Deeanna Franklin

Patients at high risk for breast cancer are not getting the full story from the genetic tests now being carried out in the United States, according to a study by Tom Walsh, Ph.D, and his associates.

Genetic testing is recommended for women with family histories of breast and ovarian cancer that suggest they may have inherited BRCA1 or BRCA2 gene mutations. To determine the frequency and type of cancer-predisposing gene mutations that are undetected by the most commonly used genetic tests, Dr. Walsh and his associates enrolled 300 representatives of cancer-afflicted families, or “probands” (JAMA 2006;295:1379–88).

“The clinical dilemma is what to offer to women with a high probability of carrying a mutation in BRCA1 and BRCA2 but with negative commercial test results,” the researchers wrote. The U.S. probands comprised 291 women with invasive breast cancer, three males with invasive breast cancer, and six women with ovarian cancer; 95% were of European ancestry. All participants had family histories of four or more cases of breast and ovarian cancer, and all had negative (wild-type) genetic test results for BRCA1 and BRCA2.

Participants were tested for complete “inherited rearrangements” of BRCA1 and BRCA2—and for other major breast cancer susceptibility genes, including CHEK2 (a cell cycle regulator), PTEN, and TP53—using multiplex ligation-dependent probe amplification (MLPA), a testing method available in Europe through a commercial firm in Amsterdam. The test is not available in the United States, and the researchers disclosed no financial interest in any company involved in this study.

“We believe that for families testing negative (wild type) for BRCA1 and BRCA2 by conventional sequencing, MLPA … is the current best choice,” Dr. Walsh and associates wrote.

Of the 300 probands with negative (wild-type) BRCA1 and BRCA2 commercial test results, 12% carried “cancer-predisposing genomic deletions or duplications in one of these genes,” the investigators reported. Additionally, 4% had inherited CHEK2 mutations, and 1% carried TP53 mutations. Of these probands, 52 (17%) carried inherited mutations in BRCA1, BRCA2, CHEK2, and TP53. This included 31 probands with rearrangements of BRCA1, four with rearrangements of BRCA2, 14 with CHEK2 mutations, and three with TP53 mutations. No PTEN inherited rearrangements were found.

The inherited BRCA1 rearrangements were more frequently found in probands younger than 40 years of age (16%). Additionally, inherited rearrangements of BRCA1 and BRCA2 were found in larger proportions in families with ovarian cancer, male breast cancer, or both (16%), compared with families with only female breast cancer (4.2%). According to the researchers, “the 52 mutation-positive families harbored 28 different mutations,” which are extremely rare, and included 14 previously unreported rearrangements.

Currently, conventional genetic testing for BRCA1 and BRCA2 mutations are done almost exclusively in the United States by one commercial laboratory in Utah. According to the researchers, this lab uses short-range polymerase chain reaction (PCR) followed by genomic sequencing to test for five specific larger mutations in BRCA1. However, recent evidence has shown that many mutations go undetected by PCR, and as a result many high-risk patients are given a negative (wild-type) genetic test result, noted Dr. Walsh of the departments of medicine and genome sciences at the University of Washington, Seattle, and colleagues.

The lifetime risk of breast cancer may be as high as 80% among U.S. women with BRCA1 and BRCA2 mutations; the lifetime risk of ovarian cancer is greater than 40% for women with BRCA1 mutations, and greater than 20% for those with BRCA2 mutations. Mutations of CHEK2 may double the risk of breast cancer, and—although extremely rare—inherited mutations of TP53 in families with Li-Fraumeni syndrome, and PTEN in families with Cowden syndrome are tied to high risk of early-onset breast cancer.

“As more breast cancer susceptibility genes of different penetrances are identified, clinicians will be increasingly challenged to offer the most appropriate genetic tests, to assist patients in interpreting the results, and to optimize risk reduction strategies,” the researchers concluded.

Patients at high risk for breast cancer are not getting the full story from the genetic tests now being carried out in the United States, according to a study by Tom Walsh, Ph.D, and his associates.

Genetic testing is recommended for women with family histories of breast and ovarian cancer that suggest they may have inherited BRCA1 or BRCA2 gene mutations. To determine the frequency and type of cancer-predisposing gene mutations that are undetected by the most commonly used genetic tests, Dr. Walsh and his associates enrolled 300 representatives of cancer-afflicted families, or “probands” (JAMA 2006;295:1379–88).

“The clinical dilemma is what to offer to women with a high probability of carrying a mutation in BRCA1 and BRCA2 but with negative commercial test results,” the researchers wrote. The U.S. probands comprised 291 women with invasive breast cancer, three males with invasive breast cancer, and six women with ovarian cancer; 95% were of European ancestry. All participants had family histories of four or more cases of breast and ovarian cancer, and all had negative (wild-type) genetic test results for BRCA1 and BRCA2.

Participants were tested for complete “inherited rearrangements” of BRCA1 and BRCA2—and for other major breast cancer susceptibility genes, including CHEK2 (a cell cycle regulator), PTEN, and TP53—using multiplex ligation-dependent probe amplification (MLPA), a testing method available in Europe through a commercial firm in Amsterdam. The test is not available in the United States, and the researchers disclosed no financial interest in any company involved in this study.

“We believe that for families testing negative (wild type) for BRCA1 and BRCA2 by conventional sequencing, MLPA … is the current best choice,” Dr. Walsh and associates wrote.

Of the 300 probands with negative (wild-type) BRCA1 and BRCA2 commercial test results, 12% carried “cancer-predisposing genomic deletions or duplications in one of these genes,” the investigators reported. Additionally, 4% had inherited CHEK2 mutations, and 1% carried TP53 mutations. Of these probands, 52 (17%) carried inherited mutations in BRCA1, BRCA2, CHEK2, and TP53. This included 31 probands with rearrangements of BRCA1, four with rearrangements of BRCA2, 14 with CHEK2 mutations, and three with TP53 mutations. No PTEN inherited rearrangements were found.

The inherited BRCA1 rearrangements were more frequently found in probands younger than 40 years of age (16%). Additionally, inherited rearrangements of BRCA1 and BRCA2 were found in larger proportions in families with ovarian cancer, male breast cancer, or both (16%), compared with families with only female breast cancer (4.2%). According to the researchers, “the 52 mutation-positive families harbored 28 different mutations,” which are extremely rare, and included 14 previously unreported rearrangements.

Currently, conventional genetic testing for BRCA1 and BRCA2 mutations are done almost exclusively in the United States by one commercial laboratory in Utah. According to the researchers, this lab uses short-range polymerase chain reaction (PCR) followed by genomic sequencing to test for five specific larger mutations in BRCA1. However, recent evidence has shown that many mutations go undetected by PCR, and as a result many high-risk patients are given a negative (wild-type) genetic test result, noted Dr. Walsh of the departments of medicine and genome sciences at the University of Washington, Seattle, and colleagues.

The lifetime risk of breast cancer may be as high as 80% among U.S. women with BRCA1 and BRCA2 mutations; the lifetime risk of ovarian cancer is greater than 40% for women with BRCA1 mutations, and greater than 20% for those with BRCA2 mutations. Mutations of CHEK2 may double the risk of breast cancer, and—although extremely rare—inherited mutations of TP53 in families with Li-Fraumeni syndrome, and PTEN in families with Cowden syndrome are tied to high risk of early-onset breast cancer.

“As more breast cancer susceptibility genes of different penetrances are identified, clinicians will be increasingly challenged to offer the most appropriate genetic tests, to assist patients in interpreting the results, and to optimize risk reduction strategies,” the researchers concluded.

Patients at high risk for breast cancer are not getting the full story from the genetic tests now being carried out in the United States, according to a study by Tom Walsh, Ph.D, and his associates.

Genetic testing is recommended for women with family histories of breast and ovarian cancer that suggest they may have inherited BRCA1 or BRCA2 gene mutations. To determine the frequency and type of cancer-predisposing gene mutations that are undetected by the most commonly used genetic tests, Dr. Walsh and his associates enrolled 300 representatives of cancer-afflicted families, or “probands” (JAMA 2006;295:1379–88).

“The clinical dilemma is what to offer to women with a high probability of carrying a mutation in BRCA1 and BRCA2 but with negative commercial test results,” the researchers wrote. The U.S. probands comprised 291 women with invasive breast cancer, three males with invasive breast cancer, and six women with ovarian cancer; 95% were of European ancestry. All participants had family histories of four or more cases of breast and ovarian cancer, and all had negative (wild-type) genetic test results for BRCA1 and BRCA2.

Participants were tested for complete “inherited rearrangements” of BRCA1 and BRCA2—and for other major breast cancer susceptibility genes, including CHEK2 (a cell cycle regulator), PTEN, and TP53—using multiplex ligation-dependent probe amplification (MLPA), a testing method available in Europe through a commercial firm in Amsterdam. The test is not available in the United States, and the researchers disclosed no financial interest in any company involved in this study.

“We believe that for families testing negative (wild type) for BRCA1 and BRCA2 by conventional sequencing, MLPA … is the current best choice,” Dr. Walsh and associates wrote.

Of the 300 probands with negative (wild-type) BRCA1 and BRCA2 commercial test results, 12% carried “cancer-predisposing genomic deletions or duplications in one of these genes,” the investigators reported. Additionally, 4% had inherited CHEK2 mutations, and 1% carried TP53 mutations. Of these probands, 52 (17%) carried inherited mutations in BRCA1, BRCA2, CHEK2, and TP53. This included 31 probands with rearrangements of BRCA1, four with rearrangements of BRCA2, 14 with CHEK2 mutations, and three with TP53 mutations. No PTEN inherited rearrangements were found.

The inherited BRCA1 rearrangements were more frequently found in probands younger than 40 years of age (16%). Additionally, inherited rearrangements of BRCA1 and BRCA2 were found in larger proportions in families with ovarian cancer, male breast cancer, or both (16%), compared with families with only female breast cancer (4.2%). According to the researchers, “the 52 mutation-positive families harbored 28 different mutations,” which are extremely rare, and included 14 previously unreported rearrangements.

Currently, conventional genetic testing for BRCA1 and BRCA2 mutations are done almost exclusively in the United States by one commercial laboratory in Utah. According to the researchers, this lab uses short-range polymerase chain reaction (PCR) followed by genomic sequencing to test for five specific larger mutations in BRCA1. However, recent evidence has shown that many mutations go undetected by PCR, and as a result many high-risk patients are given a negative (wild-type) genetic test result, noted Dr. Walsh of the departments of medicine and genome sciences at the University of Washington, Seattle, and colleagues.

