant any time between October 2010 and January 2011.

In all, 49% of respondents reported receiving the vaccine, including 32% who received it during pregnancy and 17% who received it [before or after] pregnancy," said Dr. Bridges. The rate is comparable to the 50% coverage rate reported for the previous influenza season, in response to the 2009 H1N1 influenza pandemic. And it was significantly higher than the consistently low rates of approximately 15% reported in prior seasons, she said.

Pregnant women whose providers offered them the influenza vaccination were approximately five times more likely to get vaccinated than were those whose providers did not, "which is consistent with other studies," Dr. Bridges said.

Despite the fact that the influenza vaccine given during pregnancy has been shown to decrease illness in mothers and decrease the risk of influenza and hospitalization in newborns younger than 6 months old who themselves are too young to get the vaccine, "4 out of 10 women reported not receiving an offer for vaccination from their providers," she reported.

An assessment of pregnant women’s attitudes and beliefs about vaccination during pregnancy determined that their top two concerns were safety risks to the baby and the possibility of getting influenza from the vaccine, Dr. Bridges stated. "Women who were offered the vaccine by their providers were more likely to have a positive attitude about the vaccine and its safety, she said.

The findings of both studies are reported in this week’s Morbidity and Mortality Weekly Report (2011;60:1073-7; 1078-82).

Although the 2011-2012 influenza vaccine will include the same influenza strains as last year, that’s not an excuse to skip this year’s shot, according to the CDC’s Advisory Committee on Immunization Practices.

"The levels of protective antibodies decline over the course of a year, so the ACIP continues to recommend annual immunization to ensure optimal protection, especially among the elderly, people with compromised immune systems, and those susceptible to complications of the flu," said Dr. Carolyn Bridges of the of the National Center for Immunization and Respiratory Disease.

The ACIP issued its updated influenza immunization recommendations for the 2011-2012 in the shortened format, because there were relatively few changes from last year, Dr. Bridges said.

In addition to the continued recommendation that all individuals ages 6 months and older get vaccinated, the updated guidelines include information on the selected influenza strains (an A/California/7/2009 [H1N1]–like virus; an A/Perth/16/2009 [H3N2]–like virus; and a B/Brisbane/60/2008–like virus), recommended schedules for children 6 months up to 8 years, and information about vaccination for individuals with egg allergies, she said.

Specifically, ACIP recommends that children aged 6 months to 8 years of age who were not vaccinated for influenza last year receive two doses of the vaccine this year, given at least 4 weeks apart, based on the data showing that two doses provide significantly greater protection than one.

Because this year’s vaccine covers the same selection of influenza strains, one dose is sufficient for children who were vaccinated last year, according to the committee.

For people with egg allergies, the CDC recommends that those who have experienced only hives should be vaccinated with the trivalent inactivated vaccine, not the live attenuated influenza vaccine. They should also be observed for 30 minutes after receiving the vaccine.

Before considering vaccination of patients with more serious egg allergies, they should be referred to physicians who have expertise in managing serious reactions.

The recommendation also includes information about a new formulation of the inactivated influenza vaccine, Dr. Bridges stated. The Fluzone Intradermal vaccine (Sanofi Pasteur), which uses a single-dose microinjection system for intradermal delivery, received FDA approval earlier this year. Fluzone is recommended for patients 18 years through 64 years.

Dr. Bridges reported no conflicts of interest with respect to the data presented.

To treat or not to treat? When it comes to deciding whether adjuvant chemotherapy is the appropriate management choice for patients with HER2 positive, node-negative breast cancer less than 1 cm in size, the only sure thing is that there is no sure thing, and seemingly conflicting research data exacerbates the uncertainty.

A recent study demonstrated that patients who did not receive adjuvant chemotherapy or trastuzumab for node-negative, non-metastasized HER2 positive T1a (less than or equal to 0.1 cm to 0.5 cm) or T1b (greater than 0.5 cm to 1.0 cm) tumors were at greater risk for worse recurrence-free survival and worse distant recurrence-free survival than patients with hormone-receptor–positive disease.

This was especially true for those younger than age 35 years – and also was the case in similarly staged patients with triple-negative breast cancer, according to the report from the University of Texas M.D. Anderson Cancer Center in Houston.

The authors concluded that planning systemic treatment based on disease stage alone "appears to lead to worse outcomes," and that individualized treatment plans may be better informed by taking into account aggressive biological subtypes of small, node-negative breast cancers, as well as age at diagnosis (Clin. Breast Cancer. 2011 July 15 [doi: 10.1016/j.clbc.2011.05.002]).

While the findings of this retrospective, single-institution study validate the large body of evidence suggesting that younger patients with aggressive tumor subtypes have worse outcomes when not treated with adjuvant chemotherapy or trastuzumab (Herceptin), the authors do not recommend universal treatment of this patient population.

Rather, the results provide a strong argument for the inclusion of women with small tumors that have biologically aggressive traits in prospective clinical trials "to evaluate the extent of therapeutic benefits," they wrote. Further, patient age and disease subtype "should be considered when counseling patients about treatment interventions."

No Treatment Not Worse for Some

With the absolute benefits of treatment yet to be determined, investigators also are looking closely at the risks associated with skipping adjuvant treatment.

The findings of an observational cohort study presented at the annual meeting of the American Society of Clinical Oncology (ASCO) suggest that women with early HER2 positive T1aN0M0 breast cancers can safely do so because of the low distant recurrence rate observed in this patient subgroup. A higher rate was observed in those with T1bN0M0, indicating that adjuvant systemic therapy may be more relevant in this patient population.

The study assessed outcomes among 237 women with HER2-positive T1a (116 patients) or T1b (121 patients) tumors diagnosed between 2000 and 2006, all of whom had negative nodes and no metastases. Most did not receive adjuvant chemotherapy or trastuzumab.

With a median duration of follow-up of 5.8 years, the rate of distant recurrence was 0.9% among patients with T1a tumors versus 5.8% among those with T1b, lead investigator Dr. Louis Fehrenbacher, an oncologist with Kaiser Permanente in Vallejo, Calif., reported in a poster presentation, analyzing data from the tumor registry of the Kaiser Permanente Clinical Care Program of Northern California.

The investigators chose distant recurrence-free survival as the main outcome measure, rather than the more commonly used disease-free survival rate, because they "did not want to include non-breast malignancies, contralateral malignancies, or deaths from any other cause," Dr. Fehrenbacher said. "That isn’t the real important factor in deciding to give intensive chemotherapy to these patients," he explained.

By tumor size, the rate of distant recurrence ranged from 0% to 5.8% for tumors measuring 0.1 cm to 0.9 cm, but it was 10.7% for the tumors measuring 1.0 cm. In other words, Dr. Fehrenbacher said, "the 1.0-cm tumors carried the burden of the distant recurrence risk."

Results for the actuarial distant recurrence-free interval showed a 5-year rate of 96.5% for the patients as a whole, with 99.1% and 94.0% in the T1a and T1b groups, respectively.

Overall, 25% of the study patients received chemotherapy and 8% received trastuzumab. "Most of these patients had only a smattering of chemotherapy or trastuzumab, and it didn't seem to affect outcome," Dr. Fehrenbacher commented, but he acknowledged that there may have been bias influencing who received chemotherapy. While 59% of the patients had tumors that were positive for estrogen receptors, there was little difference in recurrence rate according to estrogen receptor status, he said.

"The take-home message is, I think, the T1a’s have too low of a risk of distant invasive recurrence to justify chemotherapy or trastuzumab," Dr. Fehrenbacher said in an interview. "We need to specifically individualize the risk of the patient based on the size of their primary [tumor], because the T1a’s and T1b’s are quite different in our findings."

Dr. Lajos Pusztai, a professor in the department of breast medical oncology at M.D. Anderson, agrees with Dr. Fehrenbacher’s conclusion. "I think the findings are correct, as several other studies have also indicated a very low risk of recurrence for very small HER2-positive cancers," he said in an interview.

"It may also be important to remember that HER2 has not been considered by the ASCO biomarker review panels [to be] an important prognostic marker, but rather a predictive marker for trastuzumab therapy."

Review Warns of Cardiotoxicity

In a recent review article looking into whether the existing data supports a definitive treatment threshold for patients with T1aN0M0 or T1bN0M0 HER2-positive breast cancer, Dr. Pusztai, along with lead author Dr. Catherine M. Kelly of Waterford Regional Hospital in Waterford, Ireland and colleagues, wrote that "a blanket recommendation to treat all small HER2 positive breast cancer with trastuzumab-based therapy will almost certainly lead to clinically significant cardiotoxicity in some without any benefit in breast cancer recurrence."

Similarly, they noted, "withholding this form of adjuvant therapy from all small HER2 positive cancers will result in some otherwise avoidable breast cancer recurrence. Unfortunately, today we do not have accurate tools to identify precisely the subset of patients for whom the risks of trastuzumab outweigh the benefits."

Lacking such tools, shared medical decision making based on estimates achieved using established risk calculators and discussion of the risks with patients should be the order of the day, they said, with the decision depending upon the patients’ perspective and risk tolerance level. If trastuzumab-based treatment is an option, the authors stressed that regimens with the lowest risk of cardiotoxicity should be pursued (Ann. Oncol. 2011 Mar. 15 [doi:10.1093/annonc/mdq786]).

In the absence of randomized controlled trials to establish or refute the benefit from adjuvant trastuzumab in this patient subset, the authors called for the development of molecular predictors of prognosis within HER2 positive disease to further optimize risk/benefit estimates. The development of better prediction tools for more precise estimations of the risk of death from comorbid illnesses and the risk of cardiac death, in particular, are important, they said.

Level 1 Evidence Lacking

The lack of level 1 evidence from large, prospective trials contributes to the overall uncertainty surrounding the role of adjuvant chemotherapy in early HER2 breast cancer, according to Dr. Gabriel Hortobágyi, professor and chair of the department of Breast Medical Oncology at M.D. Anderson.

Studies examining the prognostic value of HER2 are limited by their reliance on retrospective database analyses and small cohort sized, Dr. Hortobágyi said in an interview. "I think it is critically important to perform a couple of larger trials with prospective collection of patients, HER2 checked centrally in a high-volume lab, and long enough follow-up to determine the real outcomes of these patients."

In this regard, the Southwest Oncology Group’s breast committee, chaired by Dr. Hortobágyi, is trying to activate a clinical trial for HER2 positive T1a and T1b patients comparing trastuzumab alone and in combination with lapatinib "to determine whether treatment with targeted chemotherapy would be effective enough for these patients." Additionally, he said investigators at Dana Farber Cancer Institute are completing recruitment to a single-arm trial for patients with small, HER2 positive breast cancer treated uniformly with paclitaxel and trastuzumab.

"Both trials will give us prospective data and should contribute significantly to our assessment of the real prognosis of this group of patients," he said.

In the meantime, Dr. Hortobágyi said that his group, and many others, "considers that risk of recurrence exceeding about 10% deserves adjuvant chemotherapy, and in the HER2 positive group we believe the risk exceeds, by far, that level. Therefore, we discuss trastuzumab and chemotherapy with all patients without significant comorbid conditions if they have any size-invasive, HER2 positive breast cancer."

The uncertainty regarding the role of adjuvant chemotherapy in early HER2 breast cancer touches on a "fascinating aspect of medicine: how to deal with and communicate uncertainty in diagnosis and treatment benefit," observed Dr. Pusztai.

"Medicine is a very imprecise science and the handling of imprecision is what makes it, as some would call it, an art," he said. "I suspect that what patients perceive as a ‘good’ vs. ‘not so good’ doctor often comes down to how efficiently one can make decisions under uncertainty of information and how effectively one communicates this uncertainty and the decision that is based on it."

Dr. Fehrenbacher, Dr. Pusztai, and Dr. Hortobágyi reported no relevant conflicts of interest with respect to the information presented.

Susan London contributed to this report.

