Mary Ann Moon

A high plasma folate level around the time of conception raises the chance of twinning after in vitro fertilization, but not the chance of having a successful pregnancy, reported Paul Haggarty, Ph.D., of the Rowett Research Institute, Aberdeen, Scotland, and his associates.

“Our results suggest that the high incidence of twin births associated with treatment for infertility could be reduced, while maintaining [live birth] rates, by encouraging women not to exceed recommended doses of folic acid and by identifying those at high risk of twins after double-embryo transfer on the basis of their plasma folate concentrations and age,” they wrote (Lancet 2006;367:1513–9).

“The need to increase the intake of folic acid to reduce the incidence of neural tube defects is not in doubt, but the associated risks of multiple births after IVF need to be addressed,” they noted.

High folate levels have been associated with an increase in natural twinning, and “there are good biological reasons to suspect that B-vitamin exposure” also affects twinning in IVF pregnancies. Dr. Haggarty and his associates assessed vitamin B intake, plasma and red cell levels of folate, and six variants in genes known to be involved with B-vitamin metabolism in 602 women undergoing IVF. For comparison, they also performed the same genetic analysis in 932 women who had conceived naturally and had singleton pregnancies.

Folate and vitamin B intake correlated with plasma and red-cell levels of folate. Neither one was associated with the rate of live births or the rate of pregnancy loss after IVF. However, both were associated with an increased rate of twinning in the IVF group.

Younger maternal age also was associated with an increased rate of twinning.

Women in the United Kingdom who are trying to conceive either naturally or through IVF are advised to take 400 mcg of supplementary folic acid daily before and after conception, to reduce the risk of neural tube defects. But flour and other foods are not fortified with folate in the United Kingdom as they are in the United States. If they were, the average daily intake of folate would increase another 200 mcg in the United Kingdom, which would translate into an additional 600 IVF twin births there every year, the researchers said.

This is consistent with the 11%–13% increase in the rate of multiple births after IVF that was observed in the United States when folic acid fortification was mandated by the Food and Drug Administration in 1998, Dr. Haggarty and his associates added.

In an editorial comment accompanying this report, Dr. Gary Steinman of the department of ob.gyn. at Albert Einstein College of Medicine, New York, said that the mechanism underlying this association between folate and twinning still remains to be explained.

It may involve serum levels of insulinlike growth factor (IGF). Cows that have been crossbred to enhance their spontaneous twinning rate show twice the average serum levels of IGF, and human vegans—whose IGF levels typically are 13% lower than those in the general population—have a twinning rate that is comparably lower than the rate in vegetarians and omnivores, he said (Lancet 2006;367:1461–2).

Studies in ethnic populations also support an association between diet, serum IGF level, and twinning. The Yoruba women living in rural Nigeria have an unusually high twinning rate that is attributed to their high consumption of yams, which significantly raises their serum IGF levels. When they move to the city and change their diets, their IGF levels drop significantly, as does their twinning rate. Similarly, Japanese women have one of the lowest twinning rates of any ethnic group, but when they relocate to the United States and change their diets, their serum IGF rises dramatically and their twinning rate doubles, Dr. Steinman noted.

A high plasma folate level around the time of conception raises the chance of twinning after in vitro fertilization, but not the chance of having a successful pregnancy, reported Paul Haggarty, Ph.D., of the Rowett Research Institute, Aberdeen, Scotland, and his associates.

“Our results suggest that the high incidence of twin births associated with treatment for infertility could be reduced, while maintaining [live birth] rates, by encouraging women not to exceed recommended doses of folic acid and by identifying those at high risk of twins after double-embryo transfer on the basis of their plasma folate concentrations and age,” they wrote (Lancet 2006;367:1513–9).

“The need to increase the intake of folic acid to reduce the incidence of neural tube defects is not in doubt, but the associated risks of multiple births after IVF need to be addressed,” they noted.

High folate levels have been associated with an increase in natural twinning, and “there are good biological reasons to suspect that B-vitamin exposure” also affects twinning in IVF pregnancies. Dr. Haggarty and his associates assessed vitamin B intake, plasma and red cell levels of folate, and six variants in genes known to be involved with B-vitamin metabolism in 602 women undergoing IVF. For comparison, they also performed the same genetic analysis in 932 women who had conceived naturally and had singleton pregnancies.