The lifetime risk of breast cancer may be as high as 80% among U.S. women with BRCA1 and BRCA2 mutations; the lifetime risk of ovarian cancer is greater than 40% for women with BRCA1 mutations, and greater than 20% for those with BRCA2 mutations. Mutations of CHEK2 may double the risk of breast cancer, and—although extremely rare—inherited mutations of TP53 in families with Li-Fraumeni syndrome, and PTEN in families with Cowden syndrome are tied to high risk of early-onset breast cancer.

“As more breast cancer susceptibility genes of different penetrances are identified, clinicians will be increasingly challenged to offer the most appropriate genetic tests, to assist patients in interpreting the results, and to optimize risk reduction strategies,” the researchers concluded.

Metabolic syndrome predicts a worsening of intima-media thickness in the carotid artery of elderly women, according to findings from a 12-year population-based study.

Maija Hassinen and her colleagues at the Kuopio Research Institute of Exercise Medicine in Finland randomly selected 299 women, aged 50–60 years, from a large risk-factor survey. The women were followed from 1982 to 2003, at which point complete data were available on 101 women, who were then aged 70–80 years.

Patients were considered to have metabolic syndrome if they met at least three of the following criteria from the National Cholesterol Education Program: high blood pressure (130/85 mm Hg or greater, and/or drug treatment), high blood glucose levels (110 mg/dL or greater), HDL cholesterol levels less than 50 mg/dL, triglycerides of at least 150 mg/dL, and a waist circumference greater than 88 cm.

The women had an average of 1.5 risk factors for metabolic syndrome at baseline. Of the 13 women with metabolic syndrome at baseline, their mean carotid intima-media thickness (IMT) was 18% greater than in those without metabolic syndrome (1.21 mm vs. 1.03 mm), said Ms. Hassinen and colleagues (Arch. Intern. Med. 2006;166:444–9).

By the end of the study all participants had an average of 2.3 metabolic risk factors, and 46% had metabolic syndrome. For all participants, waist circumference increased by 10%, body mass index increased by 2%, and glucose levels rose by 11% over the 12-year period. Additionally, their levels for LDL cholesterol dropped by 16%, HDL cholesterol decreased by 21%, and systolic and diastolic blood pressure levels decreased by 8% and 19%, respectively. The use of medications for hypercholesterolemia rose from 7% to 36%, and for hypertension from 23% to 56%. The mean carotid IMT for participants rose from 1.05 mm to 1.27 mm, for a 21% increase.

Of the 88 women who did not have metabolic syndrome at baseline, 34 had developed incident metabolic syndrome. After adjusting for factors such as age, prevalent cardiovascular disease, physical activity, smoking, LDL cholesterol levels, carotid IMT, and a baseline National Cholesterol Education Program score for metabolic risk, the mean carotid IMT in these 34 women was two times greater than it was for the 54 women without incident metabolic syndrome. Furthermore, “the more metabolic risk factors that occurred during the 12-year period, the greater the increase in the mean carotid IMT,” said Ms. Hassinen and her colleagues.

The researchers concluded that “incident metabolic syndrome and the increasing number of metabolic risk factors [were] able to predict the progression of carotid IMT in elderly women,” and thus provide “additional information regarding the progression of preclinical atherosclerosis beyond conventional risk factors and can therefore improve the prediction of clinical [cardiovascular disease].”

Because of the rapidly growing elderly population in many Western countries, “carefully planned health promotion programs and treatments for the metabolic syndrome are urgently needed,” they concluded.

Metabolic syndrome predicts a worsening of intima-media thickness in the carotid artery of elderly women, according to findings from a 12-year population-based study.

Maija Hassinen and her colleagues at the Kuopio Research Institute of Exercise Medicine in Finland randomly selected 299 women, aged 50–60 years, from a large risk-factor survey. The women were followed from 1982 to 2003, at which point complete data were available on 101 women, who were then aged 70–80 years.

Patients were considered to have metabolic syndrome if they met at least three of the following criteria from the National Cholesterol Education Program: high blood pressure (130/85 mm Hg or greater, and/or drug treatment), high blood glucose levels (110 mg/dL or greater), HDL cholesterol levels less than 50 mg/dL, triglycerides of at least 150 mg/dL, and a waist circumference greater than 88 cm.

The women had an average of 1.5 risk factors for metabolic syndrome at baseline. Of the 13 women with metabolic syndrome at baseline, their mean carotid intima-media thickness (IMT) was 18% greater than in those without metabolic syndrome (1.21 mm vs. 1.03 mm), said Ms. Hassinen and colleagues (Arch. Intern. Med. 2006;166:444–9).

By the end of the study all participants had an average of 2.3 metabolic risk factors, and 46% had metabolic syndrome. For all participants, waist circumference increased by 10%, body mass index increased by 2%, and glucose levels rose by 11% over the 12-year period. Additionally, their levels for LDL cholesterol dropped by 16%, HDL cholesterol decreased by 21%, and systolic and diastolic blood pressure levels decreased by 8% and 19%, respectively. The use of medications for hypercholesterolemia rose from 7% to 36%, and for hypertension from 23% to 56%. The mean carotid IMT for participants rose from 1.05 mm to 1.27 mm, for a 21% increase.

Of the 88 women who did not have metabolic syndrome at baseline, 34 had developed incident metabolic syndrome. After adjusting for factors such as age, prevalent cardiovascular disease, physical activity, smoking, LDL cholesterol levels, carotid IMT, and a baseline National Cholesterol Education Program score for metabolic risk, the mean carotid IMT in these 34 women was two times greater than it was for the 54 women without incident metabolic syndrome. Furthermore, “the more metabolic risk factors that occurred during the 12-year period, the greater the increase in the mean carotid IMT,” said Ms. Hassinen and her colleagues.

The researchers concluded that “incident metabolic syndrome and the increasing number of metabolic risk factors [were] able to predict the progression of carotid IMT in elderly women,” and thus provide “additional information regarding the progression of preclinical atherosclerosis beyond conventional risk factors and can therefore improve the prediction of clinical [cardiovascular disease].”

Because of the rapidly growing elderly population in many Western countries, “carefully planned health promotion programs and treatments for the metabolic syndrome are urgently needed,” they concluded.

Metabolic syndrome predicts a worsening of intima-media thickness in the carotid artery of elderly women, according to findings from a 12-year population-based study.

Maija Hassinen and her colleagues at the Kuopio Research Institute of Exercise Medicine in Finland randomly selected 299 women, aged 50–60 years, from a large risk-factor survey. The women were followed from 1982 to 2003, at which point complete data were available on 101 women, who were then aged 70–80 years.

Patients were considered to have metabolic syndrome if they met at least three of the following criteria from the National Cholesterol Education Program: high blood pressure (130/85 mm Hg or greater, and/or drug treatment), high blood glucose levels (110 mg/dL or greater), HDL cholesterol levels less than 50 mg/dL, triglycerides of at least 150 mg/dL, and a waist circumference greater than 88 cm.

The women had an average of 1.5 risk factors for metabolic syndrome at baseline. Of the 13 women with metabolic syndrome at baseline, their mean carotid intima-media thickness (IMT) was 18% greater than in those without metabolic syndrome (1.21 mm vs. 1.03 mm), said Ms. Hassinen and colleagues (Arch. Intern. Med. 2006;166:444–9).

By the end of the study all participants had an average of 2.3 metabolic risk factors, and 46% had metabolic syndrome. For all participants, waist circumference increased by 10%, body mass index increased by 2%, and glucose levels rose by 11% over the 12-year period. Additionally, their levels for LDL cholesterol dropped by 16%, HDL cholesterol decreased by 21%, and systolic and diastolic blood pressure levels decreased by 8% and 19%, respectively. The use of medications for hypercholesterolemia rose from 7% to 36%, and for hypertension from 23% to 56%. The mean carotid IMT for participants rose from 1.05 mm to 1.27 mm, for a 21% increase.

Of the 88 women who did not have metabolic syndrome at baseline, 34 had developed incident metabolic syndrome. After adjusting for factors such as age, prevalent cardiovascular disease, physical activity, smoking, LDL cholesterol levels, carotid IMT, and a baseline National Cholesterol Education Program score for metabolic risk, the mean carotid IMT in these 34 women was two times greater than it was for the 54 women without incident metabolic syndrome. Furthermore, “the more metabolic risk factors that occurred during the 12-year period, the greater the increase in the mean carotid IMT,” said Ms. Hassinen and her colleagues.

The researchers concluded that “incident metabolic syndrome and the increasing number of metabolic risk factors [were] able to predict the progression of carotid IMT in elderly women,” and thus provide “additional information regarding the progression of preclinical atherosclerosis beyond conventional risk factors and can therefore improve the prediction of clinical [cardiovascular disease].”

Because of the rapidly growing elderly population in many Western countries, “carefully planned health promotion programs and treatments for the metabolic syndrome are urgently needed,” they concluded.

Unlike girls born at the turn of the last century, young girls today increasingly show minimal correlation between onset of puberty and age at menarche, reported Dr. Frank Biro and his colleagues.

In their study, 541 black girls and 615 white girls, all aged 9 years, were given annual exams over 10 years. At the start, 49% of the black girls and 77% of the white girls were prepubertal.

The participants, born in 1977 and 1978 and socioeconomically diverse, were recruited from public and parochial schools in Cincinnati, Richmond (California), and an HMO in Washington (J. Pediatr. 2006;148:234–40).

The onset of puberty was defined as “the age at areolar stage 2 or at pubic hair stage 2, whichever occurred earlier. Age of menarche was calculated from the date of birth to date of first menstrual period,” said Dr. Biro of Cincinnati Children's Hospital Medical Center, and his colleagues.

At the end of the study only a moderate correlation was found between onset of puberty and age of menarche. The median age for onset of puberty for white girls was 10.2 years and a mean age at menarche was 12.6 years; for black girls, it was 9.6 years for onset of puberty and 12 years for age at menarche.

Participants completed puberty at a median age of 14.3 years for whites vs. 13.6 years for blacks. Blacks also had a significantly younger age for several other puberty parameters such as age at peak height velocity (11.5 years vs. 11.9 years for whites), end of puberty, defined as attainment of areolar 4/pubic hair 5 (13.6 years vs. 14.3 years for whites), and age at attainment of adult height (16.5 years vs. 17.1 years for whites).