To treat or not to treat? When it comes to deciding whether adjuvant chemotherapy is the appropriate management choice for patients with HER2 positive, node-negative breast cancer less than 1 cm in size, the only sure thing is that there is no sure thing, and seemingly conflicting research data exacerbates the uncertainty.

A recent study demonstrated that patients who did not receive adjuvant chemotherapy or trastuzumab for node-negative, non-metastasized HER2 positive T1a (less than or equal to 0.1 cm to 0.5 cm) or T1b (greater than 0.5 cm to 1.0 cm) tumors were at greater risk for worse recurrence-free survival and worse distant recurrence-free survival than patients with hormone-receptor–positive disease.

This was especially true for those younger than age 35 years – and also was the case in similarly staged patients with triple-negative breast cancer, according to the report from the University of Texas M.D. Anderson Cancer Center in Houston.

The authors concluded that planning systemic treatment based on disease stage alone "appears to lead to worse outcomes," and that individualized treatment plans may be better informed by taking into account aggressive biological subtypes of small, node-negative breast cancers, as well as age at diagnosis (Clin. Breast Cancer. 2011 July 15 [doi: 10.1016/j.clbc.2011.05.002]).

While the findings of this retrospective, single-institution study validate the large body of evidence suggesting that younger patients with aggressive tumor subtypes have worse outcomes when not treated with adjuvant chemotherapy or trastuzumab (Herceptin), the authors do not recommend universal treatment of this patient population.

Rather, the results provide a strong argument for the inclusion of women with small tumors that have biologically aggressive traits in prospective clinical trials "to evaluate the extent of therapeutic benefits," they wrote. Further, patient age and disease subtype "should be considered when counseling patients about treatment interventions."

No Treatment Not Worse for Some

With the absolute benefits of treatment yet to be determined, investigators also are looking closely at the risks associated with skipping adjuvant treatment.

The findings of an observational cohort study presented at the annual meeting of the American Society of Clinical Oncology (ASCO) suggest that women with early HER2 positive T1aN0M0 breast cancers can safely do so because of the low distant recurrence rate observed in this patient subgroup. A higher rate was observed in those with T1bN0M0, indicating that adjuvant systemic therapy may be more relevant in this patient population.

The study assessed outcomes among 237 women with HER2-positive T1a (116 patients) or T1b (121 patients) tumors diagnosed between 2000 and 2006, all of whom had negative nodes and no metastases. Most did not receive adjuvant chemotherapy or trastuzumab.

With a median duration of follow-up of 5.8 years, the rate of distant recurrence was 0.9% among patients with T1a tumors versus 5.8% among those with T1b, lead investigator Dr. Louis Fehrenbacher, an oncologist with Kaiser Permanente in Vallejo, Calif., reported in a poster presentation, analyzing data from the tumor registry of the Kaiser Permanente Clinical Care Program of Northern California.

The investigators chose distant recurrence-free survival as the main outcome measure, rather than the more commonly used disease-free survival rate, because they "did not want to include non-breast malignancies, contralateral malignancies, or deaths from any other cause," Dr. Fehrenbacher said. "That isn’t the real important factor in deciding to give intensive chemotherapy to these patients," he explained.

By tumor size, the rate of distant recurrence ranged from 0% to 5.8% for tumors measuring 0.1 cm to 0.9 cm, but it was 10.7% for the tumors measuring 1.0 cm. In other words, Dr. Fehrenbacher said, "the 1.0-cm tumors carried the burden of the distant recurrence risk."

Results for the actuarial distant recurrence-free interval showed a 5-year rate of 96.5% for the patients as a whole, with 99.1% and 94.0% in the T1a and T1b groups, respectively.

Overall, 25% of the study patients received chemotherapy and 8% received trastuzumab. "Most of these patients had only a smattering of chemotherapy or trastuzumab, and it didn't seem to affect outcome," Dr. Fehrenbacher commented, but he acknowledged that there may have been bias influencing who received chemotherapy. While 59% of the patients had tumors that were positive for estrogen receptors, there was little difference in recurrence rate according to estrogen receptor status, he said.

"The take-home message is, I think, the T1a’s have too low of a risk of distant invasive recurrence to justify chemotherapy or trastuzumab," Dr. Fehrenbacher said in an interview. "We need to specifically individualize the risk of the patient based on the size of their primary [tumor], because the T1a’s and T1b’s are quite different in our findings."

Dr. Lajos Pusztai, a professor in the department of breast medical oncology at M.D. Anderson, agrees with Dr. Fehrenbacher’s conclusion. "I think the findings are correct, as several other studies have also indicated a very low risk of recurrence for very small HER2-positive cancers," he said in an interview.

"It may also be important to remember that HER2 has not been considered by the ASCO biomarker review panels [to be] an important prognostic marker, but rather a predictive marker for trastuzumab therapy."

Review Warns of Cardiotoxicity

In a recent review article looking into whether the existing data supports a definitive treatment threshold for patients with T1aN0M0 or T1bN0M0 HER2-positive breast cancer, Dr. Pusztai, along with lead author Dr. Catherine M. Kelly of Waterford Regional Hospital in Waterford, Ireland and colleagues, wrote that "a blanket recommendation to treat all small HER2 positive breast cancer with trastuzumab-based therapy will almost certainly lead to clinically significant cardiotoxicity in some without any benefit in breast cancer recurrence."

Similarly, they noted, "withholding this form of adjuvant therapy from all small HER2 positive cancers will result in some otherwise avoidable breast cancer recurrence. Unfortunately, today we do not have accurate tools to identify precisely the subset of patients for whom the risks of trastuzumab outweigh the benefits."

Lacking such tools, shared medical decision making based on estimates achieved using established risk calculators and discussion of the risks with patients should be the order of the day, they said, with the decision depending upon the patients’ perspective and risk tolerance level. If trastuzumab-based treatment is an option, the authors stressed that regimens with the lowest risk of cardiotoxicity should be pursued (Ann. Oncol. 2011 Mar. 15 [doi:10.1093/annonc/mdq786]).

In the absence of randomized controlled trials to establish or refute the benefit from adjuvant trastuzumab in this patient subset, the authors called for the development of molecular predictors of prognosis within HER2 positive disease to further optimize risk/benefit estimates. The development of better prediction tools for more precise estimations of the risk of death from comorbid illnesses and the risk of cardiac death, in particular, are important, they said.

Level 1 Evidence Lacking

The lack of level 1 evidence from large, prospective trials contributes to the overall uncertainty surrounding the role of adjuvant chemotherapy in early HER2 breast cancer, according to Dr. Gabriel Hortobágyi, professor and chair of the department of Breast Medical Oncology at M.D. Anderson.

Studies examining the prognostic value of HER2 are limited by their reliance on retrospective database analyses and small cohort sized, Dr. Hortobágyi said in an interview. "I think it is critically important to perform a couple of larger trials with prospective collection of patients, HER2 checked centrally in a high-volume lab, and long enough follow-up to determine the real outcomes of these patients."

In this regard, the Southwest Oncology Group’s breast committee, chaired by Dr. Hortobágyi, is trying to activate a clinical trial for HER2 positive T1a and T1b patients comparing trastuzumab alone and in combination with lapatinib "to determine whether treatment with targeted chemotherapy would be effective enough for these patients." Additionally, he said investigators at Dana Farber Cancer Institute are completing recruitment to a single-arm trial for patients with small, HER2 positive breast cancer treated uniformly with paclitaxel and trastuzumab.

"Both trials will give us prospective data and should contribute significantly to our assessment of the real prognosis of this group of patients," he said.

In the meantime, Dr. Hortobágyi said that his group, and many others, "considers that risk of recurrence exceeding about 10% deserves adjuvant chemotherapy, and in the HER2 positive group we believe the risk exceeds, by far, that level. Therefore, we discuss trastuzumab and chemotherapy with all patients without significant comorbid conditions if they have any size-invasive, HER2 positive breast cancer."

The uncertainty regarding the role of adjuvant chemotherapy in early HER2 breast cancer touches on a "fascinating aspect of medicine: how to deal with and communicate uncertainty in diagnosis and treatment benefit," observed Dr. Pusztai.

"Medicine is a very imprecise science and the handling of imprecision is what makes it, as some would call it, an art," he said. "I suspect that what patients perceive as a ‘good’ vs. ‘not so good’ doctor often comes down to how efficiently one can make decisions under uncertainty of information and how effectively one communicates this uncertainty and the decision that is based on it."

Dr. Fehrenbacher, Dr. Pusztai, and Dr. Hortobágyi reported no relevant conflicts of interest with respect to the information presented.

Susan London contributed to this report.

To treat or not to treat? When it comes to deciding whether adjuvant chemotherapy is the appropriate management choice for patients with HER2 positive, node-negative breast cancer less than 1 cm in size, the only sure thing is that there is no sure thing, and seemingly conflicting research data exacerbates the uncertainty.

A recent study demonstrated that patients who did not receive adjuvant chemotherapy or trastuzumab for node-negative, non-metastasized HER2 positive T1a (less than or equal to 0.1 cm to 0.5 cm) or T1b (greater than 0.5 cm to 1.0 cm) tumors were at greater risk for worse recurrence-free survival and worse distant recurrence-free survival than patients with hormone-receptor–positive disease.

This was especially true for those younger than age 35 years – and also was the case in similarly staged patients with triple-negative breast cancer, according to the report from the University of Texas M.D. Anderson Cancer Center in Houston.

The authors concluded that planning systemic treatment based on disease stage alone "appears to lead to worse outcomes," and that individualized treatment plans may be better informed by taking into account aggressive biological subtypes of small, node-negative breast cancers, as well as age at diagnosis (Clin. Breast Cancer. 2011 July 15 [doi: 10.1016/j.clbc.2011.05.002]).

While the findings of this retrospective, single-institution study validate the large body of evidence suggesting that younger patients with aggressive tumor subtypes have worse outcomes when not treated with adjuvant chemotherapy or trastuzumab (Herceptin), the authors do not recommend universal treatment of this patient population.

Rather, the results provide a strong argument for the inclusion of women with small tumors that have biologically aggressive traits in prospective clinical trials "to evaluate the extent of therapeutic benefits," they wrote. Further, patient age and disease subtype "should be considered when counseling patients about treatment interventions."

No Treatment Not Worse for Some

With the absolute benefits of treatment yet to be determined, investigators also are looking closely at the risks associated with skipping adjuvant treatment.

The findings of an observational cohort study presented at the annual meeting of the American Society of Clinical Oncology (ASCO) suggest that women with early HER2 positive T1aN0M0 breast cancers can safely do so because of the low distant recurrence rate observed in this patient subgroup. A higher rate was observed in those with T1bN0M0, indicating that adjuvant systemic therapy may be more relevant in this patient population.

The study assessed outcomes among 237 women with HER2-positive T1a (116 patients) or T1b (121 patients) tumors diagnosed between 2000 and 2006, all of whom had negative nodes and no metastases. Most did not receive adjuvant chemotherapy or trastuzumab.

With a median duration of follow-up of 5.8 years, the rate of distant recurrence was 0.9% among patients with T1a tumors versus 5.8% among those with T1b, lead investigator Dr. Louis Fehrenbacher, an oncologist with Kaiser Permanente in Vallejo, Calif., reported in a poster presentation, analyzing data from the tumor registry of the Kaiser Permanente Clinical Care Program of Northern California.

The investigators chose distant recurrence-free survival as the main outcome measure, rather than the more commonly used disease-free survival rate, because they "did not want to include non-breast malignancies, contralateral malignancies, or deaths from any other cause," Dr. Fehrenbacher said. "That isn’t the real important factor in deciding to give intensive chemotherapy to these patients," he explained.

By tumor size, the rate of distant recurrence ranged from 0% to 5.8% for tumors measuring 0.1 cm to 0.9 cm, but it was 10.7% for the tumors measuring 1.0 cm. In other words, Dr. Fehrenbacher said, "the 1.0-cm tumors carried the burden of the distant recurrence risk."