Folate and vitamin B intake correlated with plasma and red-cell levels of folate. Neither one was associated with the rate of live births or the rate of pregnancy loss after IVF. However, both were associated with an increased rate of twinning in the IVF group.

Younger maternal age also was associated with an increased rate of twinning.

Women in the United Kingdom who are trying to conceive either naturally or through IVF are advised to take 400 mcg of supplementary folic acid daily before and after conception, to reduce the risk of neural tube defects. But flour and other foods are not fortified with folate in the United Kingdom as they are in the United States. If they were, the average daily intake of folate would increase another 200 mcg in the United Kingdom, which would translate into an additional 600 IVF twin births there every year, the researchers said.

This is consistent with the 11%–13% increase in the rate of multiple births after IVF that was observed in the United States when folic acid fortification was mandated by the Food and Drug Administration in 1998, Dr. Haggarty and his associates added.

In an editorial comment accompanying this report, Dr. Gary Steinman of the department of ob.gyn. at Albert Einstein College of Medicine, New York, said that the mechanism underlying this association between folate and twinning still remains to be explained.

It may involve serum levels of insulinlike growth factor (IGF). Cows that have been crossbred to enhance their spontaneous twinning rate show twice the average serum levels of IGF, and human vegans—whose IGF levels typically are 13% lower than those in the general population—have a twinning rate that is comparably lower than the rate in vegetarians and omnivores, he said (Lancet 2006;367:1461–2).

Studies in ethnic populations also support an association between diet, serum IGF level, and twinning. The Yoruba women living in rural Nigeria have an unusually high twinning rate that is attributed to their high consumption of yams, which significantly raises their serum IGF levels. When they move to the city and change their diets, their IGF levels drop significantly, as does their twinning rate. Similarly, Japanese women have one of the lowest twinning rates of any ethnic group, but when they relocate to the United States and change their diets, their serum IGF rises dramatically and their twinning rate doubles, Dr. Steinman noted.

A high plasma folate level around the time of conception raises the chance of twinning after in vitro fertilization, but not the chance of having a successful pregnancy, reported Paul Haggarty, Ph.D., of the Rowett Research Institute, Aberdeen, Scotland, and his associates.

“Our results suggest that the high incidence of twin births associated with treatment for infertility could be reduced, while maintaining [live birth] rates, by encouraging women not to exceed recommended doses of folic acid and by identifying those at high risk of twins after double-embryo transfer on the basis of their plasma folate concentrations and age,” they wrote (Lancet 2006;367:1513–9).

“The need to increase the intake of folic acid to reduce the incidence of neural tube defects is not in doubt, but the associated risks of multiple births after IVF need to be addressed,” they noted.

High folate levels have been associated with an increase in natural twinning, and “there are good biological reasons to suspect that B-vitamin exposure” also affects twinning in IVF pregnancies. Dr. Haggarty and his associates assessed vitamin B intake, plasma and red cell levels of folate, and six variants in genes known to be involved with B-vitamin metabolism in 602 women undergoing IVF. For comparison, they also performed the same genetic analysis in 932 women who had conceived naturally and had singleton pregnancies.

Folate and vitamin B intake correlated with plasma and red-cell levels of folate. Neither one was associated with the rate of live births or the rate of pregnancy loss after IVF. However, both were associated with an increased rate of twinning in the IVF group.

Younger maternal age also was associated with an increased rate of twinning.

Women in the United Kingdom who are trying to conceive either naturally or through IVF are advised to take 400 mcg of supplementary folic acid daily before and after conception, to reduce the risk of neural tube defects. But flour and other foods are not fortified with folate in the United Kingdom as they are in the United States. If they were, the average daily intake of folate would increase another 200 mcg in the United Kingdom, which would translate into an additional 600 IVF twin births there every year, the researchers said.

This is consistent with the 11%–13% increase in the rate of multiple births after IVF that was observed in the United States when folic acid fortification was mandated by the Food and Drug Administration in 1998, Dr. Haggarty and his associates added.

In an editorial comment accompanying this report, Dr. Gary Steinman of the department of ob.gyn. at Albert Einstein College of Medicine, New York, said that the mechanism underlying this association between folate and twinning still remains to be explained.