The median interval between age at onset of puberty and start of menarche was 2.7 years for blacks and 2.5 years for whites.

Researchers contrasted their results to several earlier studies including a 1948 study by Dr. E. Reynolds and Dr. J. Wines that showed a very close correlation between onset of puberty and age of menarche for girls born during the 1930s (Am. J. Dis. Child. 1948;75:329–50). However, the 1999 Bogalusa Heart Study found that the median age of menarche had dropped by almost 10 months in blacks vs. 2 months in whites for the period between 1973 and 1994 (Ethn. Dis. 1999 Spring-Summer:181–9).

According to Dr. Biro and his colleagues, the age of onset of puberty may be influenced by interplay “between genes and the environment.” The reasons for this “temporal drift” in the correlation results may “reflect interactions between body composition, environmental influences (such as endocrine disrupters) and genetic polymorphisms.”

They took into account the possible role that fat, particularly leptin, might play in this decreasing correlation. Girls with earlier menarche tended to have higher BMIs, and “leptin appears to serve as a permissive factor for the onset of puberty. Leptin levels are greater in blacks, even with adjustment for fat mass and pubertal maturation.” However, “the increases in relative weight … may be a consequence rather than a determinant of age of menarche, or secular changes in BMI and mean age at menarche could be independent phenomena,” the investigators said.

Dr. Paul Kaplowitz, a pediatric endocrinologist at Children's National Medical Center, Washington, was not surprised by the study's results. “It confirms what many of us have seen, which is that there is a lot of variability in how rapidly different girls progress through puberty, Although in general, girls who develop breasts at an early age tend to reach menarche earlier, one can see menarche less than 2 or more than 4 years after the appearance of breasts,” he said in an interview.

It is this individuality that must be weighed alongside treatment options. “Some kids are more worrisome than others because the signs of puberty progress more rapidly,” said Dr. Kaplowitz. “If the only sign of puberty is a small amount of breast tissue or pubic hair, the [physician could] observe it for 4–8 months before deciding if it is necessary to refer to a specialist. If it is changing little over time and the growth rate is not rapid, it is unlikely that any treatment will be needed.”

Unlike girls born at the turn of the last century, young girls today increasingly show minimal correlation between onset of puberty and age at menarche, reported Dr. Frank Biro and his colleagues.

In their study, 541 black girls and 615 white girls, all aged 9 years, were given annual exams over 10 years. At the start, 49% of the black girls and 77% of the white girls were prepubertal.

The participants, born in 1977 and 1978 and socioeconomically diverse, were recruited from public and parochial schools in Cincinnati, Richmond (California), and an HMO in Washington (J. Pediatr. 2006;148:234–40).

The onset of puberty was defined as “the age at areolar stage 2 or at pubic hair stage 2, whichever occurred earlier. Age of menarche was calculated from the date of birth to date of first menstrual period,” said Dr. Biro of Cincinnati Children's Hospital Medical Center, and his colleagues.

At the end of the study only a moderate correlation was found between onset of puberty and age of menarche. The median age for onset of puberty for white girls was 10.2 years and a mean age at menarche was 12.6 years; for black girls, it was 9.6 years for onset of puberty and 12 years for age at menarche.

Participants completed puberty at a median age of 14.3 years for whites vs. 13.6 years for blacks. Blacks also had a significantly younger age for several other puberty parameters such as age at peak height velocity (11.5 years vs. 11.9 years for whites), end of puberty, defined as attainment of areolar 4/pubic hair 5 (13.6 years vs. 14.3 years for whites), and age at attainment of adult height (16.5 years vs. 17.1 years for whites).

The median interval between age at onset of puberty and start of menarche was 2.7 years for blacks and 2.5 years for whites.

Researchers contrasted their results to several earlier studies including a 1948 study by Dr. E. Reynolds and Dr. J. Wines that showed a very close correlation between onset of puberty and age of menarche for girls born during the 1930s (Am. J. Dis. Child. 1948;75:329–50). However, the 1999 Bogalusa Heart Study found that the median age of menarche had dropped by almost 10 months in blacks vs. 2 months in whites for the period between 1973 and 1994 (Ethn. Dis. 1999 Spring-Summer:181–9).

According to Dr. Biro and his colleagues, the age of onset of puberty may be influenced by interplay “between genes and the environment.” The reasons for this “temporal drift” in the correlation results may “reflect interactions between body composition, environmental influences (such as endocrine disrupters) and genetic polymorphisms.”

They took into account the possible role that fat, particularly leptin, might play in this decreasing correlation. Girls with earlier menarche tended to have higher BMIs, and “leptin appears to serve as a permissive factor for the onset of puberty. Leptin levels are greater in blacks, even with adjustment for fat mass and pubertal maturation.” However, “the increases in relative weight … may be a consequence rather than a determinant of age of menarche, or secular changes in BMI and mean age at menarche could be independent phenomena,” the investigators said.

Dr. Paul Kaplowitz, a pediatric endocrinologist at Children's National Medical Center, Washington, was not surprised by the study's results. “It confirms what many of us have seen, which is that there is a lot of variability in how rapidly different girls progress through puberty, Although in general, girls who develop breasts at an early age tend to reach menarche earlier, one can see menarche less than 2 or more than 4 years after the appearance of breasts,” he said in an interview.

It is this individuality that must be weighed alongside treatment options. “Some kids are more worrisome than others because the signs of puberty progress more rapidly,” said Dr. Kaplowitz. “If the only sign of puberty is a small amount of breast tissue or pubic hair, the [physician could] observe it for 4–8 months before deciding if it is necessary to refer to a specialist. If it is changing little over time and the growth rate is not rapid, it is unlikely that any treatment will be needed.”

Unlike girls born at the turn of the last century, young girls today increasingly show minimal correlation between onset of puberty and age at menarche, reported Dr. Frank Biro and his colleagues.

In their study, 541 black girls and 615 white girls, all aged 9 years, were given annual exams over 10 years. At the start, 49% of the black girls and 77% of the white girls were prepubertal.

The participants, born in 1977 and 1978 and socioeconomically diverse, were recruited from public and parochial schools in Cincinnati, Richmond (California), and an HMO in Washington (J. Pediatr. 2006;148:234–40).

The onset of puberty was defined as “the age at areolar stage 2 or at pubic hair stage 2, whichever occurred earlier. Age of menarche was calculated from the date of birth to date of first menstrual period,” said Dr. Biro of Cincinnati Children's Hospital Medical Center, and his colleagues.

At the end of the study only a moderate correlation was found between onset of puberty and age of menarche. The median age for onset of puberty for white girls was 10.2 years and a mean age at menarche was 12.6 years; for black girls, it was 9.6 years for onset of puberty and 12 years for age at menarche.

Participants completed puberty at a median age of 14.3 years for whites vs. 13.6 years for blacks. Blacks also had a significantly younger age for several other puberty parameters such as age at peak height velocity (11.5 years vs. 11.9 years for whites), end of puberty, defined as attainment of areolar 4/pubic hair 5 (13.6 years vs. 14.3 years for whites), and age at attainment of adult height (16.5 years vs. 17.1 years for whites).

The median interval between age at onset of puberty and start of menarche was 2.7 years for blacks and 2.5 years for whites.

Researchers contrasted their results to several earlier studies including a 1948 study by Dr. E. Reynolds and Dr. J. Wines that showed a very close correlation between onset of puberty and age of menarche for girls born during the 1930s (Am. J. Dis. Child. 1948;75:329–50). However, the 1999 Bogalusa Heart Study found that the median age of menarche had dropped by almost 10 months in blacks vs. 2 months in whites for the period between 1973 and 1994 (Ethn. Dis. 1999 Spring-Summer:181–9).

According to Dr. Biro and his colleagues, the age of onset of puberty may be influenced by interplay “between genes and the environment.” The reasons for this “temporal drift” in the correlation results may “reflect interactions between body composition, environmental influences (such as endocrine disrupters) and genetic polymorphisms.”

They took into account the possible role that fat, particularly leptin, might play in this decreasing correlation. Girls with earlier menarche tended to have higher BMIs, and “leptin appears to serve as a permissive factor for the onset of puberty. Leptin levels are greater in blacks, even with adjustment for fat mass and pubertal maturation.” However, “the increases in relative weight … may be a consequence rather than a determinant of age of menarche, or secular changes in BMI and mean age at menarche could be independent phenomena,” the investigators said.

Dr. Paul Kaplowitz, a pediatric endocrinologist at Children's National Medical Center, Washington, was not surprised by the study's results. “It confirms what many of us have seen, which is that there is a lot of variability in how rapidly different girls progress through puberty, Although in general, girls who develop breasts at an early age tend to reach menarche earlier, one can see menarche less than 2 or more than 4 years after the appearance of breasts,” he said in an interview.

It is this individuality that must be weighed alongside treatment options. “Some kids are more worrisome than others because the signs of puberty progress more rapidly,” said Dr. Kaplowitz. “If the only sign of puberty is a small amount of breast tissue or pubic hair, the [physician could] observe it for 4–8 months before deciding if it is necessary to refer to a specialist. If it is changing little over time and the growth rate is not rapid, it is unlikely that any treatment will be needed.”

Unlike girls born at the turn of the last century, young girls today increasingly show minimal correlation between onset of puberty and age at menarche, reported Dr. Frank Biro and his colleagues.

In their study, 541 black girls and 615 white girls, all aged 9 years, were given annual exams over 10 years. At the start, 49% of the black girls and 77% of the white girls were prepubertal.

The participants, born in 1977 and 1978 and socioeconomically diverse, were recruited from public and parochial schools in Cincinnati, Richmond (Calif.), and an HMO in Washington (J. Pediatr. 2006;148:234–40).

The onset of puberty was defined as “the age at areolar stage 2 or at pubic hair stage 2, whichever occurred earlier. Age of menarche was calculated from the date of birth to date of first menstrual period,” said Dr. Biro of Cincinnati Children's Hospital Medical Center, and his colleagues.

At the end of the study only a moderate correlation was found between onset of puberty and age of menarche. The median age for onset of puberty for white girls was 10.2 years and a mean age at menarche was 12.6 years; for black girls, it was 9.6 years for onset of puberty and 12 years for age at menarche.

