Mary Ann Moon

Among males, an elevated body mass index during adolescence was a strong predictor of angiography-proven coronary heart disease in young adulthood, according to a report in the April 7 issue of the New England Journal of Medicine.

Male adolescents in the top 10% of BMI had a risk for developing CHD at ages 25-45 years that was nearly seven times higher than the risk in adolescents in the lowest 10% of BMI, said Dr. Amir Tirosh of the division of endocrinology, diabetes, and hypertension at Brigham and Women’s Hospital, Boston, and his associates (N. Engl. J. Med. 2011;364:1315-25).

Photo credit: Bill Branson/National Cancer Institute

"Although obesity in adulthood is a well-documented risk factor for both type 2 diabetes and CHD, it [has been] unclear whether a longer history of relative overweight, starting earlier in life, poses an additional risk," the researchers said. "Given the current obesity pandemic, it is important to determine whether elevated BMI in childhood [or] adolescence ... contributes independently to the risk of disease."

Dr. Tirosh and his colleagues examined the issue using data from an Israel Defense Forces’ study, the ongoing Metabolic, Lifestyle, and Nutrition Assessment in Young Adults study. All men in the Israeli military are examined every 3-5 years, beginning at about age 25 and continuing throughout their military careers, and the information is recorded in a database.

Also recorded are the weight and height measurements obtained during the men’s medical exam at induction into the military, usually at age 17. Those data were used to calculate BMI in adolescence.

For this study, Dr. Tirosh and his associates analyzed data on 37,674 male military personnel who were followed prospectively for a mean of 17 years, starting at about age 25, and whose BMI during adolescence was tracked retrospectively. At that time, BMI ranged from 15 to 36 kg/m².

During follow-up, there were 327 incident cases of angiography-proven CHD, diagnosed when the subjects were aged 25-45 years. After the data were adjusted to account for potential confounders such as subject age, presence or absence of a family history of CHD, blood pressure, physical activity level, smoking status, and lipid profile, elevated adolescent BMI was a significant predictor of CHD across the entire BMI range.

The nearly 4,000 subjects whose BMI was in the 90th percentile and above had a hazard ratio of 6.85 for developing CHD, compared with those in the 10th percentile and below.

The excess CHD risk was present even at BMIs that are "well within the range currently considered to be normal," rising 12% for every 1-unit increment in BMI, Dr. Tirosh and his associates reported.

"Our study may help to redefine what constitutes a ‘normal’ or ‘healthy’ BMI in adolescence and to highlight the role of elevated BMI at different ages in the pathogenesis of different diseases," the researchers said.

In contrast to CHD risk, the risk of type 2 diabetes did not correlate with adolescent BMI once the data were adjusted to account for potential confounders. Diabetes was more influenced by recent BMI and weight gain, "suggesting that BMI in adolescence has a more reversible or shorter term effect on the risk of diabetes as compared with its effect on the risk of CHD," they said.

"Our results might be explained by the fact that diabetes represents a more functional pathomechanism than CHD, which relies on anatomical changes (atherosclerosis)," Dr. Tirosh and his colleagues said.

Because the study involved only young Israeli military men, the findings may not be generalizable to other patient populations, they added.

The study was supported by the Chaim Sheba Medical Center in Tel-Hashomer, Israel, and by the Israel Defense Forces Medical Corps. The authors reported that they had no conflicts of interest.

Among males, an elevated body mass index during adolescence was a strong predictor of angiography-proven coronary heart disease in young adulthood, according to a report in the April 7 issue of the New England Journal of Medicine.

Male adolescents in the top 10% of BMI had a risk for developing CHD at ages 25-45 years that was nearly seven times higher than the risk in adolescents in the lowest 10% of BMI, said Dr. Amir Tirosh of the division of endocrinology, diabetes, and hypertension at Brigham and Women’s Hospital, Boston, and his associates (N. Engl. J. Med. 2011;364:1315-25).

Photo credit: Bill Branson/National Cancer Institute

"Although obesity in adulthood is a well-documented risk factor for both type 2 diabetes and CHD, it [has been] unclear whether a longer history of relative overweight, starting earlier in life, poses an additional risk," the researchers said. "Given the current obesity pandemic, it is important to determine whether elevated BMI in childhood [or] adolescence ... contributes independently to the risk of disease."

Dr. Tirosh and his colleagues examined the issue using data from an Israel Defense Forces’ study, the ongoing Metabolic, Lifestyle, and Nutrition Assessment in Young Adults study. All men in the Israeli military are examined every 3-5 years, beginning at about age 25 and continuing throughout their military careers, and the information is recorded in a database.

Also recorded are the weight and height measurements obtained during the men’s medical exam at induction into the military, usually at age 17. Those data were used to calculate BMI in adolescence.

For this study, Dr. Tirosh and his associates analyzed data on 37,674 male military personnel who were followed prospectively for a mean of 17 years, starting at about age 25, and whose BMI during adolescence was tracked retrospectively. At that time, BMI ranged from 15 to 36 kg/m².

During follow-up, there were 327 incident cases of angiography-proven CHD, diagnosed when the subjects were aged 25-45 years. After the data were adjusted to account for potential confounders such as subject age, presence or absence of a family history of CHD, blood pressure, physical activity level, smoking status, and lipid profile, elevated adolescent BMI was a significant predictor of CHD across the entire BMI range.

The nearly 4,000 subjects whose BMI was in the 90th percentile and above had a hazard ratio of 6.85 for developing CHD, compared with those in the 10th percentile and below.

The excess CHD risk was present even at BMIs that are "well within the range currently considered to be normal," rising 12% for every 1-unit increment in BMI, Dr. Tirosh and his associates reported.

"Our study may help to redefine what constitutes a ‘normal’ or ‘healthy’ BMI in adolescence and to highlight the role of elevated BMI at different ages in the pathogenesis of different diseases," the researchers said.

In contrast to CHD risk, the risk of type 2 diabetes did not correlate with adolescent BMI once the data were adjusted to account for potential confounders. Diabetes was more influenced by recent BMI and weight gain, "suggesting that BMI in adolescence has a more reversible or shorter term effect on the risk of diabetes as compared with its effect on the risk of CHD," they said.

"Our results might be explained by the fact that diabetes represents a more functional pathomechanism than CHD, which relies on anatomical changes (atherosclerosis)," Dr. Tirosh and his colleagues said.

Because the study involved only young Israeli military men, the findings may not be generalizable to other patient populations, they added.

The study was supported by the Chaim Sheba Medical Center in Tel-Hashomer, Israel, and by the Israel Defense Forces Medical Corps. The authors reported that they had no conflicts of interest.

Among males, an elevated body mass index during adolescence was a strong predictor of angiography-proven coronary heart disease in young adulthood, according to a report in the April 7 issue of the New England Journal of Medicine.

Male adolescents in the top 10% of BMI had a risk for developing CHD at ages 25-45 years that was nearly seven times higher than the risk in adolescents in the lowest 10% of BMI, said Dr. Amir Tirosh of the division of endocrinology, diabetes, and hypertension at Brigham and Women’s Hospital, Boston, and his associates (N. Engl. J. Med. 2011;364:1315-25).

Photo credit: Bill Branson/National Cancer Institute

"Although obesity in adulthood is a well-documented risk factor for both type 2 diabetes and CHD, it [has been] unclear whether a longer history of relative overweight, starting earlier in life, poses an additional risk," the researchers said. "Given the current obesity pandemic, it is important to determine whether elevated BMI in childhood [or] adolescence ... contributes independently to the risk of disease."

Dr. Tirosh and his colleagues examined the issue using data from an Israel Defense Forces’ study, the ongoing Metabolic, Lifestyle, and Nutrition Assessment in Young Adults study. All men in the Israeli military are examined every 3-5 years, beginning at about age 25 and continuing throughout their military careers, and the information is recorded in a database.

Also recorded are the weight and height measurements obtained during the men’s medical exam at induction into the military, usually at age 17. Those data were used to calculate BMI in adolescence.

For this study, Dr. Tirosh and his associates analyzed data on 37,674 male military personnel who were followed prospectively for a mean of 17 years, starting at about age 25, and whose BMI during adolescence was tracked retrospectively. At that time, BMI ranged from 15 to 36 kg/m².

During follow-up, there were 327 incident cases of angiography-proven CHD, diagnosed when the subjects were aged 25-45 years. After the data were adjusted to account for potential confounders such as subject age, presence or absence of a family history of CHD, blood pressure, physical activity level, smoking status, and lipid profile, elevated adolescent BMI was a significant predictor of CHD across the entire BMI range.

The nearly 4,000 subjects whose BMI was in the 90th percentile and above had a hazard ratio of 6.85 for developing CHD, compared with those in the 10th percentile and below.

The excess CHD risk was present even at BMIs that are "well within the range currently considered to be normal," rising 12% for every 1-unit increment in BMI, Dr. Tirosh and his associates reported.

"Our study may help to redefine what constitutes a ‘normal’ or ‘healthy’ BMI in adolescence and to highlight the role of elevated BMI at different ages in the pathogenesis of different diseases," the researchers said.

In contrast to CHD risk, the risk of type 2 diabetes did not correlate with adolescent BMI once the data were adjusted to account for potential confounders. Diabetes was more influenced by recent BMI and weight gain, "suggesting that BMI in adolescence has a more reversible or shorter term effect on the risk of diabetes as compared with its effect on the risk of CHD," they said.

"Our results might be explained by the fact that diabetes represents a more functional pathomechanism than CHD, which relies on anatomical changes (atherosclerosis)," Dr. Tirosh and his colleagues said.

Because the study involved only young Israeli military men, the findings may not be generalizable to other patient populations, they added.

The study was supported by the Chaim Sheba Medical Center in Tel-Hashomer, Israel, and by the Israel Defense Forces Medical Corps. The authors reported that they had no conflicts of interest.

Among males, an elevated body mass index during adolescence was a strong predictor of angiography-proven coronary heart disease in young adulthood, according to a report in the April 7 issue of the New England Journal of Medicine.

Male adolescents in the top 10% of BMI had a risk for developing CHD at ages 25-45 years that was nearly seven times higher than the risk in adolescents in the lowest 10% of BMI, said Dr. Amir Tirosh of the division of endocrinology, diabetes, and hypertension at Brigham and Women’s Hospital, Boston, and his associates (N. Engl. J. Med. 2011;364:1315-25).

Photo credit: Bill Branson/National Cancer Institute

"Although obesity in adulthood is a well-documented risk factor for both type 2 diabetes and CHD, it [has been] unclear whether a longer history of relative overweight, starting earlier in life, poses an additional risk," the researchers said. "Given the current obesity pandemic, it is important to determine whether elevated BMI in childhood [or] adolescence ... contributes independently to the risk of disease."

Dr. Tirosh and his colleagues examined the issue using data from an Israel Defense Forces’ study, the ongoing Metabolic, Lifestyle, and Nutrition Assessment in Young Adults study. All men in the Israeli military are examined every 3-5 years, beginning at about age 25 and continuing throughout their military careers, and the information is recorded in a database.

Also recorded are the weight and height measurements obtained during the men’s medical exam at induction into the military, usually at age 17. Those data were used to calculate BMI in adolescence.

For this study, Dr. Tirosh and his associates analyzed data on 37,674 male military personnel who were followed prospectively for a mean of 17 years, starting at about age 25, and whose BMI during adolescence was tracked retrospectively. At that time, BMI ranged from 15 to 36 kg/m².

During follow-up, there were 327 incident cases of angiography-proven CHD, diagnosed when the subjects were aged 25-45 years. After the data were adjusted to account for potential confounders such as subject age, presence or absence of a family history of CHD, blood pressure, physical activity level, smoking status, and lipid profile, elevated adolescent BMI was a significant predictor of CHD across the entire BMI range.

The nearly 4,000 subjects whose BMI was in the 90th percentile and above had a hazard ratio of 6.85 for developing CHD, compared with those in the 10th percentile and below.

The excess CHD risk was present even at BMIs that are "well within the range currently considered to be normal," rising 12% for every 1-unit increment in BMI, Dr. Tirosh and his associates reported.

"Our study may help to redefine what constitutes a ‘normal’ or ‘healthy’ BMI in adolescence and to highlight the role of elevated BMI at different ages in the pathogenesis of different diseases," the researchers said.

In contrast to CHD risk, the risk of type 2 diabetes did not correlate with adolescent BMI once the data were adjusted to account for potential confounders. Diabetes was more influenced by recent BMI and weight gain, "suggesting that BMI in adolescence has a more reversible or shorter term effect on the risk of diabetes as compared with its effect on the risk of CHD," they said.

"Our results might be explained by the fact that diabetes represents a more functional pathomechanism than CHD, which relies on anatomical changes (atherosclerosis)," Dr. Tirosh and his colleagues said.

Because the study involved only young Israeli military men, the findings may not be generalizable to other patient populations, they added.

The study was supported by the Chaim Sheba Medical Center in Tel-Hashomer, Israel, and by the Israel Defense Forces Medical Corps. The authors reported that they had no conflicts of interest.

Among males, an elevated body mass index during adolescence was a strong predictor of angiography-proven coronary heart disease in young adulthood, according to a report in the April 7 issue of the New England Journal of Medicine.

Male adolescents in the top 10% of BMI had a risk for developing CHD at ages 25-45 years that was nearly seven times higher than the risk in adolescents in the lowest 10% of BMI, said Dr. Amir Tirosh of the division of endocrinology, diabetes, and hypertension at Brigham and Women’s Hospital, Boston, and his associates (N. Engl. J. Med. 2011;364:1315-25).

Photo credit: Bill Branson/National Cancer Institute

"Although obesity in adulthood is a well-documented risk factor for both type 2 diabetes and CHD, it [has been] unclear whether a longer history of relative overweight, starting earlier in life, poses an additional risk," the researchers said. "Given the current obesity pandemic, it is important to determine whether elevated BMI in childhood [or] adolescence ... contributes independently to the risk of disease."

