Sherry Boschert

HOUSTON – The U.S. Environmental Protection Agency and other groups that evaluate chemicals need to assess endocrine-disrupting chemicals during critical life periods and strengthen screening programs to identify such chemicals, according to recommendations from the Endocrine Society.

"We believe now that the science behind endocrine-disrupting chemicals [EDCs] is incredibly strong," said Andrea C. Gore, Ph.D., professor of pharmacology and toxicology at the University of Texas, Austin. "The current regulatory process is not up to the standards that endocrinologists would use in their own labs," added Dr. Gore, one of the authors of a statement from the society.

For those reasons, the society released a set of principles calling for acknowledgement that changes in hormone action from EDC exposure during development are not correctable, and that they permanently and adversely affect cognitive function and other aspects of health. In addition, the newly released principles call for an acknowledgement that people are exposed to multiple EDCs in daily life, and that these exposures can have a cumulative effect.

Sherry Boschert/IMNG Medical Media

The Endocrine Society also recommended a simplified definition of endocrine-disrupting chemicals in light of mounting evidence of potential harm from exposure to them. By that definition, an EDC would be defined as an exogenous chemical (or mixture of chemicals) that interferes with any aspect of hormone action, Dr. Gore said at the annual meeting of the Endocrine Society.

The ability of a chemical to interfere with any aspect of hormone action is a clear predictor of adverse outcomes if a person is exposed during critical periods or developmental processes, said Dr. Gore.

Furthermore, "low-dose testing is absolutely critical," she said. "There is no safe dose, studies suggest."

The society released the statement of principles online in advance of publication in the journal Endocrinology (2012 June 25 [doi:10.1210/en.2012-1422]). The document updates the society’s first scientific statement about EDCs in 2009 (Endocrine Reviews 30:293-342).

A Look at the Data

Studies presented at the society’s annual meeting – along with hundreds of others in the last few years – prompted the new definition and principles.

In the first study presented at the meeting, children with higher levels of the EDC di(2-ethylhexyl) phthalate (DEHP) were more likely to be obese. In addition, serum levels of DEHP were associated with weight in a dose-dependent fashion, according to findings from the prospective study of 204 Korean schoolchildren, aged 6-13 years, including 105 obese children and 99 nonobese controls, Dr. Mi Jung Park reported at a press briefing.

Compared with the lowest quartile of serum DEHP, the risk of obesity increased by 25% in the second quartile, nearly quadrupled in the third quartile, and increased fivefold in the highest quartile after adjustment for the effects of age, sex, physical activity, household income, and daily caloric intake.

Mean serum DEHP levels were 107 ng/mL, significantly higher than the mean of 54 ng/mL in control children, said Dr. Park, a pediatric endocrinologist at Sanggye Paik Hospital in Seoul, Korea.

Serum DEHP levels showed significant positive correlations with body mass index, serum ALT, body fat mass, and uric acid levels, but did not correlate significantly with HDL cholesterol level, triglycerides, fasting blood sugar level, or fasting insulin level.

The worldwide epidemic in obesity over the past 40 years cannot be fully explained by overeating and inactivity and parallels increased use of chemicals in our societies, Dr. Park said. She called for prospective studies to determine whether DEHP exposure is a cause of childhood obesity.

Animal In Utero Studies

In the second study, eight pregnant mice exposed to the ubiquitous EDC bisphenol A (BPA) demonstrated "major and permanent changes in gene expression" in female offspring that became apparent only when they were exposed to estrogen through puberty or estrogen treatment, Dr. Hugh S. Taylor reported at the briefing.

"It seems the BPA exposure in utero was programming their response to estrogen later in life" by permanently altering the expression of more than 400 genes, said Dr. Taylor, professor of ob.gyn. and reproductive sciences and chief of reproductive endocrinology and infertility at Yale University, New Haven, Conn.

The changes may help explain the increased incidence of estrogen-related disorders seen after exposure to EDCs, he said.

Pregnant women should minimize their exposure to BPA, and their physicians should advise them on this, he added. "I think it’s something that we don’t do enough of right now as obstetricians or pediatricians. ... It’s important that all obstetricians be educated in endocrine disruptors. It’s not part of any formal medical school curriculum or obstetrics and gynecology training program," but should be, he said.

A third study randomized 23 pregnant rats to low levels of a mix of polychlorinated biphenyls (PCBs) and 22 to an inactive substance. Researchers found that these EDCs disrupted five genes that are critical to the normal hypothalamic control of reproduction. Compared with the control group, the EDC group showed delayed puberty in male offspring and disrupted reproductive cycles in adult female offspring.

The data collectively suggest that determinations of the potential risks or safety of any EDCs should be particular to specific age groups, Dr. Park said.

The EDCs identified so far are just the tip of the iceberg, she added. "Many more chemicals will be found" to be EDCs, she predicted.

Many products contain EDCs. Phthalates are part of some vinyl floor tiles, toys, blood transfusion bags, medical tubing, perfumes, lotions, cosmetics, air fresheners, laundry products, and more. BPA is found in many hard plastic bottles, cash register receipts, and the epoxy resin that lines canned goods. PCBs had been used in plastics, floor finishes, and electrical equipment before being banned in 1979 but are still present in air, water, and soil.

Tools for Clinicians

Dr. Gore and Dr. Taylor recommended these resources for clinicians who are wondering what and how to advise patients about EDCs in their environment:

• The Collaborative on Health and the Environment.

• Environment and Human Health.

Some other resources are available from the University of California's program on reproductive health and the environment.

The speakers reported having no relevant financial disclosures.

HOUSTON – The U.S. Environmental Protection Agency and other groups that evaluate chemicals need to assess endocrine-disrupting chemicals during critical life periods and strengthen screening programs to identify such chemicals, according to recommendations from the Endocrine Society.

"We believe now that the science behind endocrine-disrupting chemicals [EDCs] is incredibly strong," said Andrea C. Gore, Ph.D., professor of pharmacology and toxicology at the University of Texas, Austin. "The current regulatory process is not up to the standards that endocrinologists would use in their own labs," added Dr. Gore, one of the authors of a statement from the society.

For those reasons, the society released a set of principles calling for acknowledgement that changes in hormone action from EDC exposure during development are not correctable, and that they permanently and adversely affect cognitive function and other aspects of health. In addition, the newly released principles call for an acknowledgement that people are exposed to multiple EDCs in daily life, and that these exposures can have a cumulative effect.

Sherry Boschert/IMNG Medical Media

The Endocrine Society also recommended a simplified definition of endocrine-disrupting chemicals in light of mounting evidence of potential harm from exposure to them. By that definition, an EDC would be defined as an exogenous chemical (or mixture of chemicals) that interferes with any aspect of hormone action, Dr. Gore said at the annual meeting of the Endocrine Society.

The ability of a chemical to interfere with any aspect of hormone action is a clear predictor of adverse outcomes if a person is exposed during critical periods or developmental processes, said Dr. Gore.

Furthermore, "low-dose testing is absolutely critical," she said. "There is no safe dose, studies suggest."

The society released the statement of principles online in advance of publication in the journal Endocrinology (2012 June 25 [doi:10.1210/en.2012-1422]). The document updates the society’s first scientific statement about EDCs in 2009 (Endocrine Reviews 30:293-342).

A Look at the Data

Studies presented at the society’s annual meeting – along with hundreds of others in the last few years – prompted the new definition and principles.

In the first study presented at the meeting, children with higher levels of the EDC di(2-ethylhexyl) phthalate (DEHP) were more likely to be obese. In addition, serum levels of DEHP were associated with weight in a dose-dependent fashion, according to findings from the prospective study of 204 Korean schoolchildren, aged 6-13 years, including 105 obese children and 99 nonobese controls, Dr. Mi Jung Park reported at a press briefing.

Compared with the lowest quartile of serum DEHP, the risk of obesity increased by 25% in the second quartile, nearly quadrupled in the third quartile, and increased fivefold in the highest quartile after adjustment for the effects of age, sex, physical activity, household income, and daily caloric intake.

Mean serum DEHP levels were 107 ng/mL, significantly higher than the mean of 54 ng/mL in control children, said Dr. Park, a pediatric endocrinologist at Sanggye Paik Hospital in Seoul, Korea.

Serum DEHP levels showed significant positive correlations with body mass index, serum ALT, body fat mass, and uric acid levels, but did not correlate significantly with HDL cholesterol level, triglycerides, fasting blood sugar level, or fasting insulin level.

The worldwide epidemic in obesity over the past 40 years cannot be fully explained by overeating and inactivity and parallels increased use of chemicals in our societies, Dr. Park said. She called for prospective studies to determine whether DEHP exposure is a cause of childhood obesity.

Animal In Utero Studies

In the second study, eight pregnant mice exposed to the ubiquitous EDC bisphenol A (BPA) demonstrated "major and permanent changes in gene expression" in female offspring that became apparent only when they were exposed to estrogen through puberty or estrogen treatment, Dr. Hugh S. Taylor reported at the briefing.

"It seems the BPA exposure in utero was programming their response to estrogen later in life" by permanently altering the expression of more than 400 genes, said Dr. Taylor, professor of ob.gyn. and reproductive sciences and chief of reproductive endocrinology and infertility at Yale University, New Haven, Conn.

The changes may help explain the increased incidence of estrogen-related disorders seen after exposure to EDCs, he said.

Pregnant women should minimize their exposure to BPA, and their physicians should advise them on this, he added. "I think it’s something that we don’t do enough of right now as obstetricians or pediatricians. ... It’s important that all obstetricians be educated in endocrine disruptors. It’s not part of any formal medical school curriculum or obstetrics and gynecology training program," but should be, he said.

A third study randomized 23 pregnant rats to low levels of a mix of polychlorinated biphenyls (PCBs) and 22 to an inactive substance. Researchers found that these EDCs disrupted five genes that are critical to the normal hypothalamic control of reproduction. Compared with the control group, the EDC group showed delayed puberty in male offspring and disrupted reproductive cycles in adult female offspring.

The data collectively suggest that determinations of the potential risks or safety of any EDCs should be particular to specific age groups, Dr. Park said.

The EDCs identified so far are just the tip of the iceberg, she added. "Many more chemicals will be found" to be EDCs, she predicted.

Many products contain EDCs. Phthalates are part of some vinyl floor tiles, toys, blood transfusion bags, medical tubing, perfumes, lotions, cosmetics, air fresheners, laundry products, and more. BPA is found in many hard plastic bottles, cash register receipts, and the epoxy resin that lines canned goods. PCBs had been used in plastics, floor finishes, and electrical equipment before being banned in 1979 but are still present in air, water, and soil.

Tools for Clinicians

Dr. Gore and Dr. Taylor recommended these resources for clinicians who are wondering what and how to advise patients about EDCs in their environment:

• The Collaborative on Health and the Environment.

• Environment and Human Health.

Some other resources are available from the University of California's program on reproductive health and the environment.

The speakers reported having no relevant financial disclosures.

HOUSTON – The U.S. Environmental Protection Agency and other groups that evaluate chemicals need to assess endocrine-disrupting chemicals during critical life periods and strengthen screening programs to identify such chemicals, according to recommendations from the Endocrine Society.

"We believe now that the science behind endocrine-disrupting chemicals [EDCs] is incredibly strong," said Andrea C. Gore, Ph.D., professor of pharmacology and toxicology at the University of Texas, Austin. "The current regulatory process is not up to the standards that endocrinologists would use in their own labs," added Dr. Gore, one of the authors of a statement from the society.

For those reasons, the society released a set of principles calling for acknowledgement that changes in hormone action from EDC exposure during development are not correctable, and that they permanently and adversely affect cognitive function and other aspects of health. In addition, the newly released principles call for an acknowledgement that people are exposed to multiple EDCs in daily life, and that these exposures can have a cumulative effect.

Sherry Boschert/IMNG Medical Media

The Endocrine Society also recommended a simplified definition of endocrine-disrupting chemicals in light of mounting evidence of potential harm from exposure to them. By that definition, an EDC would be defined as an exogenous chemical (or mixture of chemicals) that interferes with any aspect of hormone action, Dr. Gore said at the annual meeting of the Endocrine Society.

The ability of a chemical to interfere with any aspect of hormone action is a clear predictor of adverse outcomes if a person is exposed during critical periods or developmental processes, said Dr. Gore.