Participants completed puberty at a median age of 14.3 years for whites vs. 13.6 years for blacks. Blacks also had a significantly younger age for several other puberty parameters such as age at peak height velocity (11.5 years vs. 11.9 years for whites), end of puberty, defined as attainment of areolar 4/pubic hair 5 (13.6 years vs. 14.3 years for whites), and age at attainment of adult height (16.5 years vs. 17.1 years for whites).

The median interval between age at onset of puberty and start of menarche was 2.7 years for blacks and 2.5 years for whites.

Researchers contrasted their results to several earlier studies including a 1948 study by Dr. E. Reynolds and Dr. J. Wines that showed a very close correlation between onset of puberty and age of menarche for girls born during the 1930s (Am. J. Dis. Child. 1948;75:329–50). However, the 1999 Bogalusa Heart Study found that the median age of menarche had dropped by almost 10 months in blacks vs. 2 months in whites for the period between 1973 and 1994 (Ethn. Dis. 1999;9:181–9).

According to Dr. Biro and his colleagues, the age of onset of puberty may be influenced by interplay “between genes and the environment.” The reasons for this “temporal drift” in the correlation results may “reflect interactions between body composition, environmental influences (such as endocrine disrupters) and genetic polymorphisms.”

They took into account the possible role that fat, particularly leptin, might play in this decreasing correlation. Girls with earlier menarche tended to have higher BMIs, and “leptin appears to serve a permissive factor for the onset of puberty. Leptin levels are greater in blacks, even with adjustment for fat mass and pubertal maturation.” However, “the increases in relative weight … may be a consequence rather than a determinant of age of menarche, or secular changes in BMI and mean age at menarche could be independent phenomena,” the investigators said.

Dr. Paul Kaplowitz, a pediatric endocrinologist at Children's National Medical Center, Washington, was not surprised by the study's results. “It confirms what many of us have seen [that] there is a lot of variability in how rapidly different girls progress through puberty.”

Unlike girls born at the turn of the last century, young girls today increasingly show minimal correlation between onset of puberty and age at menarche, reported Dr. Frank Biro and his colleagues.

In their study, 541 black girls and 615 white girls, all aged 9 years, were given annual exams over 10 years. At the start, 49% of the black girls and 77% of the white girls were prepubertal.

The participants, born in 1977 and 1978 and socioeconomically diverse, were recruited from public and parochial schools in Cincinnati, Richmond (Calif.), and an HMO in Washington (J. Pediatr. 2006;148:234–40).

The onset of puberty was defined as “the age at areolar stage 2 or at pubic hair stage 2, whichever occurred earlier. Age of menarche was calculated from the date of birth to date of first menstrual period,” said Dr. Biro of Cincinnati Children's Hospital Medical Center, and his colleagues.

At the end of the study only a moderate correlation was found between onset of puberty and age of menarche. The median age for onset of puberty for white girls was 10.2 years and a mean age at menarche was 12.6 years; for black girls, it was 9.6 years for onset of puberty and 12 years for age at menarche.

Participants completed puberty at a median age of 14.3 years for whites vs. 13.6 years for blacks. Blacks also had a significantly younger age for several other puberty parameters such as age at peak height velocity (11.5 years vs. 11.9 years for whites), end of puberty, defined as attainment of areolar 4/pubic hair 5 (13.6 years vs. 14.3 years for whites), and age at attainment of adult height (16.5 years vs. 17.1 years for whites).

The median interval between age at onset of puberty and start of menarche was 2.7 years for blacks and 2.5 years for whites.

Researchers contrasted their results to several earlier studies including a 1948 study by Dr. E. Reynolds and Dr. J. Wines that showed a very close correlation between onset of puberty and age of menarche for girls born during the 1930s (Am. J. Dis. Child. 1948;75:329–50). However, the 1999 Bogalusa Heart Study found that the median age of menarche had dropped by almost 10 months in blacks vs. 2 months in whites for the period between 1973 and 1994 (Ethn. Dis. 1999;9:181–9).

According to Dr. Biro and his colleagues, the age of onset of puberty may be influenced by interplay “between genes and the environment.” The reasons for this “temporal drift” in the correlation results may “reflect interactions between body composition, environmental influences (such as endocrine disrupters) and genetic polymorphisms.”

They took into account the possible role that fat, particularly leptin, might play in this decreasing correlation. Girls with earlier menarche tended to have higher BMIs, and “leptin appears to serve a permissive factor for the onset of puberty. Leptin levels are greater in blacks, even with adjustment for fat mass and pubertal maturation.” However, “the increases in relative weight … may be a consequence rather than a determinant of age of menarche, or secular changes in BMI and mean age at menarche could be independent phenomena,” the investigators said.

Dr. Paul Kaplowitz, a pediatric endocrinologist at Children's National Medical Center, Washington, was not surprised by the study's results. “It confirms what many of us have seen [that] there is a lot of variability in how rapidly different girls progress through puberty.”

Unlike girls born at the turn of the last century, young girls today increasingly show minimal correlation between onset of puberty and age at menarche, reported Dr. Frank Biro and his colleagues.

In their study, 541 black girls and 615 white girls, all aged 9 years, were given annual exams over 10 years. At the start, 49% of the black girls and 77% of the white girls were prepubertal.

The participants, born in 1977 and 1978 and socioeconomically diverse, were recruited from public and parochial schools in Cincinnati, Richmond (Calif.), and an HMO in Washington (J. Pediatr. 2006;148:234–40).

The onset of puberty was defined as “the age at areolar stage 2 or at pubic hair stage 2, whichever occurred earlier. Age of menarche was calculated from the date of birth to date of first menstrual period,” said Dr. Biro of Cincinnati Children's Hospital Medical Center, and his colleagues.

At the end of the study only a moderate correlation was found between onset of puberty and age of menarche. The median age for onset of puberty for white girls was 10.2 years and a mean age at menarche was 12.6 years; for black girls, it was 9.6 years for onset of puberty and 12 years for age at menarche.

Participants completed puberty at a median age of 14.3 years for whites vs. 13.6 years for blacks. Blacks also had a significantly younger age for several other puberty parameters such as age at peak height velocity (11.5 years vs. 11.9 years for whites), end of puberty, defined as attainment of areolar 4/pubic hair 5 (13.6 years vs. 14.3 years for whites), and age at attainment of adult height (16.5 years vs. 17.1 years for whites).

The median interval between age at onset of puberty and start of menarche was 2.7 years for blacks and 2.5 years for whites.

Researchers contrasted their results to several earlier studies including a 1948 study by Dr. E. Reynolds and Dr. J. Wines that showed a very close correlation between onset of puberty and age of menarche for girls born during the 1930s (Am. J. Dis. Child. 1948;75:329–50). However, the 1999 Bogalusa Heart Study found that the median age of menarche had dropped by almost 10 months in blacks vs. 2 months in whites for the period between 1973 and 1994 (Ethn. Dis. 1999;9:181–9).

According to Dr. Biro and his colleagues, the age of onset of puberty may be influenced by interplay “between genes and the environment.” The reasons for this “temporal drift” in the correlation results may “reflect interactions between body composition, environmental influences (such as endocrine disrupters) and genetic polymorphisms.”

They took into account the possible role that fat, particularly leptin, might play in this decreasing correlation. Girls with earlier menarche tended to have higher BMIs, and “leptin appears to serve a permissive factor for the onset of puberty. Leptin levels are greater in blacks, even with adjustment for fat mass and pubertal maturation.” However, “the increases in relative weight … may be a consequence rather than a determinant of age of menarche, or secular changes in BMI and mean age at menarche could be independent phenomena,” the investigators said.

Dr. Paul Kaplowitz, a pediatric endocrinologist at Children's National Medical Center, Washington, was not surprised by the study's results. “It confirms what many of us have seen [that] there is a lot of variability in how rapidly different girls progress through puberty.”

BETHESDA, MD. — A federal advisory panel unanimously voted to change two of the three strains slated to comprise the 2006–2007 influenza vaccine.

The Food and Drug Administration's Vaccines and Related Biological Products Advisory Committee recommended the changes based on shifts seen in viral activity, according to data culled from surveillance sites in Japan, England, Australia, and the United States.

The recommended vaccine changes correlate with the World Health Organization's suggested vaccine composition for the Northern Hemisphere for the 2006–2007 winter season.

The FDA advisory panel recommended that the trivalent vaccine retain the influenza A(H1N1) strain—A/New Caledonia/20/99(H1N1)-like virus—due to evidence of continued resilience.

However, they suggested replacing the A/California/7/2004(H3N2)-like virus with A/Wisconsin/67/2005(H3N2)-like virus. Also, the influenza B/Shanghai/361/2002-like virus should be replaced with the B/Malaysia/2506/2004-like virus.

According to Dr. Zhiping Ye, senior investigator for the division of viral products with the FDA's Center for Biologics Evaluation and Research, influenza A infections were inadequately covered by the 2005–2006 vaccine. It's estimated that in the pediatric population there was an overall 50% reduction in the hemagglutination inhibition (HI) reaction to the H3N2 component of the vaccine.

A similar reduction in coverage of the A/Wisconsin strain was noted in adult populations in Europe, Japan, and the United States.

“If we use Wisconsin as a vaccine, then we probably will get better coverage,” Dr. Ye said. “But this is only one piece of the puzzle.” Surveillance studies show that several other strains in the same lineage as A/Wisconsin also were inadequately covered by the current vaccine. However, there would likely be residual coverage of these strains by targeting the A/Wisconsin strain.

The current vaccine still appeared effective against the influenza A(H1N1) strain, A/New Caledonia/20/99(H1N1)-like virus, according to data from surveillance sites in North and South America, Europe, Asia, Africa, and Australia.

Data from the United States and Europe showed that several strains were inadequately covered by the influenza B component of the current vaccine, and the B/Malaysia/2506/2004-like virus was one of them, Dr. Ye noted.

The vote on the 2006–2007 vaccine composition was unanimous, but the panel members had some reservations.

Although influenza A strains are responsible for most U.S. influenza cases, in recent years the selection of an influenza B strain has been more difficult to accurately pin down. “This winter the B/Victoria has been dominant in North America, but our vaccine was the B/Yamagata strain,” said panelist Dr. Robert B. Couch, professor of medicine, microbiology, and immunology at Baylor College of Medicine, Houston.

“We do the best we can to predict the likely epidemic virus, but for roughly the last 3 years, it's been a little too much of a guess with the influenza B. If it's going to continue this way, then we need to discuss how to address this problem,” Dr. Couch said in an interview.