Results for the actuarial distant recurrence-free interval showed a 5-year rate of 96.5% for the patients as a whole, with 99.1% and 94.0% in the T1a and T1b groups, respectively.

Overall, 25% of the study patients received chemotherapy and 8% received trastuzumab. "Most of these patients had only a smattering of chemotherapy or trastuzumab, and it didn't seem to affect outcome," Dr. Fehrenbacher commented, but he acknowledged that there may have been bias influencing who received chemotherapy. While 59% of the patients had tumors that were positive for estrogen receptors, there was little difference in recurrence rate according to estrogen receptor status, he said.

"The take-home message is, I think, the T1a’s have too low of a risk of distant invasive recurrence to justify chemotherapy or trastuzumab," Dr. Fehrenbacher said in an interview. "We need to specifically individualize the risk of the patient based on the size of their primary [tumor], because the T1a’s and T1b’s are quite different in our findings."

Dr. Lajos Pusztai, a professor in the department of breast medical oncology at M.D. Anderson, agrees with Dr. Fehrenbacher’s conclusion. "I think the findings are correct, as several other studies have also indicated a very low risk of recurrence for very small HER2-positive cancers," he said in an interview.

"It may also be important to remember that HER2 has not been considered by the ASCO biomarker review panels [to be] an important prognostic marker, but rather a predictive marker for trastuzumab therapy."

Review Warns of Cardiotoxicity

In a recent review article looking into whether the existing data supports a definitive treatment threshold for patients with T1aN0M0 or T1bN0M0 HER2-positive breast cancer, Dr. Pusztai, along with lead author Dr. Catherine M. Kelly of Waterford Regional Hospital in Waterford, Ireland and colleagues, wrote that "a blanket recommendation to treat all small HER2 positive breast cancer with trastuzumab-based therapy will almost certainly lead to clinically significant cardiotoxicity in some without any benefit in breast cancer recurrence."

Similarly, they noted, "withholding this form of adjuvant therapy from all small HER2 positive cancers will result in some otherwise avoidable breast cancer recurrence. Unfortunately, today we do not have accurate tools to identify precisely the subset of patients for whom the risks of trastuzumab outweigh the benefits."

Lacking such tools, shared medical decision making based on estimates achieved using established risk calculators and discussion of the risks with patients should be the order of the day, they said, with the decision depending upon the patients’ perspective and risk tolerance level. If trastuzumab-based treatment is an option, the authors stressed that regimens with the lowest risk of cardiotoxicity should be pursued (Ann. Oncol. 2011 Mar. 15 [doi:10.1093/annonc/mdq786]).

In the absence of randomized controlled trials to establish or refute the benefit from adjuvant trastuzumab in this patient subset, the authors called for the development of molecular predictors of prognosis within HER2 positive disease to further optimize risk/benefit estimates. The development of better prediction tools for more precise estimations of the risk of death from comorbid illnesses and the risk of cardiac death, in particular, are important, they said.

Level 1 Evidence Lacking

The lack of level 1 evidence from large, prospective trials contributes to the overall uncertainty surrounding the role of adjuvant chemotherapy in early HER2 breast cancer, according to Dr. Gabriel Hortobágyi, professor and chair of the department of Breast Medical Oncology at M.D. Anderson.

Studies examining the prognostic value of HER2 are limited by their reliance on retrospective database analyses and small cohort sized, Dr. Hortobágyi said in an interview. "I think it is critically important to perform a couple of larger trials with prospective collection of patients, HER2 checked centrally in a high-volume lab, and long enough follow-up to determine the real outcomes of these patients."

In this regard, the Southwest Oncology Group’s breast committee, chaired by Dr. Hortobágyi, is trying to activate a clinical trial for HER2 positive T1a and T1b patients comparing trastuzumab alone and in combination with lapatinib "to determine whether treatment with targeted chemotherapy would be effective enough for these patients." Additionally, he said investigators at Dana Farber Cancer Institute are completing recruitment to a single-arm trial for patients with small, HER2 positive breast cancer treated uniformly with paclitaxel and trastuzumab.

"Both trials will give us prospective data and should contribute significantly to our assessment of the real prognosis of this group of patients," he said.

In the meantime, Dr. Hortobágyi said that his group, and many others, "considers that risk of recurrence exceeding about 10% deserves adjuvant chemotherapy, and in the HER2 positive group we believe the risk exceeds, by far, that level. Therefore, we discuss trastuzumab and chemotherapy with all patients without significant comorbid conditions if they have any size-invasive, HER2 positive breast cancer."

The uncertainty regarding the role of adjuvant chemotherapy in early HER2 breast cancer touches on a "fascinating aspect of medicine: how to deal with and communicate uncertainty in diagnosis and treatment benefit," observed Dr. Pusztai.

"Medicine is a very imprecise science and the handling of imprecision is what makes it, as some would call it, an art," he said. "I suspect that what patients perceive as a ‘good’ vs. ‘not so good’ doctor often comes down to how efficiently one can make decisions under uncertainty of information and how effectively one communicates this uncertainty and the decision that is based on it."

Dr. Fehrenbacher, Dr. Pusztai, and Dr. Hortobágyi reported no relevant conflicts of interest with respect to the information presented.

Susan London contributed to this report.

The science supporting vitamin D supplementation in lupus patients is catching up to the recommendation that all patients with the autoimmune disease increase their intake of the fat-soluble secosteroids.

Findings from a new study by Dr. Suzan Abou-Raya, professor of geriatric medicine at the University of Alexandria (Egypt), and her associates demonstrate that there is a high prevalence of vitamin-D deficiency associated with an increased inflammatory burden and thrombophilic state in patients with systemic lupus erythematosus (SLE). The findings also suggest that oral vitamin D supplementation ameliorates chronic inflammatory and hemostatic markers in this patient group.

The use of supplementary calcium and vitamin D is routinely recommended for SLE patients to help minimize the bone loss and increased risk of developing osteoporosis associated with the disease and its treatment. Beyond supporting bone and mineral hemostasis, "vitamin D is now recognized as having additional pleiotropic roles," according to Dr. Abou-Raya. "We’ve learned that it has potent immunomodulatory properties that have promoted its potential use in the treatment of autoimmune conditions, including lupus."

The study was designed to evaluate vitamin D status in lupus patients and to assess alterations in disease-related inflammatory and hemostatic markers before and after vitamin D supplementation.

To do this, Dr. Abou-Raya and her fellow researchers conducted a randomized, placebo-controlled trial comprising 148 males and premenopausal females who fulfilled the ACR (American College of Rheumatology) classification criteria for SLE. Also enrolled in the study were 75 lupus-free adults who served as controls and who matched the cases in age, sex, ethnicity, and body mass index. Individuals with other inflammatory disorders and those taking supplemental vitamin D at the time of the study were excluded from participation, she noted.

Study patients were randomized in a 1:1 fashion to receive either 2,000 IU per day of oral cholecalciferol (vitamin D₃) or placebo for 6 months together with standard SLE treatment, Dr. Abou-Raya explained. Before and after 6 months of vitamin D supplementation, the investigators evaluated disease activity using the SLE disease activity index (SLEDAI), levels of serum 25-hydroxyvitamin D (25[OH]D) via DiaSorin’s Liaison immunoassay, levels of proinflammatory cytokines interleukin-1 (IL-1), IL-6, IL-18, tumor necrosis factor (TNF)–alpha, C-reactive protein (CRP), and the hemostatic markers fibrinogen and von Willebrand factor (vWF), she explained. Individuals with 25(OH)D levels of 10-30 ng/mL were classified as having vitamin D insufficiency and those with levels lower than 10 ng/mL were considered vitamin D deficient, she noted.

With respect to baseline demographics, the mean age of the SLE patients was 38.8 years and the mean disease duration was 5.2 years. The mean baseline vitamin D level in the SLE patients was 19.8 ng/mL, which was significantly lower than the mean 28.7 ng/mL in the control group, Dr. Abou-Raya reported. The baseline levels of the inflammatory and hemostatic markers were significantly higher in the SLE patients. "The overall prevalence of vitamin D insufficiency and deficiency, respectively, was 69% and 39%," she said.

At 6 months, "there was a significant decrease in levels of inflammatory and hemostatic makers in lupus patients who were supplemented with vitamin D" compared with patients who were given placebo together with ongoing therapy, Dr. Abou-Raya reported at the annual European Congress of Rheumatology in London. After multivariate adjustment, the investigators observed a negative correlation between vitamin D levels and IL-1, IL-6, IL-18, TNF-alpha, CRP, fibrinogen, and vWF, "and lower vitamin D levels were associated with significantly higher SLEDAI scores," she said.

The results suggest that hypovitaminosis D contributes to a chronic inflammatory and thrombophilic state in SLE patients, said Dr. Abou-Raya. "The findings support the routine recommendation for oral vitamin D supplementation in these patients," she said.

Dr. Abou-Raya disclosed having no financial conflicts of interest related to her presentation.

The science supporting vitamin D supplementation in lupus patients is catching up to the recommendation that all patients with the autoimmune disease increase their intake of the fat-soluble secosteroids.

Findings from a new study by Dr. Suzan Abou-Raya, professor of geriatric medicine at the University of Alexandria (Egypt), and her associates demonstrate that there is a high prevalence of vitamin-D deficiency associated with an increased inflammatory burden and thrombophilic state in patients with systemic lupus erythematosus (SLE). The findings also suggest that oral vitamin D supplementation ameliorates chronic inflammatory and hemostatic markers in this patient group.

The use of supplementary calcium and vitamin D is routinely recommended for SLE patients to help minimize the bone loss and increased risk of developing osteoporosis associated with the disease and its treatment. Beyond supporting bone and mineral hemostasis, "vitamin D is now recognized as having additional pleiotropic roles," according to Dr. Abou-Raya. "We’ve learned that it has potent immunomodulatory properties that have promoted its potential use in the treatment of autoimmune conditions, including lupus."

The study was designed to evaluate vitamin D status in lupus patients and to assess alterations in disease-related inflammatory and hemostatic markers before and after vitamin D supplementation.

To do this, Dr. Abou-Raya and her fellow researchers conducted a randomized, placebo-controlled trial comprising 148 males and premenopausal females who fulfilled the ACR (American College of Rheumatology) classification criteria for SLE. Also enrolled in the study were 75 lupus-free adults who served as controls and who matched the cases in age, sex, ethnicity, and body mass index. Individuals with other inflammatory disorders and those taking supplemental vitamin D at the time of the study were excluded from participation, she noted.

Study patients were randomized in a 1:1 fashion to receive either 2,000 IU per day of oral cholecalciferol (vitamin D₃) or placebo for 6 months together with standard SLE treatment, Dr. Abou-Raya explained. Before and after 6 months of vitamin D supplementation, the investigators evaluated disease activity using the SLE disease activity index (SLEDAI), levels of serum 25-hydroxyvitamin D (25[OH]D) via DiaSorin’s Liaison immunoassay, levels of proinflammatory cytokines interleukin-1 (IL-1), IL-6, IL-18, tumor necrosis factor (TNF)–alpha, C-reactive protein (CRP), and the hemostatic markers fibrinogen and von Willebrand factor (vWF), she explained. Individuals with 25(OH)D levels of 10-30 ng/mL were classified as having vitamin D insufficiency and those with levels lower than 10 ng/mL were considered vitamin D deficient, she noted.

With respect to baseline demographics, the mean age of the SLE patients was 38.8 years and the mean disease duration was 5.2 years. The mean baseline vitamin D level in the SLE patients was 19.8 ng/mL, which was significantly lower than the mean 28.7 ng/mL in the control group, Dr. Abou-Raya reported. The baseline levels of the inflammatory and hemostatic markers were significantly higher in the SLE patients. "The overall prevalence of vitamin D insufficiency and deficiency, respectively, was 69% and 39%," she said.