Furthermore, "low-dose testing is absolutely critical," she said. "There is no safe dose, studies suggest."

The society released the statement of principles online in advance of publication in the journal Endocrinology (2012 June 25 [doi:10.1210/en.2012-1422]). The document updates the society’s first scientific statement about EDCs in 2009 (Endocrine Reviews 30:293-342).

A Look at the Data

Studies presented at the society’s annual meeting – along with hundreds of others in the last few years – prompted the new definition and principles.

In the first study presented at the meeting, children with higher levels of the EDC di(2-ethylhexyl) phthalate (DEHP) were more likely to be obese. In addition, serum levels of DEHP were associated with weight in a dose-dependent fashion, according to findings from the prospective study of 204 Korean schoolchildren, aged 6-13 years, including 105 obese children and 99 nonobese controls, Dr. Mi Jung Park reported at a press briefing.

Compared with the lowest quartile of serum DEHP, the risk of obesity increased by 25% in the second quartile, nearly quadrupled in the third quartile, and increased fivefold in the highest quartile after adjustment for the effects of age, sex, physical activity, household income, and daily caloric intake.

Mean serum DEHP levels were 107 ng/mL, significantly higher than the mean of 54 ng/mL in control children, said Dr. Park, a pediatric endocrinologist at Sanggye Paik Hospital in Seoul, Korea.

Serum DEHP levels showed significant positive correlations with body mass index, serum ALT, body fat mass, and uric acid levels, but did not correlate significantly with HDL cholesterol level, triglycerides, fasting blood sugar level, or fasting insulin level.

The worldwide epidemic in obesity over the past 40 years cannot be fully explained by overeating and inactivity and parallels increased use of chemicals in our societies, Dr. Park said. She called for prospective studies to determine whether DEHP exposure is a cause of childhood obesity.

Animal In Utero Studies

In the second study, eight pregnant mice exposed to the ubiquitous EDC bisphenol A (BPA) demonstrated "major and permanent changes in gene expression" in female offspring that became apparent only when they were exposed to estrogen through puberty or estrogen treatment, Dr. Hugh S. Taylor reported at the briefing.

"It seems the BPA exposure in utero was programming their response to estrogen later in life" by permanently altering the expression of more than 400 genes, said Dr. Taylor, professor of ob.gyn. and reproductive sciences and chief of reproductive endocrinology and infertility at Yale University, New Haven, Conn.

The changes may help explain the increased incidence of estrogen-related disorders seen after exposure to EDCs, he said.

Pregnant women should minimize their exposure to BPA, and their physicians should advise them on this, he added. "I think it’s something that we don’t do enough of right now as obstetricians or pediatricians. ... It’s important that all obstetricians be educated in endocrine disruptors. It’s not part of any formal medical school curriculum or obstetrics and gynecology training program," but should be, he said.

A third study randomized 23 pregnant rats to low levels of a mix of polychlorinated biphenyls (PCBs) and 22 to an inactive substance. Researchers found that these EDCs disrupted five genes that are critical to the normal hypothalamic control of reproduction. Compared with the control group, the EDC group showed delayed puberty in male offspring and disrupted reproductive cycles in adult female offspring.

The data collectively suggest that determinations of the potential risks or safety of any EDCs should be particular to specific age groups, Dr. Park said.

The EDCs identified so far are just the tip of the iceberg, she added. "Many more chemicals will be found" to be EDCs, she predicted.

Many products contain EDCs. Phthalates are part of some vinyl floor tiles, toys, blood transfusion bags, medical tubing, perfumes, lotions, cosmetics, air fresheners, laundry products, and more. BPA is found in many hard plastic bottles, cash register receipts, and the epoxy resin that lines canned goods. PCBs had been used in plastics, floor finishes, and electrical equipment before being banned in 1979 but are still present in air, water, and soil.

Tools for Clinicians

Dr. Gore and Dr. Taylor recommended these resources for clinicians who are wondering what and how to advise patients about EDCs in their environment:

• The Collaborative on Health and the Environment.

• Environment and Human Health.

Some other resources are available from the University of California's program on reproductive health and the environment.

The speakers reported having no relevant financial disclosures.

HOUSTON – In all, 53% of 142 young men with type 2 diabetes were resistant to the anticlotting effects of aspirin in a retrospective analysis, suggesting that they may need higher-than-usual doses of prophylactic aspirin to prevent heart attacks and strokes.

The study shows that aspirin resistance is common in men with type 2 diabetes, even in those with good glycemic control, Dr. Subhashini Yaturu and her associates reported in a poster presentation at the annual meeting of the Endocrine Society.

The investigators combined test results and information that had been gathered at one institution for a previous study with supplemental analyses of urine samples in order to measure concentrations of 11-dehydro-thromboxane beta-2 (11-DH-TXB₂), a major urinary metabolite of thromboxane that is formed during blood clotting. High urinary levels of 11-DH-TXB₂, measured using an enzyme immunoassay kit, indicate resistance to aspirin. Aspirin resistance was defined as a urine level of at least 1,500 pg 11-DH-TXB₂ per mg of creatinine.

The men had a mean age of 49 years and a mean body mass index of 34 kg/m². They’d had diabetes for a mean of 8 years; 88% of them had hypertension, and 23% had a history of coronary artery disease.

The investigators had hypothesized that aspirin resistance might be associated with high insulin levels and inflammatory markers. They found that 11-DH-TXB₂ per creatinine levels correlated with a history of coronary artery disease, abdominal fat content, and interleukin-6 levels. Levels were highest in patients with a longer duration of diabetes and increased urinary microalbumin levels, an indicator of early kidney disease in diabetes, said Dr. Yaturu, section chief of the endocrinology and metabolism department at the Albany (N.Y.) Stratton Veterans Affairs Medical Center.

Although high blood pressure and greater abdominal-fat distribution conventionally are associated with increased risk of cardiovascular disease, these were not associated with aspirin resistance in this study. Patients with or without aspirin resistance did not differ significantly in age, BMI, history of hypertension, or waist-to-hip ratio. They also did not differ significantly in biochemical parameters such as creatinine, thyroid function tests, lipid parameters, or glycosylated hemoglobin (HbA_1C) measurements.

Patients with aspirin resistance had a mean HbA_1c of 8.1%, compared with 7.7% in those without aspirin resistance.

Knowing that aspirin resistance is so common is important clinically because it may allow for additional measures. Giving patients higher medication doses or additional prophylactic therapy might be considered to prevent heart attacks and strokes, Dr. Yaturu said.

Identifying patients with aspirin resistance isn’t easy, however, given the lack of correlation with obvious clinical markers, she said in an interview. The measures used in the study are still a research tool. But if aspirin resistance is identified in a patient, consider doubling the standard low dose of aspirin, she suggested.

Cardiovascular risk in patients with type 2 diabetes is equivalent to that of patients without diabetes who have had a coronary event, she noted. The American Diabetes Association recommends enteric-coated aspirin at a dosage of 81-325 mg/day for the prevention of cardiovascular events in high-risk patients with diabetes, including those older than 40 years or patients with risk factors other than diabetes, such as hypertension, smoking, dyslipidemia, albuminuria, or a family history of cardiovascular disease.

Causes of aspirin resistance include concurrent use of NSAIDs that may compete with aspirin at the cyclooxygenase-1 receptor site; polymorphisms in the COX1 gene; poor glucose control; body weight; and conditions associated with a high turnover of platelets, she said.

Dr. Yaturu reported having no financial disclosures.

HOUSTON – In all, 53% of 142 young men with type 2 diabetes were resistant to the anticlotting effects of aspirin in a retrospective analysis, suggesting that they may need higher-than-usual doses of prophylactic aspirin to prevent heart attacks and strokes.

The study shows that aspirin resistance is common in men with type 2 diabetes, even in those with good glycemic control, Dr. Subhashini Yaturu and her associates reported in a poster presentation at the annual meeting of the Endocrine Society.

The investigators combined test results and information that had been gathered at one institution for a previous study with supplemental analyses of urine samples in order to measure concentrations of 11-dehydro-thromboxane beta-2 (11-DH-TXB₂), a major urinary metabolite of thromboxane that is formed during blood clotting. High urinary levels of 11-DH-TXB₂, measured using an enzyme immunoassay kit, indicate resistance to aspirin. Aspirin resistance was defined as a urine level of at least 1,500 pg 11-DH-TXB₂ per mg of creatinine.

The men had a mean age of 49 years and a mean body mass index of 34 kg/m². They’d had diabetes for a mean of 8 years; 88% of them had hypertension, and 23% had a history of coronary artery disease.

The investigators had hypothesized that aspirin resistance might be associated with high insulin levels and inflammatory markers. They found that 11-DH-TXB₂ per creatinine levels correlated with a history of coronary artery disease, abdominal fat content, and interleukin-6 levels. Levels were highest in patients with a longer duration of diabetes and increased urinary microalbumin levels, an indicator of early kidney disease in diabetes, said Dr. Yaturu, section chief of the endocrinology and metabolism department at the Albany (N.Y.) Stratton Veterans Affairs Medical Center.

Although high blood pressure and greater abdominal-fat distribution conventionally are associated with increased risk of cardiovascular disease, these were not associated with aspirin resistance in this study. Patients with or without aspirin resistance did not differ significantly in age, BMI, history of hypertension, or waist-to-hip ratio. They also did not differ significantly in biochemical parameters such as creatinine, thyroid function tests, lipid parameters, or glycosylated hemoglobin (HbA_1C) measurements.

Patients with aspirin resistance had a mean HbA_1c of 8.1%, compared with 7.7% in those without aspirin resistance.

Knowing that aspirin resistance is so common is important clinically because it may allow for additional measures. Giving patients higher medication doses or additional prophylactic therapy might be considered to prevent heart attacks and strokes, Dr. Yaturu said.

Identifying patients with aspirin resistance isn’t easy, however, given the lack of correlation with obvious clinical markers, she said in an interview. The measures used in the study are still a research tool. But if aspirin resistance is identified in a patient, consider doubling the standard low dose of aspirin, she suggested.

Cardiovascular risk in patients with type 2 diabetes is equivalent to that of patients without diabetes who have had a coronary event, she noted. The American Diabetes Association recommends enteric-coated aspirin at a dosage of 81-325 mg/day for the prevention of cardiovascular events in high-risk patients with diabetes, including those older than 40 years or patients with risk factors other than diabetes, such as hypertension, smoking, dyslipidemia, albuminuria, or a family history of cardiovascular disease.

Causes of aspirin resistance include concurrent use of NSAIDs that may compete with aspirin at the cyclooxygenase-1 receptor site; polymorphisms in the COX1 gene; poor glucose control; body weight; and conditions associated with a high turnover of platelets, she said.

Dr. Yaturu reported having no financial disclosures.

HOUSTON – In all, 53% of 142 young men with type 2 diabetes were resistant to the anticlotting effects of aspirin in a retrospective analysis, suggesting that they may need higher-than-usual doses of prophylactic aspirin to prevent heart attacks and strokes.

The study shows that aspirin resistance is common in men with type 2 diabetes, even in those with good glycemic control, Dr. Subhashini Yaturu and her associates reported in a poster presentation at the annual meeting of the Endocrine Society.

The investigators combined test results and information that had been gathered at one institution for a previous study with supplemental analyses of urine samples in order to measure concentrations of 11-dehydro-thromboxane beta-2 (11-DH-TXB₂), a major urinary metabolite of thromboxane that is formed during blood clotting. High urinary levels of 11-DH-TXB₂, measured using an enzyme immunoassay kit, indicate resistance to aspirin. Aspirin resistance was defined as a urine level of at least 1,500 pg 11-DH-TXB₂ per mg of creatinine.

The men had a mean age of 49 years and a mean body mass index of 34 kg/m². They’d had diabetes for a mean of 8 years; 88% of them had hypertension, and 23% had a history of coronary artery disease.

The investigators had hypothesized that aspirin resistance might be associated with high insulin levels and inflammatory markers. They found that 11-DH-TXB₂ per creatinine levels correlated with a history of coronary artery disease, abdominal fat content, and interleukin-6 levels. Levels were highest in patients with a longer duration of diabetes and increased urinary microalbumin levels, an indicator of early kidney disease in diabetes, said Dr. Yaturu, section chief of the endocrinology and metabolism department at the Albany (N.Y.) Stratton Veterans Affairs Medical Center.