Dr. Tirosh and his colleagues examined the issue using data from an Israel Defense Forces’ study, the ongoing Metabolic, Lifestyle, and Nutrition Assessment in Young Adults study. All men in the Israeli military are examined every 3-5 years, beginning at about age 25 and continuing throughout their military careers, and the information is recorded in a database.

Also recorded are the weight and height measurements obtained during the men’s medical exam at induction into the military, usually at age 17. Those data were used to calculate BMI in adolescence.

For this study, Dr. Tirosh and his associates analyzed data on 37,674 male military personnel who were followed prospectively for a mean of 17 years, starting at about age 25, and whose BMI during adolescence was tracked retrospectively. At that time, BMI ranged from 15 to 36 kg/m².

During follow-up, there were 327 incident cases of angiography-proven CHD, diagnosed when the subjects were aged 25-45 years. After the data were adjusted to account for potential confounders such as subject age, presence or absence of a family history of CHD, blood pressure, physical activity level, smoking status, and lipid profile, elevated adolescent BMI was a significant predictor of CHD across the entire BMI range.

The nearly 4,000 subjects whose BMI was in the 90th percentile and above had a hazard ratio of 6.85 for developing CHD, compared with those in the 10th percentile and below.

The excess CHD risk was present even at BMIs that are "well within the range currently considered to be normal," rising 12% for every 1-unit increment in BMI, Dr. Tirosh and his associates reported.

"Our study may help to redefine what constitutes a ‘normal’ or ‘healthy’ BMI in adolescence and to highlight the role of elevated BMI at different ages in the pathogenesis of different diseases," the researchers said.

In contrast to CHD risk, the risk of type 2 diabetes did not correlate with adolescent BMI once the data were adjusted to account for potential confounders. Diabetes was more influenced by recent BMI and weight gain, "suggesting that BMI in adolescence has a more reversible or shorter term effect on the risk of diabetes as compared with its effect on the risk of CHD," they said.

"Our results might be explained by the fact that diabetes represents a more functional pathomechanism than CHD, which relies on anatomical changes (atherosclerosis)," Dr. Tirosh and his colleagues said.

Because the study involved only young Israeli military men, the findings may not be generalizable to other patient populations, they added.

The study was supported by the Chaim Sheba Medical Center in Tel-Hashomer, Israel, and by the Israel Defense Forces Medical Corps. The authors reported that they had no conflicts of interest.

Among males, an elevated body mass index during adolescence was a strong predictor of angiography-proven coronary heart disease in young adulthood, according to a report in the April 7 issue of the New England Journal of Medicine.

Male adolescents in the top 10% of BMI had a risk for developing CHD at ages 25-45 years that was nearly seven times higher than the risk in adolescents in the lowest 10% of BMI, said Dr. Amir Tirosh of the division of endocrinology, diabetes, and hypertension at Brigham and Women’s Hospital, Boston, and his associates (N. Engl. J. Med. 2011;364:1315-25).

Photo credit: Bill Branson/National Cancer Institute

"Although obesity in adulthood is a well-documented risk factor for both type 2 diabetes and CHD, it [has been] unclear whether a longer history of relative overweight, starting earlier in life, poses an additional risk," the researchers said. "Given the current obesity pandemic, it is important to determine whether elevated BMI in childhood [or] adolescence ... contributes independently to the risk of disease."

Dr. Tirosh and his colleagues examined the issue using data from an Israel Defense Forces’ study, the ongoing Metabolic, Lifestyle, and Nutrition Assessment in Young Adults study. All men in the Israeli military are examined every 3-5 years, beginning at about age 25 and continuing throughout their military careers, and the information is recorded in a database.

Also recorded are the weight and height measurements obtained during the men’s medical exam at induction into the military, usually at age 17. Those data were used to calculate BMI in adolescence.

For this study, Dr. Tirosh and his associates analyzed data on 37,674 male military personnel who were followed prospectively for a mean of 17 years, starting at about age 25, and whose BMI during adolescence was tracked retrospectively. At that time, BMI ranged from 15 to 36 kg/m².

During follow-up, there were 327 incident cases of angiography-proven CHD, diagnosed when the subjects were aged 25-45 years. After the data were adjusted to account for potential confounders such as subject age, presence or absence of a family history of CHD, blood pressure, physical activity level, smoking status, and lipid profile, elevated adolescent BMI was a significant predictor of CHD across the entire BMI range.

The nearly 4,000 subjects whose BMI was in the 90th percentile and above had a hazard ratio of 6.85 for developing CHD, compared with those in the 10th percentile and below.

The excess CHD risk was present even at BMIs that are "well within the range currently considered to be normal," rising 12% for every 1-unit increment in BMI, Dr. Tirosh and his associates reported.

"Our study may help to redefine what constitutes a ‘normal’ or ‘healthy’ BMI in adolescence and to highlight the role of elevated BMI at different ages in the pathogenesis of different diseases," the researchers said.

In contrast to CHD risk, the risk of type 2 diabetes did not correlate with adolescent BMI once the data were adjusted to account for potential confounders. Diabetes was more influenced by recent BMI and weight gain, "suggesting that BMI in adolescence has a more reversible or shorter term effect on the risk of diabetes as compared with its effect on the risk of CHD," they said.

"Our results might be explained by the fact that diabetes represents a more functional pathomechanism than CHD, which relies on anatomical changes (atherosclerosis)," Dr. Tirosh and his colleagues said.

Because the study involved only young Israeli military men, the findings may not be generalizable to other patient populations, they added.

The study was supported by the Chaim Sheba Medical Center in Tel-Hashomer, Israel, and by the Israel Defense Forces Medical Corps. The authors reported that they had no conflicts of interest.

Higher doses of opioids – the equivalent of 50 mg/dL or more of morphine – are more likely than are lower doses to lead to unintentional overdose, according to a report in the April 6 issue of JAMA.

However, the practice of adding a prescription for as-needed opioids to an existing prescription for regularly scheduled opioids, which allows patients to deal with acute exacerbations of pain, does not raise the risk of unintentional overdose in most patients, as some experts have feared, said Amy S.B. Bohnert, Ph.D., of the Department of Veterans Affairs and the University of Michigan, both in Ann Arbor, and her associates.

Citing a "troubling and dramatic" 124% increase in unintentional deaths from opioid overdose in the United States in recent years, the investigators examined the relationship between opioid-prescribing patterns and opioid-related deaths using a nationally representative sample of 155,434 cases in the VA’s National Patient Care Database.

The study subjects included patients taking opioids for cancer pain, chronic bodily pain, headache, neuropathy, and injuries; the prescribed opioid analgesics included codeine, morphine, oxycodone, hydrocodone, oxymorphone, and hydromorphone.

There were 750 deaths attributed to unintentional overdose, for an overall rate of 0.04% among all patients treated with opioids. The risk of overdose increased when the opioid dose was equivalent to 50 mg/dL of morphine, and there was a dose-response relationship in which increasing daily prescribed doses of opioids correlated with increasing risk of overdose death.

As an example, prescribed doses of 100 mg/dL or higher were associated with a hazard ratio of approximately 12.

Dr. Bohnert and her colleagues described their study as the first to assess concurrent prescribing of regularly scheduled opioids plus as-needed opioids. With the exception of cancer patients, participants treated with this strategy showed no excess risk of overdose. "Recent treatment guidelines have indicated that the long-term safety of this strategy for pain exacerbations has not been established, [but] in [this] study we did not find evidence of greater overdose risk associated with this treatment practice, after accounting for maximum daily dose and patient characteristics," they noted (JAMA 2011;305:1315-21).

The researchers also said theirs is the first study of this issue to include patients with cancer. The overall rate of opioid overdose was lower in cancer patients, compared with other subjects, but clinicians should be mindful that renal and liver impairment in this patient group can interfere with the metabolism of opioids and that high doses can place cancer patients at risk.

Cancer patients also were at increased risk of overdose if they were prescribed as-needed opioids alone, rather than regularly scheduled opioids. "Pain for patients with cancer can be particularly rapid in onset, unpredictable, and severe, and taking opioid doses as needed may result in [sudden] high doses being taken without the benefit of tolerance developed through a regularly scheduled opioid," the investigators said.

In a research letter accompanying this report, Dr. Nora D. Volkow, director of the National Institute on Drug Abuse, and her associates presented data from their study of prescription practices, which was aimed at identifying possible contributors to the high rate of opioid abuse. They drew on information in a national prescription database that included about 80 million prescriptions for opioid analgesics.

The main prescribers were general, family medicine, and osteopathic physicians, who accounted for 29% of these prescriptions, followed by internists (15%), dentists (8%), and orthopedic surgeons (8%).

Across all specialties, more than half of these prescriptions (56%, or 45 million) were given to patients who had already filled another opioid prescription during the preceding month. The data could not show whether such prescribing was "justified" or rather "suggests the need to improve information infrastructures that could enhance the safety of prescribed opioid analgesics and minimize diversion," Dr. Volkow and her colleagues said (JAMA 2011;305:1299-1301).

In addition, they found a fivefold increase in drug-treatment admissions for pharmaceutical opioids, from 19,941 to 121,091 in the past 10 years. Emergency department visits related to opioid overdose rose from 144,644 to 305,885 between 2004 and 2008. And deaths from unintentional opioid overdose have quadrupled, from approximately 3,000 in 1999 to 12,000 in 2007.

"Opioid overdose is now the second leading cause of unintentional death in the United States, second only to motor vehicle crashes," they noted.

The study by Dr. Bohnert and her colleagues was supported by the U.S. Department of Veterans Affairs’ Office of Mental Health Services and Office of Patient Care Services. One of Dr. Bohnert’s associates reported ties to Purdue Pharma. Dr. Volkow and her colleagues reported no disclosures.

Higher doses of opioids – the equivalent of 50 mg/dL or more of morphine – are more likely than are lower doses to lead to unintentional overdose, according to a report in the April 6 issue of JAMA.

However, the practice of adding a prescription for as-needed opioids to an existing prescription for regularly scheduled opioids, which allows patients to deal with acute exacerbations of pain, does not raise the risk of unintentional overdose in most patients, as some experts have feared, said Amy S.B. Bohnert, Ph.D., of the Department of Veterans Affairs and the University of Michigan, both in Ann Arbor, and her associates.

Citing a "troubling and dramatic" 124% increase in unintentional deaths from opioid overdose in the United States in recent years, the investigators examined the relationship between opioid-prescribing patterns and opioid-related deaths using a nationally representative sample of 155,434 cases in the VA’s National Patient Care Database.

The study subjects included patients taking opioids for cancer pain, chronic bodily pain, headache, neuropathy, and injuries; the prescribed opioid analgesics included codeine, morphine, oxycodone, hydrocodone, oxymorphone, and hydromorphone.

There were 750 deaths attributed to unintentional overdose, for an overall rate of 0.04% among all patients treated with opioids. The risk of overdose increased when the opioid dose was equivalent to 50 mg/dL of morphine, and there was a dose-response relationship in which increasing daily prescribed doses of opioids correlated with increasing risk of overdose death.

As an example, prescribed doses of 100 mg/dL or higher were associated with a hazard ratio of approximately 12.

Dr. Bohnert and her colleagues described their study as the first to assess concurrent prescribing of regularly scheduled opioids plus as-needed opioids. With the exception of cancer patients, participants treated with this strategy showed no excess risk of overdose. "Recent treatment guidelines have indicated that the long-term safety of this strategy for pain exacerbations has not been established, [but] in [this] study we did not find evidence of greater overdose risk associated with this treatment practice, after accounting for maximum daily dose and patient characteristics," they noted (JAMA 2011;305:1315-21).

The researchers also said theirs is the first study of this issue to include patients with cancer. The overall rate of opioid overdose was lower in cancer patients, compared with other subjects, but clinicians should be mindful that renal and liver impairment in this patient group can interfere with the metabolism of opioids and that high doses can place cancer patients at risk.

Cancer patients also were at increased risk of overdose if they were prescribed as-needed opioids alone, rather than regularly scheduled opioids. "Pain for patients with cancer can be particularly rapid in onset, unpredictable, and severe, and taking opioid doses as needed may result in [sudden] high doses being taken without the benefit of tolerance developed through a regularly scheduled opioid," the investigators said.

In a research letter accompanying this report, Dr. Nora D. Volkow, director of the National Institute on Drug Abuse, and her associates presented data from their study of prescription practices, which was aimed at identifying possible contributors to the high rate of opioid abuse. They drew on information in a national prescription database that included about 80 million prescriptions for opioid analgesics.

The main prescribers were general, family medicine, and osteopathic physicians, who accounted for 29% of these prescriptions, followed by internists (15%), dentists (8%), and orthopedic surgeons (8%).

Across all specialties, more than half of these prescriptions (56%, or 45 million) were given to patients who had already filled another opioid prescription during the preceding month. The data could not show whether such prescribing was "justified" or rather "suggests the need to improve information infrastructures that could enhance the safety of prescribed opioid analgesics and minimize diversion," Dr. Volkow and her colleagues said (JAMA 2011;305:1299-1301).

In addition, they found a fivefold increase in drug-treatment admissions for pharmaceutical opioids, from 19,941 to 121,091 in the past 10 years. Emergency department visits related to opioid overdose rose from 144,644 to 305,885 between 2004 and 2008. And deaths from unintentional opioid overdose have quadrupled, from approximately 3,000 in 1999 to 12,000 in 2007.

"Opioid overdose is now the second leading cause of unintentional death in the United States, second only to motor vehicle crashes," they noted.

The study by Dr. Bohnert and her colleagues was supported by the U.S. Department of Veterans Affairs’ Office of Mental Health Services and Office of Patient Care Services. One of Dr. Bohnert’s associates reported ties to Purdue Pharma. Dr. Volkow and her colleagues reported no disclosures.

Higher doses of opioids – the equivalent of 50 mg/dL or more of morphine – are more likely than are lower doses to lead to unintentional overdose, according to a report in the April 6 issue of JAMA.