At 6 months, "there was a significant decrease in levels of inflammatory and hemostatic makers in lupus patients who were supplemented with vitamin D" compared with patients who were given placebo together with ongoing therapy, Dr. Abou-Raya reported at the annual European Congress of Rheumatology in London. After multivariate adjustment, the investigators observed a negative correlation between vitamin D levels and IL-1, IL-6, IL-18, TNF-alpha, CRP, fibrinogen, and vWF, "and lower vitamin D levels were associated with significantly higher SLEDAI scores," she said.

The results suggest that hypovitaminosis D contributes to a chronic inflammatory and thrombophilic state in SLE patients, said Dr. Abou-Raya. "The findings support the routine recommendation for oral vitamin D supplementation in these patients," she said.

Dr. Abou-Raya disclosed having no financial conflicts of interest related to her presentation.

The science supporting vitamin D supplementation in lupus patients is catching up to the recommendation that all patients with the autoimmune disease increase their intake of the fat-soluble secosteroids.

Findings from a new study by Dr. Suzan Abou-Raya, professor of geriatric medicine at the University of Alexandria (Egypt), and her associates demonstrate that there is a high prevalence of vitamin-D deficiency associated with an increased inflammatory burden and thrombophilic state in patients with systemic lupus erythematosus (SLE). The findings also suggest that oral vitamin D supplementation ameliorates chronic inflammatory and hemostatic markers in this patient group.

The use of supplementary calcium and vitamin D is routinely recommended for SLE patients to help minimize the bone loss and increased risk of developing osteoporosis associated with the disease and its treatment. Beyond supporting bone and mineral hemostasis, "vitamin D is now recognized as having additional pleiotropic roles," according to Dr. Abou-Raya. "We’ve learned that it has potent immunomodulatory properties that have promoted its potential use in the treatment of autoimmune conditions, including lupus."

The study was designed to evaluate vitamin D status in lupus patients and to assess alterations in disease-related inflammatory and hemostatic markers before and after vitamin D supplementation.

To do this, Dr. Abou-Raya and her fellow researchers conducted a randomized, placebo-controlled trial comprising 148 males and premenopausal females who fulfilled the ACR (American College of Rheumatology) classification criteria for SLE. Also enrolled in the study were 75 lupus-free adults who served as controls and who matched the cases in age, sex, ethnicity, and body mass index. Individuals with other inflammatory disorders and those taking supplemental vitamin D at the time of the study were excluded from participation, she noted.

Study patients were randomized in a 1:1 fashion to receive either 2,000 IU per day of oral cholecalciferol (vitamin D₃) or placebo for 6 months together with standard SLE treatment, Dr. Abou-Raya explained. Before and after 6 months of vitamin D supplementation, the investigators evaluated disease activity using the SLE disease activity index (SLEDAI), levels of serum 25-hydroxyvitamin D (25[OH]D) via DiaSorin’s Liaison immunoassay, levels of proinflammatory cytokines interleukin-1 (IL-1), IL-6, IL-18, tumor necrosis factor (TNF)–alpha, C-reactive protein (CRP), and the hemostatic markers fibrinogen and von Willebrand factor (vWF), she explained. Individuals with 25(OH)D levels of 10-30 ng/mL were classified as having vitamin D insufficiency and those with levels lower than 10 ng/mL were considered vitamin D deficient, she noted.

With respect to baseline demographics, the mean age of the SLE patients was 38.8 years and the mean disease duration was 5.2 years. The mean baseline vitamin D level in the SLE patients was 19.8 ng/mL, which was significantly lower than the mean 28.7 ng/mL in the control group, Dr. Abou-Raya reported. The baseline levels of the inflammatory and hemostatic markers were significantly higher in the SLE patients. "The overall prevalence of vitamin D insufficiency and deficiency, respectively, was 69% and 39%," she said.

At 6 months, "there was a significant decrease in levels of inflammatory and hemostatic makers in lupus patients who were supplemented with vitamin D" compared with patients who were given placebo together with ongoing therapy, Dr. Abou-Raya reported at the annual European Congress of Rheumatology in London. After multivariate adjustment, the investigators observed a negative correlation between vitamin D levels and IL-1, IL-6, IL-18, TNF-alpha, CRP, fibrinogen, and vWF, "and lower vitamin D levels were associated with significantly higher SLEDAI scores," she said.

The results suggest that hypovitaminosis D contributes to a chronic inflammatory and thrombophilic state in SLE patients, said Dr. Abou-Raya. "The findings support the routine recommendation for oral vitamin D supplementation in these patients," she said.

Dr. Abou-Raya disclosed having no financial conflicts of interest related to her presentation.

Major Finding: After 12 months, mean area under the curve SLEDAI scores were 18.7 for raloxifene-treated patients and 20.3 for placebo-treated patients, and mean area under the curve patient assessment scores were 2.2 in the treated group and 2.3 in the placebo group.

Data Source: A subgroup analysis of data from a 12-month randomized controlled trial looking at the effect of raloxifene and placebo on bone turnover, BMD, and disease activity in 62 postmenopausal women with SLE.

Disclosures: Dr. Mok reported having no financial conflicts of interest to disclose.

LONDON– Raloxifene did not increase lupus activity or flares in a 1-year trial of postmenopausal women who had systemic lupus erythematosus without hypercoagulability risk factors, Dr. Chi Chiu Mok reported.

Raloxifene has been shown in previous studies to preserve bone mineral density (BMD) after menopause in women with systemic lupus erythematosus (SLE). However, mild to moderate disease flares occurred in some patients in these small studies. Lupus flares are rare in postmenopausal women, so this finding suggested a possible association between raloxifene (Evista) and disease activity, explained Dr. Mok of Tuen Mun Hospital in Hong Kong.

Dr. Mok and his colleagues analyzed subgroup data from a 12-month, randomized, controlled trial that assessed bone turnover and BMD in 62 postmenopausal women who had no risk factors for arterial or venous thromboembolism and were being treated with glucocorticoids. The women were randomized to receive either 60 mg/day of raloxifene (30) or placebo (32) in addition to 1,000 mg/day of calcium and 0.25 mcg/day of calcitriol, Dr. Mok explained.

“The primary study outcome was [BMD] of the hip and spine, and secondary outcomes were bone-turnover markers and new vertebral fractures at 12 months,” he said.

In the overall study population, the mean duration of menopause was 7.2 years, the mean duration of treatment with prednisolone (mean daily dose of 6.8 mg) was 87 months, and the mean Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score at entry was 1.8, Dr. Mok said. The basic clinical characteristics were similar between the two groups, he noted.

After 12 months, “there was a significant gain in bone mineral density at the lumbar spine in the raloxifene patients but not in the placebo group. And there was a gain, though not significant, in the bone mineral density of the hip in the raloxifene-treated patients,” Dr. Mok reported. Similarly, markers of bone resorption and formation decreased significantly in the treatment group, he said.

At 12 months, there was no significant difference in the mean area under the curve SLEDAI scores, which were 18.7 in the raloxifene group and 20.3 in the placebo group, or in the mean area under the curve patient global assessments, which were 2.2 for raloxifene patients and 2.3 for placebo patients, Dr. Mok said.

Regarding disease flares, “there were three episodes of mild to moderate flares in the raloxifene patients, compared with nine in the placebo group,” he stated.

The researchers also assessed the effect of raloxifene on homocysteine and high-sensitivity C-reactive protein (hsCRP) levels and changes in atherosclerotic risk factors.

They observed a trend of decrease in homocysteine level in raloxifene patients only, no statistically significant changes in hsCRP levels in either group, significant increases in total and LDL cholesterol in the placebo-treated patients only, and no significant changes in systolic and diastolic blood pressure values in either group, Dr. Mok stated. “In the treatment group, [raloxifene] was well tolerated and there were no thromboembolic complications,” he said.

“As previous studies have shown, raloxifene offers protection against bone mineral density loss in postmenopausal women with lupus receiving long-term glucocorticoids,” Dr. Mok said in an interview. “These results show that it's safe and well tolerated in this population and does not increase lupus disease activity or disease flares.”

Dr. Mok disclosed having no financial conflicts of interest.

Major Finding: After 12 months, mean area under the curve SLEDAI scores were 18.7 for raloxifene-treated patients and 20.3 for placebo-treated patients, and mean area under the curve patient assessment scores were 2.2 in the treated group and 2.3 in the placebo group.

Data Source: A subgroup analysis of data from a 12-month randomized controlled trial looking at the effect of raloxifene and placebo on bone turnover, BMD, and disease activity in 62 postmenopausal women with SLE.

Disclosures: Dr. Mok reported having no financial conflicts of interest to disclose.

LONDON– Raloxifene did not increase lupus activity or flares in a 1-year trial of postmenopausal women who had systemic lupus erythematosus without hypercoagulability risk factors, Dr. Chi Chiu Mok reported.

Raloxifene has been shown in previous studies to preserve bone mineral density (BMD) after menopause in women with systemic lupus erythematosus (SLE). However, mild to moderate disease flares occurred in some patients in these small studies. Lupus flares are rare in postmenopausal women, so this finding suggested a possible association between raloxifene (Evista) and disease activity, explained Dr. Mok of Tuen Mun Hospital in Hong Kong.

Dr. Mok and his colleagues analyzed subgroup data from a 12-month, randomized, controlled trial that assessed bone turnover and BMD in 62 postmenopausal women who had no risk factors for arterial or venous thromboembolism and were being treated with glucocorticoids. The women were randomized to receive either 60 mg/day of raloxifene (30) or placebo (32) in addition to 1,000 mg/day of calcium and 0.25 mcg/day of calcitriol, Dr. Mok explained.

“The primary study outcome was [BMD] of the hip and spine, and secondary outcomes were bone-turnover markers and new vertebral fractures at 12 months,” he said.

In the overall study population, the mean duration of menopause was 7.2 years, the mean duration of treatment with prednisolone (mean daily dose of 6.8 mg) was 87 months, and the mean Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score at entry was 1.8, Dr. Mok said. The basic clinical characteristics were similar between the two groups, he noted.

After 12 months, “there was a significant gain in bone mineral density at the lumbar spine in the raloxifene patients but not in the placebo group. And there was a gain, though not significant, in the bone mineral density of the hip in the raloxifene-treated patients,” Dr. Mok reported. Similarly, markers of bone resorption and formation decreased significantly in the treatment group, he said.

At 12 months, there was no significant difference in the mean area under the curve SLEDAI scores, which were 18.7 in the raloxifene group and 20.3 in the placebo group, or in the mean area under the curve patient global assessments, which were 2.2 for raloxifene patients and 2.3 for placebo patients, Dr. Mok said.

Regarding disease flares, “there were three episodes of mild to moderate flares in the raloxifene patients, compared with nine in the placebo group,” he stated.

The researchers also assessed the effect of raloxifene on homocysteine and high-sensitivity C-reactive protein (hsCRP) levels and changes in atherosclerotic risk factors.

They observed a trend of decrease in homocysteine level in raloxifene patients only, no statistically significant changes in hsCRP levels in either group, significant increases in total and LDL cholesterol in the placebo-treated patients only, and no significant changes in systolic and diastolic blood pressure values in either group, Dr. Mok stated. “In the treatment group, [raloxifene] was well tolerated and there were no thromboembolic complications,” he said.

“As previous studies have shown, raloxifene offers protection against bone mineral density loss in postmenopausal women with lupus receiving long-term glucocorticoids,” Dr. Mok said in an interview. “These results show that it's safe and well tolerated in this population and does not increase lupus disease activity or disease flares.”

Dr. Mok disclosed having no financial conflicts of interest.

Major Finding: After 12 months, mean area under the curve SLEDAI scores were 18.7 for raloxifene-treated patients and 20.3 for placebo-treated patients, and mean area under the curve patient assessment scores were 2.2 in the treated group and 2.3 in the placebo group.

Data Source: A subgroup analysis of data from a 12-month randomized controlled trial looking at the effect of raloxifene and placebo on bone turnover, BMD, and disease activity in 62 postmenopausal women with SLE.

Disclosures: Dr. Mok reported having no financial conflicts of interest to disclose.