Although high blood pressure and greater abdominal-fat distribution conventionally are associated with increased risk of cardiovascular disease, these were not associated with aspirin resistance in this study. Patients with or without aspirin resistance did not differ significantly in age, BMI, history of hypertension, or waist-to-hip ratio. They also did not differ significantly in biochemical parameters such as creatinine, thyroid function tests, lipid parameters, or glycosylated hemoglobin (HbA_1C) measurements.

Patients with aspirin resistance had a mean HbA_1c of 8.1%, compared with 7.7% in those without aspirin resistance.

Knowing that aspirin resistance is so common is important clinically because it may allow for additional measures. Giving patients higher medication doses or additional prophylactic therapy might be considered to prevent heart attacks and strokes, Dr. Yaturu said.

Identifying patients with aspirin resistance isn’t easy, however, given the lack of correlation with obvious clinical markers, she said in an interview. The measures used in the study are still a research tool. But if aspirin resistance is identified in a patient, consider doubling the standard low dose of aspirin, she suggested.

Cardiovascular risk in patients with type 2 diabetes is equivalent to that of patients without diabetes who have had a coronary event, she noted. The American Diabetes Association recommends enteric-coated aspirin at a dosage of 81-325 mg/day for the prevention of cardiovascular events in high-risk patients with diabetes, including those older than 40 years or patients with risk factors other than diabetes, such as hypertension, smoking, dyslipidemia, albuminuria, or a family history of cardiovascular disease.

Causes of aspirin resistance include concurrent use of NSAIDs that may compete with aspirin at the cyclooxygenase-1 receptor site; polymorphisms in the COX1 gene; poor glucose control; body weight; and conditions associated with a high turnover of platelets, she said.

Dr. Yaturu reported having no financial disclosures.

HOUSTON – Fifty-four percent of 219 obese adolescents being evaluated for bariatric surgery were deficient in vitamin D, including 9% who were severely deficient, a retrospective analysis of preoperative laboratory measures found.

Eighty-two percent of the adolescents had insufficient levels of 25-hydroxyvitamin D (25OHD) in their blood, Dr. Marisa Censani and her associates reported at the annual meeting of the Endocrine Society.

The findings are so striking that all morbidly obese adolescents should be screened for vitamin D deficiency, and those who are deficient should be treated to replete vitamin D levels, suggested Dr. Censani of Columbia University, New York.

It’s particularly important to screen adolescents before bariatric surgery procedures, some of which have been associated with bone loss, which results from weight loss and decreased calcium and vitamin D absorption. Preoperative vitamin D deficiency could put adolescent patients at greater risk because they have not reached their peak bone mass, she said.

Previous studies have shown that obese adults undergoing bariatric surgery commonly are vitamin D deficient before surgery, but these are some of the first data in preoperative adolescent patients.

Of all adolescents undergoing bariatric surgery at her institution from March 2006 to June 2011, 219 had records on serum 25OHD and parathyroid hormone levels. The cohort was 65% female, 43% white, 35% Hispanic, and 15% African American, with the rest being other races/ethnicities. Patients had a mean age of 16 years (ranging from 13-18 years) and a mean body mass index of 48 kg/m².

The mean serum 25OHD level was 21 ng/mL, which was considered insufficient. The study defined adequate levels of serum 25OHD as at least 30 ng/mL, insufficient levels as 20-29 ng/mL, deficient levels as less than 20 ng/mL, and severely deficient levels as less than 10 ng/mL.

Only 18% of patients had sufficient 25OHD levels. Twenty-nine percent had insufficient levels, 45% were vitamin D deficient, and 9% were severely deficient.

Patients with the highest BMIs were most likely to have deficient levels of 25OHD. Every kilogram increase in BMI correlated with a 0.2-ng decrease in 25OHD levels, Dr. Censani said.

Vitamin D deficiency was most common in African Americans, 82% of whom were deficient and none of whom had levels in the normal range. Fifty-nine percent of Hispanics and 37% of whites had vitamin D deficiency. Race was the strongest predictor of 25OHD levels.

Roughly 80% of African American patients were deficient in vitamin D and the rest had insufficient levels. In Hispanics, nearly 60% were deficient in vitamin D, close to 25% had insufficient levels, and about 25% had adequate levels. In whites, deficient or insufficient levels each were seen in nearly 40% of patients, with adequate levels in more than 20%.

Clear secondary hyperparathyroidism was seen in 5% of patients, though serum parathyroid levels varied inversely with 25OHD. African American race, BMI, and parathyroid levels explained 21% of the variance in 25OHD levels between patients.

To be eligible for bariatric surgery, adolescents had to have reached Tanner stage IV or V and had to have a BMI greater than 50, or above 35 kg/m² if they had comorbidities.

A physician in the audience challenged Dr. Censani’s recommendation that all obese adolescents be screened and possibly treated for vitamin D deficiency, saying there is no evidence yet of clinical benefit from that approach. Dr. Censani agreed that more research is needed to support this strategy.

The current study was limited by the lack of a community-based, nonobese control group and lack of data on dietary calcium and vitamin D intake, sun exposure, or bone mineral density. The study’s large size and relatively good ethnic diversity are strengths, she said.

The U.S. adolescent obesity rate has more than tripled in the past 30 years, with 16% of children and adolescents now overweight, 4% obese, and 4% morbidly obese, studies suggest.

Dr. Censani reported having no financial disclosures. The National Institutes of Health funded the study.

HOUSTON – Fifty-four percent of 219 obese adolescents being evaluated for bariatric surgery were deficient in vitamin D, including 9% who were severely deficient, a retrospective analysis of preoperative laboratory measures found.

Eighty-two percent of the adolescents had insufficient levels of 25-hydroxyvitamin D (25OHD) in their blood, Dr. Marisa Censani and her associates reported at the annual meeting of the Endocrine Society.

The findings are so striking that all morbidly obese adolescents should be screened for vitamin D deficiency, and those who are deficient should be treated to replete vitamin D levels, suggested Dr. Censani of Columbia University, New York.

It’s particularly important to screen adolescents before bariatric surgery procedures, some of which have been associated with bone loss, which results from weight loss and decreased calcium and vitamin D absorption. Preoperative vitamin D deficiency could put adolescent patients at greater risk because they have not reached their peak bone mass, she said.

Previous studies have shown that obese adults undergoing bariatric surgery commonly are vitamin D deficient before surgery, but these are some of the first data in preoperative adolescent patients.

Of all adolescents undergoing bariatric surgery at her institution from March 2006 to June 2011, 219 had records on serum 25OHD and parathyroid hormone levels. The cohort was 65% female, 43% white, 35% Hispanic, and 15% African American, with the rest being other races/ethnicities. Patients had a mean age of 16 years (ranging from 13-18 years) and a mean body mass index of 48 kg/m².

The mean serum 25OHD level was 21 ng/mL, which was considered insufficient. The study defined adequate levels of serum 25OHD as at least 30 ng/mL, insufficient levels as 20-29 ng/mL, deficient levels as less than 20 ng/mL, and severely deficient levels as less than 10 ng/mL.

Only 18% of patients had sufficient 25OHD levels. Twenty-nine percent had insufficient levels, 45% were vitamin D deficient, and 9% were severely deficient.

Patients with the highest BMIs were most likely to have deficient levels of 25OHD. Every kilogram increase in BMI correlated with a 0.2-ng decrease in 25OHD levels, Dr. Censani said.

Vitamin D deficiency was most common in African Americans, 82% of whom were deficient and none of whom had levels in the normal range. Fifty-nine percent of Hispanics and 37% of whites had vitamin D deficiency. Race was the strongest predictor of 25OHD levels.

Roughly 80% of African American patients were deficient in vitamin D and the rest had insufficient levels. In Hispanics, nearly 60% were deficient in vitamin D, close to 25% had insufficient levels, and about 25% had adequate levels. In whites, deficient or insufficient levels each were seen in nearly 40% of patients, with adequate levels in more than 20%.

Clear secondary hyperparathyroidism was seen in 5% of patients, though serum parathyroid levels varied inversely with 25OHD. African American race, BMI, and parathyroid levels explained 21% of the variance in 25OHD levels between patients.

To be eligible for bariatric surgery, adolescents had to have reached Tanner stage IV or V and had to have a BMI greater than 50, or above 35 kg/m² if they had comorbidities.

A physician in the audience challenged Dr. Censani’s recommendation that all obese adolescents be screened and possibly treated for vitamin D deficiency, saying there is no evidence yet of clinical benefit from that approach. Dr. Censani agreed that more research is needed to support this strategy.

The current study was limited by the lack of a community-based, nonobese control group and lack of data on dietary calcium and vitamin D intake, sun exposure, or bone mineral density. The study’s large size and relatively good ethnic diversity are strengths, she said.

The U.S. adolescent obesity rate has more than tripled in the past 30 years, with 16% of children and adolescents now overweight, 4% obese, and 4% morbidly obese, studies suggest.

Dr. Censani reported having no financial disclosures. The National Institutes of Health funded the study.

HOUSTON – Fifty-four percent of 219 obese adolescents being evaluated for bariatric surgery were deficient in vitamin D, including 9% who were severely deficient, a retrospective analysis of preoperative laboratory measures found.

Eighty-two percent of the adolescents had insufficient levels of 25-hydroxyvitamin D (25OHD) in their blood, Dr. Marisa Censani and her associates reported at the annual meeting of the Endocrine Society.

The findings are so striking that all morbidly obese adolescents should be screened for vitamin D deficiency, and those who are deficient should be treated to replete vitamin D levels, suggested Dr. Censani of Columbia University, New York.

It’s particularly important to screen adolescents before bariatric surgery procedures, some of which have been associated with bone loss, which results from weight loss and decreased calcium and vitamin D absorption. Preoperative vitamin D deficiency could put adolescent patients at greater risk because they have not reached their peak bone mass, she said.

Previous studies have shown that obese adults undergoing bariatric surgery commonly are vitamin D deficient before surgery, but these are some of the first data in preoperative adolescent patients.

Of all adolescents undergoing bariatric surgery at her institution from March 2006 to June 2011, 219 had records on serum 25OHD and parathyroid hormone levels. The cohort was 65% female, 43% white, 35% Hispanic, and 15% African American, with the rest being other races/ethnicities. Patients had a mean age of 16 years (ranging from 13-18 years) and a mean body mass index of 48 kg/m².

The mean serum 25OHD level was 21 ng/mL, which was considered insufficient. The study defined adequate levels of serum 25OHD as at least 30 ng/mL, insufficient levels as 20-29 ng/mL, deficient levels as less than 20 ng/mL, and severely deficient levels as less than 10 ng/mL.

Only 18% of patients had sufficient 25OHD levels. Twenty-nine percent had insufficient levels, 45% were vitamin D deficient, and 9% were severely deficient.

Patients with the highest BMIs were most likely to have deficient levels of 25OHD. Every kilogram increase in BMI correlated with a 0.2-ng decrease in 25OHD levels, Dr. Censani said.

Vitamin D deficiency was most common in African Americans, 82% of whom were deficient and none of whom had levels in the normal range. Fifty-nine percent of Hispanics and 37% of whites had vitamin D deficiency. Race was the strongest predictor of 25OHD levels.

Roughly 80% of African American patients were deficient in vitamin D and the rest had insufficient levels. In Hispanics, nearly 60% were deficient in vitamin D, close to 25% had insufficient levels, and about 25% had adequate levels. In whites, deficient or insufficient levels each were seen in nearly 40% of patients, with adequate levels in more than 20%.

Clear secondary hyperparathyroidism was seen in 5% of patients, though serum parathyroid levels varied inversely with 25OHD. African American race, BMI, and parathyroid levels explained 21% of the variance in 25OHD levels between patients.

To be eligible for bariatric surgery, adolescents had to have reached Tanner stage IV or V and had to have a BMI greater than 50, or above 35 kg/m² if they had comorbidities.

A physician in the audience challenged Dr. Censani’s recommendation that all obese adolescents be screened and possibly treated for vitamin D deficiency, saying there is no evidence yet of clinical benefit from that approach. Dr. Censani agreed that more research is needed to support this strategy.

The current study was limited by the lack of a community-based, nonobese control group and lack of data on dietary calcium and vitamin D intake, sun exposure, or bone mineral density. The study’s large size and relatively good ethnic diversity are strengths, she said.