Despite these misgivings, he voted in favor of the B/Malaysia strain, which is part of the B/Victoria/2/87 lineage.

BETHESDA, MD. — A federal advisory panel unanimously voted to change two of the three strains slated to comprise the 2006–2007 influenza vaccine.

The Food and Drug Administration's Vaccines and Related Biological Products Advisory Committee recommended the changes based on shifts seen in viral activity, according to data culled from surveillance sites in Japan, England, Australia, and the United States.

The recommended vaccine changes correlate with the World Health Organization's suggested vaccine composition for the Northern Hemisphere for the 2006–2007 winter season.

The FDA advisory panel recommended that the trivalent vaccine retain the influenza A(H1N1) strain—A/New Caledonia/20/99(H1N1)-like virus—due to evidence of continued resilience.

However, they suggested replacing the A/California/7/2004(H3N2)-like virus with A/Wisconsin/67/2005(H3N2)-like virus. Also, the influenza B/Shanghai/361/2002-like virus should be replaced with the B/Malaysia/2506/2004-like virus.

According to Dr. Zhiping Ye, senior investigator for the division of viral products with the FDA's Center for Biologics Evaluation and Research, influenza A infections were inadequately covered by the 2005–2006 vaccine. It's estimated that in the pediatric population there was an overall 50% reduction in the hemagglutination inhibition (HI) reaction to the H3N2 component of the vaccine.

A similar reduction in coverage of the A/Wisconsin strain was noted in adult populations in Europe, Japan, and the United States.

“If we use Wisconsin as a vaccine, then we probably will get better coverage,” Dr. Ye said. “But this is only one piece of the puzzle.” Surveillance studies show that several other strains in the same lineage as A/Wisconsin also were inadequately covered by the current vaccine. However, there would likely be residual coverage of these strains by targeting the A/Wisconsin strain.

The current vaccine still appeared effective against the influenza A(H1N1) strain, A/New Caledonia/20/99(H1N1)-like virus, according to data from surveillance sites in North and South America, Europe, Asia, Africa, and Australia.

Data from the United States and Europe showed that several strains were inadequately covered by the influenza B component of the current vaccine, and the B/Malaysia/2506/2004-like virus was one of them, Dr. Ye noted.

The vote on the 2006–2007 vaccine composition was unanimous, but the panel members had some reservations.

Although influenza A strains are responsible for most U.S. influenza cases, in recent years the selection of an influenza B strain has been more difficult to accurately pin down. “This winter the B/Victoria has been dominant in North America, but our vaccine was the B/Yamagata strain,” said panelist Dr. Robert B. Couch, professor of medicine, microbiology, and immunology at Baylor College of Medicine, Houston.

“We do the best we can to predict the likely epidemic virus, but for roughly the last 3 years, it's been a little too much of a guess with the influenza B. If it's going to continue this way, then we need to discuss how to address this problem,” Dr. Couch said in an interview.

Despite these misgivings, he voted in favor of the B/Malaysia strain, which is part of the B/Victoria/2/87 lineage.

BETHESDA, MD. — A federal advisory panel unanimously voted to change two of the three strains slated to comprise the 2006–2007 influenza vaccine.

The Food and Drug Administration's Vaccines and Related Biological Products Advisory Committee recommended the changes based on shifts seen in viral activity, according to data culled from surveillance sites in Japan, England, Australia, and the United States.

The recommended vaccine changes correlate with the World Health Organization's suggested vaccine composition for the Northern Hemisphere for the 2006–2007 winter season.

The FDA advisory panel recommended that the trivalent vaccine retain the influenza A(H1N1) strain—A/New Caledonia/20/99(H1N1)-like virus—due to evidence of continued resilience.

However, they suggested replacing the A/California/7/2004(H3N2)-like virus with A/Wisconsin/67/2005(H3N2)-like virus. Also, the influenza B/Shanghai/361/2002-like virus should be replaced with the B/Malaysia/2506/2004-like virus.

According to Dr. Zhiping Ye, senior investigator for the division of viral products with the FDA's Center for Biologics Evaluation and Research, influenza A infections were inadequately covered by the 2005–2006 vaccine. It's estimated that in the pediatric population there was an overall 50% reduction in the hemagglutination inhibition (HI) reaction to the H3N2 component of the vaccine.

A similar reduction in coverage of the A/Wisconsin strain was noted in adult populations in Europe, Japan, and the United States.

“If we use Wisconsin as a vaccine, then we probably will get better coverage,” Dr. Ye said. “But this is only one piece of the puzzle.” Surveillance studies show that several other strains in the same lineage as A/Wisconsin also were inadequately covered by the current vaccine. However, there would likely be residual coverage of these strains by targeting the A/Wisconsin strain.

The current vaccine still appeared effective against the influenza A(H1N1) strain, A/New Caledonia/20/99(H1N1)-like virus, according to data from surveillance sites in North and South America, Europe, Asia, Africa, and Australia.

Data from the United States and Europe showed that several strains were inadequately covered by the influenza B component of the current vaccine, and the B/Malaysia/2506/2004-like virus was one of them, Dr. Ye noted.

The vote on the 2006–2007 vaccine composition was unanimous, but the panel members had some reservations.

Although influenza A strains are responsible for most U.S. influenza cases, in recent years the selection of an influenza B strain has been more difficult to accurately pin down. “This winter the B/Victoria has been dominant in North America, but our vaccine was the B/Yamagata strain,” said panelist Dr. Robert B. Couch, professor of medicine, microbiology, and immunology at Baylor College of Medicine, Houston.

“We do the best we can to predict the likely epidemic virus, but for roughly the last 3 years, it's been a little too much of a guess with the influenza B. If it's going to continue this way, then we need to discuss how to address this problem,” Dr. Couch said in an interview.

Despite these misgivings, he voted in favor of the B/Malaysia strain, which is part of the B/Victoria/2/87 lineage.

BETHESDA, MD. — A federal advisory panel unanimously voted to change two of the three strains slated to compose the 2006–2007 influenza vaccine.

The Food and Drug Administration's Vaccines and Related Biological Products Advisory Committee recommended the changes based on shifts in viral activity, based on data culled from surveillance sites in Japan, England, Australia, and the United States.

The recommended vaccine changes correlate with the World Health Organization's suggested vaccine composition for the Northern Hemisphere for the 2006–2007 winter season.

The advisory panel recommended that the trivalent vaccine retain the influenza A(H1N1) strain—A/New Caledonia/20/99(H1N1)-like strain—due to evidence of continued resilience.

But the panel suggested replacing the A/California/7/2004(H3N2)-like virus with A/Wisconsin/67/2005(H3N2)-like virus. Also, the influenza B/Shanghai/361/2002-like virus should be replaced by the B/Malaysia/2506/2004-like virus.

According to Dr. Zhiping Ye, senior investigator of the division of viral products at the FDA's Center for Biologics Evaluation and Research, influenza A infections were inadequately covered by the 2005–2006 vaccine. It's estimated that in the pediatric population there was an overall 50% reduction in the hemagglutination inhibition (HI) reaction to the H3N2 component of the vaccine.

A similar reduction in coverage of the A/Wisconsin strain was noted in adult populations in Europe, Japan, and the United States.

“If we use Wisconsin as a vaccine, then we probably will get better coverage,” Dr. Ye said. “But this is only one piece of the puzzle.” Surveillance studies show that several other strains in the same lineage as A/Wisconsin also were inadequately covered by the current vaccine. However, there would likely be residual coverage of these strains by targeting the A/Wisconsin strain.

The current vaccine still appeared effective against the influenza A (H1N1) strain, A/New Caledonia/20/99(H1N1)-like virus, according to data from surveillance sites in North America, South America, Europe, Asia, Africa, and Australia.

Data from the United States and Europe showed that several strains were inadequately covered by the influenza B component of the current vaccine, and the B/Malaysia/2506/2004-like virus was one of them, Dr. Ye noted.

The vote on the 2006–2007 vaccine composition was unanimous, but the panel members had some reservations.

Although influenza A strains are responsible for most U.S. influenza cases, in recent years the selection of an influenza B strain has been more difficult to accurately pin down. “This winter the B/Victoria has been dominant in North America, but our vaccine was the B/Yamagata strain,” said panelist Dr. Robert B. Couch, professor of medicine, microbiology, and immunology at Baylor College of Medicine, Houston.

“We do the best we can to predict the likely epidemic virus, but for roughly the last 3 years, it's been a little too much of a guess with the influenza B. If it's going to continue this way, then we need to discuss how to address this problem,” Dr. Couch said in an interview.

Despite these misgivings, he voted in favor of the B/Malaysia strain, which is part of the B/Victoria/2/87 lineage. The B/Shanghai/361/2002-like virus in the current vaccine is a part of the B/Yamagata/16/88 lineage, which, despite last year's predictions, did not become the dominant virus for the 2005–2006 flu season.

In response to Dr. Couch's admonitions, the panel urged the FDA to convene a workshop to address future use of a quadrivalent vaccine with two influenza B components.

“There is less of an issue about a second B component this year than there has been in previous years. Last year we had a particularly difficult time in deciding on a B component, however, the issue … will continue to arise” and should be dealt with by the proposed workshop, said Dr. Ruth Karron, committee chair and professor of international health at the Johns Hopkins Bloomberg School of Public Health, Baltimore.

Albert Thomas, director of viral manufacturing at Sanofi-Pasteur, noted that in the interest of building an adequate supply, vaccine production at the France-based company had already begun with the influenza A (H1N1) strain A/New Caledonia/20/99(N1H1)-like virus prior to a formal recommendation by the WHO and the FDA. Distribution of Sanofi Pasteur's vaccine is scheduled for late August 2006.

BETHESDA, MD. — A federal advisory panel unanimously voted to change two of the three strains slated to compose the 2006–2007 influenza vaccine.

The Food and Drug Administration's Vaccines and Related Biological Products Advisory Committee recommended the changes based on shifts in viral activity, based on data culled from surveillance sites in Japan, England, Australia, and the United States.

The recommended vaccine changes correlate with the World Health Organization's suggested vaccine composition for the Northern Hemisphere for the 2006–2007 winter season.

The advisory panel recommended that the trivalent vaccine retain the influenza A(H1N1) strain—A/New Caledonia/20/99(H1N1)-like strain—due to evidence of continued resilience.