LONDON– Raloxifene did not increase lupus activity or flares in a 1-year trial of postmenopausal women who had systemic lupus erythematosus without hypercoagulability risk factors, Dr. Chi Chiu Mok reported.

Raloxifene has been shown in previous studies to preserve bone mineral density (BMD) after menopause in women with systemic lupus erythematosus (SLE). However, mild to moderate disease flares occurred in some patients in these small studies. Lupus flares are rare in postmenopausal women, so this finding suggested a possible association between raloxifene (Evista) and disease activity, explained Dr. Mok of Tuen Mun Hospital in Hong Kong.

Dr. Mok and his colleagues analyzed subgroup data from a 12-month, randomized, controlled trial that assessed bone turnover and BMD in 62 postmenopausal women who had no risk factors for arterial or venous thromboembolism and were being treated with glucocorticoids. The women were randomized to receive either 60 mg/day of raloxifene (30) or placebo (32) in addition to 1,000 mg/day of calcium and 0.25 mcg/day of calcitriol, Dr. Mok explained.

“The primary study outcome was [BMD] of the hip and spine, and secondary outcomes were bone-turnover markers and new vertebral fractures at 12 months,” he said.

In the overall study population, the mean duration of menopause was 7.2 years, the mean duration of treatment with prednisolone (mean daily dose of 6.8 mg) was 87 months, and the mean Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score at entry was 1.8, Dr. Mok said. The basic clinical characteristics were similar between the two groups, he noted.

After 12 months, “there was a significant gain in bone mineral density at the lumbar spine in the raloxifene patients but not in the placebo group. And there was a gain, though not significant, in the bone mineral density of the hip in the raloxifene-treated patients,” Dr. Mok reported. Similarly, markers of bone resorption and formation decreased significantly in the treatment group, he said.

At 12 months, there was no significant difference in the mean area under the curve SLEDAI scores, which were 18.7 in the raloxifene group and 20.3 in the placebo group, or in the mean area under the curve patient global assessments, which were 2.2 for raloxifene patients and 2.3 for placebo patients, Dr. Mok said.

Regarding disease flares, “there were three episodes of mild to moderate flares in the raloxifene patients, compared with nine in the placebo group,” he stated.

The researchers also assessed the effect of raloxifene on homocysteine and high-sensitivity C-reactive protein (hsCRP) levels and changes in atherosclerotic risk factors.

They observed a trend of decrease in homocysteine level in raloxifene patients only, no statistically significant changes in hsCRP levels in either group, significant increases in total and LDL cholesterol in the placebo-treated patients only, and no significant changes in systolic and diastolic blood pressure values in either group, Dr. Mok stated. “In the treatment group, [raloxifene] was well tolerated and there were no thromboembolic complications,” he said.

“As previous studies have shown, raloxifene offers protection against bone mineral density loss in postmenopausal women with lupus receiving long-term glucocorticoids,” Dr. Mok said in an interview. “These results show that it's safe and well tolerated in this population and does not increase lupus disease activity or disease flares.”

Dr. Mok disclosed having no financial conflicts of interest.

The science supporting vitamin D supplementation in lupus patients is catching up to the recommendation that all patients with the autoimmune disease increase their intake of the fat-soluble secosteroids.

Findings from a new study by Dr. Suzan Abou-Raya, professor of geriatric medicine at the University of Alexandria (Egypt), and her associates demonstrate that there is a high prevalence of vitamin D deficiency associated with an increased inflammatory burden and thrombophilic state in patients with systemic lupus erythematosus (SLE).

The findings also suggest that oral vitamin D supplementation ameliorates chronic inflammatory and hemostatic markers in this patient group.

The use of supplementary calcium and vitamin D is routinely recommended for SLE patients to help minimize the bone loss and increased risk of developing osteoporosis associated with the disease and its treatment. Beyond supporting bone and mineral hemostasis, “vitamin D is now recognized as having additional pleiotropic roles,” according to Dr. Abou-Raya.

“We've learned that it has potent immunomodulatory properties that have promoted its potential use in the treatment of autoimmune conditions, including lupus,” she said.

The study was designed to evaluate vitamin D status in lupus patients and to assess alterations in disease-related inflammatory and hemostatic markers before and after vitamin D supplementation.

To do this, Dr. Abou-Raya and her fellow researchers conducted a randomized, placebo-controlled trial comprising 148 males and premenopausal females who fulfilled the ACR (American College of Rheumatology) classification criteria for SLE. Also enrolled in the study were 75 lupus-free adults who served as controls and who matched the cases in age, sex, ethnicity, and body mass index. Individuals with other inflammatory disorders and those taking supplemental vitamin D at the time of the study were excluded, she noted.

Study patients were randomized in a 1:1 fashion to receive either 2,000 IU per day of oral cholecalciferol (vitamin D₃) or placebo for 6 months together with standard SLE treatment, Dr. Abou-Raya explained.

Before and after 6 months of vitamin D supplementation, the investigators evaluated disease activity using the SLE disease activity index (SLEDAI), levels of serum 25-hydroxyvitamin D (25[OH]D) via DiaSorin's Liaison immunoassay, levels of proinflammatory cytokines interleukin-1 (IL-1), IL-6, IL-18, tumor necrosis factor (TNF)–alpha, C-reactive protein (CRP), and the hemostatic markers fibrinogen and von Willebrand factor (vWF). Individuals with 25(OH)D levels of 10-30 ng/mL were classified as having vitamin D insufficiency; those with levels lower than 10 ng/mL were considered vitamin D deficient, she noted.

The mean age of the SLE patients was 38.8 years and the mean disease duration was 5.2 years. The mean baseline vitamin D level in the SLE patients, 19.8 ng/mL, was significantly lower than the mean 28.7 ng/mL in the control group. The baseline levels of the inflammatory and hemostatic markers were significantly higher in the SLE patients. “The overall prevalence of vitamin D insufficiency and deficiency, respectively, was 69% and 39%,” she said.

At 6 months, “there was a significant decrease in levels of inflammatory and hemostatic makers in lupus patients who were supplemented with vitamin D” compared with patients who were given placebo together with ongoing therapy, Dr. Abou-Raya reported at the annual European Congress of Rheumatology in London. After multivariate adjustment, there was a negative correlation between vitamin D levels and IL-1, IL-6, IL-18, TNF-alpha, CRP, fibrinogen, and vWF, “and lower vitamin D levels were associated with significantly higher SLEDAI scores,” she said.

The results suggest that hypovitaminosis D contributes to a chronic inflammatory and thrombophilic state in SLE patients, said Dr. Abou-Raya. “The findings support the routine recommendation for oral vitamin D supplementation,” she said.

Dr. Abou-Raya disclosed having no financial conflicts of interest related to her presentation.

The science supporting vitamin D supplementation in lupus patients is catching up to the recommendation that all patients with the autoimmune disease increase their intake of the fat-soluble secosteroids.

Findings from a new study by Dr. Suzan Abou-Raya, professor of geriatric medicine at the University of Alexandria (Egypt), and her associates demonstrate that there is a high prevalence of vitamin D deficiency associated with an increased inflammatory burden and thrombophilic state in patients with systemic lupus erythematosus (SLE).

The findings also suggest that oral vitamin D supplementation ameliorates chronic inflammatory and hemostatic markers in this patient group.

The use of supplementary calcium and vitamin D is routinely recommended for SLE patients to help minimize the bone loss and increased risk of developing osteoporosis associated with the disease and its treatment. Beyond supporting bone and mineral hemostasis, “vitamin D is now recognized as having additional pleiotropic roles,” according to Dr. Abou-Raya.

“We've learned that it has potent immunomodulatory properties that have promoted its potential use in the treatment of autoimmune conditions, including lupus,” she said.

The study was designed to evaluate vitamin D status in lupus patients and to assess alterations in disease-related inflammatory and hemostatic markers before and after vitamin D supplementation.

To do this, Dr. Abou-Raya and her fellow researchers conducted a randomized, placebo-controlled trial comprising 148 males and premenopausal females who fulfilled the ACR (American College of Rheumatology) classification criteria for SLE. Also enrolled in the study were 75 lupus-free adults who served as controls and who matched the cases in age, sex, ethnicity, and body mass index. Individuals with other inflammatory disorders and those taking supplemental vitamin D at the time of the study were excluded, she noted.

Study patients were randomized in a 1:1 fashion to receive either 2,000 IU per day of oral cholecalciferol (vitamin D₃) or placebo for 6 months together with standard SLE treatment, Dr. Abou-Raya explained.

Before and after 6 months of vitamin D supplementation, the investigators evaluated disease activity using the SLE disease activity index (SLEDAI), levels of serum 25-hydroxyvitamin D (25[OH]D) via DiaSorin's Liaison immunoassay, levels of proinflammatory cytokines interleukin-1 (IL-1), IL-6, IL-18, tumor necrosis factor (TNF)–alpha, C-reactive protein (CRP), and the hemostatic markers fibrinogen and von Willebrand factor (vWF). Individuals with 25(OH)D levels of 10-30 ng/mL were classified as having vitamin D insufficiency; those with levels lower than 10 ng/mL were considered vitamin D deficient, she noted.

The mean age of the SLE patients was 38.8 years and the mean disease duration was 5.2 years. The mean baseline vitamin D level in the SLE patients, 19.8 ng/mL, was significantly lower than the mean 28.7 ng/mL in the control group. The baseline levels of the inflammatory and hemostatic markers were significantly higher in the SLE patients. “The overall prevalence of vitamin D insufficiency and deficiency, respectively, was 69% and 39%,” she said.

At 6 months, “there was a significant decrease in levels of inflammatory and hemostatic makers in lupus patients who were supplemented with vitamin D” compared with patients who were given placebo together with ongoing therapy, Dr. Abou-Raya reported at the annual European Congress of Rheumatology in London. After multivariate adjustment, there was a negative correlation between vitamin D levels and IL-1, IL-6, IL-18, TNF-alpha, CRP, fibrinogen, and vWF, “and lower vitamin D levels were associated with significantly higher SLEDAI scores,” she said.

The results suggest that hypovitaminosis D contributes to a chronic inflammatory and thrombophilic state in SLE patients, said Dr. Abou-Raya. “The findings support the routine recommendation for oral vitamin D supplementation,” she said.

Dr. Abou-Raya disclosed having no financial conflicts of interest related to her presentation.

The science supporting vitamin D supplementation in lupus patients is catching up to the recommendation that all patients with the autoimmune disease increase their intake of the fat-soluble secosteroids.

Findings from a new study by Dr. Suzan Abou-Raya, professor of geriatric medicine at the University of Alexandria (Egypt), and her associates demonstrate that there is a high prevalence of vitamin D deficiency associated with an increased inflammatory burden and thrombophilic state in patients with systemic lupus erythematosus (SLE).

The findings also suggest that oral vitamin D supplementation ameliorates chronic inflammatory and hemostatic markers in this patient group.

The use of supplementary calcium and vitamin D is routinely recommended for SLE patients to help minimize the bone loss and increased risk of developing osteoporosis associated with the disease and its treatment. Beyond supporting bone and mineral hemostasis, “vitamin D is now recognized as having additional pleiotropic roles,” according to Dr. Abou-Raya.

“We've learned that it has potent immunomodulatory properties that have promoted its potential use in the treatment of autoimmune conditions, including lupus,” she said.

The study was designed to evaluate vitamin D status in lupus patients and to assess alterations in disease-related inflammatory and hemostatic markers before and after vitamin D supplementation.

To do this, Dr. Abou-Raya and her fellow researchers conducted a randomized, placebo-controlled trial comprising 148 males and premenopausal females who fulfilled the ACR (American College of Rheumatology) classification criteria for SLE. Also enrolled in the study were 75 lupus-free adults who served as controls and who matched the cases in age, sex, ethnicity, and body mass index. Individuals with other inflammatory disorders and those taking supplemental vitamin D at the time of the study were excluded, she noted.