The U.S. adolescent obesity rate has more than tripled in the past 30 years, with 16% of children and adolescents now overweight, 4% obese, and 4% morbidly obese, studies suggest.

Dr. Censani reported having no financial disclosures. The National Institutes of Health funded the study.

SAN FRANCISCO – Patients on selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors when they were admitted to an intensive care unit were 73% more likely to die in the hospital, compared with ICU patients who were not on these antidepressants, a retrospective study found.

Dr. Katherine M. Berg and her associates analyzed electronic records from admissions to four ICUs in 2001-2008 to compare outcomes for 1,876 patients who were on a selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrine reuptake inhibitor (SNRI) and 8,692 control patients who were not taking an SSRI or SNRI before admission.

Sherry Boschert/IMNG Medical Media

The mortality risk remained elevated at 1,000 days after ICU admission, she reported in a late-breaking poster presentation and discussion session at an international conference of the American Thoracic Society.

Certain subgroups were at even greater risk of dying in the hospital if they were on an SSRI or SNRI when admitted to the ICU. Patients who had acute coronary syndrome or had undergone cardiac surgery were more than twice as likely to die if they were on an SSRI/SNRI when entering the ICU, compared with controls, said Dr. Berg, a pulmonary/critical care fellow at Massachusetts General Hospital and Harvard University, Boston.

The increased mortality risk appeared to be associated mainly with medications that have higher degrees of serotonin reuptake inhibition. "Citalopram, which is a lower-potency drug, by itself did not incur a higher mortality risk, but sertraline, which is one of the more potent drugs, did. Even comparing the two drugs to each other, if you were on sertraline, your mortality risk was higher" than if you were on citalopram, Dr. Berg said in an interview.

Fluoxetine, paroxetine, and sertraline were associated with significantly higher mortality, but no significant mortality differences were seen between patients on citalopram or escitalopram and control patients.

Of the 8,692 control patients, 7% died in the hospital, compared with in-hospital death rates of 10% in 286 patients on fluoxetine, 13% in 320 patients on paroxetine, and 15% in 426 patients on sertraline at the time of ICU admission. The remaining 844 patients were on other antidepressants.

The study adjusted for the effects of each patient’s age, Simplified Acute Physiology Score, and combined Elixhauser comorbidity score on in-hospital mortality risk.

Slight but statistically significant differences in the characteristics of the two groups included a greater proportion of women in the SSRI/SNRI group, compared with controls (57% vs. 40%), and a higher prevalence of diabetes (21% vs. 17%) or chronic obstructive pulmonary disease (11% vs. 7%) in patients on an SSRI/SNRI, compared with controls. Patients in the SSRI/SNRI group were more likely to have an infection than were controls (11% vs. 8%), but less likely to have acute coronary syndrome (8% vs. 10%) or cardiovascular disease (67% vs. 70%).

Further studies are needed to ascertain if this is a causal relationship or just an association between SSRI/SNRI use and mortality in ICU patients, she said. The findings are limited by the retrospective nature of the study, which also was unable to control for the effects of potentially important confounders such as smoking status or the presence of depression.

The data came from the Multiparameter Intelligent Monitoring in Intensive Care II database, a public collection of data with patient identifiers removed.

Antidepressants were the most commonly prescribed medication class in the United States in 2011, and SSRIs were the most common type of antidepressant, she said. SSRI use has been associated with increased risk of bleeding, falls, bradycardia, and stroke in previous studies, which also suggest a possible protective effect of SSRIs in patients with coronary artery disease.

Dr. Berg reported having no financial disclosures.

SAN FRANCISCO – Patients on selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors when they were admitted to an intensive care unit were 73% more likely to die in the hospital, compared with ICU patients who were not on these antidepressants, a retrospective study found.

Dr. Katherine M. Berg and her associates analyzed electronic records from admissions to four ICUs in 2001-2008 to compare outcomes for 1,876 patients who were on a selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrine reuptake inhibitor (SNRI) and 8,692 control patients who were not taking an SSRI or SNRI before admission.

Sherry Boschert/IMNG Medical Media

The mortality risk remained elevated at 1,000 days after ICU admission, she reported in a late-breaking poster presentation and discussion session at an international conference of the American Thoracic Society.

Certain subgroups were at even greater risk of dying in the hospital if they were on an SSRI or SNRI when admitted to the ICU. Patients who had acute coronary syndrome or had undergone cardiac surgery were more than twice as likely to die if they were on an SSRI/SNRI when entering the ICU, compared with controls, said Dr. Berg, a pulmonary/critical care fellow at Massachusetts General Hospital and Harvard University, Boston.

The increased mortality risk appeared to be associated mainly with medications that have higher degrees of serotonin reuptake inhibition. "Citalopram, which is a lower-potency drug, by itself did not incur a higher mortality risk, but sertraline, which is one of the more potent drugs, did. Even comparing the two drugs to each other, if you were on sertraline, your mortality risk was higher" than if you were on citalopram, Dr. Berg said in an interview.

Fluoxetine, paroxetine, and sertraline were associated with significantly higher mortality, but no significant mortality differences were seen between patients on citalopram or escitalopram and control patients.

Of the 8,692 control patients, 7% died in the hospital, compared with in-hospital death rates of 10% in 286 patients on fluoxetine, 13% in 320 patients on paroxetine, and 15% in 426 patients on sertraline at the time of ICU admission. The remaining 844 patients were on other antidepressants.

The study adjusted for the effects of each patient’s age, Simplified Acute Physiology Score, and combined Elixhauser comorbidity score on in-hospital mortality risk.

Slight but statistically significant differences in the characteristics of the two groups included a greater proportion of women in the SSRI/SNRI group, compared with controls (57% vs. 40%), and a higher prevalence of diabetes (21% vs. 17%) or chronic obstructive pulmonary disease (11% vs. 7%) in patients on an SSRI/SNRI, compared with controls. Patients in the SSRI/SNRI group were more likely to have an infection than were controls (11% vs. 8%), but less likely to have acute coronary syndrome (8% vs. 10%) or cardiovascular disease (67% vs. 70%).

Further studies are needed to ascertain if this is a causal relationship or just an association between SSRI/SNRI use and mortality in ICU patients, she said. The findings are limited by the retrospective nature of the study, which also was unable to control for the effects of potentially important confounders such as smoking status or the presence of depression.

The data came from the Multiparameter Intelligent Monitoring in Intensive Care II database, a public collection of data with patient identifiers removed.

Antidepressants were the most commonly prescribed medication class in the United States in 2011, and SSRIs were the most common type of antidepressant, she said. SSRI use has been associated with increased risk of bleeding, falls, bradycardia, and stroke in previous studies, which also suggest a possible protective effect of SSRIs in patients with coronary artery disease.

Dr. Berg reported having no financial disclosures.

SAN FRANCISCO – Patients on selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors when they were admitted to an intensive care unit were 73% more likely to die in the hospital, compared with ICU patients who were not on these antidepressants, a retrospective study found.

Dr. Katherine M. Berg and her associates analyzed electronic records from admissions to four ICUs in 2001-2008 to compare outcomes for 1,876 patients who were on a selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrine reuptake inhibitor (SNRI) and 8,692 control patients who were not taking an SSRI or SNRI before admission.

Sherry Boschert/IMNG Medical Media

The mortality risk remained elevated at 1,000 days after ICU admission, she reported in a late-breaking poster presentation and discussion session at an international conference of the American Thoracic Society.

Certain subgroups were at even greater risk of dying in the hospital if they were on an SSRI or SNRI when admitted to the ICU. Patients who had acute coronary syndrome or had undergone cardiac surgery were more than twice as likely to die if they were on an SSRI/SNRI when entering the ICU, compared with controls, said Dr. Berg, a pulmonary/critical care fellow at Massachusetts General Hospital and Harvard University, Boston.

The increased mortality risk appeared to be associated mainly with medications that have higher degrees of serotonin reuptake inhibition. "Citalopram, which is a lower-potency drug, by itself did not incur a higher mortality risk, but sertraline, which is one of the more potent drugs, did. Even comparing the two drugs to each other, if you were on sertraline, your mortality risk was higher" than if you were on citalopram, Dr. Berg said in an interview.

Fluoxetine, paroxetine, and sertraline were associated with significantly higher mortality, but no significant mortality differences were seen between patients on citalopram or escitalopram and control patients.

Of the 8,692 control patients, 7% died in the hospital, compared with in-hospital death rates of 10% in 286 patients on fluoxetine, 13% in 320 patients on paroxetine, and 15% in 426 patients on sertraline at the time of ICU admission. The remaining 844 patients were on other antidepressants.

The study adjusted for the effects of each patient’s age, Simplified Acute Physiology Score, and combined Elixhauser comorbidity score on in-hospital mortality risk.

Slight but statistically significant differences in the characteristics of the two groups included a greater proportion of women in the SSRI/SNRI group, compared with controls (57% vs. 40%), and a higher prevalence of diabetes (21% vs. 17%) or chronic obstructive pulmonary disease (11% vs. 7%) in patients on an SSRI/SNRI, compared with controls. Patients in the SSRI/SNRI group were more likely to have an infection than were controls (11% vs. 8%), but less likely to have acute coronary syndrome (8% vs. 10%) or cardiovascular disease (67% vs. 70%).

Further studies are needed to ascertain if this is a causal relationship or just an association between SSRI/SNRI use and mortality in ICU patients, she said. The findings are limited by the retrospective nature of the study, which also was unable to control for the effects of potentially important confounders such as smoking status or the presence of depression.

The data came from the Multiparameter Intelligent Monitoring in Intensive Care II database, a public collection of data with patient identifiers removed.

Antidepressants were the most commonly prescribed medication class in the United States in 2011, and SSRIs were the most common type of antidepressant, she said. SSRI use has been associated with increased risk of bleeding, falls, bradycardia, and stroke in previous studies, which also suggest a possible protective effect of SSRIs in patients with coronary artery disease.

Dr. Berg reported having no financial disclosures.

HOUSTON – A novel gene expression test could eliminate the need for a third of operations done for cytologically indeterminate thyroid nodules by winnowing out low-risk nodules, a large, prospective, double-blind, multicenter study suggests.

The study included fine-needle aspirates of thyroid nodules 1 cm or larger that were classified as indeterminate on cytology and that had corresponding histopathological specimens from excised lesions. A test that measures the expression of 167 genes was applied to 265 cytologically indeterminate nodules, with the patients, physicians, and pathology laboratories blinded to the results of the Afirma gene expression classifier test during management.

In general, cytologically indeterminate thyroid aspirates get classified one of three ways. The negative predictive value of results from the Afirma gene expression classifier test was 95% for the subset cytologically classified as "atypia (or follicular lesion) of undetermined clinical significance," 94% for "follicular neoplasm or lesion suspicious for follicular neoplasm," and 85% for "suspicious cytologic findings," Dr. Erik K. Alexander and his associates reported in a press briefing at the annual meeting of the Endocrine Society.

The Afirma test correctly identified as "suspicious" 78 of the 85 nodules that ultimately were found to be malignant, for a sensitivity of 92% and a specificity of 52%, he said.

A closer look at the seven aspirates that had false negative results from Afirma testing found that six samples lacked a sufficient quantity of thyroid follicular cells to be considered a sufficient sampling of the nodule, said Dr. Alexander of Brigham and Women’s Hospital and Harvard University, Boston.

The results are good enough that clinicians could take a conservative approach to managing most patients whose thyroid nodules are cytologically indeterminate on fine-needle aspiration but benign on the gene expression classifier test, he said.

The New England Journal of Medicine published the study online on June 25 (doi: 10.1056/NEJMoa1203208).

The new gene expression test could eliminate the need for 25,000 of the 75,000 surgeries each year in patients with cytologically indeterminate thyroid aspirates, but at the risk of likely malignancy in 5%-10% of nodules classified as benign, particularly nodules that are cytologically indeterminate but suggestive of cancer, Dr. J. Larry Jameson said in an editorial published simultaneously online by the journal (doi: 10.1056/NEJMe1205893).

In this high-risk group, repeating the fine-needle aspiration biopsy or performing a diagnostic hemithyroidectomy might be reasonable even when the gene expression classifier suggests a benign nodule, said Dr. Jameson of the University of Pennsylvania, Philadelphia.