But the panel suggested replacing the A/California/7/2004(H3N2)-like virus with A/Wisconsin/67/2005(H3N2)-like virus. Also, the influenza B/Shanghai/361/2002-like virus should be replaced by the B/Malaysia/2506/2004-like virus.

According to Dr. Zhiping Ye, senior investigator of the division of viral products at the FDA's Center for Biologics Evaluation and Research, influenza A infections were inadequately covered by the 2005–2006 vaccine. It's estimated that in the pediatric population there was an overall 50% reduction in the hemagglutination inhibition (HI) reaction to the H3N2 component of the vaccine.

A similar reduction in coverage of the A/Wisconsin strain was noted in adult populations in Europe, Japan, and the United States.

“If we use Wisconsin as a vaccine, then we probably will get better coverage,” Dr. Ye said. “But this is only one piece of the puzzle.” Surveillance studies show that several other strains in the same lineage as A/Wisconsin also were inadequately covered by the current vaccine. However, there would likely be residual coverage of these strains by targeting the A/Wisconsin strain.

The current vaccine still appeared effective against the influenza A (H1N1) strain, A/New Caledonia/20/99(H1N1)-like virus, according to data from surveillance sites in North America, South America, Europe, Asia, Africa, and Australia.

Data from the United States and Europe showed that several strains were inadequately covered by the influenza B component of the current vaccine, and the B/Malaysia/2506/2004-like virus was one of them, Dr. Ye noted.

The vote on the 2006–2007 vaccine composition was unanimous, but the panel members had some reservations.

Although influenza A strains are responsible for most U.S. influenza cases, in recent years the selection of an influenza B strain has been more difficult to accurately pin down. “This winter the B/Victoria has been dominant in North America, but our vaccine was the B/Yamagata strain,” said panelist Dr. Robert B. Couch, professor of medicine, microbiology, and immunology at Baylor College of Medicine, Houston.

“We do the best we can to predict the likely epidemic virus, but for roughly the last 3 years, it's been a little too much of a guess with the influenza B. If it's going to continue this way, then we need to discuss how to address this problem,” Dr. Couch said in an interview.

Despite these misgivings, he voted in favor of the B/Malaysia strain, which is part of the B/Victoria/2/87 lineage. The B/Shanghai/361/2002-like virus in the current vaccine is a part of the B/Yamagata/16/88 lineage, which, despite last year's predictions, did not become the dominant virus for the 2005–2006 flu season.

In response to Dr. Couch's admonitions, the panel urged the FDA to convene a workshop to address future use of a quadrivalent vaccine with two influenza B components.

“There is less of an issue about a second B component this year than there has been in previous years. Last year we had a particularly difficult time in deciding on a B component, however, the issue … will continue to arise” and should be dealt with by the proposed workshop, said Dr. Ruth Karron, committee chair and professor of international health at the Johns Hopkins Bloomberg School of Public Health, Baltimore.

Albert Thomas, director of viral manufacturing at Sanofi-Pasteur, noted that in the interest of building an adequate supply, vaccine production at the France-based company had already begun with the influenza A (H1N1) strain A/New Caledonia/20/99(N1H1)-like virus prior to a formal recommendation by the WHO and the FDA. Distribution of Sanofi Pasteur's vaccine is scheduled for late August 2006.

BETHESDA, MD. — A federal advisory panel unanimously voted to change two of the three strains slated to compose the 2006–2007 influenza vaccine.

The Food and Drug Administration's Vaccines and Related Biological Products Advisory Committee recommended the changes based on shifts in viral activity, based on data culled from surveillance sites in Japan, England, Australia, and the United States.

The recommended vaccine changes correlate with the World Health Organization's suggested vaccine composition for the Northern Hemisphere for the 2006–2007 winter season.

The advisory panel recommended that the trivalent vaccine retain the influenza A(H1N1) strain—A/New Caledonia/20/99(H1N1)-like strain—due to evidence of continued resilience.

But the panel suggested replacing the A/California/7/2004(H3N2)-like virus with A/Wisconsin/67/2005(H3N2)-like virus. Also, the influenza B/Shanghai/361/2002-like virus should be replaced by the B/Malaysia/2506/2004-like virus.

According to Dr. Zhiping Ye, senior investigator of the division of viral products at the FDA's Center for Biologics Evaluation and Research, influenza A infections were inadequately covered by the 2005–2006 vaccine. It's estimated that in the pediatric population there was an overall 50% reduction in the hemagglutination inhibition (HI) reaction to the H3N2 component of the vaccine.

A similar reduction in coverage of the A/Wisconsin strain was noted in adult populations in Europe, Japan, and the United States.

“If we use Wisconsin as a vaccine, then we probably will get better coverage,” Dr. Ye said. “But this is only one piece of the puzzle.” Surveillance studies show that several other strains in the same lineage as A/Wisconsin also were inadequately covered by the current vaccine. However, there would likely be residual coverage of these strains by targeting the A/Wisconsin strain.

The current vaccine still appeared effective against the influenza A (H1N1) strain, A/New Caledonia/20/99(H1N1)-like virus, according to data from surveillance sites in North America, South America, Europe, Asia, Africa, and Australia.

Data from the United States and Europe showed that several strains were inadequately covered by the influenza B component of the current vaccine, and the B/Malaysia/2506/2004-like virus was one of them, Dr. Ye noted.

The vote on the 2006–2007 vaccine composition was unanimous, but the panel members had some reservations.

Although influenza A strains are responsible for most U.S. influenza cases, in recent years the selection of an influenza B strain has been more difficult to accurately pin down. “This winter the B/Victoria has been dominant in North America, but our vaccine was the B/Yamagata strain,” said panelist Dr. Robert B. Couch, professor of medicine, microbiology, and immunology at Baylor College of Medicine, Houston.

“We do the best we can to predict the likely epidemic virus, but for roughly the last 3 years, it's been a little too much of a guess with the influenza B. If it's going to continue this way, then we need to discuss how to address this problem,” Dr. Couch said in an interview.

Despite these misgivings, he voted in favor of the B/Malaysia strain, which is part of the B/Victoria/2/87 lineage. The B/Shanghai/361/2002-like virus in the current vaccine is a part of the B/Yamagata/16/88 lineage, which, despite last year's predictions, did not become the dominant virus for the 2005–2006 flu season.

In response to Dr. Couch's admonitions, the panel urged the FDA to convene a workshop to address future use of a quadrivalent vaccine with two influenza B components.

“There is less of an issue about a second B component this year than there has been in previous years. Last year we had a particularly difficult time in deciding on a B component, however, the issue … will continue to arise” and should be dealt with by the proposed workshop, said Dr. Ruth Karron, committee chair and professor of international health at the Johns Hopkins Bloomberg School of Public Health, Baltimore.

Albert Thomas, director of viral manufacturing at Sanofi-Pasteur, noted that in the interest of building an adequate supply, vaccine production at the France-based company had already begun with the influenza A (H1N1) strain A/New Caledonia/20/99(N1H1)-like virus prior to a formal recommendation by the WHO and the FDA. Distribution of Sanofi Pasteur's vaccine is scheduled for late August 2006.

WASHINGTON — The Centers for Medicare and Medicaid Services may issue a national coverage determination that would deny coverage of nesiritide (Natrecor) for the treatment of chronic heart failure in Medicare beneficiaries.

Nesiritide is indicated only for the intravenous treatment of acute decompensated heart failure (ADHF) in hospitalized patients with dyspnea at rest or with minimal activity, such as talking, eating, or bathing. The CMS proposal would change only one aspect of existing coverage of the drug, specifically its off-label use in patients with chronic heart failure.

“We're keeping it for the [Food and Drug Administration] approved [indication] and for all the other off-label uses. It's just this one thing that seems more risky than we thought,” said Don McLeod of the CMS press office. The agency will weigh public comments as well as other evidence before issuing a final determination.

According to Mark Wolfe, a spokesperson with Scios Inc.'s parent company, Johnson & Johnson, “The proposed national coverage determination is consistent with our own recommended use of Natrecor. Scios has ongoing studies involving Natrecor and will be keeping the [CMS] informed regarding this research.”

In an October letter sent to health care providers, Scios emphasized that nesiritide “is safe and effective” when used for its current indication. It rebutted recent reports that suggested nesiritide adversely affected renal function and short-term mortality more than other drugs for ADHF. “These reports have included inaccurate information and selective analysis of data previously included in the prescribing information,” stated the letter's author, Dr. Darlene Horton, senior vice president at Scios.

However, Dr. Jonathan Sackner-Bernstein, a prominent New York cardiologist and coauthor of several metaanalyses critical of nesiritide (N. Engl. J. Med. 2005;353:1525–7, JAMA 2005;293:1900–5) is unflinching in his contention that nesiritide “should be withdrawn from the market.”

“No analysis by anyone in any context can be used to support the statement that nesiritide is shown to be safe. Therefore, according to the law, it should not be legal to sell it,” Dr. Sackner-Bernstein said.

Many of his colleagues remain unconvinced that nesiritide should be withdrawn or that CMs' current action portends the drug's future withdrawal. “The FDA approval was for the treatment of decompensated heart failure in hospitalized patients, although the word 'hospitalized' wasn't used, that was implied … and it was indicated for symptomatic relief. I support its use for that indication,” said Dr. Wilson Colucci, chief of cardiovascular medicine at Boston Medical Center and Boston University. Further, he agreed with CMS that there is not a sufficient amount of data to support the use of nesiritide as a treatment for chronic heart failure.

However, Dr. Colucci disagreed with Dr. Sackner-Bernstein when it came to removing nesiritide from the market, “at least based on the current data.”

“With regard to renal function, there has been a lack of substantial benefit, but relatively very little effect one way or the other when one looks at the totality of the renal effect. That's not the indication, and that's not the reason to give the drug,” said Dr. Colucci.

He went on to say that Dr. Sackner-Bernstein's metaanalysis fell short of establishing any kind of risk with the drug.

Dr. Colucci disclosed that he was an investigator involved in the studies that led to nesiritide's FDA approval for treatment of ADHF.

WASHINGTON — The Centers for Medicare and Medicaid Services may issue a national coverage determination that would deny coverage of nesiritide (Natrecor) for the treatment of chronic heart failure in Medicare beneficiaries.

Nesiritide is indicated only for the intravenous treatment of acute decompensated heart failure (ADHF) in hospitalized patients with dyspnea at rest or with minimal activity, such as talking, eating, or bathing. The CMS proposal would change only one aspect of existing coverage of the drug, specifically its off-label use in patients with chronic heart failure.