Study patients were randomized in a 1:1 fashion to receive either 2,000 IU per day of oral cholecalciferol (vitamin D₃) or placebo for 6 months together with standard SLE treatment, Dr. Abou-Raya explained.

Before and after 6 months of vitamin D supplementation, the investigators evaluated disease activity using the SLE disease activity index (SLEDAI), levels of serum 25-hydroxyvitamin D (25[OH]D) via DiaSorin's Liaison immunoassay, levels of proinflammatory cytokines interleukin-1 (IL-1), IL-6, IL-18, tumor necrosis factor (TNF)–alpha, C-reactive protein (CRP), and the hemostatic markers fibrinogen and von Willebrand factor (vWF). Individuals with 25(OH)D levels of 10-30 ng/mL were classified as having vitamin D insufficiency; those with levels lower than 10 ng/mL were considered vitamin D deficient, she noted.

The mean age of the SLE patients was 38.8 years and the mean disease duration was 5.2 years. The mean baseline vitamin D level in the SLE patients, 19.8 ng/mL, was significantly lower than the mean 28.7 ng/mL in the control group. The baseline levels of the inflammatory and hemostatic markers were significantly higher in the SLE patients. “The overall prevalence of vitamin D insufficiency and deficiency, respectively, was 69% and 39%,” she said.

At 6 months, “there was a significant decrease in levels of inflammatory and hemostatic makers in lupus patients who were supplemented with vitamin D” compared with patients who were given placebo together with ongoing therapy, Dr. Abou-Raya reported at the annual European Congress of Rheumatology in London. After multivariate adjustment, there was a negative correlation between vitamin D levels and IL-1, IL-6, IL-18, TNF-alpha, CRP, fibrinogen, and vWF, “and lower vitamin D levels were associated with significantly higher SLEDAI scores,” she said.

The results suggest that hypovitaminosis D contributes to a chronic inflammatory and thrombophilic state in SLE patients, said Dr. Abou-Raya. “The findings support the routine recommendation for oral vitamin D supplementation,” she said.

Dr. Abou-Raya disclosed having no financial conflicts of interest related to her presentation.

Major Finding: The prevalence of suboptimal vitamin D levels in a cohort of elderly patients with chronic musculoskeletal pain was significantly higher, at 70%, than the 32% observed in age-, sex-, and BMI-matched patients who were pain free.

Data Source: An observational study comparing the serum vitamin D levels of 265 community-dwelling adults with chronic musculoskeletal pain aged 65 and older with those of 200 pain-free matched controls.

Disclosures: Dr. Abou-Raya reported having no financial conflicts of interest to disclose.

Is vitamin D a neglected analgesic for chronic musculoskeletal pain? Dr. Suzan Abou-Raya, professor of geriatric medicine at the University of Alexandria in Egypt, thinks it could be and recommends that physicians consider oral supplementation for all pain patients. Dr. Abou-Raya based her opinion on a recent study in which she and her colleagues evaluated the association between vitamin D status and chronic musculoskeletal pain in a cohort of community-dwelling older adults.

The investigators compared the vitamin D status of 265 adults aged 65 years and older who presented to their institution for musculoskeletal pain management with that of 200 other adults who were free of chronic musculoskeletal pain. These controls were matched to the cases by age, sex, and body mass index, said Dr. Abou-Raya. Individuals with known vitamin D deficiency and calcium abnormality were excluded from the study, as were those with severe cognitive impairment or infectious, blood, hepatic, and renal disorders.

All of the participants in the study (conducted during the months of April through September to account for seasonal variation) were surveyd about sun exposure and nutritional intake to assess daily intake of vitamin D and calcium, Dr. Abou-Raya said. They underwent a comprehensive clinical examination, with pain assessed using the Brief Pain Inventory and Visual Analogue Scale.

“Chronic pain was defined as pain that was present in the previous month and for at least 3 months during the previous year, and it was assessed according to the site of pain, the overall severity of the pain, and interference with daily activities,” she said. Also, all of the patients completed a joint pain questionnaire to assess chronic musculoskeletal pain in the hands and wrists, shoulders, back, hips, knees, and feet, and they were directed to record daily pain in a diary.

Levels of pain were assessed at monthly intervals, as was physical performance using activities of daily living, grip strength, 6-minute walk distance, and the timed Get up and Go Test of mobility. Additionally, serum vitamin D was measured by Liaison immunoassay and levels between 10 and 30 ng/ml were classified as vitamin D insufficiency and levels lower than 10 ng/ml were classified as vitamin D deficiency, she noted.

In musculoskeletal patients, the mean 25-hydroxyvitamin D level was 18.4 ng/ml compared with 28.9 ng/ml in the control group, which represents a statistically significant difference, Dr. Abou-Raya reported. “The overall prevalence of suboptimal vitamin D levels among patients was 70% vs. 32% in the controls,” she said, noting that 41% of the chronic musculoskeletal pain patients and only 1% of the controls met the criteria for vitamin D deficiency.

After multivariate adjustment, “chronic, multisite, musculoskeletal pain was associated with lower levels of 25-hydroxy-vitamin D, and lower levels of vitamin D correlated with pain severity and poor physical performance,” Dr. Abou-Raya stated. Sun exposure in the chronic pain group was significantly lower, with 40% of pain patients reporting they received fewer than 15 minutes of sun exposure weekly versus 11% of the controls.

“The possibility of inadequate vitamin D should be considered in the differential diagnosis of chronic musculoskeletal pain sufferers,” she said at the annual European Congress of Rheumatology.

Major Finding: The prevalence of suboptimal vitamin D levels in a cohort of elderly patients with chronic musculoskeletal pain was significantly higher, at 70%, than the 32% observed in age-, sex-, and BMI-matched patients who were pain free.

Data Source: An observational study comparing the serum vitamin D levels of 265 community-dwelling adults with chronic musculoskeletal pain aged 65 and older with those of 200 pain-free matched controls.

Disclosures: Dr. Abou-Raya reported having no financial conflicts of interest to disclose.

Is vitamin D a neglected analgesic for chronic musculoskeletal pain? Dr. Suzan Abou-Raya, professor of geriatric medicine at the University of Alexandria in Egypt, thinks it could be and recommends that physicians consider oral supplementation for all pain patients. Dr. Abou-Raya based her opinion on a recent study in which she and her colleagues evaluated the association between vitamin D status and chronic musculoskeletal pain in a cohort of community-dwelling older adults.

The investigators compared the vitamin D status of 265 adults aged 65 years and older who presented to their institution for musculoskeletal pain management with that of 200 other adults who were free of chronic musculoskeletal pain. These controls were matched to the cases by age, sex, and body mass index, said Dr. Abou-Raya. Individuals with known vitamin D deficiency and calcium abnormality were excluded from the study, as were those with severe cognitive impairment or infectious, blood, hepatic, and renal disorders.

All of the participants in the study (conducted during the months of April through September to account for seasonal variation) were surveyd about sun exposure and nutritional intake to assess daily intake of vitamin D and calcium, Dr. Abou-Raya said. They underwent a comprehensive clinical examination, with pain assessed using the Brief Pain Inventory and Visual Analogue Scale.

“Chronic pain was defined as pain that was present in the previous month and for at least 3 months during the previous year, and it was assessed according to the site of pain, the overall severity of the pain, and interference with daily activities,” she said. Also, all of the patients completed a joint pain questionnaire to assess chronic musculoskeletal pain in the hands and wrists, shoulders, back, hips, knees, and feet, and they were directed to record daily pain in a diary.

Levels of pain were assessed at monthly intervals, as was physical performance using activities of daily living, grip strength, 6-minute walk distance, and the timed Get up and Go Test of mobility. Additionally, serum vitamin D was measured by Liaison immunoassay and levels between 10 and 30 ng/ml were classified as vitamin D insufficiency and levels lower than 10 ng/ml were classified as vitamin D deficiency, she noted.

In musculoskeletal patients, the mean 25-hydroxyvitamin D level was 18.4 ng/ml compared with 28.9 ng/ml in the control group, which represents a statistically significant difference, Dr. Abou-Raya reported. “The overall prevalence of suboptimal vitamin D levels among patients was 70% vs. 32% in the controls,” she said, noting that 41% of the chronic musculoskeletal pain patients and only 1% of the controls met the criteria for vitamin D deficiency.

After multivariate adjustment, “chronic, multisite, musculoskeletal pain was associated with lower levels of 25-hydroxy-vitamin D, and lower levels of vitamin D correlated with pain severity and poor physical performance,” Dr. Abou-Raya stated. Sun exposure in the chronic pain group was significantly lower, with 40% of pain patients reporting they received fewer than 15 minutes of sun exposure weekly versus 11% of the controls.

“The possibility of inadequate vitamin D should be considered in the differential diagnosis of chronic musculoskeletal pain sufferers,” she said at the annual European Congress of Rheumatology.

Major Finding: The prevalence of suboptimal vitamin D levels in a cohort of elderly patients with chronic musculoskeletal pain was significantly higher, at 70%, than the 32% observed in age-, sex-, and BMI-matched patients who were pain free.

Data Source: An observational study comparing the serum vitamin D levels of 265 community-dwelling adults with chronic musculoskeletal pain aged 65 and older with those of 200 pain-free matched controls.

Disclosures: Dr. Abou-Raya reported having no financial conflicts of interest to disclose.

Is vitamin D a neglected analgesic for chronic musculoskeletal pain? Dr. Suzan Abou-Raya, professor of geriatric medicine at the University of Alexandria in Egypt, thinks it could be and recommends that physicians consider oral supplementation for all pain patients. Dr. Abou-Raya based her opinion on a recent study in which she and her colleagues evaluated the association between vitamin D status and chronic musculoskeletal pain in a cohort of community-dwelling older adults.

The investigators compared the vitamin D status of 265 adults aged 65 years and older who presented to their institution for musculoskeletal pain management with that of 200 other adults who were free of chronic musculoskeletal pain. These controls were matched to the cases by age, sex, and body mass index, said Dr. Abou-Raya. Individuals with known vitamin D deficiency and calcium abnormality were excluded from the study, as were those with severe cognitive impairment or infectious, blood, hepatic, and renal disorders.

All of the participants in the study (conducted during the months of April through September to account for seasonal variation) were surveyd about sun exposure and nutritional intake to assess daily intake of vitamin D and calcium, Dr. Abou-Raya said. They underwent a comprehensive clinical examination, with pain assessed using the Brief Pain Inventory and Visual Analogue Scale.

“Chronic pain was defined as pain that was present in the previous month and for at least 3 months during the previous year, and it was assessed according to the site of pain, the overall severity of the pain, and interference with daily activities,” she said. Also, all of the patients completed a joint pain questionnaire to assess chronic musculoskeletal pain in the hands and wrists, shoulders, back, hips, knees, and feet, and they were directed to record daily pain in a diary.

Levels of pain were assessed at monthly intervals, as was physical performance using activities of daily living, grip strength, 6-minute walk distance, and the timed Get up and Go Test of mobility. Additionally, serum vitamin D was measured by Liaison immunoassay and levels between 10 and 30 ng/ml were classified as vitamin D insufficiency and levels lower than 10 ng/ml were classified as vitamin D deficiency, she noted.

In musculoskeletal patients, the mean 25-hydroxyvitamin D level was 18.4 ng/ml compared with 28.9 ng/ml in the control group, which represents a statistically significant difference, Dr. Abou-Raya reported. “The overall prevalence of suboptimal vitamin D levels among patients was 70% vs. 32% in the controls,” she said, noting that 41% of the chronic musculoskeletal pain patients and only 1% of the controls met the criteria for vitamin D deficiency.

After multivariate adjustment, “chronic, multisite, musculoskeletal pain was associated with lower levels of 25-hydroxy-vitamin D, and lower levels of vitamin D correlated with pain severity and poor physical performance,” Dr. Abou-Raya stated. Sun exposure in the chronic pain group was significantly lower, with 40% of pain patients reporting they received fewer than 15 minutes of sun exposure weekly versus 11% of the controls.