For patients with indeterminate aspirates and negative Afirma test results who are monitored rather than sent to surgery, clinicians should have a low threshold for repeating fine-needle aspiration if ultrasound tests show rapid nodule growth or characteristics suggestive of cancer, he suggested.

Dr. Jameson called the new gene expression classifier test a "welcome addition" to tools for managing thyroid nodules that could substantially reduce costs by avoiding operations, even when considering the added cost of the test.

One of the strengths of the 49-site study was that 80% of participants came from community-based sites and 20% from academic medical sites, representing a real-world sample, coinvestigator Dr. Bryan R. Haugen said at the press briefing.

He described recent use of the Afirma test at his institution on aspirates from 126 patients with indeterminate cytology results from January 2011 to April 2012. The gene expression classifier results said 56% were benign, 41% were suspicious, and 3% could not produce a result. Seventy patients avoided surgery. Among patients who underwent surgery, 52% of nodes were malignant, said Dr. Haugen, head of endocrinology, metabolism, and diabetes at the University of Colorado, Denver.

Dr. Haugen and Dr. Alexander emphasized that the Afirma test should only be used for aspirates with indeterminate cytology, not for biopsies classified as cytologically benign, because of the 70% specificity when used on benign lesions.

Thyroid nodules are common and can be found in 25%-50% of adults. When fine-needle aspiration biopsy produces indeterminate cytological results, most patients have undergone hemithyroidectomy or total thyroidectomy for diagnosis and treatment.

Veracyte, which makes the gene expression classifier, funded the study and tested the samples in its laboratory. Veracyte employees helped design and supervise the study, conducted the statistical analysis, and made up 6 of the 18 investigators. Dr. Alexander disclosed financial associations with Veracyte, Asuragen, Genzyme, and the Boston Clinical Research Institute. His coinvestigators disclosed financial associations with Veracyte and multiple other companies. Dr. Jameson disclosed financial associations with Quest Diagnostics, Novartis, and Ferring, and said that he knows some of the investigators professionally.

HOUSTON – A novel gene expression test could eliminate the need for a third of operations done for cytologically indeterminate thyroid nodules by winnowing out low-risk nodules, a large, prospective, double-blind, multicenter study suggests.

The study included fine-needle aspirates of thyroid nodules 1 cm or larger that were classified as indeterminate on cytology and that had corresponding histopathological specimens from excised lesions. A test that measures the expression of 167 genes was applied to 265 cytologically indeterminate nodules, with the patients, physicians, and pathology laboratories blinded to the results of the Afirma gene expression classifier test during management.

In general, cytologically indeterminate thyroid aspirates get classified one of three ways. The negative predictive value of results from the Afirma gene expression classifier test was 95% for the subset cytologically classified as "atypia (or follicular lesion) of undetermined clinical significance," 94% for "follicular neoplasm or lesion suspicious for follicular neoplasm," and 85% for "suspicious cytologic findings," Dr. Erik K. Alexander and his associates reported in a press briefing at the annual meeting of the Endocrine Society.

The Afirma test correctly identified as "suspicious" 78 of the 85 nodules that ultimately were found to be malignant, for a sensitivity of 92% and a specificity of 52%, he said.

A closer look at the seven aspirates that had false negative results from Afirma testing found that six samples lacked a sufficient quantity of thyroid follicular cells to be considered a sufficient sampling of the nodule, said Dr. Alexander of Brigham and Women’s Hospital and Harvard University, Boston.

The results are good enough that clinicians could take a conservative approach to managing most patients whose thyroid nodules are cytologically indeterminate on fine-needle aspiration but benign on the gene expression classifier test, he said.

The New England Journal of Medicine published the study online on June 25 (doi: 10.1056/NEJMoa1203208).

The new gene expression test could eliminate the need for 25,000 of the 75,000 surgeries each year in patients with cytologically indeterminate thyroid aspirates, but at the risk of likely malignancy in 5%-10% of nodules classified as benign, particularly nodules that are cytologically indeterminate but suggestive of cancer, Dr. J. Larry Jameson said in an editorial published simultaneously online by the journal (doi: 10.1056/NEJMe1205893).

In this high-risk group, repeating the fine-needle aspiration biopsy or performing a diagnostic hemithyroidectomy might be reasonable even when the gene expression classifier suggests a benign nodule, said Dr. Jameson of the University of Pennsylvania, Philadelphia.

For patients with indeterminate aspirates and negative Afirma test results who are monitored rather than sent to surgery, clinicians should have a low threshold for repeating fine-needle aspiration if ultrasound tests show rapid nodule growth or characteristics suggestive of cancer, he suggested.

Dr. Jameson called the new gene expression classifier test a "welcome addition" to tools for managing thyroid nodules that could substantially reduce costs by avoiding operations, even when considering the added cost of the test.

One of the strengths of the 49-site study was that 80% of participants came from community-based sites and 20% from academic medical sites, representing a real-world sample, coinvestigator Dr. Bryan R. Haugen said at the press briefing.

He described recent use of the Afirma test at his institution on aspirates from 126 patients with indeterminate cytology results from January 2011 to April 2012. The gene expression classifier results said 56% were benign, 41% were suspicious, and 3% could not produce a result. Seventy patients avoided surgery. Among patients who underwent surgery, 52% of nodes were malignant, said Dr. Haugen, head of endocrinology, metabolism, and diabetes at the University of Colorado, Denver.

Dr. Haugen and Dr. Alexander emphasized that the Afirma test should only be used for aspirates with indeterminate cytology, not for biopsies classified as cytologically benign, because of the 70% specificity when used on benign lesions.

Thyroid nodules are common and can be found in 25%-50% of adults. When fine-needle aspiration biopsy produces indeterminate cytological results, most patients have undergone hemithyroidectomy or total thyroidectomy for diagnosis and treatment.

Veracyte, which makes the gene expression classifier, funded the study and tested the samples in its laboratory. Veracyte employees helped design and supervise the study, conducted the statistical analysis, and made up 6 of the 18 investigators. Dr. Alexander disclosed financial associations with Veracyte, Asuragen, Genzyme, and the Boston Clinical Research Institute. His coinvestigators disclosed financial associations with Veracyte and multiple other companies. Dr. Jameson disclosed financial associations with Quest Diagnostics, Novartis, and Ferring, and said that he knows some of the investigators professionally.

HOUSTON – A novel gene expression test could eliminate the need for a third of operations done for cytologically indeterminate thyroid nodules by winnowing out low-risk nodules, a large, prospective, double-blind, multicenter study suggests.

The study included fine-needle aspirates of thyroid nodules 1 cm or larger that were classified as indeterminate on cytology and that had corresponding histopathological specimens from excised lesions. A test that measures the expression of 167 genes was applied to 265 cytologically indeterminate nodules, with the patients, physicians, and pathology laboratories blinded to the results of the Afirma gene expression classifier test during management.

In general, cytologically indeterminate thyroid aspirates get classified one of three ways. The negative predictive value of results from the Afirma gene expression classifier test was 95% for the subset cytologically classified as "atypia (or follicular lesion) of undetermined clinical significance," 94% for "follicular neoplasm or lesion suspicious for follicular neoplasm," and 85% for "suspicious cytologic findings," Dr. Erik K. Alexander and his associates reported in a press briefing at the annual meeting of the Endocrine Society.

The Afirma test correctly identified as "suspicious" 78 of the 85 nodules that ultimately were found to be malignant, for a sensitivity of 92% and a specificity of 52%, he said.

A closer look at the seven aspirates that had false negative results from Afirma testing found that six samples lacked a sufficient quantity of thyroid follicular cells to be considered a sufficient sampling of the nodule, said Dr. Alexander of Brigham and Women’s Hospital and Harvard University, Boston.

The results are good enough that clinicians could take a conservative approach to managing most patients whose thyroid nodules are cytologically indeterminate on fine-needle aspiration but benign on the gene expression classifier test, he said.

The New England Journal of Medicine published the study online on June 25 (doi: 10.1056/NEJMoa1203208).

The new gene expression test could eliminate the need for 25,000 of the 75,000 surgeries each year in patients with cytologically indeterminate thyroid aspirates, but at the risk of likely malignancy in 5%-10% of nodules classified as benign, particularly nodules that are cytologically indeterminate but suggestive of cancer, Dr. J. Larry Jameson said in an editorial published simultaneously online by the journal (doi: 10.1056/NEJMe1205893).

In this high-risk group, repeating the fine-needle aspiration biopsy or performing a diagnostic hemithyroidectomy might be reasonable even when the gene expression classifier suggests a benign nodule, said Dr. Jameson of the University of Pennsylvania, Philadelphia.

For patients with indeterminate aspirates and negative Afirma test results who are monitored rather than sent to surgery, clinicians should have a low threshold for repeating fine-needle aspiration if ultrasound tests show rapid nodule growth or characteristics suggestive of cancer, he suggested.

Dr. Jameson called the new gene expression classifier test a "welcome addition" to tools for managing thyroid nodules that could substantially reduce costs by avoiding operations, even when considering the added cost of the test.

One of the strengths of the 49-site study was that 80% of participants came from community-based sites and 20% from academic medical sites, representing a real-world sample, coinvestigator Dr. Bryan R. Haugen said at the press briefing.

He described recent use of the Afirma test at his institution on aspirates from 126 patients with indeterminate cytology results from January 2011 to April 2012. The gene expression classifier results said 56% were benign, 41% were suspicious, and 3% could not produce a result. Seventy patients avoided surgery. Among patients who underwent surgery, 52% of nodes were malignant, said Dr. Haugen, head of endocrinology, metabolism, and diabetes at the University of Colorado, Denver.

Dr. Haugen and Dr. Alexander emphasized that the Afirma test should only be used for aspirates with indeterminate cytology, not for biopsies classified as cytologically benign, because of the 70% specificity when used on benign lesions.

Thyroid nodules are common and can be found in 25%-50% of adults. When fine-needle aspiration biopsy produces indeterminate cytological results, most patients have undergone hemithyroidectomy or total thyroidectomy for diagnosis and treatment.

Veracyte, which makes the gene expression classifier, funded the study and tested the samples in its laboratory. Veracyte employees helped design and supervise the study, conducted the statistical analysis, and made up 6 of the 18 investigators. Dr. Alexander disclosed financial associations with Veracyte, Asuragen, Genzyme, and the Boston Clinical Research Institute. His coinvestigators disclosed financial associations with Veracyte and multiple other companies. Dr. Jameson disclosed financial associations with Quest Diagnostics, Novartis, and Ferring, and said that he knows some of the investigators professionally.

HOUSTON – Applying transdermal gels containing off-label testosterone and an experimental nonandrogenic progestin showed promise as a form of reversible contraception for men in a randomized, double-blind, controlled pilot study in 99 men.

Healthy male volunteers were randomized in three groups to apply gels containing 10 g of testosterone plus placebo or testosterone plus either 8 mg or 12 mg of Nestorone, an investigational synthetic nonandrogenic progestin. They were asked to apply the gels daily for 20-24 weeks, and 56 complied.

Among those who completed the study, sperm concentrations in men on the combination gels were significantly more likely to decrease to 1 million/mL or lower (a level that previously has been proven to provide contraception), compared with men on testosterone/placebo gels. Eighty-nine percent of men in the 8-mg Nestorone group and 88% in the 12-mg group reached this sperm concentration threshold, compared with 23% on testosterone/placebo, Dr. Niloufar Ilani and her associates reported at the annual meeting of the Endocrine Society.

Men on the combination gels also were significantly more likely to have a complete absence of sperm. Azoospermia rates were 78% in the 8-mg group, 69% in the 12-mg group, and 23% on testosterone/placebo, said Dr. Ilani of Harbor–University of California, Los Angeles Medical Center.

Testosterone gel in the United States is approved to treat androgen deficiency in men but not for contraception. Long-term testosterone via injection is available in some non-U.S. countries.

Decreases in sperm concentration were accompanied by decreases in sperm motility and normal morphology. The combination-gel groups showed greater suppression of median serum luteinizing hormone and follicular stimulating hormone concentrations, compared with the testosterone-alone group.

Median total and free testosterone concentrations increased with treatment but remained within the adult male range in all treatment groups.

After treatment stopped, sperm concentrations recovered to greater than 3 million/mL in all subjects by 40 weeks after the start of the study.