However, the practice of adding a prescription for as-needed opioids to an existing prescription for regularly scheduled opioids, which allows patients to deal with acute exacerbations of pain, does not raise the risk of unintentional overdose in most patients, as some experts have feared, said Amy S.B. Bohnert, Ph.D., of the Department of Veterans Affairs and the University of Michigan, both in Ann Arbor, and her associates.

Citing a "troubling and dramatic" 124% increase in unintentional deaths from opioid overdose in the United States in recent years, the investigators examined the relationship between opioid-prescribing patterns and opioid-related deaths using a nationally representative sample of 155,434 cases in the VA’s National Patient Care Database.

The study subjects included patients taking opioids for cancer pain, chronic bodily pain, headache, neuropathy, and injuries; the prescribed opioid analgesics included codeine, morphine, oxycodone, hydrocodone, oxymorphone, and hydromorphone.

There were 750 deaths attributed to unintentional overdose, for an overall rate of 0.04% among all patients treated with opioids. The risk of overdose increased when the opioid dose was equivalent to 50 mg/dL of morphine, and there was a dose-response relationship in which increasing daily prescribed doses of opioids correlated with increasing risk of overdose death.

As an example, prescribed doses of 100 mg/dL or higher were associated with a hazard ratio of approximately 12.

Dr. Bohnert and her colleagues described their study as the first to assess concurrent prescribing of regularly scheduled opioids plus as-needed opioids. With the exception of cancer patients, participants treated with this strategy showed no excess risk of overdose. "Recent treatment guidelines have indicated that the long-term safety of this strategy for pain exacerbations has not been established, [but] in [this] study we did not find evidence of greater overdose risk associated with this treatment practice, after accounting for maximum daily dose and patient characteristics," they noted (JAMA 2011;305:1315-21).

The researchers also said theirs is the first study of this issue to include patients with cancer. The overall rate of opioid overdose was lower in cancer patients, compared with other subjects, but clinicians should be mindful that renal and liver impairment in this patient group can interfere with the metabolism of opioids and that high doses can place cancer patients at risk.

Cancer patients also were at increased risk of overdose if they were prescribed as-needed opioids alone, rather than regularly scheduled opioids. "Pain for patients with cancer can be particularly rapid in onset, unpredictable, and severe, and taking opioid doses as needed may result in [sudden] high doses being taken without the benefit of tolerance developed through a regularly scheduled opioid," the investigators said.

In a research letter accompanying this report, Dr. Nora D. Volkow, director of the National Institute on Drug Abuse, and her associates presented data from their study of prescription practices, which was aimed at identifying possible contributors to the high rate of opioid abuse. They drew on information in a national prescription database that included about 80 million prescriptions for opioid analgesics.

The main prescribers were general, family medicine, and osteopathic physicians, who accounted for 29% of these prescriptions, followed by internists (15%), dentists (8%), and orthopedic surgeons (8%).

Across all specialties, more than half of these prescriptions (56%, or 45 million) were given to patients who had already filled another opioid prescription during the preceding month. The data could not show whether such prescribing was "justified" or rather "suggests the need to improve information infrastructures that could enhance the safety of prescribed opioid analgesics and minimize diversion," Dr. Volkow and her colleagues said (JAMA 2011;305:1299-1301).

In addition, they found a fivefold increase in drug-treatment admissions for pharmaceutical opioids, from 19,941 to 121,091 in the past 10 years. Emergency department visits related to opioid overdose rose from 144,644 to 305,885 between 2004 and 2008. And deaths from unintentional opioid overdose have quadrupled, from approximately 3,000 in 1999 to 12,000 in 2007.

"Opioid overdose is now the second leading cause of unintentional death in the United States, second only to motor vehicle crashes," they noted.

The study by Dr. Bohnert and her colleagues was supported by the U.S. Department of Veterans Affairs’ Office of Mental Health Services and Office of Patient Care Services. One of Dr. Bohnert’s associates reported ties to Purdue Pharma. Dr. Volkow and her colleagues reported no disclosures.

Higher doses of opioids – the equivalent of 50 mg/dL or more of morphine – are more likely than are lower doses to lead to unintentional overdose, according to a report in the April 6 issue of JAMA.

However, the practice of adding a prescription for as-needed opioids to an existing prescription for regularly scheduled opioids, which allows patients to deal with acute exacerbations of pain, does not raise the risk of unintentional overdose in most patients, as some experts have feared, said Amy S.B. Bohnert, Ph.D., of the Department of Veterans Affairs and the University of Michigan, both in Ann Arbor, and her associates.

Citing a "troubling and dramatic" 124% increase in unintentional deaths from opioid overdose in the United States in recent years, the investigators examined the relationship between opioid-prescribing patterns and opioid-related deaths using a nationally representative sample of 155,434 cases in the VA’s National Patient Care Database.

The study subjects included patients taking opioids for cancer pain, chronic bodily pain, headache, neuropathy, and injuries; the prescribed opioid analgesics included codeine, morphine, oxycodone, hydrocodone, oxymorphone, and hydromorphone.

There were 750 deaths attributed to unintentional overdose, for an overall rate of 0.04% among all patients treated with opioids. The risk of overdose increased when the opioid dose was equivalent to 50 mg/dL of morphine, and there was a dose-response relationship in which increasing daily prescribed doses of opioids correlated with increasing risk of overdose death.

As an example, prescribed doses of 100 mg/dL or higher were associated with a hazard ratio of approximately 12.

Dr. Bohnert and her colleagues described their study as the first to assess concurrent prescribing of regularly scheduled opioids plus as-needed opioids. With the exception of cancer patients, participants treated with this strategy showed no excess risk of overdose. "Recent treatment guidelines have indicated that the long-term safety of this strategy for pain exacerbations has not been established, [but] in [this] study we did not find evidence of greater overdose risk associated with this treatment practice, after accounting for maximum daily dose and patient characteristics," they noted (JAMA 2011;305:1315-21).

The researchers also said theirs is the first study of this issue to include patients with cancer. The overall rate of opioid overdose was lower in cancer patients, compared with other subjects, but clinicians should be mindful that renal and liver impairment in this patient group can interfere with the metabolism of opioids and that high doses can place cancer patients at risk.

Cancer patients also were at increased risk of overdose if they were prescribed as-needed opioids alone, rather than regularly scheduled opioids. "Pain for patients with cancer can be particularly rapid in onset, unpredictable, and severe, and taking opioid doses as needed may result in [sudden] high doses being taken without the benefit of tolerance developed through a regularly scheduled opioid," the investigators said.

In a research letter accompanying this report, Dr. Nora D. Volkow, director of the National Institute on Drug Abuse, and her associates presented data from their study of prescription practices, which was aimed at identifying possible contributors to the high rate of opioid abuse. They drew on information in a national prescription database that included about 80 million prescriptions for opioid analgesics.

The main prescribers were general, family medicine, and osteopathic physicians, who accounted for 29% of these prescriptions, followed by internists (15%), dentists (8%), and orthopedic surgeons (8%).

Across all specialties, more than half of these prescriptions (56%, or 45 million) were given to patients who had already filled another opioid prescription during the preceding month. The data could not show whether such prescribing was "justified" or rather "suggests the need to improve information infrastructures that could enhance the safety of prescribed opioid analgesics and minimize diversion," Dr. Volkow and her colleagues said (JAMA 2011;305:1299-1301).

In addition, they found a fivefold increase in drug-treatment admissions for pharmaceutical opioids, from 19,941 to 121,091 in the past 10 years. Emergency department visits related to opioid overdose rose from 144,644 to 305,885 between 2004 and 2008. And deaths from unintentional opioid overdose have quadrupled, from approximately 3,000 in 1999 to 12,000 in 2007.

"Opioid overdose is now the second leading cause of unintentional death in the United States, second only to motor vehicle crashes," they noted.

The study by Dr. Bohnert and her colleagues was supported by the U.S. Department of Veterans Affairs’ Office of Mental Health Services and Office of Patient Care Services. One of Dr. Bohnert’s associates reported ties to Purdue Pharma. Dr. Volkow and her colleagues reported no disclosures.

Higher doses of opioids – the equivalent of 50 mg/dL or more of morphine – are more likely than are lower doses to lead to unintentional overdose, according to a report in the April 6 issue of JAMA.

However, the practice of adding a prescription for as-needed opioids to an existing prescription for regularly scheduled opioids, which allows patients to deal with acute exacerbations of pain, does not raise the risk of unintentional overdose in most patients, as some experts have feared, said Amy S.B. Bohnert, Ph.D., of the Department of Veterans Affairs and the University of Michigan, both in Ann Arbor, and her associates.

Citing a "troubling and dramatic" 124% increase in unintentional deaths from opioid overdose in the United States in recent years, the investigators examined the relationship between opioid-prescribing patterns and opioid-related deaths using a nationally representative sample of 155,434 cases in the VA’s National Patient Care Database.

The study subjects included patients taking opioids for cancer pain, chronic bodily pain, headache, neuropathy, and injuries; the prescribed opioid analgesics included codeine, morphine, oxycodone, hydrocodone, oxymorphone, and hydromorphone.

There were 750 deaths attributed to unintentional overdose, for an overall rate of 0.04% among all patients treated with opioids. The risk of overdose increased when the opioid dose was equivalent to 50 mg/dL of morphine, and there was a dose-response relationship in which increasing daily prescribed doses of opioids correlated with increasing risk of overdose death.

As an example, prescribed doses of 100 mg/dL or higher were associated with a hazard ratio of approximately 12.

Dr. Bohnert and her colleagues described their study as the first to assess concurrent prescribing of regularly scheduled opioids plus as-needed opioids. With the exception of cancer patients, participants treated with this strategy showed no excess risk of overdose. "Recent treatment guidelines have indicated that the long-term safety of this strategy for pain exacerbations has not been established, [but] in [this] study we did not find evidence of greater overdose risk associated with this treatment practice, after accounting for maximum daily dose and patient characteristics," they noted (JAMA 2011;305:1315-21).

The researchers also said theirs is the first study of this issue to include patients with cancer. The overall rate of opioid overdose was lower in cancer patients, compared with other subjects, but clinicians should be mindful that renal and liver impairment in this patient group can interfere with the metabolism of opioids and that high doses can place cancer patients at risk.

Cancer patients also were at increased risk of overdose if they were prescribed as-needed opioids alone, rather than regularly scheduled opioids. "Pain for patients with cancer can be particularly rapid in onset, unpredictable, and severe, and taking opioid doses as needed may result in [sudden] high doses being taken without the benefit of tolerance developed through a regularly scheduled opioid," the investigators said.

In a research letter accompanying this report, Dr. Nora D. Volkow, director of the National Institute on Drug Abuse, and her associates presented data from their study of prescription practices, which was aimed at identifying possible contributors to the high rate of opioid abuse. They drew on information in a national prescription database that included about 80 million prescriptions for opioid analgesics.

The main prescribers were general, family medicine, and osteopathic physicians, who accounted for 29% of these prescriptions, followed by internists (15%), dentists (8%), and orthopedic surgeons (8%).

Across all specialties, more than half of these prescriptions (56%, or 45 million) were given to patients who had already filled another opioid prescription during the preceding month. The data could not show whether such prescribing was "justified" or rather "suggests the need to improve information infrastructures that could enhance the safety of prescribed opioid analgesics and minimize diversion," Dr. Volkow and her colleagues said (JAMA 2011;305:1299-1301).

In addition, they found a fivefold increase in drug-treatment admissions for pharmaceutical opioids, from 19,941 to 121,091 in the past 10 years. Emergency department visits related to opioid overdose rose from 144,644 to 305,885 between 2004 and 2008. And deaths from unintentional opioid overdose have quadrupled, from approximately 3,000 in 1999 to 12,000 in 2007.

"Opioid overdose is now the second leading cause of unintentional death in the United States, second only to motor vehicle crashes," they noted.

The study by Dr. Bohnert and her colleagues was supported by the U.S. Department of Veterans Affairs’ Office of Mental Health Services and Office of Patient Care Services. One of Dr. Bohnert’s associates reported ties to Purdue Pharma. Dr. Volkow and her colleagues reported no disclosures.

Higher doses of opioids – the equivalent of 50 mg/dL or more of morphine – are more likely than are lower doses to lead to unintentional overdose, according to a report in the April 6 issue of JAMA.

However, the practice of adding a prescription for as-needed opioids to an existing prescription for regularly scheduled opioids, which allows patients to deal with acute exacerbations of pain, does not raise the risk of unintentional overdose in most patients, as some experts have feared, said Amy S.B. Bohnert, Ph.D., of the Department of Veterans Affairs and the University of Michigan, both in Ann Arbor, and her associates.

Citing a "troubling and dramatic" 124% increase in unintentional deaths from opioid overdose in the United States in recent years, the investigators examined the relationship between opioid-prescribing patterns and opioid-related deaths using a nationally representative sample of 155,434 cases in the VA’s National Patient Care Database.

The study subjects included patients taking opioids for cancer pain, chronic bodily pain, headache, neuropathy, and injuries; the prescribed opioid analgesics included codeine, morphine, oxycodone, hydrocodone, oxymorphone, and hydromorphone.

There were 750 deaths attributed to unintentional overdose, for an overall rate of 0.04% among all patients treated with opioids. The risk of overdose increased when the opioid dose was equivalent to 50 mg/dL of morphine, and there was a dose-response relationship in which increasing daily prescribed doses of opioids correlated with increasing risk of overdose death.

As an example, prescribed doses of 100 mg/dL or higher were associated with a hazard ratio of approximately 12.

Dr. Bohnert and her colleagues described their study as the first to assess concurrent prescribing of regularly scheduled opioids plus as-needed opioids. With the exception of cancer patients, participants treated with this strategy showed no excess risk of overdose. "Recent treatment guidelines have indicated that the long-term safety of this strategy for pain exacerbations has not been established, [but] in [this] study we did not find evidence of greater overdose risk associated with this treatment practice, after accounting for maximum daily dose and patient characteristics," they noted (JAMA 2011;305:1315-21).