“We're keeping it for the [Food and Drug Administration] approved [indication] and for all the other off-label uses. It's just this one thing that seems more risky than we thought,” said Don McLeod of the CMS press office. The agency will weigh public comments as well as other evidence before issuing a final determination.

According to Mark Wolfe, a spokesperson with Scios Inc.'s parent company, Johnson & Johnson, “The proposed national coverage determination is consistent with our own recommended use of Natrecor. Scios has ongoing studies involving Natrecor and will be keeping the [CMS] informed regarding this research.”

In an October letter sent to health care providers, Scios emphasized that nesiritide “is safe and effective” when used for its current indication. It rebutted recent reports that suggested nesiritide adversely affected renal function and short-term mortality more than other drugs for ADHF. “These reports have included inaccurate information and selective analysis of data previously included in the prescribing information,” stated the letter's author, Dr. Darlene Horton, senior vice president at Scios.

However, Dr. Jonathan Sackner-Bernstein, a prominent New York cardiologist and coauthor of several metaanalyses critical of nesiritide (N. Engl. J. Med. 2005;353:1525–7, JAMA 2005;293:1900–5) is unflinching in his contention that nesiritide “should be withdrawn from the market.”

“No analysis by anyone in any context can be used to support the statement that nesiritide is shown to be safe. Therefore, according to the law, it should not be legal to sell it,” Dr. Sackner-Bernstein said.

Many of his colleagues remain unconvinced that nesiritide should be withdrawn or that CMs' current action portends the drug's future withdrawal. “The FDA approval was for the treatment of decompensated heart failure in hospitalized patients, although the word 'hospitalized' wasn't used, that was implied … and it was indicated for symptomatic relief. I support its use for that indication,” said Dr. Wilson Colucci, chief of cardiovascular medicine at Boston Medical Center and Boston University. Further, he agreed with CMS that there is not a sufficient amount of data to support the use of nesiritide as a treatment for chronic heart failure.

However, Dr. Colucci disagreed with Dr. Sackner-Bernstein when it came to removing nesiritide from the market, “at least based on the current data.”

“With regard to renal function, there has been a lack of substantial benefit, but relatively very little effect one way or the other when one looks at the totality of the renal effect. That's not the indication, and that's not the reason to give the drug,” said Dr. Colucci.

He went on to say that Dr. Sackner-Bernstein's metaanalysis fell short of establishing any kind of risk with the drug.

Dr. Colucci disclosed that he was an investigator involved in the studies that led to nesiritide's FDA approval for treatment of ADHF.

WASHINGTON — The Centers for Medicare and Medicaid Services may issue a national coverage determination that would deny coverage of nesiritide (Natrecor) for the treatment of chronic heart failure in Medicare beneficiaries.

Nesiritide is indicated only for the intravenous treatment of acute decompensated heart failure (ADHF) in hospitalized patients with dyspnea at rest or with minimal activity, such as talking, eating, or bathing. The CMS proposal would change only one aspect of existing coverage of the drug, specifically its off-label use in patients with chronic heart failure.

“We're keeping it for the [Food and Drug Administration] approved [indication] and for all the other off-label uses. It's just this one thing that seems more risky than we thought,” said Don McLeod of the CMS press office. The agency will weigh public comments as well as other evidence before issuing a final determination.

According to Mark Wolfe, a spokesperson with Scios Inc.'s parent company, Johnson & Johnson, “The proposed national coverage determination is consistent with our own recommended use of Natrecor. Scios has ongoing studies involving Natrecor and will be keeping the [CMS] informed regarding this research.”

In an October letter sent to health care providers, Scios emphasized that nesiritide “is safe and effective” when used for its current indication. It rebutted recent reports that suggested nesiritide adversely affected renal function and short-term mortality more than other drugs for ADHF. “These reports have included inaccurate information and selective analysis of data previously included in the prescribing information,” stated the letter's author, Dr. Darlene Horton, senior vice president at Scios.

However, Dr. Jonathan Sackner-Bernstein, a prominent New York cardiologist and coauthor of several metaanalyses critical of nesiritide (N. Engl. J. Med. 2005;353:1525–7, JAMA 2005;293:1900–5) is unflinching in his contention that nesiritide “should be withdrawn from the market.”

“No analysis by anyone in any context can be used to support the statement that nesiritide is shown to be safe. Therefore, according to the law, it should not be legal to sell it,” Dr. Sackner-Bernstein said.

Many of his colleagues remain unconvinced that nesiritide should be withdrawn or that CMs' current action portends the drug's future withdrawal. “The FDA approval was for the treatment of decompensated heart failure in hospitalized patients, although the word 'hospitalized' wasn't used, that was implied … and it was indicated for symptomatic relief. I support its use for that indication,” said Dr. Wilson Colucci, chief of cardiovascular medicine at Boston Medical Center and Boston University. Further, he agreed with CMS that there is not a sufficient amount of data to support the use of nesiritide as a treatment for chronic heart failure.

However, Dr. Colucci disagreed with Dr. Sackner-Bernstein when it came to removing nesiritide from the market, “at least based on the current data.”

“With regard to renal function, there has been a lack of substantial benefit, but relatively very little effect one way or the other when one looks at the totality of the renal effect. That's not the indication, and that's not the reason to give the drug,” said Dr. Colucci.

He went on to say that Dr. Sackner-Bernstein's metaanalysis fell short of establishing any kind of risk with the drug.

Dr. Colucci disclosed that he was an investigator involved in the studies that led to nesiritide's FDA approval for treatment of ADHF.

The Food and Drug Administration's MedWatch program has announced a voluntary recall of one lot of Methotrexate for Injection (preservative free) due to the presence of low levels of ethylene glycol.

Bedford Laboratories, a division of Ben Venue Laboratories Inc., last month announced a recall of Methotrexate for Injection (preservative free), USP 1 gram per vial (NDC 55390–143–01), Lot &num;859142, exp. 09/07. The company was informed by the manufacturer that the active drug substance used to create this lot contained low levels of ethylene glycol, a solvent used in antifreeze among other products.<[par]>

Methotrexate is an antimetabolite used in the treatment of adult rheumatoid arthritis, severe psoriasis, and certain neoplastic diseases.

Methotrexate for Injection was distributed to wholesalers and hospitals throughout the United States in October and November 2005.

Bedford Laboratories instructed customers to discontinue distribution and use of this lot, and to call the company at 800-562-4797 with any questions.

The Food and Drug Administration's MedWatch program has announced a voluntary recall of one lot of Methotrexate for Injection (preservative free) due to the presence of low levels of ethylene glycol.

Bedford Laboratories, a division of Ben Venue Laboratories Inc., last month announced a recall of Methotrexate for Injection (preservative free), USP 1 gram per vial (NDC 55390–143–01), Lot &num;859142, exp. 09/07. The company was informed by the manufacturer that the active drug substance used to create this lot contained low levels of ethylene glycol, a solvent used in antifreeze among other products.<[par]>

Methotrexate is an antimetabolite used in the treatment of adult rheumatoid arthritis, severe psoriasis, and certain neoplastic diseases.

Methotrexate for Injection was distributed to wholesalers and hospitals throughout the United States in October and November 2005.

Bedford Laboratories instructed customers to discontinue distribution and use of this lot, and to call the company at 800-562-4797 with any questions.

The Food and Drug Administration's MedWatch program has announced a voluntary recall of one lot of Methotrexate for Injection (preservative free) due to the presence of low levels of ethylene glycol.

Bedford Laboratories, a division of Ben Venue Laboratories Inc., last month announced a recall of Methotrexate for Injection (preservative free), USP 1 gram per vial (NDC 55390–143–01), Lot &num;859142, exp. 09/07. The company was informed by the manufacturer that the active drug substance used to create this lot contained low levels of ethylene glycol, a solvent used in antifreeze among other products.<[par]>

Methotrexate is an antimetabolite used in the treatment of adult rheumatoid arthritis, severe psoriasis, and certain neoplastic diseases.

Methotrexate for Injection was distributed to wholesalers and hospitals throughout the United States in October and November 2005.

Bedford Laboratories instructed customers to discontinue distribution and use of this lot, and to call the company at 800-562-4797 with any questions.

People with symptoms of pathological gambling and kleptomania, regardless of severity, seem to have a very poor quality of life, reported Jon Grant, M.D., of Brown University, Providence, R.I., and Suck-Won Kim, M.D., of the University of Minnesota, Minneapolis.

Their study comprised three groups. A group of 30 kleptomania patients included 18 women and had a mean age of 42 years. The pathological gambling group had 43 patients, 18 of them women, with a mean age of 45 years. The control group consisted of 30 adults (15 women) with a mean age of 40 (Compr. Psychiatry 2005;46:34–7).

No correlation was seen between quality of life scores and age, gender, marital status, and current comorbidity. Kleptomania and gambling patients scored significantly lower on the Quality of Life Inventory, compared with controls. No kleptomania patients and only one gambling patient reported a high quality of life, and a very low quality of life was reported by 43% of kleptomania subjects. No correlation was seen between symptom severity and quality of life scores.

Kleptomania patients may have had such low scores because they struggle with the symptoms of their illness as well as with legal and moral repercussions. The researchers said that prior poor quality of life might have raised the risk of developing kleptomania and pathological gambling. Study participants saw the behaviors as causing their dissatisfaction and believed quality of life would improve if their disorders were better controlled.

People with symptoms of pathological gambling and kleptomania, regardless of severity, seem to have a very poor quality of life, reported Jon Grant, M.D., of Brown University, Providence, R.I., and Suck-Won Kim, M.D., of the University of Minnesota, Minneapolis.

Their study comprised three groups. A group of 30 kleptomania patients included 18 women and had a mean age of 42 years. The pathological gambling group had 43 patients, 18 of them women, with a mean age of 45 years. The control group consisted of 30 adults (15 women) with a mean age of 40 (Compr. Psychiatry 2005;46:34–7).

No correlation was seen between quality of life scores and age, gender, marital status, and current comorbidity. Kleptomania and gambling patients scored significantly lower on the Quality of Life Inventory, compared with controls. No kleptomania patients and only one gambling patient reported a high quality of life, and a very low quality of life was reported by 43% of kleptomania subjects. No correlation was seen between symptom severity and quality of life scores.