No serious side effects were seen. Adverse events that may be related to the medications included acne in 21% of the entire cohort (28% in the control group, 21% in the 8-mg group, and 15% in the 12-mg group). Using a lower dose of testosterone may limit this androgen-related effect, the investigators suggested.

Seven percent reported weight gain (3% in the control group, 12% in the 8-mg group, and 6% in the 12-mg group). Six percent of subjects in each group reported insomnia. Four percent of all subjects reported dry skin, among other potential side effects. Results of psychosocial measures and assessments of mood stability did not change significantly in any group during or after treatment, compared with baseline.

Now that this study has proved the concept, investigators may try to combine the testosterone gel and Nestorone gel into a single gel that men could apply more conveniently. They also will test the combination in a study that recruits couples and asks participants not to use other contraceptives. In the current study, men were required to use a proven method of contraception and not rely on the gels.

Combining 8 mg Nestorone and testosterone seemed to be the best dosing combination because the higher dose of Nestorone did not offer greater sperm suppression, Dr. Ilani said.

Patient and sperm characteristics were similar between groups at the start of the study.

Dr. Ilani reported having no financial disclosures. Besins Healthcare International provided the testosterone gel. The Population Council, a nonprofit organization that is developing Nestorone, supplied the drug. The Eunice Kennedy Shriver National Institute of Child Health and Human Development funded the study.

HOUSTON – Applying transdermal gels containing off-label testosterone and an experimental nonandrogenic progestin showed promise as a form of reversible contraception for men in a randomized, double-blind, controlled pilot study in 99 men.

Healthy male volunteers were randomized in three groups to apply gels containing 10 g of testosterone plus placebo or testosterone plus either 8 mg or 12 mg of Nestorone, an investigational synthetic nonandrogenic progestin. They were asked to apply the gels daily for 20-24 weeks, and 56 complied.

Among those who completed the study, sperm concentrations in men on the combination gels were significantly more likely to decrease to 1 million/mL or lower (a level that previously has been proven to provide contraception), compared with men on testosterone/placebo gels. Eighty-nine percent of men in the 8-mg Nestorone group and 88% in the 12-mg group reached this sperm concentration threshold, compared with 23% on testosterone/placebo, Dr. Niloufar Ilani and her associates reported at the annual meeting of the Endocrine Society.

Men on the combination gels also were significantly more likely to have a complete absence of sperm. Azoospermia rates were 78% in the 8-mg group, 69% in the 12-mg group, and 23% on testosterone/placebo, said Dr. Ilani of Harbor–University of California, Los Angeles Medical Center.

Testosterone gel in the United States is approved to treat androgen deficiency in men but not for contraception. Long-term testosterone via injection is available in some non-U.S. countries.

Decreases in sperm concentration were accompanied by decreases in sperm motility and normal morphology. The combination-gel groups showed greater suppression of median serum luteinizing hormone and follicular stimulating hormone concentrations, compared with the testosterone-alone group.

Median total and free testosterone concentrations increased with treatment but remained within the adult male range in all treatment groups.

After treatment stopped, sperm concentrations recovered to greater than 3 million/mL in all subjects by 40 weeks after the start of the study.

No serious side effects were seen. Adverse events that may be related to the medications included acne in 21% of the entire cohort (28% in the control group, 21% in the 8-mg group, and 15% in the 12-mg group). Using a lower dose of testosterone may limit this androgen-related effect, the investigators suggested.

Seven percent reported weight gain (3% in the control group, 12% in the 8-mg group, and 6% in the 12-mg group). Six percent of subjects in each group reported insomnia. Four percent of all subjects reported dry skin, among other potential side effects. Results of psychosocial measures and assessments of mood stability did not change significantly in any group during or after treatment, compared with baseline.

Now that this study has proved the concept, investigators may try to combine the testosterone gel and Nestorone gel into a single gel that men could apply more conveniently. They also will test the combination in a study that recruits couples and asks participants not to use other contraceptives. In the current study, men were required to use a proven method of contraception and not rely on the gels.

Combining 8 mg Nestorone and testosterone seemed to be the best dosing combination because the higher dose of Nestorone did not offer greater sperm suppression, Dr. Ilani said.

Patient and sperm characteristics were similar between groups at the start of the study.

Dr. Ilani reported having no financial disclosures. Besins Healthcare International provided the testosterone gel. The Population Council, a nonprofit organization that is developing Nestorone, supplied the drug. The Eunice Kennedy Shriver National Institute of Child Health and Human Development funded the study.

HOUSTON – Applying transdermal gels containing off-label testosterone and an experimental nonandrogenic progestin showed promise as a form of reversible contraception for men in a randomized, double-blind, controlled pilot study in 99 men.

Healthy male volunteers were randomized in three groups to apply gels containing 10 g of testosterone plus placebo or testosterone plus either 8 mg or 12 mg of Nestorone, an investigational synthetic nonandrogenic progestin. They were asked to apply the gels daily for 20-24 weeks, and 56 complied.

Among those who completed the study, sperm concentrations in men on the combination gels were significantly more likely to decrease to 1 million/mL or lower (a level that previously has been proven to provide contraception), compared with men on testosterone/placebo gels. Eighty-nine percent of men in the 8-mg Nestorone group and 88% in the 12-mg group reached this sperm concentration threshold, compared with 23% on testosterone/placebo, Dr. Niloufar Ilani and her associates reported at the annual meeting of the Endocrine Society.

Men on the combination gels also were significantly more likely to have a complete absence of sperm. Azoospermia rates were 78% in the 8-mg group, 69% in the 12-mg group, and 23% on testosterone/placebo, said Dr. Ilani of Harbor–University of California, Los Angeles Medical Center.

Testosterone gel in the United States is approved to treat androgen deficiency in men but not for contraception. Long-term testosterone via injection is available in some non-U.S. countries.

Decreases in sperm concentration were accompanied by decreases in sperm motility and normal morphology. The combination-gel groups showed greater suppression of median serum luteinizing hormone and follicular stimulating hormone concentrations, compared with the testosterone-alone group.

Median total and free testosterone concentrations increased with treatment but remained within the adult male range in all treatment groups.

After treatment stopped, sperm concentrations recovered to greater than 3 million/mL in all subjects by 40 weeks after the start of the study.

No serious side effects were seen. Adverse events that may be related to the medications included acne in 21% of the entire cohort (28% in the control group, 21% in the 8-mg group, and 15% in the 12-mg group). Using a lower dose of testosterone may limit this androgen-related effect, the investigators suggested.

Seven percent reported weight gain (3% in the control group, 12% in the 8-mg group, and 6% in the 12-mg group). Six percent of subjects in each group reported insomnia. Four percent of all subjects reported dry skin, among other potential side effects. Results of psychosocial measures and assessments of mood stability did not change significantly in any group during or after treatment, compared with baseline.

Now that this study has proved the concept, investigators may try to combine the testosterone gel and Nestorone gel into a single gel that men could apply more conveniently. They also will test the combination in a study that recruits couples and asks participants not to use other contraceptives. In the current study, men were required to use a proven method of contraception and not rely on the gels.

Combining 8 mg Nestorone and testosterone seemed to be the best dosing combination because the higher dose of Nestorone did not offer greater sperm suppression, Dr. Ilani said.

Patient and sperm characteristics were similar between groups at the start of the study.

Dr. Ilani reported having no financial disclosures. Besins Healthcare International provided the testosterone gel. The Population Council, a nonprofit organization that is developing Nestorone, supplied the drug. The Eunice Kennedy Shriver National Institute of Child Health and Human Development funded the study.

Treating childhood sleep apnea normalized levels of neuronal metabolites in the brain and improved attention at other measures of cognitive function, explains Dr. Ann Halbower.

Treating childhood sleep apnea normalized levels of neuronal metabolites in the brain and improved attention at other measures of cognitive function, explains Dr. Ann Halbower.

Treating childhood sleep apnea normalized levels of neuronal metabolites in the brain and improved attention at other measures of cognitive function, explains Dr. Ann Halbower.

SAN FRANCISCO – The recent findings of significantly increased risk for cancer incidence and mortality in people with sleep apnea echo previous in vitro and animal studies that found repeated episodes of hypoxia were associated with accelerated cancer progression.

In one of two new studies, people with obstructive sleep apnea were 10%-480% more likely to die of cancer, depending on apnea severity, compared with people without OSA, in a 20-year follow-up study of 1,522 participants in the Wisconsin Sleep Cohort.

Both the number of dips in oxygen level during sleep and the severity of hypoxia during those episodes were associated with increased risk of cancer mortality, but the association was stronger with hypoxia severity. Patients who spent much of their sleep time getting less than 90% oxyhemoglobin saturation were nearly nine times more likely to die of cancer during the study, compared with controls, said Dr. F. Javier Nieto and his associates reported in a press briefing at the annual meeting of the American Thoracic Society.

In a separate prospective 5-year study of 5,618 patients who were referred to seven sleep clinics in Spain, severe hypoxemia during sleep was associated with significantly increased incidence of cancer. Patients with OSA who spent more than 30% of their sleep time getting less than 90% oxyhemoglobin saturation had more than twice the risk for a new diagnosis of cancer during 5 years of follow-up, compared with patients without sleep apnea, Dr. Miguel A. Martinez-Garcia and his associates reported at the briefing.

"In both studies, when they looked at the amount of low oxygen that they were getting, that’s when the incidence and mortality from cancer went up," said Mary J. Morrell, Ph.D., who moderated the press briefing. "What it suggests is that there’s something associated with low oxygen that’s triggering the cancer, which would fit with the initial animal work that caused them to look into the two large cohorts" of people, added Dr. Morrell, professor of sleep and respiratory physiology at Imperial College, London.

The U.S. study analyzed mortality data for participants in the Wisconsin Sleep Cohort, a prospective, community-based study of the predictors and natural history of sleep disorders. All underwent polysomnography at the start of the study. Sleep-disordered breathing was defined as an apnea-hypopnea index (AHI) score of 5 or greater, representing the mean number of apnea and hypopnea events per hour of sleep.

The mortality risks were associated with the presence and severity of sleep apnea in a dose-response fashion, said Dr. Nieto, chair of the department of population health sciences at the University of Wisconsin, Madison.

Compared with participants who did not have sleep apnea, those with mild sleep apnea (defined as an AHI of 5-14.9) were 10% more likely to die of cancer during the follow-up years. People with moderate sleep apnea (an AHI of 15-29.9) were twice as likely and those with severe apnea (an AHI of 30 or greater) were nearly five times as likely to die of cancer, compared with the control group without sleep apnea. The results were adjusted for the confounding effects of age, sex, body mass index, and smoking, Dr. Nieto said.

"The key thing is that it’s the amount of low oxygen that the patients are getting, not essentially how many times it occurs, which is the apnea-hypopnea index. It’s the amount that they’re getting" that matters most, Dr. Morrell noted.

When the results of the Spanish study were analyzed according to scores on the AHI, which includes both hypopnea and hypoxemia, the increased incidence of cancer in patients with sleep apnea became statistically nonsignificant after adjusting for the confounding effects of age, gender, and body mass index, said Dr. Martinez-Garcia of Le Fe University and Polytechnic Hospital, Valencia, Spain. Subset analyses suggest that the association between the hypoxemia index and cancer incidence may be limited to males and younger patients, Dr. Martinez-Garcia said.

Dr. Nieto, Dr. Martinez-Garcia, and Dr. Morrell reported having no financial disclosures.

SAN FRANCISCO – The recent findings of significantly increased risk for cancer incidence and mortality in people with sleep apnea echo previous in vitro and animal studies that found repeated episodes of hypoxia were associated with accelerated cancer progression.

In one of two new studies, people with obstructive sleep apnea were 10%-480% more likely to die of cancer, depending on apnea severity, compared with people without OSA, in a 20-year follow-up study of 1,522 participants in the Wisconsin Sleep Cohort.

Both the number of dips in oxygen level during sleep and the severity of hypoxia during those episodes were associated with increased risk of cancer mortality, but the association was stronger with hypoxia severity. Patients who spent much of their sleep time getting less than 90% oxyhemoglobin saturation were nearly nine times more likely to die of cancer during the study, compared with controls, said Dr. F. Javier Nieto and his associates reported in a press briefing at the annual meeting of the American Thoracic Society.