The researchers also said theirs is the first study of this issue to include patients with cancer. The overall rate of opioid overdose was lower in cancer patients, compared with other subjects, but clinicians should be mindful that renal and liver impairment in this patient group can interfere with the metabolism of opioids and that high doses can place cancer patients at risk.

Cancer patients also were at increased risk of overdose if they were prescribed as-needed opioids alone, rather than regularly scheduled opioids. "Pain for patients with cancer can be particularly rapid in onset, unpredictable, and severe, and taking opioid doses as needed may result in [sudden] high doses being taken without the benefit of tolerance developed through a regularly scheduled opioid," the investigators said.

In a research letter accompanying this report, Dr. Nora D. Volkow, director of the National Institute on Drug Abuse, and her associates presented data from their study of prescription practices, which was aimed at identifying possible contributors to the high rate of opioid abuse. They drew on information in a national prescription database that included about 80 million prescriptions for opioid analgesics.

The main prescribers were general, family medicine, and osteopathic physicians, who accounted for 29% of these prescriptions, followed by internists (15%), dentists (8%), and orthopedic surgeons (8%).

Across all specialties, more than half of these prescriptions (56%, or 45 million) were given to patients who had already filled another opioid prescription during the preceding month. The data could not show whether such prescribing was "justified" or rather "suggests the need to improve information infrastructures that could enhance the safety of prescribed opioid analgesics and minimize diversion," Dr. Volkow and her colleagues said (JAMA 2011;305:1299-1301).

In addition, they found a fivefold increase in drug-treatment admissions for pharmaceutical opioids, from 19,941 to 121,091 in the past 10 years. Emergency department visits related to opioid overdose rose from 144,644 to 305,885 between 2004 and 2008. And deaths from unintentional opioid overdose have quadrupled, from approximately 3,000 in 1999 to 12,000 in 2007.

"Opioid overdose is now the second leading cause of unintentional death in the United States, second only to motor vehicle crashes," they noted.

The study by Dr. Bohnert and her colleagues was supported by the U.S. Department of Veterans Affairs’ Office of Mental Health Services and Office of Patient Care Services. One of Dr. Bohnert’s associates reported ties to Purdue Pharma. Dr. Volkow and her colleagues reported no disclosures.

Higher doses of opioids – the equivalent of 50 mg/dL or more of morphine – are more likely than are lower doses to lead to unintentional overdose, according to a report in the April 6 issue of JAMA.

However, the practice of adding a prescription for as-needed opioids to an existing prescription for regularly scheduled opioids, which allows patients to deal with acute exacerbations of pain, does not raise the risk of unintentional overdose in most patients, as some experts have feared, said Amy S.B. Bohnert, Ph.D., of the Department of Veterans Affairs and the University of Michigan, both in Ann Arbor, and her associates.

Citing a "troubling and dramatic" 124% increase in unintentional deaths from opioid overdose in the United States in recent years, the investigators examined the relationship between opioid-prescribing patterns and opioid-related deaths using a nationally representative sample of 155,434 cases in the VA’s National Patient Care Database.

The study subjects included patients taking opioids for cancer pain, chronic bodily pain, headache, neuropathy, and injuries; the prescribed opioid analgesics included codeine, morphine, oxycodone, hydrocodone, oxymorphone, and hydromorphone.

There were 750 deaths attributed to unintentional overdose, for an overall rate of 0.04% among all patients treated with opioids. The risk of overdose increased when the opioid dose was equivalent to 50 mg/dL of morphine, and there was a dose-response relationship in which increasing daily prescribed doses of opioids correlated with increasing risk of overdose death.

As an example, prescribed doses of 100 mg/dL or higher were associated with a hazard ratio of approximately 12.

Dr. Bohnert and her colleagues described their study as the first to assess concurrent prescribing of regularly scheduled opioids plus as-needed opioids. With the exception of cancer patients, participants treated with this strategy showed no excess risk of overdose. "Recent treatment guidelines have indicated that the long-term safety of this strategy for pain exacerbations has not been established, [but] in [this] study we did not find evidence of greater overdose risk associated with this treatment practice, after accounting for maximum daily dose and patient characteristics," they noted (JAMA 2011;305:1315-21).

The researchers also said theirs is the first study of this issue to include patients with cancer. The overall rate of opioid overdose was lower in cancer patients, compared with other subjects, but clinicians should be mindful that renal and liver impairment in this patient group can interfere with the metabolism of opioids and that high doses can place cancer patients at risk.

Cancer patients also were at increased risk of overdose if they were prescribed as-needed opioids alone, rather than regularly scheduled opioids. "Pain for patients with cancer can be particularly rapid in onset, unpredictable, and severe, and taking opioid doses as needed may result in [sudden] high doses being taken without the benefit of tolerance developed through a regularly scheduled opioid," the investigators said.

In a research letter accompanying this report, Dr. Nora D. Volkow, director of the National Institute on Drug Abuse, and her associates presented data from their study of prescription practices, which was aimed at identifying possible contributors to the high rate of opioid abuse. They drew on information in a national prescription database that included about 80 million prescriptions for opioid analgesics.

The main prescribers were general, family medicine, and osteopathic physicians, who accounted for 29% of these prescriptions, followed by internists (15%), dentists (8%), and orthopedic surgeons (8%).

Across all specialties, more than half of these prescriptions (56%, or 45 million) were given to patients who had already filled another opioid prescription during the preceding month. The data could not show whether such prescribing was "justified" or rather "suggests the need to improve information infrastructures that could enhance the safety of prescribed opioid analgesics and minimize diversion," Dr. Volkow and her colleagues said (JAMA 2011;305:1299-1301).

In addition, they found a fivefold increase in drug-treatment admissions for pharmaceutical opioids, from 19,941 to 121,091 in the past 10 years. Emergency department visits related to opioid overdose rose from 144,644 to 305,885 between 2004 and 2008. And deaths from unintentional opioid overdose have quadrupled, from approximately 3,000 in 1999 to 12,000 in 2007.

"Opioid overdose is now the second leading cause of unintentional death in the United States, second only to motor vehicle crashes," they noted.

The study by Dr. Bohnert and her colleagues was supported by the U.S. Department of Veterans Affairs’ Office of Mental Health Services and Office of Patient Care Services. One of Dr. Bohnert’s associates reported ties to Purdue Pharma. Dr. Volkow and her colleagues reported no disclosures.

Higher doses of opioids – the equivalent of 50 mg/dL or more of morphine – are more likely than are lower doses to lead to unintentional overdose, according to a report in the April 6 issue of JAMA.

However, the practice of adding a prescription for as-needed opioids to an existing prescription for regularly scheduled opioids, which allows patients to deal with acute exacerbations of pain, does not raise the risk of unintentional overdose in most patients, as some experts have feared, said Amy S.B. Bohnert, Ph.D., of the Department of Veterans Affairs and the University of Michigan, both in Ann Arbor, and her associates.

Citing a "troubling and dramatic" 124% increase in unintentional deaths from opioid overdose in the United States in recent years, the investigators examined the relationship between opioid-prescribing patterns and opioid-related deaths using a nationally representative sample of 155,434 cases in the VA’s National Patient Care Database.

The study subjects included patients taking opioids for cancer pain, chronic bodily pain, headache, neuropathy, and injuries; the prescribed opioid analgesics included codeine, morphine, oxycodone, hydrocodone, oxymorphone, and hydromorphone.

There were 750 deaths attributed to unintentional overdose, for an overall rate of 0.04% among all patients treated with opioids. The risk of overdose increased when the opioid dose was equivalent to 50 mg/dL of morphine, and there was a dose-response relationship in which increasing daily prescribed doses of opioids correlated with increasing risk of overdose death.

As an example, prescribed doses of 100 mg/dL or higher were associated with a hazard ratio of approximately 12.

Dr. Bohnert and her colleagues described their study as the first to assess concurrent prescribing of regularly scheduled opioids plus as-needed opioids. With the exception of cancer patients, participants treated with this strategy showed no excess risk of overdose. "Recent treatment guidelines have indicated that the long-term safety of this strategy for pain exacerbations has not been established, [but] in [this] study we did not find evidence of greater overdose risk associated with this treatment practice, after accounting for maximum daily dose and patient characteristics," they noted (JAMA 2011;305:1315-21).

The researchers also said theirs is the first study of this issue to include patients with cancer. The overall rate of opioid overdose was lower in cancer patients, compared with other subjects, but clinicians should be mindful that renal and liver impairment in this patient group can interfere with the metabolism of opioids and that high doses can place cancer patients at risk.

Cancer patients also were at increased risk of overdose if they were prescribed as-needed opioids alone, rather than regularly scheduled opioids. "Pain for patients with cancer can be particularly rapid in onset, unpredictable, and severe, and taking opioid doses as needed may result in [sudden] high doses being taken without the benefit of tolerance developed through a regularly scheduled opioid," the investigators said.

In a research letter accompanying this report, Dr. Nora D. Volkow, director of the National Institute on Drug Abuse, and her associates presented data from their study of prescription practices, which was aimed at identifying possible contributors to the high rate of opioid abuse. They drew on information in a national prescription database that included about 80 million prescriptions for opioid analgesics.

The main prescribers were general, family medicine, and osteopathic physicians, who accounted for 29% of these prescriptions, followed by internists (15%), dentists (8%), and orthopedic surgeons (8%).

Across all specialties, more than half of these prescriptions (56%, or 45 million) were given to patients who had already filled another opioid prescription during the preceding month. The data could not show whether such prescribing was "justified" or rather "suggests the need to improve information infrastructures that could enhance the safety of prescribed opioid analgesics and minimize diversion," Dr. Volkow and her colleagues said (JAMA 2011;305:1299-1301).

In addition, they found a fivefold increase in drug-treatment admissions for pharmaceutical opioids, from 19,941 to 121,091 in the past 10 years. Emergency department visits related to opioid overdose rose from 144,644 to 305,885 between 2004 and 2008. And deaths from unintentional opioid overdose have quadrupled, from approximately 3,000 in 1999 to 12,000 in 2007.

"Opioid overdose is now the second leading cause of unintentional death in the United States, second only to motor vehicle crashes," they noted.

The study by Dr. Bohnert and her colleagues was supported by the U.S. Department of Veterans Affairs’ Office of Mental Health Services and Office of Patient Care Services. One of Dr. Bohnert’s associates reported ties to Purdue Pharma. Dr. Volkow and her colleagues reported no disclosures.

Higher doses of opioids – the equivalent of 50 mg/dL or more of morphine – are more likely than are lower doses to lead to unintentional overdose, according to a report in the April 6 issue of JAMA.

However, the practice of adding a prescription for as-needed opioids to an existing prescription for regularly scheduled opioids, which allows patients to deal with acute exacerbations of pain, does not raise the risk of unintentional overdose in most patients, as some experts have feared, said Amy S.B. Bohnert, Ph.D., of the Department of Veterans Affairs and the University of Michigan, both in Ann Arbor, and her associates.

Citing a "troubling and dramatic" 124% increase in unintentional deaths from opioid overdose in the United States in recent years, the investigators examined the relationship between opioid-prescribing patterns and opioid-related deaths using a nationally representative sample of 155,434 cases in the VA’s National Patient Care Database.

The study subjects included patients taking opioids for cancer pain, chronic bodily pain, headache, neuropathy, and injuries; the prescribed opioid analgesics included codeine, morphine, oxycodone, hydrocodone, oxymorphone, and hydromorphone.

There were 750 deaths attributed to unintentional overdose, for an overall rate of 0.04% among all patients treated with opioids. The risk of overdose increased when the opioid dose was equivalent to 50 mg/dL of morphine, and there was a dose-response relationship in which increasing daily prescribed doses of opioids correlated with increasing risk of overdose death.

As an example, prescribed doses of 100 mg/dL or higher were associated with a hazard ratio of approximately 12.

Dr. Bohnert and her colleagues described their study as the first to assess concurrent prescribing of regularly scheduled opioids plus as-needed opioids. With the exception of cancer patients, participants treated with this strategy showed no excess risk of overdose. "Recent treatment guidelines have indicated that the long-term safety of this strategy for pain exacerbations has not been established, [but] in [this] study we did not find evidence of greater overdose risk associated with this treatment practice, after accounting for maximum daily dose and patient characteristics," they noted (JAMA 2011;305:1315-21).

The researchers also said theirs is the first study of this issue to include patients with cancer. The overall rate of opioid overdose was lower in cancer patients, compared with other subjects, but clinicians should be mindful that renal and liver impairment in this patient group can interfere with the metabolism of opioids and that high doses can place cancer patients at risk.

Cancer patients also were at increased risk of overdose if they were prescribed as-needed opioids alone, rather than regularly scheduled opioids. "Pain for patients with cancer can be particularly rapid in onset, unpredictable, and severe, and taking opioid doses as needed may result in [sudden] high doses being taken without the benefit of tolerance developed through a regularly scheduled opioid," the investigators said.

In a research letter accompanying this report, Dr. Nora D. Volkow, director of the National Institute on Drug Abuse, and her associates presented data from their study of prescription practices, which was aimed at identifying possible contributors to the high rate of opioid abuse. They drew on information in a national prescription database that included about 80 million prescriptions for opioid analgesics.

The main prescribers were general, family medicine, and osteopathic physicians, who accounted for 29% of these prescriptions, followed by internists (15%), dentists (8%), and orthopedic surgeons (8%).

Across all specialties, more than half of these prescriptions (56%, or 45 million) were given to patients who had already filled another opioid prescription during the preceding month. The data could not show whether such prescribing was "justified" or rather "suggests the need to improve information infrastructures that could enhance the safety of prescribed opioid analgesics and minimize diversion," Dr. Volkow and her colleagues said (JAMA 2011;305:1299-1301).

In addition, they found a fivefold increase in drug-treatment admissions for pharmaceutical opioids, from 19,941 to 121,091 in the past 10 years. Emergency department visits related to opioid overdose rose from 144,644 to 305,885 between 2004 and 2008. And deaths from unintentional opioid overdose have quadrupled, from approximately 3,000 in 1999 to 12,000 in 2007.