“The possibility of inadequate vitamin D should be considered in the differential diagnosis of chronic musculoskeletal pain sufferers,” she said at the annual European Congress of Rheumatology.

“Any senior scientist will tell you that the biggest conflict of interest he or she has has nothing to do with the [disclosures] they list on their PowerPoints or in their publications,” Dr. Paul M. Ridker said at his talk on the inflammatory hypothesis of atherosclerosis at the meeting of the International Society on Hypertension in Blacks in Boston. “It has to do with our individual belief in the biology of what we're doing.”

For this reason, his lengthy disclosure slide was less relevant than his fundamental bias, which is his belief that inflammation is “part and parcel, if not the cause, of atherosclerosis.” That type of bias, not industry support, “is what drives my work, and it is what drives most scientists,” stressed Dr. Ridker of Brigham and Women's Hospital in Boston.

That contention is likely a nod to the diatribe that followed the 2008 publication of the JUPITER trial results, in which he and his coinvestigators attributed a 44% reduction in cardiovascular events to the ability of rosuvastatin (Crestor) to both lower LDL cholesterol and reduce C-reactive protein (CRP) levels (N. Engl. J. Med. 2008;359:2195-207).

Following the publication of the findings, cardiology colleagues questioned the interpretation and veracity of the data in the face of what they deemed to be an unacceptable degree of commercial bias. They were referring not only to the fact that the study was funded by AstraZeneca, the drug's manufacturer, and that 9 of the 14 authors disclosed financial ties to the company, but also that Dr. Ridker holds the legal patent on CRP testing technology. Without question, the skeptics argued, Dr. Ridker had much to gain from the acceptance of his research.

For his part, Dr. Ridker vigorously defends the quality of the JUPITER data. He has also introduced a salient argument, that the COIs that have the most potential to bias research are the ones that defy enumeration. He does not argue against financial disclosures, but he does warn that they don't tell the “whole story.”

“Any senior scientist will tell you that the biggest conflict of interest he or she has has nothing to do with the [disclosures] they list on their PowerPoints or in their publications,” Dr. Paul M. Ridker said at his talk on the inflammatory hypothesis of atherosclerosis at the meeting of the International Society on Hypertension in Blacks in Boston. “It has to do with our individual belief in the biology of what we're doing.”

For this reason, his lengthy disclosure slide was less relevant than his fundamental bias, which is his belief that inflammation is “part and parcel, if not the cause, of atherosclerosis.” That type of bias, not industry support, “is what drives my work, and it is what drives most scientists,” stressed Dr. Ridker of Brigham and Women's Hospital in Boston.

That contention is likely a nod to the diatribe that followed the 2008 publication of the JUPITER trial results, in which he and his coinvestigators attributed a 44% reduction in cardiovascular events to the ability of rosuvastatin (Crestor) to both lower LDL cholesterol and reduce C-reactive protein (CRP) levels (N. Engl. J. Med. 2008;359:2195-207).

Following the publication of the findings, cardiology colleagues questioned the interpretation and veracity of the data in the face of what they deemed to be an unacceptable degree of commercial bias. They were referring not only to the fact that the study was funded by AstraZeneca, the drug's manufacturer, and that 9 of the 14 authors disclosed financial ties to the company, but also that Dr. Ridker holds the legal patent on CRP testing technology. Without question, the skeptics argued, Dr. Ridker had much to gain from the acceptance of his research.

For his part, Dr. Ridker vigorously defends the quality of the JUPITER data. He has also introduced a salient argument, that the COIs that have the most potential to bias research are the ones that defy enumeration. He does not argue against financial disclosures, but he does warn that they don't tell the “whole story.”

“Any senior scientist will tell you that the biggest conflict of interest he or she has has nothing to do with the [disclosures] they list on their PowerPoints or in their publications,” Dr. Paul M. Ridker said at his talk on the inflammatory hypothesis of atherosclerosis at the meeting of the International Society on Hypertension in Blacks in Boston. “It has to do with our individual belief in the biology of what we're doing.”

For this reason, his lengthy disclosure slide was less relevant than his fundamental bias, which is his belief that inflammation is “part and parcel, if not the cause, of atherosclerosis.” That type of bias, not industry support, “is what drives my work, and it is what drives most scientists,” stressed Dr. Ridker of Brigham and Women's Hospital in Boston.

That contention is likely a nod to the diatribe that followed the 2008 publication of the JUPITER trial results, in which he and his coinvestigators attributed a 44% reduction in cardiovascular events to the ability of rosuvastatin (Crestor) to both lower LDL cholesterol and reduce C-reactive protein (CRP) levels (N. Engl. J. Med. 2008;359:2195-207).

Following the publication of the findings, cardiology colleagues questioned the interpretation and veracity of the data in the face of what they deemed to be an unacceptable degree of commercial bias. They were referring not only to the fact that the study was funded by AstraZeneca, the drug's manufacturer, and that 9 of the 14 authors disclosed financial ties to the company, but also that Dr. Ridker holds the legal patent on CRP testing technology. Without question, the skeptics argued, Dr. Ridker had much to gain from the acceptance of his research.

For his part, Dr. Ridker vigorously defends the quality of the JUPITER data. He has also introduced a salient argument, that the COIs that have the most potential to bias research are the ones that defy enumeration. He does not argue against financial disclosures, but he does warn that they don't tell the “whole story.”

Is vitamin D a neglected analgesic for chronic musculoskeletal pain? Dr. Suzan Abou-Raya, professor of geriatric medicine at the University of Alexandria in Egypt, thinks it could be and recommends that physicians should consider oral supplementation for all pain patients. Dr. Abou-Raya based her opinion on the findings of a recent study in which she and her colleagues evaluated the association between vitamin D status and chronic musculoskeletal pain in a cohort of community-dwelling older adults.

The investigators compared the vitamin D status of 265 adults aged 65 years and older who presented to their institution for musculoskeletal pain management with that of 200 other adults who were free of chronic musculoskeletal pain. These controls were matched to the cases by age, sex, and body mass index, according to Dr. Abou-Raya. Individuals with known vitamin D deficiency and calcium abnormality were excluded from the study, as were those with severe cognitive impairment or infectious, blood, hepatic, and renal disorders.

All of the participants in the study, which was conducted during the months of April through September to account for seasonal variation, underwent an initial survey about sun exposure and nutritional intake to assess daily intake of vitamin D and calcium, Dr. Abou-Raya explained. All of the participants underwent a comprehensive clinical examination, during which pain was assessed using the Brief Pain Inventory and Visual Analogue Scale. "Chronic pain was defined as pain that was present in the previous month and for at least 3 months during the previous year, and it was assessed according to the site of pain, the overall severity of the pain, and interference with daily activities," she said. Additionally, all of the patients completed a joint pain questionnaire to assess chronic musculoskeletal pain in the hands and wrists, shoulders, back, hips, knees, and feet, and they were directed to record daily pain in a diary.

Levels of pain were assessed at monthly intervals during follow-up, as was physical performance using activities of daily living, grip strength, six-minute walk distance, and the timed Get up and Go Test of mobility, Dr. Abou-Raya stated. Additionally, serum vitamin D was measured by Liaison immunoassay and levels between 10 and 30 ng/ml were classified as vitamin D insufficiency and levels lower than 10 ng/ml were classified as vitamin D deficiency, she noted.

In musculoskeletal patients, the mean 25-hydroxy vitamin D level was 18.4 ng/ml compared with 28.9 ng/ml in the control group, which represents a statistically significant difference, Dr. Abou-Raya reported. "The overall prevalence of suboptimal vitamin D levels among patients was 70% vs. 32% in the controls," she said, noting that 41% of the chronic musculoskeletal pain patients and only 1% of the controls met the criteria for vitamin D deficiency. "We also found that patients with multisite chronic pain had significantly lower levels of vitamin D compared with patients reporting sing-site chronic pain, and patients with more severe pain at baseline had significantly lower vitamin D levels than those with less severe pain."

After multivariate adjustment, "chronic, multisite, musculoskeletal pain was associated with lower levels of 25-hydroxy vitamin D, and lower levels of vitamin D correlated with pain severity and poor physical performance," Dr. Abou-Raya stated. One likely contributing factor is that sun exposure in the chronic pain group was significantly lower than that of the controls, with 40% of the pain patients reporting that they received fewer than 15 minutes of sun exposure weekly compared with 11% of the controls, likely due to limitations on physical activity associated with chronic pain, she said.

The results of this observational study should not be used to infer causation, Dr. Abou-Raya stressed. "They simply demonstrate that patients with chronic musculoskeletal pain have lower levels of vitamin D compared with individuals who are pain free, thus the possibility of inadequate vitamin D should be considered in the differential diagnosis of chronic musculoskeletal pain sufferers," she said at the annual European Congress of Rheumatology.

The implication of the findings, she continued, "is that all patients with chronic musculoskeletal pain should receive oral vitamin D supplementation, as optimal vitamin D levels appear to be associated with less pain and better physical performance."

Dr. Abou-Raya disclosed having no financial conflicts of interest related to her presentation.

Is vitamin D a neglected analgesic for chronic musculoskeletal pain? Dr. Suzan Abou-Raya, professor of geriatric medicine at the University of Alexandria in Egypt, thinks it could be and recommends that physicians should consider oral supplementation for all pain patients. Dr. Abou-Raya based her opinion on the findings of a recent study in which she and her colleagues evaluated the association between vitamin D status and chronic musculoskeletal pain in a cohort of community-dwelling older adults.

The investigators compared the vitamin D status of 265 adults aged 65 years and older who presented to their institution for musculoskeletal pain management with that of 200 other adults who were free of chronic musculoskeletal pain. These controls were matched to the cases by age, sex, and body mass index, according to Dr. Abou-Raya. Individuals with known vitamin D deficiency and calcium abnormality were excluded from the study, as were those with severe cognitive impairment or infectious, blood, hepatic, and renal disorders.

All of the participants in the study, which was conducted during the months of April through September to account for seasonal variation, underwent an initial survey about sun exposure and nutritional intake to assess daily intake of vitamin D and calcium, Dr. Abou-Raya explained. All of the participants underwent a comprehensive clinical examination, during which pain was assessed using the Brief Pain Inventory and Visual Analogue Scale. "Chronic pain was defined as pain that was present in the previous month and for at least 3 months during the previous year, and it was assessed according to the site of pain, the overall severity of the pain, and interference with daily activities," she said. Additionally, all of the patients completed a joint pain questionnaire to assess chronic musculoskeletal pain in the hands and wrists, shoulders, back, hips, knees, and feet, and they were directed to record daily pain in a diary.

Levels of pain were assessed at monthly intervals during follow-up, as was physical performance using activities of daily living, grip strength, six-minute walk distance, and the timed Get up and Go Test of mobility, Dr. Abou-Raya stated. Additionally, serum vitamin D was measured by Liaison immunoassay and levels between 10 and 30 ng/ml were classified as vitamin D insufficiency and levels lower than 10 ng/ml were classified as vitamin D deficiency, she noted.

In musculoskeletal patients, the mean 25-hydroxy vitamin D level was 18.4 ng/ml compared with 28.9 ng/ml in the control group, which represents a statistically significant difference, Dr. Abou-Raya reported. "The overall prevalence of suboptimal vitamin D levels among patients was 70% vs. 32% in the controls," she said, noting that 41% of the chronic musculoskeletal pain patients and only 1% of the controls met the criteria for vitamin D deficiency. "We also found that patients with multisite chronic pain had significantly lower levels of vitamin D compared with patients reporting sing-site chronic pain, and patients with more severe pain at baseline had significantly lower vitamin D levels than those with less severe pain."

After multivariate adjustment, "chronic, multisite, musculoskeletal pain was associated with lower levels of 25-hydroxy vitamin D, and lower levels of vitamin D correlated with pain severity and poor physical performance," Dr. Abou-Raya stated. One likely contributing factor is that sun exposure in the chronic pain group was significantly lower than that of the controls, with 40% of the pain patients reporting that they received fewer than 15 minutes of sun exposure weekly compared with 11% of the controls, likely due to limitations on physical activity associated with chronic pain, she said.