In a separate prospective 5-year study of 5,618 patients who were referred to seven sleep clinics in Spain, severe hypoxemia during sleep was associated with significantly increased incidence of cancer. Patients with OSA who spent more than 30% of their sleep time getting less than 90% oxyhemoglobin saturation had more than twice the risk for a new diagnosis of cancer during 5 years of follow-up, compared with patients without sleep apnea, Dr. Miguel A. Martinez-Garcia and his associates reported at the briefing.

"In both studies, when they looked at the amount of low oxygen that they were getting, that’s when the incidence and mortality from cancer went up," said Mary J. Morrell, Ph.D., who moderated the press briefing. "What it suggests is that there’s something associated with low oxygen that’s triggering the cancer, which would fit with the initial animal work that caused them to look into the two large cohorts" of people, added Dr. Morrell, professor of sleep and respiratory physiology at Imperial College, London.

The U.S. study analyzed mortality data for participants in the Wisconsin Sleep Cohort, a prospective, community-based study of the predictors and natural history of sleep disorders. All underwent polysomnography at the start of the study. Sleep-disordered breathing was defined as an apnea-hypopnea index (AHI) score of 5 or greater, representing the mean number of apnea and hypopnea events per hour of sleep.

The mortality risks were associated with the presence and severity of sleep apnea in a dose-response fashion, said Dr. Nieto, chair of the department of population health sciences at the University of Wisconsin, Madison.

Compared with participants who did not have sleep apnea, those with mild sleep apnea (defined as an AHI of 5-14.9) were 10% more likely to die of cancer during the follow-up years. People with moderate sleep apnea (an AHI of 15-29.9) were twice as likely and those with severe apnea (an AHI of 30 or greater) were nearly five times as likely to die of cancer, compared with the control group without sleep apnea. The results were adjusted for the confounding effects of age, sex, body mass index, and smoking, Dr. Nieto said.

"The key thing is that it’s the amount of low oxygen that the patients are getting, not essentially how many times it occurs, which is the apnea-hypopnea index. It’s the amount that they’re getting" that matters most, Dr. Morrell noted.

When the results of the Spanish study were analyzed according to scores on the AHI, which includes both hypopnea and hypoxemia, the increased incidence of cancer in patients with sleep apnea became statistically nonsignificant after adjusting for the confounding effects of age, gender, and body mass index, said Dr. Martinez-Garcia of Le Fe University and Polytechnic Hospital, Valencia, Spain. Subset analyses suggest that the association between the hypoxemia index and cancer incidence may be limited to males and younger patients, Dr. Martinez-Garcia said.

Dr. Nieto, Dr. Martinez-Garcia, and Dr. Morrell reported having no financial disclosures.

SAN FRANCISCO – The recent findings of significantly increased risk for cancer incidence and mortality in people with sleep apnea echo previous in vitro and animal studies that found repeated episodes of hypoxia were associated with accelerated cancer progression.

In one of two new studies, people with obstructive sleep apnea were 10%-480% more likely to die of cancer, depending on apnea severity, compared with people without OSA, in a 20-year follow-up study of 1,522 participants in the Wisconsin Sleep Cohort.

Both the number of dips in oxygen level during sleep and the severity of hypoxia during those episodes were associated with increased risk of cancer mortality, but the association was stronger with hypoxia severity. Patients who spent much of their sleep time getting less than 90% oxyhemoglobin saturation were nearly nine times more likely to die of cancer during the study, compared with controls, said Dr. F. Javier Nieto and his associates reported in a press briefing at the annual meeting of the American Thoracic Society.

In a separate prospective 5-year study of 5,618 patients who were referred to seven sleep clinics in Spain, severe hypoxemia during sleep was associated with significantly increased incidence of cancer. Patients with OSA who spent more than 30% of their sleep time getting less than 90% oxyhemoglobin saturation had more than twice the risk for a new diagnosis of cancer during 5 years of follow-up, compared with patients without sleep apnea, Dr. Miguel A. Martinez-Garcia and his associates reported at the briefing.

"In both studies, when they looked at the amount of low oxygen that they were getting, that’s when the incidence and mortality from cancer went up," said Mary J. Morrell, Ph.D., who moderated the press briefing. "What it suggests is that there’s something associated with low oxygen that’s triggering the cancer, which would fit with the initial animal work that caused them to look into the two large cohorts" of people, added Dr. Morrell, professor of sleep and respiratory physiology at Imperial College, London.

The U.S. study analyzed mortality data for participants in the Wisconsin Sleep Cohort, a prospective, community-based study of the predictors and natural history of sleep disorders. All underwent polysomnography at the start of the study. Sleep-disordered breathing was defined as an apnea-hypopnea index (AHI) score of 5 or greater, representing the mean number of apnea and hypopnea events per hour of sleep.

The mortality risks were associated with the presence and severity of sleep apnea in a dose-response fashion, said Dr. Nieto, chair of the department of population health sciences at the University of Wisconsin, Madison.

Compared with participants who did not have sleep apnea, those with mild sleep apnea (defined as an AHI of 5-14.9) were 10% more likely to die of cancer during the follow-up years. People with moderate sleep apnea (an AHI of 15-29.9) were twice as likely and those with severe apnea (an AHI of 30 or greater) were nearly five times as likely to die of cancer, compared with the control group without sleep apnea. The results were adjusted for the confounding effects of age, sex, body mass index, and smoking, Dr. Nieto said.

"The key thing is that it’s the amount of low oxygen that the patients are getting, not essentially how many times it occurs, which is the apnea-hypopnea index. It’s the amount that they’re getting" that matters most, Dr. Morrell noted.

When the results of the Spanish study were analyzed according to scores on the AHI, which includes both hypopnea and hypoxemia, the increased incidence of cancer in patients with sleep apnea became statistically nonsignificant after adjusting for the confounding effects of age, gender, and body mass index, said Dr. Martinez-Garcia of Le Fe University and Polytechnic Hospital, Valencia, Spain. Subset analyses suggest that the association between the hypoxemia index and cancer incidence may be limited to males and younger patients, Dr. Martinez-Garcia said.

Dr. Nieto, Dr. Martinez-Garcia, and Dr. Morrell reported having no financial disclosures.

SAN FRANCISCO – Black women with a history of sarcoidosis have a mortality rate twice that of women without sarcoidosis, according to an analysis of data from approximately 59,000 women in the Black Women’s Health Study during 1995-2009.

The age-adjusted mortality rate was 17/10,000 person-years in black women with a history of sarcoidosis and 8/10,000 person-years in those without a history of sarcoidosis, Dr. Melissa H. Tukey reported.

A total of 686 women had a diagnosis of sarcoidosis at the start of the Black Women's Health Study in 1995, and 506 women developed sarcoidosis during follow-up; of these, 121 died. Among the remaining women without sarcoidosis, 2,813 died. Cumulative mortality rates were 10% in those with sarcoidosis and 5% in those without sarcoidosis, Dr. Tukey and her associates reported in a poster presentation and discussion at an international conference of the American Thoracic Society.

Sarcoidosis was the leading cause of death in women with the disease who died. Of deaths among women with a history of sarcoidosis, 24% were directly attributable to the disease, and 47% of these deaths were caused by respiratory failure, an analysis of National Death Index data showed. Another 6% died from pulmonary fibrosis or pulmonary hypertension.

The current analysis is the largest epidemiologic study specifically focused on mortality in black women with sarcoidosis, said Dr. Tukey of Boston University. Previous data suggesting that African American women are disproportionately affected by sarcoidosis and have a higher mortality from the disease come primarily from single-site studies, she added.

Other causes of death among black women with a history of sarcoidosis in the Black Women’s Health Study were listed as cancer in 23%, infection in 11%, coronary artery disease in 8%, other cardiac disease in 10%, chronic obstructive pulmonary disease in 2%, and other causes in 16%.

In each age category at the end of the follow-up period, the all-cause mortality rate among women with a history of sarcoidosis was higher than for women with no history of sarcoidosis.

For most black women with sarcoidosis, "it’s primarily a benign disease," Dr. Tukey said. "But there is this cohort of patients that just have a more progressive and severe course, and often end up dying of their disease. Now we’re finally able to really quantify what that actual risk is."

A clinician who has a female black patient with sarcoidosis who starts to develop pulmonary fibrosis or signs of severe disease should discuss the option of more aggressive treatment with the patient, she suggested.

The Black Women’s Health Study relied on self-report of a sarcoidosis diagnosis, but Dr. Tukey and her associates confirmed the diagnosis in 96% of patients for whom medical records or physician checklists were obtained. The Black Women’s Health Study is not a random sample of black women in the United States, so results may not be generalizable to the entire population of black women.

Dr. Tukey reported having no financial disclosures.

SAN FRANCISCO – Black women with a history of sarcoidosis have a mortality rate twice that of women without sarcoidosis, according to an analysis of data from approximately 59,000 women in the Black Women’s Health Study during 1995-2009.

The age-adjusted mortality rate was 17/10,000 person-years in black women with a history of sarcoidosis and 8/10,000 person-years in those without a history of sarcoidosis, Dr. Melissa H. Tukey reported.

A total of 686 women had a diagnosis of sarcoidosis at the start of the Black Women's Health Study in 1995, and 506 women developed sarcoidosis during follow-up; of these, 121 died. Among the remaining women without sarcoidosis, 2,813 died. Cumulative mortality rates were 10% in those with sarcoidosis and 5% in those without sarcoidosis, Dr. Tukey and her associates reported in a poster presentation and discussion at an international conference of the American Thoracic Society.

Sarcoidosis was the leading cause of death in women with the disease who died. Of deaths among women with a history of sarcoidosis, 24% were directly attributable to the disease, and 47% of these deaths were caused by respiratory failure, an analysis of National Death Index data showed. Another 6% died from pulmonary fibrosis or pulmonary hypertension.

The current analysis is the largest epidemiologic study specifically focused on mortality in black women with sarcoidosis, said Dr. Tukey of Boston University. Previous data suggesting that African American women are disproportionately affected by sarcoidosis and have a higher mortality from the disease come primarily from single-site studies, she added.

Other causes of death among black women with a history of sarcoidosis in the Black Women’s Health Study were listed as cancer in 23%, infection in 11%, coronary artery disease in 8%, other cardiac disease in 10%, chronic obstructive pulmonary disease in 2%, and other causes in 16%.

In each age category at the end of the follow-up period, the all-cause mortality rate among women with a history of sarcoidosis was higher than for women with no history of sarcoidosis.

For most black women with sarcoidosis, "it’s primarily a benign disease," Dr. Tukey said. "But there is this cohort of patients that just have a more progressive and severe course, and often end up dying of their disease. Now we’re finally able to really quantify what that actual risk is."

A clinician who has a female black patient with sarcoidosis who starts to develop pulmonary fibrosis or signs of severe disease should discuss the option of more aggressive treatment with the patient, she suggested.

The Black Women’s Health Study relied on self-report of a sarcoidosis diagnosis, but Dr. Tukey and her associates confirmed the diagnosis in 96% of patients for whom medical records or physician checklists were obtained. The Black Women’s Health Study is not a random sample of black women in the United States, so results may not be generalizable to the entire population of black women.

Dr. Tukey reported having no financial disclosures.

SAN FRANCISCO – Black women with a history of sarcoidosis have a mortality rate twice that of women without sarcoidosis, according to an analysis of data from approximately 59,000 women in the Black Women’s Health Study during 1995-2009.

The age-adjusted mortality rate was 17/10,000 person-years in black women with a history of sarcoidosis and 8/10,000 person-years in those without a history of sarcoidosis, Dr. Melissa H. Tukey reported.

A total of 686 women had a diagnosis of sarcoidosis at the start of the Black Women's Health Study in 1995, and 506 women developed sarcoidosis during follow-up; of these, 121 died. Among the remaining women without sarcoidosis, 2,813 died. Cumulative mortality rates were 10% in those with sarcoidosis and 5% in those without sarcoidosis, Dr. Tukey and her associates reported in a poster presentation and discussion at an international conference of the American Thoracic Society.

Sarcoidosis was the leading cause of death in women with the disease who died. Of deaths among women with a history of sarcoidosis, 24% were directly attributable to the disease, and 47% of these deaths were caused by respiratory failure, an analysis of National Death Index data showed. Another 6% died from pulmonary fibrosis or pulmonary hypertension.