"Opioid overdose is now the second leading cause of unintentional death in the United States, second only to motor vehicle crashes," they noted.

The study by Dr. Bohnert and her colleagues was supported by the U.S. Department of Veterans Affairs’ Office of Mental Health Services and Office of Patient Care Services. One of Dr. Bohnert’s associates reported ties to Purdue Pharma. Dr. Volkow and her colleagues reported no disclosures.

Higher doses of opioids – the equivalent of 50 mg/dL or more of morphine – are more likely than are lower doses to lead to unintentional overdose, according to a report in the April 6 issue of JAMA.

However, the practice of adding a prescription for as-needed opioids to an existing prescription for regularly scheduled opioids, which allows patients to deal with acute exacerbations of pain, does not raise the risk of unintentional overdose in most patients, as some experts have feared, said Amy S.B. Bohnert, Ph.D., of the Department of Veterans Affairs and the University of Michigan, both in Ann Arbor, and her associates.

Citing a "troubling and dramatic" 124% increase in unintentional deaths from opioid overdose in the United States in recent years, the investigators examined the relationship between opioid-prescribing patterns and opioid-related deaths using a nationally representative sample of 155,434 cases in the VA’s National Patient Care Database.

The study subjects included patients taking opioids for cancer pain, chronic bodily pain, headache, neuropathy, and injuries; the prescribed opioid analgesics included codeine, morphine, oxycodone, hydrocodone, oxymorphone, and hydromorphone.

There were 750 deaths attributed to unintentional overdose, for an overall rate of 0.04% among all patients treated with opioids. The risk of overdose increased when the opioid dose was equivalent to 50 mg/dL of morphine, and there was a dose-response relationship in which increasing daily prescribed doses of opioids correlated with increasing risk of overdose death.

As an example, prescribed doses of 100 mg/dL or higher were associated with a hazard ratio of approximately 12.

Dr. Bohnert and her colleagues described their study as the first to assess concurrent prescribing of regularly scheduled opioids plus as-needed opioids. With the exception of cancer patients, participants treated with this strategy showed no excess risk of overdose. "Recent treatment guidelines have indicated that the long-term safety of this strategy for pain exacerbations has not been established, [but] in [this] study we did not find evidence of greater overdose risk associated with this treatment practice, after accounting for maximum daily dose and patient characteristics," they noted (JAMA 2011;305:1315-21).

The researchers also said theirs is the first study of this issue to include patients with cancer. The overall rate of opioid overdose was lower in cancer patients, compared with other subjects, but clinicians should be mindful that renal and liver impairment in this patient group can interfere with the metabolism of opioids and that high doses can place cancer patients at risk.

Cancer patients also were at increased risk of overdose if they were prescribed as-needed opioids alone, rather than regularly scheduled opioids. "Pain for patients with cancer can be particularly rapid in onset, unpredictable, and severe, and taking opioid doses as needed may result in [sudden] high doses being taken without the benefit of tolerance developed through a regularly scheduled opioid," the investigators said.

In a research letter accompanying this report, Dr. Nora D. Volkow, director of the National Institute on Drug Abuse, and her associates presented data from their study of prescription practices, which was aimed at identifying possible contributors to the high rate of opioid abuse. They drew on information in a national prescription database that included about 80 million prescriptions for opioid analgesics.

The main prescribers were general, family medicine, and osteopathic physicians, who accounted for 29% of these prescriptions, followed by internists (15%), dentists (8%), and orthopedic surgeons (8%).

Across all specialties, more than half of these prescriptions (56%, or 45 million) were given to patients who had already filled another opioid prescription during the preceding month. The data could not show whether such prescribing was "justified" or rather "suggests the need to improve information infrastructures that could enhance the safety of prescribed opioid analgesics and minimize diversion," Dr. Volkow and her colleagues said (JAMA 2011;305:1299-1301).

In addition, they found a fivefold increase in drug-treatment admissions for pharmaceutical opioids, from 19,941 to 121,091 in the past 10 years. Emergency department visits related to opioid overdose rose from 144,644 to 305,885 between 2004 and 2008. And deaths from unintentional opioid overdose have quadrupled, from approximately 3,000 in 1999 to 12,000 in 2007.

"Opioid overdose is now the second leading cause of unintentional death in the United States, second only to motor vehicle crashes," they noted.

The study by Dr. Bohnert and her colleagues was supported by the U.S. Department of Veterans Affairs’ Office of Mental Health Services and Office of Patient Care Services. One of Dr. Bohnert’s associates reported ties to Purdue Pharma. Dr. Volkow and her colleagues reported no disclosures.

Higher doses of opioids – the equivalent of 50 mg/dL or more of morphine – are more likely than are lower doses to lead to unintentional overdose, according to a report in the April 6 issue of JAMA.

However, the practice of adding a prescription for as-needed opioids to an existing prescription for regularly scheduled opioids, which allows patients to deal with acute exacerbations of pain, does not raise the risk of unintentional overdose in most patients, as some experts have feared, said Amy S.B. Bohnert, Ph.D., of the Department of Veterans Affairs and the University of Michigan, both in Ann Arbor, and her associates.

Citing a "troubling and dramatic" 124% increase in unintentional deaths from opioid overdose in the United States in recent years, the investigators examined the relationship between opioid-prescribing patterns and opioid-related deaths using a nationally representative sample of 155,434 cases in the VA’s National Patient Care Database.

The study subjects included patients taking opioids for cancer pain, chronic bodily pain, headache, neuropathy, and injuries; the prescribed opioid analgesics included codeine, morphine, oxycodone, hydrocodone, oxymorphone, and hydromorphone.

There were 750 deaths attributed to unintentional overdose, for an overall rate of 0.04% among all patients treated with opioids. The risk of overdose increased when the opioid dose was equivalent to 50 mg/dL of morphine, and there was a dose-response relationship in which increasing daily prescribed doses of opioids correlated with increasing risk of overdose death.

As an example, prescribed doses of 100 mg/dL or higher were associated with a hazard ratio of approximately 12.

Dr. Bohnert and her colleagues described their study as the first to assess concurrent prescribing of regularly scheduled opioids plus as-needed opioids. With the exception of cancer patients, participants treated with this strategy showed no excess risk of overdose. "Recent treatment guidelines have indicated that the long-term safety of this strategy for pain exacerbations has not been established, [but] in [this] study we did not find evidence of greater overdose risk associated with this treatment practice, after accounting for maximum daily dose and patient characteristics," they noted (JAMA 2011;305:1315-21).

The researchers also said theirs is the first study of this issue to include patients with cancer. The overall rate of opioid overdose was lower in cancer patients, compared with other subjects, but clinicians should be mindful that renal and liver impairment in this patient group can interfere with the metabolism of opioids and that high doses can place cancer patients at risk.

Cancer patients also were at increased risk of overdose if they were prescribed as-needed opioids alone, rather than regularly scheduled opioids. "Pain for patients with cancer can be particularly rapid in onset, unpredictable, and severe, and taking opioid doses as needed may result in [sudden] high doses being taken without the benefit of tolerance developed through a regularly scheduled opioid," the investigators said.

In a research letter accompanying this report, Dr. Nora D. Volkow, director of the National Institute on Drug Abuse, and her associates presented data from their study of prescription practices, which was aimed at identifying possible contributors to the high rate of opioid abuse. They drew on information in a national prescription database that included about 80 million prescriptions for opioid analgesics.

The main prescribers were general, family medicine, and osteopathic physicians, who accounted for 29% of these prescriptions, followed by internists (15%), dentists (8%), and orthopedic surgeons (8%).

Across all specialties, more than half of these prescriptions (56%, or 45 million) were given to patients who had already filled another opioid prescription during the preceding month. The data could not show whether such prescribing was "justified" or rather "suggests the need to improve information infrastructures that could enhance the safety of prescribed opioid analgesics and minimize diversion," Dr. Volkow and her colleagues said (JAMA 2011;305:1299-1301).

In addition, they found a fivefold increase in drug-treatment admissions for pharmaceutical opioids, from 19,941 to 121,091 in the past 10 years. Emergency department visits related to opioid overdose rose from 144,644 to 305,885 between 2004 and 2008. And deaths from unintentional opioid overdose have quadrupled, from approximately 3,000 in 1999 to 12,000 in 2007.

"Opioid overdose is now the second leading cause of unintentional death in the United States, second only to motor vehicle crashes," they noted.

The study by Dr. Bohnert and her colleagues was supported by the U.S. Department of Veterans Affairs’ Office of Mental Health Services and Office of Patient Care Services. One of Dr. Bohnert’s associates reported ties to Purdue Pharma. Dr. Volkow and her colleagues reported no disclosures.

Higher doses of opioids – the equivalent of 50 mg/dL or more of morphine – are more likely than are lower doses to lead to unintentional overdose, according to a report in the April 6 issue of JAMA.

However, the practice of adding a prescription for as-needed opioids to an existing prescription for regularly scheduled opioids, which allows patients to deal with acute exacerbations of pain, does not raise the risk of unintentional overdose in most patients, as some experts have feared, said Amy S.B. Bohnert, Ph.D., of the Department of Veterans Affairs and the University of Michigan, both in Ann Arbor, and her associates.

Citing a "troubling and dramatic" 124% increase in unintentional deaths from opioid overdose in the United States in recent years, the investigators examined the relationship between opioid-prescribing patterns and opioid-related deaths using a nationally representative sample of 155,434 cases in the VA’s National Patient Care Database.

The study subjects included patients taking opioids for cancer pain, chronic bodily pain, headache, neuropathy, and injuries; the prescribed opioid analgesics included codeine, morphine, oxycodone, hydrocodone, oxymorphone, and hydromorphone.

There were 750 deaths attributed to unintentional overdose, for an overall rate of 0.04% among all patients treated with opioids. The risk of overdose increased when the opioid dose was equivalent to 50 mg/dL of morphine, and there was a dose-response relationship in which increasing daily prescribed doses of opioids correlated with increasing risk of overdose death.

As an example, prescribed doses of 100 mg/dL or higher were associated with a hazard ratio of approximately 12.

Dr. Bohnert and her colleagues described their study as the first to assess concurrent prescribing of regularly scheduled opioids plus as-needed opioids. With the exception of cancer patients, participants treated with this strategy showed no excess risk of overdose. "Recent treatment guidelines have indicated that the long-term safety of this strategy for pain exacerbations has not been established, [but] in [this] study we did not find evidence of greater overdose risk associated with this treatment practice, after accounting for maximum daily dose and patient characteristics," they noted (JAMA 2011;305:1315-21).

The researchers also said theirs is the first study of this issue to include patients with cancer. The overall rate of opioid overdose was lower in cancer patients, compared with other subjects, but clinicians should be mindful that renal and liver impairment in this patient group can interfere with the metabolism of opioids and that high doses can place cancer patients at risk.

Cancer patients also were at increased risk of overdose if they were prescribed as-needed opioids alone, rather than regularly scheduled opioids. "Pain for patients with cancer can be particularly rapid in onset, unpredictable, and severe, and taking opioid doses as needed may result in [sudden] high doses being taken without the benefit of tolerance developed through a regularly scheduled opioid," the investigators said.

In a research letter accompanying this report, Dr. Nora D. Volkow, director of the National Institute on Drug Abuse, and her associates presented data from their study of prescription practices, which was aimed at identifying possible contributors to the high rate of opioid abuse. They drew on information in a national prescription database that included about 80 million prescriptions for opioid analgesics.

The main prescribers were general, family medicine, and osteopathic physicians, who accounted for 29% of these prescriptions, followed by internists (15%), dentists (8%), and orthopedic surgeons (8%).

Across all specialties, more than half of these prescriptions (56%, or 45 million) were given to patients who had already filled another opioid prescription during the preceding month. The data could not show whether such prescribing was "justified" or rather "suggests the need to improve information infrastructures that could enhance the safety of prescribed opioid analgesics and minimize diversion," Dr. Volkow and her colleagues said (JAMA 2011;305:1299-1301).

In addition, they found a fivefold increase in drug-treatment admissions for pharmaceutical opioids, from 19,941 to 121,091 in the past 10 years. Emergency department visits related to opioid overdose rose from 144,644 to 305,885 between 2004 and 2008. And deaths from unintentional opioid overdose have quadrupled, from approximately 3,000 in 1999 to 12,000 in 2007.

"Opioid overdose is now the second leading cause of unintentional death in the United States, second only to motor vehicle crashes," they noted.

The study by Dr. Bohnert and her colleagues was supported by the U.S. Department of Veterans Affairs’ Office of Mental Health Services and Office of Patient Care Services. One of Dr. Bohnert’s associates reported ties to Purdue Pharma. Dr. Volkow and her colleagues reported no disclosures.

The most recent findings from the Women’s Health Initiative study of short-term unopposed estrogen therapy suggest that after 10 years, the treatment neither increases nor decreases risks for coronary heart disease, deep vein thrombosis, stroke, hip fracture, colorectal cancer, or total mortality, according to a report in the April 6 issue of JAMA.

This portion of the WHI study was halted early when interim analysis in 2004 showed an increased risk of stroke in women taking conjugated equine estrogens (CEE) compared with those taking placebo. "All previous reports of this trial were limited to outcomes occurring during the intervention phase. [Now] we report data on postintervention outcomes through a mean of 10.7 years of follow-up," said Andrea Z. LaCroix, Ph.D., of Fred Hutchinson Cancer Research Center, Seattle, and her associates (JAMA 2011;305:1305-14).

In the estrogen-only portion of the WHI study, 10,739 postmenopausal women who had undergone hysterectomy had been randomly assigned to receive either CEE or placebo. They were followed during this intervention phase for a median of 6 years, but the median "adherent time" – the interval during which the women actually took more than 80% of their study pills – was only 3.5 years because more than half stopped taking the pills even before the early halt of the trial.

Approximately 78% of the surviving study subjects (3,778 who took CEE and 3,867 who took placebo) agreed to participate in the extended follow-up reported here.