The results of this observational study should not be used to infer causation, Dr. Abou-Raya stressed. "They simply demonstrate that patients with chronic musculoskeletal pain have lower levels of vitamin D compared with individuals who are pain free, thus the possibility of inadequate vitamin D should be considered in the differential diagnosis of chronic musculoskeletal pain sufferers," she said at the annual European Congress of Rheumatology.

The implication of the findings, she continued, "is that all patients with chronic musculoskeletal pain should receive oral vitamin D supplementation, as optimal vitamin D levels appear to be associated with less pain and better physical performance."

Dr. Abou-Raya disclosed having no financial conflicts of interest related to her presentation.

Is vitamin D a neglected analgesic for chronic musculoskeletal pain? Dr. Suzan Abou-Raya, professor of geriatric medicine at the University of Alexandria in Egypt, thinks it could be and recommends that physicians should consider oral supplementation for all pain patients. Dr. Abou-Raya based her opinion on the findings of a recent study in which she and her colleagues evaluated the association between vitamin D status and chronic musculoskeletal pain in a cohort of community-dwelling older adults.

The investigators compared the vitamin D status of 265 adults aged 65 years and older who presented to their institution for musculoskeletal pain management with that of 200 other adults who were free of chronic musculoskeletal pain. These controls were matched to the cases by age, sex, and body mass index, according to Dr. Abou-Raya. Individuals with known vitamin D deficiency and calcium abnormality were excluded from the study, as were those with severe cognitive impairment or infectious, blood, hepatic, and renal disorders.

All of the participants in the study, which was conducted during the months of April through September to account for seasonal variation, underwent an initial survey about sun exposure and nutritional intake to assess daily intake of vitamin D and calcium, Dr. Abou-Raya explained. All of the participants underwent a comprehensive clinical examination, during which pain was assessed using the Brief Pain Inventory and Visual Analogue Scale. "Chronic pain was defined as pain that was present in the previous month and for at least 3 months during the previous year, and it was assessed according to the site of pain, the overall severity of the pain, and interference with daily activities," she said. Additionally, all of the patients completed a joint pain questionnaire to assess chronic musculoskeletal pain in the hands and wrists, shoulders, back, hips, knees, and feet, and they were directed to record daily pain in a diary.

Levels of pain were assessed at monthly intervals during follow-up, as was physical performance using activities of daily living, grip strength, six-minute walk distance, and the timed Get up and Go Test of mobility, Dr. Abou-Raya stated. Additionally, serum vitamin D was measured by Liaison immunoassay and levels between 10 and 30 ng/ml were classified as vitamin D insufficiency and levels lower than 10 ng/ml were classified as vitamin D deficiency, she noted.

In musculoskeletal patients, the mean 25-hydroxy vitamin D level was 18.4 ng/ml compared with 28.9 ng/ml in the control group, which represents a statistically significant difference, Dr. Abou-Raya reported. "The overall prevalence of suboptimal vitamin D levels among patients was 70% vs. 32% in the controls," she said, noting that 41% of the chronic musculoskeletal pain patients and only 1% of the controls met the criteria for vitamin D deficiency. "We also found that patients with multisite chronic pain had significantly lower levels of vitamin D compared with patients reporting sing-site chronic pain, and patients with more severe pain at baseline had significantly lower vitamin D levels than those with less severe pain."

After multivariate adjustment, "chronic, multisite, musculoskeletal pain was associated with lower levels of 25-hydroxy vitamin D, and lower levels of vitamin D correlated with pain severity and poor physical performance," Dr. Abou-Raya stated. One likely contributing factor is that sun exposure in the chronic pain group was significantly lower than that of the controls, with 40% of the pain patients reporting that they received fewer than 15 minutes of sun exposure weekly compared with 11% of the controls, likely due to limitations on physical activity associated with chronic pain, she said.

The results of this observational study should not be used to infer causation, Dr. Abou-Raya stressed. "They simply demonstrate that patients with chronic musculoskeletal pain have lower levels of vitamin D compared with individuals who are pain free, thus the possibility of inadequate vitamin D should be considered in the differential diagnosis of chronic musculoskeletal pain sufferers," she said at the annual European Congress of Rheumatology.

The implication of the findings, she continued, "is that all patients with chronic musculoskeletal pain should receive oral vitamin D supplementation, as optimal vitamin D levels appear to be associated with less pain and better physical performance."

Dr. Abou-Raya disclosed having no financial conflicts of interest related to her presentation.

MINNEAPOLIS – Simpler may be better when it comes to screening pregnant women for sleep apnea, a study has shown.

In a cohort of pregnant women who completed a sleep survey and participated in an overnight sleep evaluation, a two-question screening approach yielded more accurate results than did standard screening tools, including the Berlin Questionnaire (BQ) and the Epworth Sleepiness Scale (ESS), Dr. Francesca L. Facco reported at the annual meeting of the Associated Professional Sleep Societies.

"Using prepregnancy body mass index and self-reported snoring had a much better sensitivity than the conventional methods, without sacrificing much specificity," she said.

To compare the screening approaches, Dr. Facco of the department of ob.gyn. at Northwestern University, Chicago, and her colleagues recruited 86 high-risk pregnant women, including those with chronic hypertension, pregestational diabetes, obesity, or a prior history of pre-eclampsia, to complete the sleep survey, which consisted of the BQ and ESS measures.

The women also underwent an overnight sleep evaluation using Itamar Medical’s Watch-PAT100 (WP100), a wrist-mounted, ambulatory device designed to diagnose sleep apnea. For this study, sleep apnea was defined as an apnea-hypopnea index score of five or more episodes of disturbed sleep per hour. Patients’ prepregnancy BMI and self-reporting snoring status were recorded as well. "Patients with a prepregnancy BMI of 25 [kg/m²] or higher who also reported snoring were considered to be screen positive" for apnea, Dr. Facco said.

The investigators assessed the performance of the BQ, ESS, and two-question measures relative to the data acquired from the WP100 devices using receiver operating characteristic (ROC) curves, and determined that the two-question approach performed better than the BQ alone, the BQ and ESS combined, and the null hypothesis, according to Dr. Facco. The sensitivity of the combined BQ and ESS was 35% and the specificity was 69%, compared with 74% and 59%, respectively, for the two-question approach.

"The results suggest that standard screening tools for sleep apnea, which have a high sensitivity and specificity in nonpregnant individuals, are inadequate for the assessment of sleep apnea in pregnancy," Dr. Facco said. Modifications that take into account the predictive value of prepregnancy BMI and snoring are warranted, she said, stressing that additional studies are needed to design and test the most appropriate measure for sleep apnea screening in pregnancy.

Because sleep apnea may be associated with complications during pregnancy and with adverse pregnancy outcomes, screening for the disorder should be considered for all pregnant women, and particularly those who are considered to be at high risk, Dr. Facco said.

Dr. Facco disclosed no financial conflicts of interest related to this presentation.

MINNEAPOLIS – Simpler may be better when it comes to screening pregnant women for sleep apnea, a study has shown.

In a cohort of pregnant women who completed a sleep survey and participated in an overnight sleep evaluation, a two-question screening approach yielded more accurate results than did standard screening tools, including the Berlin Questionnaire (BQ) and the Epworth Sleepiness Scale (ESS), Dr. Francesca L. Facco reported at the annual meeting of the Associated Professional Sleep Societies.

"Using prepregnancy body mass index and self-reported snoring had a much better sensitivity than the conventional methods, without sacrificing much specificity," she said.

To compare the screening approaches, Dr. Facco of the department of ob.gyn. at Northwestern University, Chicago, and her colleagues recruited 86 high-risk pregnant women, including those with chronic hypertension, pregestational diabetes, obesity, or a prior history of pre-eclampsia, to complete the sleep survey, which consisted of the BQ and ESS measures.

The women also underwent an overnight sleep evaluation using Itamar Medical’s Watch-PAT100 (WP100), a wrist-mounted, ambulatory device designed to diagnose sleep apnea. For this study, sleep apnea was defined as an apnea-hypopnea index score of five or more episodes of disturbed sleep per hour. Patients’ prepregnancy BMI and self-reporting snoring status were recorded as well. "Patients with a prepregnancy BMI of 25 [kg/m²] or higher who also reported snoring were considered to be screen positive" for apnea, Dr. Facco said.

The investigators assessed the performance of the BQ, ESS, and two-question measures relative to the data acquired from the WP100 devices using receiver operating characteristic (ROC) curves, and determined that the two-question approach performed better than the BQ alone, the BQ and ESS combined, and the null hypothesis, according to Dr. Facco. The sensitivity of the combined BQ and ESS was 35% and the specificity was 69%, compared with 74% and 59%, respectively, for the two-question approach.

"The results suggest that standard screening tools for sleep apnea, which have a high sensitivity and specificity in nonpregnant individuals, are inadequate for the assessment of sleep apnea in pregnancy," Dr. Facco said. Modifications that take into account the predictive value of prepregnancy BMI and snoring are warranted, she said, stressing that additional studies are needed to design and test the most appropriate measure for sleep apnea screening in pregnancy.

Because sleep apnea may be associated with complications during pregnancy and with adverse pregnancy outcomes, screening for the disorder should be considered for all pregnant women, and particularly those who are considered to be at high risk, Dr. Facco said.

Dr. Facco disclosed no financial conflicts of interest related to this presentation.

MINNEAPOLIS – Simpler may be better when it comes to screening pregnant women for sleep apnea, a study has shown.

In a cohort of pregnant women who completed a sleep survey and participated in an overnight sleep evaluation, a two-question screening approach yielded more accurate results than did standard screening tools, including the Berlin Questionnaire (BQ) and the Epworth Sleepiness Scale (ESS), Dr. Francesca L. Facco reported at the annual meeting of the Associated Professional Sleep Societies.

"Using prepregnancy body mass index and self-reported snoring had a much better sensitivity than the conventional methods, without sacrificing much specificity," she said.

To compare the screening approaches, Dr. Facco of the department of ob.gyn. at Northwestern University, Chicago, and her colleagues recruited 86 high-risk pregnant women, including those with chronic hypertension, pregestational diabetes, obesity, or a prior history of pre-eclampsia, to complete the sleep survey, which consisted of the BQ and ESS measures.

The women also underwent an overnight sleep evaluation using Itamar Medical’s Watch-PAT100 (WP100), a wrist-mounted, ambulatory device designed to diagnose sleep apnea. For this study, sleep apnea was defined as an apnea-hypopnea index score of five or more episodes of disturbed sleep per hour. Patients’ prepregnancy BMI and self-reporting snoring status were recorded as well. "Patients with a prepregnancy BMI of 25 [kg/m²] or higher who also reported snoring were considered to be screen positive" for apnea, Dr. Facco said.

The investigators assessed the performance of the BQ, ESS, and two-question measures relative to the data acquired from the WP100 devices using receiver operating characteristic (ROC) curves, and determined that the two-question approach performed better than the BQ alone, the BQ and ESS combined, and the null hypothesis, according to Dr. Facco. The sensitivity of the combined BQ and ESS was 35% and the specificity was 69%, compared with 74% and 59%, respectively, for the two-question approach.

"The results suggest that standard screening tools for sleep apnea, which have a high sensitivity and specificity in nonpregnant individuals, are inadequate for the assessment of sleep apnea in pregnancy," Dr. Facco said. Modifications that take into account the predictive value of prepregnancy BMI and snoring are warranted, she said, stressing that additional studies are needed to design and test the most appropriate measure for sleep apnea screening in pregnancy.

Because sleep apnea may be associated with complications during pregnancy and with adverse pregnancy outcomes, screening for the disorder should be considered for all pregnant women, and particularly those who are considered to be at high risk, Dr. Facco said.

Dr. Facco disclosed no financial conflicts of interest related to this presentation.