The current analysis is the largest epidemiologic study specifically focused on mortality in black women with sarcoidosis, said Dr. Tukey of Boston University. Previous data suggesting that African American women are disproportionately affected by sarcoidosis and have a higher mortality from the disease come primarily from single-site studies, she added.

Other causes of death among black women with a history of sarcoidosis in the Black Women’s Health Study were listed as cancer in 23%, infection in 11%, coronary artery disease in 8%, other cardiac disease in 10%, chronic obstructive pulmonary disease in 2%, and other causes in 16%.

In each age category at the end of the follow-up period, the all-cause mortality rate among women with a history of sarcoidosis was higher than for women with no history of sarcoidosis.

For most black women with sarcoidosis, "it’s primarily a benign disease," Dr. Tukey said. "But there is this cohort of patients that just have a more progressive and severe course, and often end up dying of their disease. Now we’re finally able to really quantify what that actual risk is."

A clinician who has a female black patient with sarcoidosis who starts to develop pulmonary fibrosis or signs of severe disease should discuss the option of more aggressive treatment with the patient, she suggested.

The Black Women’s Health Study relied on self-report of a sarcoidosis diagnosis, but Dr. Tukey and her associates confirmed the diagnosis in 96% of patients for whom medical records or physician checklists were obtained. The Black Women’s Health Study is not a random sample of black women in the United States, so results may not be generalizable to the entire population of black women.

Dr. Tukey reported having no financial disclosures.

SAN FRANCISCO – Newborn lung function was significantly better in pregnant smokers who took vitamin C supplements, compared with smoking mothers on placebo, in a double-blind trial that randomized 179 women.

Among 159 infants who underwent pulmonary function tests at around 48 hours of age, results in the 76 newborns of smokers getting vitamin C were similar to results for 76 newborns of nonsmoking women in a nonrandomized comparison group. Both subgroups had better pulmonary function than did the 83 newborns of placebo-treated smokers, Dr. Cindy T. McEvoy and her associates reported at an international conference of the American Thoracic Society.

Photo Courtesy Dr. Cindy T. McEvoy

"We speculate that vitamin C supplementation in pregnant women who cannot quit smoking is helpful," said Dr. McEvoy of Oregon Health and Science University, Portland.

The current study randomized pregnant smokers aged 15 years and older, and prior to 22 weeks gestation of their singletons, to take 500 mg/day of vitamin C or placebo until delivery. The women were counseled throughout the trial to quit smoking but declined to do so.

Maternal plasma levels of ascorbic acid were significantly lower in the two smoking groups at randomization, compared with levels in nonsmokers. By mid-gestation, ascorbic acid levels in the vitamin C group were similar to levels in nonsmokers (59 and 58 micromol/L, respectively), but levels in the placebo group remained significantly lower (40 micromol/L).

Infant pulmonary flow volume, characterized as a ratio of the time to peak tidal expiratory flow to expiratory time, was significantly lower in the placebo group (0.345), compared with the vitamin C group (0.383) and the nonsmoking group (0.399), Dr. McEvoy said.

Investigators also measured the newborns’ passive respiratory mechanics, or compliance of the respiratory system (Crs/kg), and found significantly lower results in the placebo group (1.2 Crs/kg), compared with the vitamin C group (1.32 Crs/kg) or the nonsmoking group (1.36 Crs/kg).

Treatment did not significantly affect respiratory rate.

There were no significant differences between the randomized groups at the start of the study in characteristics including maternal age, insurance coverage, cotinine levels, medication adherence, history of asthma, or the proportion of women smoking 10 or more cigarettes per day.

Infant demographics were similar in the two groups of smokers and the reference group of nonsmokers, including birth weight, gestational age at delivery, sex, rate of delivery before 32 weeks’ gestation, and rate of vaginal delivery.

The investigators plan to perform infant pulmonary function tests again when the study babies are 1 year old and compare it with clinical outcomes such as episodes of wheezing. They have secured support from the National Heart, Lung, and Blood Institute to randomize a new cohort and measure newborn forced expiratory flows as the primary outcome, she said.

The investigators did not give vitamin C supplementation to infants, but that strategy may deserve study as well, Dr. McEvoy said.

The study excluded pregnancies with multiple gestation or fetal congenital anomalies and women who currently used illicit drugs or abused alcohol, had a history of kidney stones, had insulin-dependent diabetes, or who had been taking vitamin C daily since their last menstrual period. Before the treatment period began, participants were asked to take a daily placebo; those who complied with fewer than 75% of placebo doses were excluded from randomization.

Approximately 12% of U.S. women smoke during pregnancy and at least 500,000 newborns each year have been exposed to smoke in utero. Previous studies have shown that infants of smokers have worse lung function at birth and a higher risk of developing lung diseases, including asthma, bronchitis, and pneumonia, compared with infants of nonsmokers.

The current findings support evidence from nonhuman primates that daily vitamin C can block the in utero effects of nicotine on lung development and newborn pulmonary function (Am. J. Respir. Crit. Care Med. 2005;171:1032-9).

Dr. McEvoy reported having no financial disclosures. The National Heart, Lung, and Blood Institute funded the study.

SAN FRANCISCO – Newborn lung function was significantly better in pregnant smokers who took vitamin C supplements, compared with smoking mothers on placebo, in a double-blind trial that randomized 179 women.

Among 159 infants who underwent pulmonary function tests at around 48 hours of age, results in the 76 newborns of smokers getting vitamin C were similar to results for 76 newborns of nonsmoking women in a nonrandomized comparison group. Both subgroups had better pulmonary function than did the 83 newborns of placebo-treated smokers, Dr. Cindy T. McEvoy and her associates reported at an international conference of the American Thoracic Society.

Photo Courtesy Dr. Cindy T. McEvoy

"We speculate that vitamin C supplementation in pregnant women who cannot quit smoking is helpful," said Dr. McEvoy of Oregon Health and Science University, Portland.

The current study randomized pregnant smokers aged 15 years and older, and prior to 22 weeks gestation of their singletons, to take 500 mg/day of vitamin C or placebo until delivery. The women were counseled throughout the trial to quit smoking but declined to do so.

Maternal plasma levels of ascorbic acid were significantly lower in the two smoking groups at randomization, compared with levels in nonsmokers. By mid-gestation, ascorbic acid levels in the vitamin C group were similar to levels in nonsmokers (59 and 58 micromol/L, respectively), but levels in the placebo group remained significantly lower (40 micromol/L).

Infant pulmonary flow volume, characterized as a ratio of the time to peak tidal expiratory flow to expiratory time, was significantly lower in the placebo group (0.345), compared with the vitamin C group (0.383) and the nonsmoking group (0.399), Dr. McEvoy said.

Investigators also measured the newborns’ passive respiratory mechanics, or compliance of the respiratory system (Crs/kg), and found significantly lower results in the placebo group (1.2 Crs/kg), compared with the vitamin C group (1.32 Crs/kg) or the nonsmoking group (1.36 Crs/kg).

Treatment did not significantly affect respiratory rate.

There were no significant differences between the randomized groups at the start of the study in characteristics including maternal age, insurance coverage, cotinine levels, medication adherence, history of asthma, or the proportion of women smoking 10 or more cigarettes per day.

Infant demographics were similar in the two groups of smokers and the reference group of nonsmokers, including birth weight, gestational age at delivery, sex, rate of delivery before 32 weeks’ gestation, and rate of vaginal delivery.

The investigators plan to perform infant pulmonary function tests again when the study babies are 1 year old and compare it with clinical outcomes such as episodes of wheezing. They have secured support from the National Heart, Lung, and Blood Institute to randomize a new cohort and measure newborn forced expiratory flows as the primary outcome, she said.

The investigators did not give vitamin C supplementation to infants, but that strategy may deserve study as well, Dr. McEvoy said.

The study excluded pregnancies with multiple gestation or fetal congenital anomalies and women who currently used illicit drugs or abused alcohol, had a history of kidney stones, had insulin-dependent diabetes, or who had been taking vitamin C daily since their last menstrual period. Before the treatment period began, participants were asked to take a daily placebo; those who complied with fewer than 75% of placebo doses were excluded from randomization.

Approximately 12% of U.S. women smoke during pregnancy and at least 500,000 newborns each year have been exposed to smoke in utero. Previous studies have shown that infants of smokers have worse lung function at birth and a higher risk of developing lung diseases, including asthma, bronchitis, and pneumonia, compared with infants of nonsmokers.

The current findings support evidence from nonhuman primates that daily vitamin C can block the in utero effects of nicotine on lung development and newborn pulmonary function (Am. J. Respir. Crit. Care Med. 2005;171:1032-9).

Dr. McEvoy reported having no financial disclosures. The National Heart, Lung, and Blood Institute funded the study.

SAN FRANCISCO – Newborn lung function was significantly better in pregnant smokers who took vitamin C supplements, compared with smoking mothers on placebo, in a double-blind trial that randomized 179 women.

Among 159 infants who underwent pulmonary function tests at around 48 hours of age, results in the 76 newborns of smokers getting vitamin C were similar to results for 76 newborns of nonsmoking women in a nonrandomized comparison group. Both subgroups had better pulmonary function than did the 83 newborns of placebo-treated smokers, Dr. Cindy T. McEvoy and her associates reported at an international conference of the American Thoracic Society.

Photo Courtesy Dr. Cindy T. McEvoy

"We speculate that vitamin C supplementation in pregnant women who cannot quit smoking is helpful," said Dr. McEvoy of Oregon Health and Science University, Portland.

The current study randomized pregnant smokers aged 15 years and older, and prior to 22 weeks gestation of their singletons, to take 500 mg/day of vitamin C or placebo until delivery. The women were counseled throughout the trial to quit smoking but declined to do so.

Maternal plasma levels of ascorbic acid were significantly lower in the two smoking groups at randomization, compared with levels in nonsmokers. By mid-gestation, ascorbic acid levels in the vitamin C group were similar to levels in nonsmokers (59 and 58 micromol/L, respectively), but levels in the placebo group remained significantly lower (40 micromol/L).

Infant pulmonary flow volume, characterized as a ratio of the time to peak tidal expiratory flow to expiratory time, was significantly lower in the placebo group (0.345), compared with the vitamin C group (0.383) and the nonsmoking group (0.399), Dr. McEvoy said.

Investigators also measured the newborns’ passive respiratory mechanics, or compliance of the respiratory system (Crs/kg), and found significantly lower results in the placebo group (1.2 Crs/kg), compared with the vitamin C group (1.32 Crs/kg) or the nonsmoking group (1.36 Crs/kg).

Treatment did not significantly affect respiratory rate.

There were no significant differences between the randomized groups at the start of the study in characteristics including maternal age, insurance coverage, cotinine levels, medication adherence, history of asthma, or the proportion of women smoking 10 or more cigarettes per day.

Infant demographics were similar in the two groups of smokers and the reference group of nonsmokers, including birth weight, gestational age at delivery, sex, rate of delivery before 32 weeks’ gestation, and rate of vaginal delivery.

The investigators plan to perform infant pulmonary function tests again when the study babies are 1 year old and compare it with clinical outcomes such as episodes of wheezing. They have secured support from the National Heart, Lung, and Blood Institute to randomize a new cohort and measure newborn forced expiratory flows as the primary outcome, she said.

The investigators did not give vitamin C supplementation to infants, but that strategy may deserve study as well, Dr. McEvoy said.

The study excluded pregnancies with multiple gestation or fetal congenital anomalies and women who currently used illicit drugs or abused alcohol, had a history of kidney stones, had insulin-dependent diabetes, or who had been taking vitamin C daily since their last menstrual period. Before the treatment period began, participants were asked to take a daily placebo; those who complied with fewer than 75% of placebo doses were excluded from randomization.

Approximately 12% of U.S. women smoke during pregnancy and at least 500,000 newborns each year have been exposed to smoke in utero. Previous studies have shown that infants of smokers have worse lung function at birth and a higher risk of developing lung diseases, including asthma, bronchitis, and pneumonia, compared with infants of nonsmokers.

The current findings support evidence from nonhuman primates that daily vitamin C can block the in utero effects of nicotine on lung development and newborn pulmonary function (Am. J. Respir. Crit. Care Med. 2005;171:1032-9).

Dr. McEvoy reported having no financial disclosures. The National Heart, Lung, and Blood Institute funded the study.