The increased risks of stroke, deep vein thrombosis, and pulmonary embolism that had been noted during the intervention phase did not persist during extended follow-up. In addition, active treatment, which had showed no effect on CHD risks during the intervention, continued to show no effect on CHD risks. For all cardiovascular events, the cumulative hazard ratio was 2.26% with active treatment and 2.12% with placebo, a nonsignificant difference.

Colorectal cancer incidence did not differ between women who received CEE and those who received placebo during the intervention phase, and this lack of effect persisted during extended follow-up.

Hip fracture risk had been reduced with CEE therapy during the intervention phase, but this benefit did not persist during the extended follow-up. Numerically, hip fracture incidence was slightly higher in the CEE group than in the placebo group.

Total mortality risk remained similar between the two study groups both during the intervention and during extended follow-up.

Only one benefit of CEE therapy that was seen during the intervention phase persisted in the extended follow-up and became statistically significant: Breast cancer incidence was 0.27% with active treatment and 0.35% with placebo. The researchers noted that these results differ from those of the other portion of the WHI trial in which subjects received combined estrogen-plus-progestin. In that study arm, active treatment impeded mammographic accuracy and was associated with significantly higher rates of breast cancer and breast cancer mortality, they noted.

The women’s age at commencing treatment showed a significant interaction with outcomes, both during the intervention phase and during extended follow-up. The results suggest that there may be greater benefit and safety for women who start CEE in their early 50s, and less benefit with more potential harm for women who are older when they begin treatment.

"Among younger women, no new safety concerns emerged and some risk reductions became apparent during the postintervention period. Among older women, risks of colorectal cancer, death, and the global index of chronic diseases were elevated over the cumulative follow-up period," Dr. LaCroix and her associates said.

The WHI was funded by the National Heart, Lung, and Blood Institute, the National Institutes of Health, and the U.S. Department of Health and Human Services. Wyeth Ayerst donated the study drugs. Dr. LaCroix reported ties to Warner Chilcott, Sanofi-Aventis, Amgen, and Pfizer. Her associates reported ties to numerous other industry sources.

The most recent findings from the Women’s Health Initiative study of short-term unopposed estrogen therapy suggest that after 10 years, the treatment neither increases nor decreases risks for coronary heart disease, deep vein thrombosis, stroke, hip fracture, colorectal cancer, or total mortality, according to a report in the April 6 issue of JAMA.

This portion of the WHI study was halted early when interim analysis in 2004 showed an increased risk of stroke in women taking conjugated equine estrogens (CEE) compared with those taking placebo. "All previous reports of this trial were limited to outcomes occurring during the intervention phase. [Now] we report data on postintervention outcomes through a mean of 10.7 years of follow-up," said Andrea Z. LaCroix, Ph.D., of Fred Hutchinson Cancer Research Center, Seattle, and her associates (JAMA 2011;305:1305-14).

In the estrogen-only portion of the WHI study, 10,739 postmenopausal women who had undergone hysterectomy had been randomly assigned to receive either CEE or placebo. They were followed during this intervention phase for a median of 6 years, but the median "adherent time" – the interval during which the women actually took more than 80% of their study pills – was only 3.5 years because more than half stopped taking the pills even before the early halt of the trial.

Approximately 78% of the surviving study subjects (3,778 who took CEE and 3,867 who took placebo) agreed to participate in the extended follow-up reported here.

The increased risks of stroke, deep vein thrombosis, and pulmonary embolism that had been noted during the intervention phase did not persist during extended follow-up. In addition, active treatment, which had showed no effect on CHD risks during the intervention, continued to show no effect on CHD risks. For all cardiovascular events, the cumulative hazard ratio was 2.26% with active treatment and 2.12% with placebo, a nonsignificant difference.

Colorectal cancer incidence did not differ between women who received CEE and those who received placebo during the intervention phase, and this lack of effect persisted during extended follow-up.

Hip fracture risk had been reduced with CEE therapy during the intervention phase, but this benefit did not persist during the extended follow-up. Numerically, hip fracture incidence was slightly higher in the CEE group than in the placebo group.

Total mortality risk remained similar between the two study groups both during the intervention and during extended follow-up.

Only one benefit of CEE therapy that was seen during the intervention phase persisted in the extended follow-up and became statistically significant: Breast cancer incidence was 0.27% with active treatment and 0.35% with placebo. The researchers noted that these results differ from those of the other portion of the WHI trial in which subjects received combined estrogen-plus-progestin. In that study arm, active treatment impeded mammographic accuracy and was associated with significantly higher rates of breast cancer and breast cancer mortality, they noted.

The women’s age at commencing treatment showed a significant interaction with outcomes, both during the intervention phase and during extended follow-up. The results suggest that there may be greater benefit and safety for women who start CEE in their early 50s, and less benefit with more potential harm for women who are older when they begin treatment.

"Among younger women, no new safety concerns emerged and some risk reductions became apparent during the postintervention period. Among older women, risks of colorectal cancer, death, and the global index of chronic diseases were elevated over the cumulative follow-up period," Dr. LaCroix and her associates said.

The WHI was funded by the National Heart, Lung, and Blood Institute, the National Institutes of Health, and the U.S. Department of Health and Human Services. Wyeth Ayerst donated the study drugs. Dr. LaCroix reported ties to Warner Chilcott, Sanofi-Aventis, Amgen, and Pfizer. Her associates reported ties to numerous other industry sources.

The most recent findings from the Women’s Health Initiative study of short-term unopposed estrogen therapy suggest that after 10 years, the treatment neither increases nor decreases risks for coronary heart disease, deep vein thrombosis, stroke, hip fracture, colorectal cancer, or total mortality, according to a report in the April 6 issue of JAMA.

This portion of the WHI study was halted early when interim analysis in 2004 showed an increased risk of stroke in women taking conjugated equine estrogens (CEE) compared with those taking placebo. "All previous reports of this trial were limited to outcomes occurring during the intervention phase. [Now] we report data on postintervention outcomes through a mean of 10.7 years of follow-up," said Andrea Z. LaCroix, Ph.D., of Fred Hutchinson Cancer Research Center, Seattle, and her associates (JAMA 2011;305:1305-14).

In the estrogen-only portion of the WHI study, 10,739 postmenopausal women who had undergone hysterectomy had been randomly assigned to receive either CEE or placebo. They were followed during this intervention phase for a median of 6 years, but the median "adherent time" – the interval during which the women actually took more than 80% of their study pills – was only 3.5 years because more than half stopped taking the pills even before the early halt of the trial.

Approximately 78% of the surviving study subjects (3,778 who took CEE and 3,867 who took placebo) agreed to participate in the extended follow-up reported here.

The increased risks of stroke, deep vein thrombosis, and pulmonary embolism that had been noted during the intervention phase did not persist during extended follow-up. In addition, active treatment, which had showed no effect on CHD risks during the intervention, continued to show no effect on CHD risks. For all cardiovascular events, the cumulative hazard ratio was 2.26% with active treatment and 2.12% with placebo, a nonsignificant difference.

Colorectal cancer incidence did not differ between women who received CEE and those who received placebo during the intervention phase, and this lack of effect persisted during extended follow-up.

Hip fracture risk had been reduced with CEE therapy during the intervention phase, but this benefit did not persist during the extended follow-up. Numerically, hip fracture incidence was slightly higher in the CEE group than in the placebo group.

Total mortality risk remained similar between the two study groups both during the intervention and during extended follow-up.

Only one benefit of CEE therapy that was seen during the intervention phase persisted in the extended follow-up and became statistically significant: Breast cancer incidence was 0.27% with active treatment and 0.35% with placebo. The researchers noted that these results differ from those of the other portion of the WHI trial in which subjects received combined estrogen-plus-progestin. In that study arm, active treatment impeded mammographic accuracy and was associated with significantly higher rates of breast cancer and breast cancer mortality, they noted.

The women’s age at commencing treatment showed a significant interaction with outcomes, both during the intervention phase and during extended follow-up. The results suggest that there may be greater benefit and safety for women who start CEE in their early 50s, and less benefit with more potential harm for women who are older when they begin treatment.

"Among younger women, no new safety concerns emerged and some risk reductions became apparent during the postintervention period. Among older women, risks of colorectal cancer, death, and the global index of chronic diseases were elevated over the cumulative follow-up period," Dr. LaCroix and her associates said.

The WHI was funded by the National Heart, Lung, and Blood Institute, the National Institutes of Health, and the U.S. Department of Health and Human Services. Wyeth Ayerst donated the study drugs. Dr. LaCroix reported ties to Warner Chilcott, Sanofi-Aventis, Amgen, and Pfizer. Her associates reported ties to numerous other industry sources.

The most recent findings from the Women’s Health Initiative study of short-term unopposed estrogen therapy suggest that after 10 years, the treatment neither increases nor decreases risks for coronary heart disease, deep vein thrombosis, stroke, hip fracture, colorectal cancer, or total mortality, according to a report in the April 6 issue of JAMA.

This portion of the WHI study was halted early when interim analysis in 2004 showed an increased risk of stroke in women taking conjugated equine estrogens (CEE) compared with those taking placebo. "All previous reports of this trial were limited to outcomes occurring during the intervention phase. [Now] we report data on postintervention outcomes through a mean of 10.7 years of follow-up," said Andrea Z. LaCroix, Ph.D., of Fred Hutchinson Cancer Research Center, Seattle, and her associates (JAMA 2011;305:1305-14).

In the estrogen-only portion of the WHI study, 10,739 postmenopausal women who had undergone hysterectomy had been randomly assigned to receive either CEE or placebo. They were followed during this intervention phase for a median of 6 years, but the median "adherent time" – the interval during which the women actually took more than 80% of their study pills – was only 3.5 years because more than half stopped taking the pills even before the early halt of the trial.

Approximately 78% of the surviving study subjects (3,778 who took CEE and 3,867 who took placebo) agreed to participate in the extended follow-up reported here.

The increased risks of stroke, deep vein thrombosis, and pulmonary embolism that had been noted during the intervention phase did not persist during extended follow-up. In addition, active treatment, which had showed no effect on CHD risks during the intervention, continued to show no effect on CHD risks. For all cardiovascular events, the cumulative hazard ratio was 2.26% with active treatment and 2.12% with placebo, a nonsignificant difference.

Colorectal cancer incidence did not differ between women who received CEE and those who received placebo during the intervention phase, and this lack of effect persisted during extended follow-up.

Hip fracture risk had been reduced with CEE therapy during the intervention phase, but this benefit did not persist during the extended follow-up. Numerically, hip fracture incidence was slightly higher in the CEE group than in the placebo group.

Total mortality risk remained similar between the two study groups both during the intervention and during extended follow-up.

Only one benefit of CEE therapy that was seen during the intervention phase persisted in the extended follow-up and became statistically significant: Breast cancer incidence was 0.27% with active treatment and 0.35% with placebo. The researchers noted that these results differ from those of the other portion of the WHI trial in which subjects received combined estrogen-plus-progestin. In that study arm, active treatment impeded mammographic accuracy and was associated with significantly higher rates of breast cancer and breast cancer mortality, they noted.

The women’s age at commencing treatment showed a significant interaction with outcomes, both during the intervention phase and during extended follow-up. The results suggest that there may be greater benefit and safety for women who start CEE in their early 50s, and less benefit with more potential harm for women who are older when they begin treatment.

"Among younger women, no new safety concerns emerged and some risk reductions became apparent during the postintervention period. Among older women, risks of colorectal cancer, death, and the global index of chronic diseases were elevated over the cumulative follow-up period," Dr. LaCroix and her associates said.

The WHI was funded by the National Heart, Lung, and Blood Institute, the National Institutes of Health, and the U.S. Department of Health and Human Services. Wyeth Ayerst donated the study drugs. Dr. LaCroix reported ties to Warner Chilcott, Sanofi-Aventis, Amgen, and Pfizer. Her associates reported ties to numerous other industry sources.

The most recent findings from the Women’s Health Initiative study of short-term unopposed estrogen therapy suggest that after 10 years, the treatment neither increases nor decreases risks for coronary heart disease, deep vein thrombosis, stroke, hip fracture, colorectal cancer, or total mortality, according to a report in the April 6 issue of JAMA.

This portion of the WHI study was halted early when interim analysis in 2004 showed an increased risk of stroke in women taking conjugated equine estrogens (CEE) compared with those taking placebo. "All previous reports of this trial were limited to outcomes occurring during the intervention phase. [Now] we report data on postintervention outcomes through a mean of 10.7 years of follow-up," said Andrea Z. LaCroix, Ph.D., of Fred Hutchinson Cancer Research Center, Seattle, and her associates (JAMA 2011;305:1305-14).

In the estrogen-only portion of the WHI study, 10,739 postmenopausal women who had undergone hysterectomy had been randomly assigned to receive either CEE or placebo. They were followed during this intervention phase for a median of 6 years, but the median "adherent time" – the interval during which the women actually took more than 80% of their study pills – was only 3.5 years because more than half stopped taking the pills even before the early halt of the trial.

Approximately 78% of the surviving study subjects (3,778 who took CEE and 3,867 who took placebo) agreed to participate in the extended follow-up reported here.

The increased risks of stroke, deep vein thrombosis, and pulmonary embolism that had been noted during the intervention phase did not persist during extended follow-up. In addition, active treatment, which had showed no effect on CHD risks during the intervention, continued to show no effect on CHD risks. For all cardiovascular events, the cumulative hazard ratio was 2.26% with active treatment and 2.12% with placebo, a nonsignificant difference.

Colorectal cancer incidence did not differ between women who received CEE and those who received placebo during the intervention phase, and this lack of effect persisted during extended follow-up.

Hip fracture risk had been reduced with CEE therapy during the intervention phase, but this benefit did not persist during the extended follow-up. Numerically, hip fracture incidence was slightly higher in the CEE group than in the placebo group.

Total mortality risk remained similar between the two study groups both during the intervention and during extended follow-up.