Kleptomania patients may have had such low scores because they struggle with the symptoms of their illness as well as with legal and moral repercussions. The researchers said that prior poor quality of life might have raised the risk of developing kleptomania and pathological gambling. Study participants saw the behaviors as causing their dissatisfaction and believed quality of life would improve if their disorders were better controlled.

People with symptoms of pathological gambling and kleptomania, regardless of severity, seem to have a very poor quality of life, reported Jon Grant, M.D., of Brown University, Providence, R.I., and Suck-Won Kim, M.D., of the University of Minnesota, Minneapolis.

Their study comprised three groups. A group of 30 kleptomania patients included 18 women and had a mean age of 42 years. The pathological gambling group had 43 patients, 18 of them women, with a mean age of 45 years. The control group consisted of 30 adults (15 women) with a mean age of 40 (Compr. Psychiatry 2005;46:34–7).

No correlation was seen between quality of life scores and age, gender, marital status, and current comorbidity. Kleptomania and gambling patients scored significantly lower on the Quality of Life Inventory, compared with controls. No kleptomania patients and only one gambling patient reported a high quality of life, and a very low quality of life was reported by 43% of kleptomania subjects. No correlation was seen between symptom severity and quality of life scores.

Kleptomania patients may have had such low scores because they struggle with the symptoms of their illness as well as with legal and moral repercussions. The researchers said that prior poor quality of life might have raised the risk of developing kleptomania and pathological gambling. Study participants saw the behaviors as causing their dissatisfaction and believed quality of life would improve if their disorders were better controlled.

Patients on methadone maintenance often have chronic pain, and those with more intense pain receive higher doses of methadone, said Einat Peles, Ph.D., and colleagues at Tel-Aviv Elias Sourasky Medical Center.

The researchers nonselectively enrolled 170 consecutive drug-abuse patients and found that 94 (55%) had experienced chronic pain (J. Pain 2005;113:340–6).

The mean duration of methadone maintenance treatment (MMT) was equivalent for the chronic pain and non-chronic pain groups. The patients completed a cross-sectional survey on chronic pain, and all met addiction criteria similar to the DSM-IV criteria for dependence on multiadministrations of heroin for at least 1 year.

Dr. Peles and her colleagues defined chronic pain as lasting 6 months or longer, and chronic severe pain was defined as pain of moderate to very severe intensity. Urine samples taken 1 month before the study and during the first month of treatment were analyzed for cocaine metabolites, opiates, benzodiazepines, cannabis, amphetamines, and methadone, and “the threshold for positive urine for benzodiazepines was higher than the therapeutic range,” they said.

There was no significant difference between the two groups in terms of Axes I and II: Axis I disorders were seen in 54% of chronic pain patients and 47% of non-chronic pain patients, while Axis II disorders were seen in 72% and 71%, respectively.

Pain was present before admission in 63.8% of the patients, and after MMT in 36.2%. However, duration of MMT was not related to pain duration or severity.

MMT dose was associated with pain severity and pain duration. The mean methadone dose was 147.1 mg/day for the 76 non-chronic pain patients, 134.6 mg/day for 12 patients with mild chronic pain, 159.8 mg/day for 38 patients with moderately severe pain, 175.5 mg/day for the 22 patients with severe pain, and 176.7 mg/day for the 22 patients with very severe pain.

The 26 patients with chronic pain for over 10 years got the highest methadone doses (182.1 mg/day). The 59 patients with pain for 1–10 years received 160.9 mg/day; doses of 134.2 mg/day went to patients with pain of less than 1 year. The researchers noted, however, “that methadone treatment was not initiated or directed toward pain relief.”

According to Dr. Peles and her associates, “it is probable that such high dosages of methadone may also be beneficial for pain, regardless of the primary indication for the treatment and the regimen of administration, which differed from that indicated for pain (i.e., once daily and not every few hours).”

Some MMT patients were given take-home dosages for the week, and against clinic directions, may have split their high doses, which might have reduced pain, the researchers speculated. Patients may also have misinterpreted pain as a withdrawal symptom, which may have led to requests for increased doses. Patients taking higher doses also may have built up a tolerance to the methadone.

Current positive urine test for benzodiazepines, and positive antibody to hepatitis C, correlated with significantly higher methadone doses. Benzodiazepine abuse may start as a form of self-medication to relieve pain, but the investigators suggested that it might also be that abuse of these drugs is a cause of “repeated rather than chronic pain.”

“We cannot conclude from these analyses whether or not pain was a cause or a consequence of the drug abuse,” said Dr. Peles and her associates.

Patients on methadone maintenance often have chronic pain, and those with more intense pain receive higher doses of methadone, said Einat Peles, Ph.D., and colleagues at Tel-Aviv Elias Sourasky Medical Center.

The researchers nonselectively enrolled 170 consecutive drug-abuse patients and found that 94 (55%) had experienced chronic pain (J. Pain 2005;113:340–6).

The mean duration of methadone maintenance treatment (MMT) was equivalent for the chronic pain and non-chronic pain groups. The patients completed a cross-sectional survey on chronic pain, and all met addiction criteria similar to the DSM-IV criteria for dependence on multiadministrations of heroin for at least 1 year.

Dr. Peles and her colleagues defined chronic pain as lasting 6 months or longer, and chronic severe pain was defined as pain of moderate to very severe intensity. Urine samples taken 1 month before the study and during the first month of treatment were analyzed for cocaine metabolites, opiates, benzodiazepines, cannabis, amphetamines, and methadone, and “the threshold for positive urine for benzodiazepines was higher than the therapeutic range,” they said.

There was no significant difference between the two groups in terms of Axes I and II: Axis I disorders were seen in 54% of chronic pain patients and 47% of non-chronic pain patients, while Axis II disorders were seen in 72% and 71%, respectively.

Pain was present before admission in 63.8% of the patients, and after MMT in 36.2%. However, duration of MMT was not related to pain duration or severity.

MMT dose was associated with pain severity and pain duration. The mean methadone dose was 147.1 mg/day for the 76 non-chronic pain patients, 134.6 mg/day for 12 patients with mild chronic pain, 159.8 mg/day for 38 patients with moderately severe pain, 175.5 mg/day for the 22 patients with severe pain, and 176.7 mg/day for the 22 patients with very severe pain.

The 26 patients with chronic pain for over 10 years got the highest methadone doses (182.1 mg/day). The 59 patients with pain for 1–10 years received 160.9 mg/day; doses of 134.2 mg/day went to patients with pain of less than 1 year. The researchers noted, however, “that methadone treatment was not initiated or directed toward pain relief.”

According to Dr. Peles and her associates, “it is probable that such high dosages of methadone may also be beneficial for pain, regardless of the primary indication for the treatment and the regimen of administration, which differed from that indicated for pain (i.e., once daily and not every few hours).”

Some MMT patients were given take-home dosages for the week, and against clinic directions, may have split their high doses, which might have reduced pain, the researchers speculated. Patients may also have misinterpreted pain as a withdrawal symptom, which may have led to requests for increased doses. Patients taking higher doses also may have built up a tolerance to the methadone.

Current positive urine test for benzodiazepines, and positive antibody to hepatitis C, correlated with significantly higher methadone doses. Benzodiazepine abuse may start as a form of self-medication to relieve pain, but the investigators suggested that it might also be that abuse of these drugs is a cause of “repeated rather than chronic pain.”

“We cannot conclude from these analyses whether or not pain was a cause or a consequence of the drug abuse,” said Dr. Peles and her associates.

Patients on methadone maintenance often have chronic pain, and those with more intense pain receive higher doses of methadone, said Einat Peles, Ph.D., and colleagues at Tel-Aviv Elias Sourasky Medical Center.

The researchers nonselectively enrolled 170 consecutive drug-abuse patients and found that 94 (55%) had experienced chronic pain (J. Pain 2005;113:340–6).

The mean duration of methadone maintenance treatment (MMT) was equivalent for the chronic pain and non-chronic pain groups. The patients completed a cross-sectional survey on chronic pain, and all met addiction criteria similar to the DSM-IV criteria for dependence on multiadministrations of heroin for at least 1 year.

Dr. Peles and her colleagues defined chronic pain as lasting 6 months or longer, and chronic severe pain was defined as pain of moderate to very severe intensity. Urine samples taken 1 month before the study and during the first month of treatment were analyzed for cocaine metabolites, opiates, benzodiazepines, cannabis, amphetamines, and methadone, and “the threshold for positive urine for benzodiazepines was higher than the therapeutic range,” they said.

There was no significant difference between the two groups in terms of Axes I and II: Axis I disorders were seen in 54% of chronic pain patients and 47% of non-chronic pain patients, while Axis II disorders were seen in 72% and 71%, respectively.

Pain was present before admission in 63.8% of the patients, and after MMT in 36.2%. However, duration of MMT was not related to pain duration or severity.

MMT dose was associated with pain severity and pain duration. The mean methadone dose was 147.1 mg/day for the 76 non-chronic pain patients, 134.6 mg/day for 12 patients with mild chronic pain, 159.8 mg/day for 38 patients with moderately severe pain, 175.5 mg/day for the 22 patients with severe pain, and 176.7 mg/day for the 22 patients with very severe pain.

The 26 patients with chronic pain for over 10 years got the highest methadone doses (182.1 mg/day). The 59 patients with pain for 1–10 years received 160.9 mg/day; doses of 134.2 mg/day went to patients with pain of less than 1 year. The researchers noted, however, “that methadone treatment was not initiated or directed toward pain relief.”

According to Dr. Peles and her associates, “it is probable that such high dosages of methadone may also be beneficial for pain, regardless of the primary indication for the treatment and the regimen of administration, which differed from that indicated for pain (i.e., once daily and not every few hours).”

Some MMT patients were given take-home dosages for the week, and against clinic directions, may have split their high doses, which might have reduced pain, the researchers speculated. Patients may also have misinterpreted pain as a withdrawal symptom, which may have led to requests for increased doses. Patients taking higher doses also may have built up a tolerance to the methadone.

Current positive urine test for benzodiazepines, and positive antibody to hepatitis C, correlated with significantly higher methadone doses. Benzodiazepine abuse may start as a form of self-medication to relieve pain, but the investigators suggested that it might also be that abuse of these drugs is a cause of “repeated rather than chronic pain.”

“We cannot conclude from these analyses whether or not pain was a cause or a consequence of the drug abuse,” said Dr. Peles and her associates.