Only one benefit of CEE therapy that was seen during the intervention phase persisted in the extended follow-up and became statistically significant: Breast cancer incidence was 0.27% with active treatment and 0.35% with placebo. The researchers noted that these results differ from those of the other portion of the WHI trial in which subjects received combined estrogen-plus-progestin. In that study arm, active treatment impeded mammographic accuracy and was associated with significantly higher rates of breast cancer and breast cancer mortality, they noted.

The women’s age at commencing treatment showed a significant interaction with outcomes, both during the intervention phase and during extended follow-up. The results suggest that there may be greater benefit and safety for women who start CEE in their early 50s, and less benefit with more potential harm for women who are older when they begin treatment.

"Among younger women, no new safety concerns emerged and some risk reductions became apparent during the postintervention period. Among older women, risks of colorectal cancer, death, and the global index of chronic diseases were elevated over the cumulative follow-up period," Dr. LaCroix and her associates said.

The WHI was funded by the National Heart, Lung, and Blood Institute, the National Institutes of Health, and the U.S. Department of Health and Human Services. Wyeth Ayerst donated the study drugs. Dr. LaCroix reported ties to Warner Chilcott, Sanofi-Aventis, Amgen, and Pfizer. Her associates reported ties to numerous other industry sources.

The most recent findings from the Women’s Health Initiative study of short-term unopposed estrogen therapy suggest that after 10 years, the treatment neither increases nor decreases risks for coronary heart disease, deep vein thrombosis, stroke, hip fracture, colorectal cancer, or total mortality, according to a report in the April 6 issue of JAMA.

This portion of the WHI study was halted early when interim analysis in 2004 showed an increased risk of stroke in women taking conjugated equine estrogens (CEE) compared with those taking placebo. "All previous reports of this trial were limited to outcomes occurring during the intervention phase. [Now] we report data on postintervention outcomes through a mean of 10.7 years of follow-up," said Andrea Z. LaCroix, Ph.D., of Fred Hutchinson Cancer Research Center, Seattle, and her associates (JAMA 2011;305:1305-14).

In the estrogen-only portion of the WHI study, 10,739 postmenopausal women who had undergone hysterectomy had been randomly assigned to receive either CEE or placebo. They were followed during this intervention phase for a median of 6 years, but the median "adherent time" – the interval during which the women actually took more than 80% of their study pills – was only 3.5 years because more than half stopped taking the pills even before the early halt of the trial.

Approximately 78% of the surviving study subjects (3,778 who took CEE and 3,867 who took placebo) agreed to participate in the extended follow-up reported here.

The increased risks of stroke, deep vein thrombosis, and pulmonary embolism that had been noted during the intervention phase did not persist during extended follow-up. In addition, active treatment, which had showed no effect on CHD risks during the intervention, continued to show no effect on CHD risks. For all cardiovascular events, the cumulative hazard ratio was 2.26% with active treatment and 2.12% with placebo, a nonsignificant difference.

Colorectal cancer incidence did not differ between women who received CEE and those who received placebo during the intervention phase, and this lack of effect persisted during extended follow-up.

Hip fracture risk had been reduced with CEE therapy during the intervention phase, but this benefit did not persist during the extended follow-up. Numerically, hip fracture incidence was slightly higher in the CEE group than in the placebo group.

Total mortality risk remained similar between the two study groups both during the intervention and during extended follow-up.

Only one benefit of CEE therapy that was seen during the intervention phase persisted in the extended follow-up and became statistically significant: Breast cancer incidence was 0.27% with active treatment and 0.35% with placebo. The researchers noted that these results differ from those of the other portion of the WHI trial in which subjects received combined estrogen-plus-progestin. In that study arm, active treatment impeded mammographic accuracy and was associated with significantly higher rates of breast cancer and breast cancer mortality, they noted.

The women’s age at commencing treatment showed a significant interaction with outcomes, both during the intervention phase and during extended follow-up. The results suggest that there may be greater benefit and safety for women who start CEE in their early 50s, and less benefit with more potential harm for women who are older when they begin treatment.

"Among younger women, no new safety concerns emerged and some risk reductions became apparent during the postintervention period. Among older women, risks of colorectal cancer, death, and the global index of chronic diseases were elevated over the cumulative follow-up period," Dr. LaCroix and her associates said.

The WHI was funded by the National Heart, Lung, and Blood Institute, the National Institutes of Health, and the U.S. Department of Health and Human Services. Wyeth Ayerst donated the study drugs. Dr. LaCroix reported ties to Warner Chilcott, Sanofi-Aventis, Amgen, and Pfizer. Her associates reported ties to numerous other industry sources.

A nearly 10-fold increase in the prevalence of plagiocephaly has been noted in Texas, and the cause has not yet been identified, according to a report published online April 4 in Archives of Pediatrics and Adolescent Medicine.

Between 1999 and 2007, the most recent year for which "cleaned" state registry data were available for analysis, the prevalence of plagiocephaly rose from 3.0 cases to 28.8 cases per 10,000 live births. "This was equivalent to an average annual increase of 21.2% per year, which is highly statistically significant," said Shane U. Sheu of the TB/HIV/STD epidemiology branch, Texas Department of State Health Services, Austin, and her associates.

Photo credit: © Jenny Swanson/istock.com

Plagiocephaly is characterized by unilateral flattening of the head in either the frontal or occipital region, and can occur in utero or in infancy.

It is thought in some congenital cases to result from intrauterine constraint of the fetal head, perhaps caused by multiple gestation, prolonged labor with the fetal head positioned low in the pelvis, or oligohydramnios. Acquired plagiocephaly is sometimes attributed to the infant remaining in the same horizontal position for extended periods, and has reportedly increased since 1992, when the American Academy of Pediatrics recommended infants sleep on their backs to reduce the risk of sudden infant death syndrome.

A marked increase in plagiocephaly was noted in the Texas Birth Defects Registry in recent years, with definitive diagnoses of 6,295 cases in 1999-2007. Ms. Sheu and her colleagues investigated factors that might help explain this rise (Arch. Ped. Adolesc. Med. 2011 [doi:10.1001/archpediatrics.2011.42]).

The registry did not distinguish congenital from acquired cases. However, the AAP recommendation "was not likely to explain our observed dramatic increase, because our study period began 7 years after the recommendation was released," they noted.

The researchers found that the prevalence of plagiocephaly increased across all demographic groups, regardless of maternal age, maternal race/ethnicity, infant sex, gestational age, or the presence or absence of multiple fetuses. Moreover, the proportion of cases related to multiple gestation remained stable over time.

The prevalence also increased across all clinical groups studied, regardless of the severity of the deformity; whether the infant had related torticollis or oligohydramnios; or what diagnostic or therapeutic procedures were used. The mean age at diagnosis also remained consistent over time.

Analysis of data on other birth defects of the skull or face during the same period showed that all but one also significantly increased, including deformities described as "depressions in skull"; "other skull deformity"; "craniosynostosis"; "Goldenhar syndrome/hemifacial microsomia"; "hypertelorism, telecanthus, wide-set eyes"; and "other skull or face bone anomalies." Only "asymmetrical head" declined over time, and that decline was not great enough to account for the rise in defects described as "plagiocephaly."

There was a slight increase over time in the proportion of cases born preterm, but "it would not explain the ninefold increase in plagiocephaly," Ms. Sheu and her associates said.

In short, "we were unable to pin down an explanation for the temporal increase," they said.

Although the increase in plagiocephaly was seen across the entire state of Texas, the bulk of that increase occurred in the Dallas/Fort Worth area, where the prevalence rose from 2.6 cases per 10,000 live births in 1999 to 60.5 cases per 10,000 live births in 2007. This trend appears to have been driven by the fact that five of the seven hospitals where most cases were diagnosed are located in the Dallas/Fort Worth region, and six of them have specialized craniofacial clinics.

This finding suggests that the rise in cases of plagiocephaly is related to increased referral to or increased treatment at these centers. It is possible that more parents are now requesting referrals, that more primary care physicians are recommending them, that marketing of assessment or treatment services has increased, or that reimbursement now offers incentives to have infants evaluated or treated.

For example, reimbursable procedures such as the use of orthotic helmets may have been developed or marketed during this time span, prompting increased referrals and diagnoses. Such factors were not within the scope of this study because the birth defects registry doesn’t collect that type of information, the investigators noted.

This study was supported in part by the Centers for Disease Control and Prevention, the Health Resources and Services Administration, and the Texas Department of State Health Services. Ms. Sheu and her associates reported no relevant financial disclosures.

A nearly 10-fold increase in the prevalence of plagiocephaly has been noted in Texas, and the cause has not yet been identified, according to a report published online April 4 in Archives of Pediatrics and Adolescent Medicine.

Between 1999 and 2007, the most recent year for which "cleaned" state registry data were available for analysis, the prevalence of plagiocephaly rose from 3.0 cases to 28.8 cases per 10,000 live births. "This was equivalent to an average annual increase of 21.2% per year, which is highly statistically significant," said Shane U. Sheu of the TB/HIV/STD epidemiology branch, Texas Department of State Health Services, Austin, and her associates.

Photo credit: © Jenny Swanson/istock.com

Plagiocephaly is characterized by unilateral flattening of the head in either the frontal or occipital region, and can occur in utero or in infancy.

It is thought in some congenital cases to result from intrauterine constraint of the fetal head, perhaps caused by multiple gestation, prolonged labor with the fetal head positioned low in the pelvis, or oligohydramnios. Acquired plagiocephaly is sometimes attributed to the infant remaining in the same horizontal position for extended periods, and has reportedly increased since 1992, when the American Academy of Pediatrics recommended infants sleep on their backs to reduce the risk of sudden infant death syndrome.

A marked increase in plagiocephaly was noted in the Texas Birth Defects Registry in recent years, with definitive diagnoses of 6,295 cases in 1999-2007. Ms. Sheu and her colleagues investigated factors that might help explain this rise (Arch. Ped. Adolesc. Med. 2011 [doi:10.1001/archpediatrics.2011.42]).

The registry did not distinguish congenital from acquired cases. However, the AAP recommendation "was not likely to explain our observed dramatic increase, because our study period began 7 years after the recommendation was released," they noted.

The researchers found that the prevalence of plagiocephaly increased across all demographic groups, regardless of maternal age, maternal race/ethnicity, infant sex, gestational age, or the presence or absence of multiple fetuses. Moreover, the proportion of cases related to multiple gestation remained stable over time.

The prevalence also increased across all clinical groups studied, regardless of the severity of the deformity; whether the infant had related torticollis or oligohydramnios; or what diagnostic or therapeutic procedures were used. The mean age at diagnosis also remained consistent over time.

Analysis of data on other birth defects of the skull or face during the same period showed that all but one also significantly increased, including deformities described as "depressions in skull"; "other skull deformity"; "craniosynostosis"; "Goldenhar syndrome/hemifacial microsomia"; "hypertelorism, telecanthus, wide-set eyes"; and "other skull or face bone anomalies." Only "asymmetrical head" declined over time, and that decline was not great enough to account for the rise in defects described as "plagiocephaly."

There was a slight increase over time in the proportion of cases born preterm, but "it would not explain the ninefold increase in plagiocephaly," Ms. Sheu and her associates said.

In short, "we were unable to pin down an explanation for the temporal increase," they said.

Although the increase in plagiocephaly was seen across the entire state of Texas, the bulk of that increase occurred in the Dallas/Fort Worth area, where the prevalence rose from 2.6 cases per 10,000 live births in 1999 to 60.5 cases per 10,000 live births in 2007. This trend appears to have been driven by the fact that five of the seven hospitals where most cases were diagnosed are located in the Dallas/Fort Worth region, and six of them have specialized craniofacial clinics.

This finding suggests that the rise in cases of plagiocephaly is related to increased referral to or increased treatment at these centers. It is possible that more parents are now requesting referrals, that more primary care physicians are recommending them, that marketing of assessment or treatment services has increased, or that reimbursement now offers incentives to have infants evaluated or treated.

For example, reimbursable procedures such as the use of orthotic helmets may have been developed or marketed during this time span, prompting increased referrals and diagnoses. Such factors were not within the scope of this study because the birth defects registry doesn’t collect that type of information, the investigators noted.

This study was supported in part by the Centers for Disease Control and Prevention, the Health Resources and Services Administration, and the Texas Department of State Health Services. Ms. Sheu and her associates reported no relevant financial disclosures.

A nearly 10-fold increase in the prevalence of plagiocephaly has been noted in Texas, and the cause has not yet been identified, according to a report published online April 4 in Archives of Pediatrics and Adolescent Medicine.

Between 1999 and 2007, the most recent year for which "cleaned" state registry data were available for analysis, the prevalence of plagiocephaly rose from 3.0 cases to 28.8 cases per 10,000 live births. "This was equivalent to an average annual increase of 21.2% per year, which is highly statistically significant," said Shane U. Sheu of the TB/HIV/STD epidemiology branch, Texas Department of State Health Services, Austin, and her associates.

Photo credit: © Jenny Swanson/istock.com

Plagiocephaly is characterized by unilateral flattening of the head in either the frontal or occipital region, and can occur in utero or in infancy.

It is thought in some congenital cases to result from intrauterine constraint of the fetal head, perhaps caused by multiple gestation, prolonged labor with the fetal head positioned low in the pelvis, or oligohydramnios. Acquired plagiocephaly is sometimes attributed to the infant remaining in the same horizontal position for extended periods, and has reportedly increased since 1992, when the American Academy of Pediatrics recommended infants sleep on their backs to reduce the risk of sudden infant death syndrome.

A marked increase in plagiocephaly was noted in the Texas Birth Defects Registry in recent years, with definitive diagnoses of 6,295 cases in 1999-2007. Ms. Sheu and her colleagues investigated factors that might help explain this rise (Arch. Ped. Adolesc. Med. 2011 [doi:10.1001/archpediatrics.2011.42]).

The registry did not distinguish congenital from acquired cases. However, the AAP recommendation "was not likely to explain our observed dramatic increase, because our study period began 7 years after the recommendation was released," they noted.

The researchers found that the prevalence of plagiocephaly increased across all demographic groups, regardless of maternal age, maternal race/ethnicity, infant sex, gestational age, or the presence or absence of multiple fetuses. Moreover, the proportion of cases related to multiple gestation remained stable over time.

The prevalence also increased across all clinical groups studied, regardless of the severity of the deformity; whether the infant had related torticollis or oligohydramnios; or what diagnostic or therapeutic procedures were used. The mean age at diagnosis also remained consistent over time.

Analysis of data on other birth defects of the skull or face during the same period showed that all but one also significantly increased, including deformities described as "depressions in skull"; "other skull deformity"; "craniosynostosis"; "Goldenhar syndrome/hemifacial microsomia"; "hypertelorism, telecanthus, wide-set eyes"; and "other skull or face bone anomalies." Only "asymmetrical head" declined over time, and that decline was not great enough to account for the rise in defects described as "plagiocephaly."

There was a slight increase over time in the proportion of cases born preterm, but "it would not explain the ninefold increase in plagiocephaly," Ms. Sheu and her associates said.

In short, "we were unable to pin down an explanation for the temporal increase," they said.

Although the increase in plagiocephaly was seen across the entire state of Texas, the bulk of that increase occurred in the Dallas/Fort Worth area, where the prevalence rose from 2.6 cases per 10,000 live births in 1999 to 60.5 cases per 10,000 live births in 2007. This trend appears to have been driven by the fact that five of the seven hospitals where most cases were diagnosed are located in the Dallas/Fort Worth region, and six of them have specialized craniofacial clinics.

This finding suggests that the rise in cases of plagiocephaly is related to increased referral to or increased treatment at these centers. It is possible that more parents are now requesting referrals, that more primary care physicians are recommending them, that marketing of assessment or treatment services has increased, or that reimbursement now offers incentives to have infants evaluated or treated.

For example, reimbursable procedures such as the use of orthotic helmets may have been developed or marketed during this time span, prompting increased referrals and diagnoses. Such factors were not within the scope of this study because the birth defects registry doesn’t collect that type of information, the investigators noted.

This study was supported in part by the Centers for Disease Control and Prevention, the Health Resources and Services Administration, and the Texas Department of State Health Services. Ms. Sheu and her associates reported no relevant financial disclosures.

A nearly 10-fold increase in the prevalence of plagiocephaly has been noted in Texas, and the cause has not yet been identified, according to a report published online April 4 in Archives of Pediatrics and Adolescent Medicine.

Between 1999 and 2007, the most recent year for which "cleaned" state registry data were available for analysis, the prevalence of plagiocephaly rose from 3.0 cases to 28.8 cases per 10,000 live births. "This was equivalent to an average annual increase of 21.2% per year, which is highly statistically significant," said Shane U. Sheu of the TB/HIV/STD epidemiology branch, Texas Department of State Health Services, Austin, and her associates.

Photo credit: © Jenny Swanson/istock.com

Plagiocephaly is characterized by unilateral flattening of the head in either the frontal or occipital region, and can occur in utero or in infancy.

It is thought in some congenital cases to result from intrauterine constraint of the fetal head, perhaps caused by multiple gestation, prolonged labor with the fetal head positioned low in the pelvis, or oligohydramnios. Acquired plagiocephaly is sometimes attributed to the infant remaining in the same horizontal position for extended periods, and has reportedly increased since 1992, when the American Academy of Pediatrics recommended infants sleep on their backs to reduce the risk of sudden infant death syndrome.

A marked increase in plagiocephaly was noted in the Texas Birth Defects Registry in recent years, with definitive diagnoses of 6,295 cases in 1999-2007. Ms. Sheu and her colleagues investigated factors that might help explain this rise (Arch. Ped. Adolesc. Med. 2011 [doi:10.1001/archpediatrics.2011.42]).

The registry did not distinguish congenital from acquired cases. However, the AAP recommendation "was not likely to explain our observed dramatic increase, because our study period began 7 years after the recommendation was released," they noted.

The researchers found that the prevalence of plagiocephaly increased across all demographic groups, regardless of maternal age, maternal race/ethnicity, infant sex, gestational age, or the presence or absence of multiple fetuses. Moreover, the proportion of cases related to multiple gestation remained stable over time.

The prevalence also increased across all clinical groups studied, regardless of the severity of the deformity; whether the infant had related torticollis or oligohydramnios; or what diagnostic or therapeutic procedures were used. The mean age at diagnosis also remained consistent over time.

Analysis of data on other birth defects of the skull or face during the same period showed that all but one also significantly increased, including deformities described as "depressions in skull"; "other skull deformity"; "craniosynostosis"; "Goldenhar syndrome/hemifacial microsomia"; "hypertelorism, telecanthus, wide-set eyes"; and "other skull or face bone anomalies." Only "asymmetrical head" declined over time, and that decline was not great enough to account for the rise in defects described as "plagiocephaly."

There was a slight increase over time in the proportion of cases born preterm, but "it would not explain the ninefold increase in plagiocephaly," Ms. Sheu and her associates said.

In short, "we were unable to pin down an explanation for the temporal increase," they said.

Although the increase in plagiocephaly was seen across the entire state of Texas, the bulk of that increase occurred in the Dallas/Fort Worth area, where the prevalence rose from 2.6 cases per 10,000 live births in 1999 to 60.5 cases per 10,000 live births in 2007. This trend appears to have been driven by the fact that five of the seven hospitals where most cases were diagnosed are located in the Dallas/Fort Worth region, and six of them have specialized craniofacial clinics.

This finding suggests that the rise in cases of plagiocephaly is related to increased referral to or increased treatment at these centers. It is possible that more parents are now requesting referrals, that more primary care physicians are recommending them, that marketing of assessment or treatment services has increased, or that reimbursement now offers incentives to have infants evaluated or treated.

For example, reimbursable procedures such as the use of orthotic helmets may have been developed or marketed during this time span, prompting increased referrals and diagnoses. Such factors were not within the scope of this study because the birth defects registry doesn’t collect that type of information, the investigators noted.

This study was supported in part by the Centers for Disease Control and Prevention, the Health Resources and Services Administration, and the Texas Department of State Health Services. Ms. Sheu and her associates reported no relevant financial disclosures.

A nearly 10-fold increase in the prevalence of plagiocephaly has been noted in Texas, and the cause has not yet been identified, according to a report published online April 4 in Archives of Pediatrics and Adolescent Medicine.

Between 1999 and 2007, the most recent year for which "cleaned" state registry data were available for analysis, the prevalence of plagiocephaly rose from 3.0 cases to 28.8 cases per 10,000 live births. "This was equivalent to an average annual increase of 21.2% per year, which is highly statistically significant," said Shane U. Sheu of the TB/HIV/STD epidemiology branch, Texas Department of State Health Services, Austin, and her associates.

Photo credit: © Jenny Swanson/istock.com

Plagiocephaly is characterized by unilateral flattening of the head in either the frontal or occipital region, and can occur in utero or in infancy.

It is thought in some congenital cases to result from intrauterine constraint of the fetal head, perhaps caused by multiple gestation, prolonged labor with the fetal head positioned low in the pelvis, or oligohydramnios. Acquired plagiocephaly is sometimes attributed to the infant remaining in the same horizontal position for extended periods, and has reportedly increased since 1992, when the American Academy of Pediatrics recommended infants sleep on their backs to reduce the risk of sudden infant death syndrome.

A marked increase in plagiocephaly was noted in the Texas Birth Defects Registry in recent years, with definitive diagnoses of 6,295 cases in 1999-2007. Ms. Sheu and her colleagues investigated factors that might help explain this rise (Arch. Ped. Adolesc. Med. 2011 [doi:10.1001/archpediatrics.2011.42]).

The registry did not distinguish congenital from acquired cases. However, the AAP recommendation "was not likely to explain our observed dramatic increase, because our study period began 7 years after the recommendation was released," they noted.

The researchers found that the prevalence of plagiocephaly increased across all demographic groups, regardless of maternal age, maternal race/ethnicity, infant sex, gestational age, or the presence or absence of multiple fetuses. Moreover, the proportion of cases related to multiple gestation remained stable over time.

The prevalence also increased across all clinical groups studied, regardless of the severity of the deformity; whether the infant had related torticollis or oligohydramnios; or what diagnostic or therapeutic procedures were used. The mean age at diagnosis also remained consistent over time.

Analysis of data on other birth defects of the skull or face during the same period showed that all but one also significantly increased, including deformities described as "depressions in skull"; "other skull deformity"; "craniosynostosis"; "Goldenhar syndrome/hemifacial microsomia"; "hypertelorism, telecanthus, wide-set eyes"; and "other skull or face bone anomalies." Only "asymmetrical head" declined over time, and that decline was not great enough to account for the rise in defects described as "plagiocephaly."

There was a slight increase over time in the proportion of cases born preterm, but "it would not explain the ninefold increase in plagiocephaly," Ms. Sheu and her associates said.

In short, "we were unable to pin down an explanation for the temporal increase," they said.

Although the increase in plagiocephaly was seen across the entire state of Texas, the bulk of that increase occurred in the Dallas/Fort Worth area, where the prevalence rose from 2.6 cases per 10,000 live births in 1999 to 60.5 cases per 10,000 live births in 2007. This trend appears to have been driven by the fact that five of the seven hospitals where most cases were diagnosed are located in the Dallas/Fort Worth region, and six of them have specialized craniofacial clinics.

This finding suggests that the rise in cases of plagiocephaly is related to increased referral to or increased treatment at these centers. It is possible that more parents are now requesting referrals, that more primary care physicians are recommending them, that marketing of assessment or treatment services has increased, or that reimbursement now offers incentives to have infants evaluated or treated.

For example, reimbursable procedures such as the use of orthotic helmets may have been developed or marketed during this time span, prompting increased referrals and diagnoses. Such factors were not within the scope of this study because the birth defects registry doesn’t collect that type of information, the investigators noted.

This study was supported in part by the Centers for Disease Control and Prevention, the Health Resources and Services Administration, and the Texas Department of State Health Services. Ms. Sheu and her associates reported no relevant financial disclosures.

A nearly 10-fold increase in the prevalence of plagiocephaly has been noted in Texas, and the cause has not yet been identified, according to a report published online April 4 in Archives of Pediatrics and Adolescent Medicine.

Between 1999 and 2007, the most recent year for which "cleaned" state registry data were available for analysis, the prevalence of plagiocephaly rose from 3.0 cases to 28.8 cases per 10,000 live births. "This was equivalent to an average annual increase of 21.2% per year, which is highly statistically significant," said Shane U. Sheu of the TB/HIV/STD epidemiology branch, Texas Department of State Health Services, Austin, and her associates.

Photo credit: © Jenny Swanson/istock.com

Plagiocephaly is characterized by unilateral flattening of the head in either the frontal or occipital region, and can occur in utero or in infancy.

It is thought in some congenital cases to result from intrauterine constraint of the fetal head, perhaps caused by multiple gestation, prolonged labor with the fetal head positioned low in the pelvis, or oligohydramnios. Acquired plagiocephaly is sometimes attributed to the infant remaining in the same horizontal position for extended periods, and has reportedly increased since 1992, when the American Academy of Pediatrics recommended infants sleep on their backs to reduce the risk of sudden infant death syndrome.

A marked increase in plagiocephaly was noted in the Texas Birth Defects Registry in recent years, with definitive diagnoses of 6,295 cases in 1999-2007. Ms. Sheu and her colleagues investigated factors that might help explain this rise (Arch. Ped. Adolesc. Med. 2011 [doi:10.1001/archpediatrics.2011.42]).

The registry did not distinguish congenital from acquired cases. However, the AAP recommendation "was not likely to explain our observed dramatic increase, because our study period began 7 years after the recommendation was released," they noted.

The researchers found that the prevalence of plagiocephaly increased across all demographic groups, regardless of maternal age, maternal race/ethnicity, infant sex, gestational age, or the presence or absence of multiple fetuses. Moreover, the proportion of cases related to multiple gestation remained stable over time.

The prevalence also increased across all clinical groups studied, regardless of the severity of the deformity; whether the infant had related torticollis or oligohydramnios; or what diagnostic or therapeutic procedures were used. The mean age at diagnosis also remained consistent over time.

Analysis of data on other birth defects of the skull or face during the same period showed that all but one also significantly increased, including deformities described as "depressions in skull"; "other skull deformity"; "craniosynostosis"; "Goldenhar syndrome/hemifacial microsomia"; "hypertelorism, telecanthus, wide-set eyes"; and "other skull or face bone anomalies." Only "asymmetrical head" declined over time, and that decline was not great enough to account for the rise in defects described as "plagiocephaly."

There was a slight increase over time in the proportion of cases born preterm, but "it would not explain the ninefold increase in plagiocephaly," Ms. Sheu and her associates said.

In short, "we were unable to pin down an explanation for the temporal increase," they said.

Although the increase in plagiocephaly was seen across the entire state of Texas, the bulk of that increase occurred in the Dallas/Fort Worth area, where the prevalence rose from 2.6 cases per 10,000 live births in 1999 to 60.5 cases per 10,000 live births in 2007. This trend appears to have been driven by the fact that five of the seven hospitals where most cases were diagnosed are located in the Dallas/Fort Worth region, and six of them have specialized craniofacial clinics.

This finding suggests that the rise in cases of plagiocephaly is related to increased referral to or increased treatment at these centers. It is possible that more parents are now requesting referrals, that more primary care physicians are recommending them, that marketing of assessment or treatment services has increased, or that reimbursement now offers incentives to have infants evaluated or treated.

For example, reimbursable procedures such as the use of orthotic helmets may have been developed or marketed during this time span, prompting increased referrals and diagnoses. Such factors were not within the scope of this study because the birth defects registry doesn’t collect that type of information, the investigators noted.

This study was supported in part by the Centers for Disease Control and Prevention, the Health Resources and Services Administration, and the Texas Department of State Health Services. Ms. Sheu and her associates reported no relevant financial disclosures.