It may involve serum levels of insulinlike growth factor (IGF). Cows that have been crossbred to enhance their spontaneous twinning rate show twice the average serum levels of IGF, and human vegans—whose IGF levels typically are 13% lower than those in the general population—have a twinning rate that is comparably lower than the rate in vegetarians and omnivores, he said (Lancet 2006;367:1461–2).

Studies in ethnic populations also support an association between diet, serum IGF level, and twinning. The Yoruba women living in rural Nigeria have an unusually high twinning rate that is attributed to their high consumption of yams, which significantly raises their serum IGF levels. When they move to the city and change their diets, their IGF levels drop significantly, as does their twinning rate. Similarly, Japanese women have one of the lowest twinning rates of any ethnic group, but when they relocate to the United States and change their diets, their serum IGF rises dramatically and their twinning rate doubles, Dr. Steinman noted.

Etanercept, a tumor necrosis factor-α antagonist usually used to treat inflammatory arthritis, decreased C-reactive protein levels and improved other inflammatory markers in patients with metabolic syndrome, reported Dr. L. Elizabeth Bernstein and her associates at Massachusetts General Hospital and Harvard Medical School, Boston.

Etanercept interferes with tumor necrosis factor-α's ability to bind with cell receptors, blocking the inflammatory response. The investigators examined the drug's effects on C-reactive protein (CRP) and other inflammatory markers associated with cardiovascular disease in 52 men and women with metabolic syndrome.

These subjects (mean age 46 years) had either hyperinsulinemia or impaired glucose tolerance; an elevated body mass index or a high waist-hip ratio; elevated serum triglycerides or low HDL cholesterol levels; and hypertension. All the subjects had elevated CRP levels at baseline, which was likely linked to an obesity-associated activation of the tumor necrosis factor system, since none had any other known inflammatory condition.

Half the subjects were randomly assigned to receive etanercept in two 25-mg subcutaneous injections weekly for 4 weeks, and the other half received placebo injections.

Etanercept reduced CRP levels by more than 2 mg/L, a 34% reduction within 4 weeks. Weight, nutritional status, and body composition remained unchanged, indicating that the drug acted independently of these factors to improve CRP, the researchers said (Arch. Intern. Med. 2006;166:902–8). At the same time, adiponectin levels rose significantly. Adiponectin, an adipocyte-derived cytokine that has anti-inflammatory and antiatherosclerotic properties, is decreased in obese people. Etanercept also decreased the subjects' markedly high levels of fibrinogen, a clotting factor and marker of inflammation and abnormal hemostasis. The drug also tended to reduce levels of interleukin-6 levels, another indicator of inflammation. It did not affect insulin sensitivity.

Etanercept was well tolerated in these subjects. However, they had been well screened before enrollment for contraindications to the drug, known to impair immune function in some patients. “Further studies with longer duration will be necessary to determine the safety” of etanercept in people with metabolic syndrome, the investigators noted.

The findings “suggest a novel and physiologically relevant approach to improve the increased inflammatory milieu associated with abdominal obesity” and metabolic syndrome. But additional studies are needed to investigate such a hypothesis.

Etanercept, a tumor necrosis factor-α antagonist usually used to treat inflammatory arthritis, decreased C-reactive protein levels and improved other inflammatory markers in patients with metabolic syndrome, reported Dr. L. Elizabeth Bernstein and her associates at Massachusetts General Hospital and Harvard Medical School, Boston.

Etanercept interferes with tumor necrosis factor-α's ability to bind with cell receptors, blocking the inflammatory response. The investigators examined the drug's effects on C-reactive protein (CRP) and other inflammatory markers associated with cardiovascular disease in 52 men and women with metabolic syndrome.

These subjects (mean age 46 years) had either hyperinsulinemia or impaired glucose tolerance; an elevated body mass index or a high waist-hip ratio; elevated serum triglycerides or low HDL cholesterol levels; and hypertension. All the subjects had elevated CRP levels at baseline, which was likely linked to an obesity-associated activation of the tumor necrosis factor system, since none had any other known inflammatory condition.

Half the subjects were randomly assigned to receive etanercept in two 25-mg subcutaneous injections weekly for 4 weeks, and the other half received placebo injections.

Etanercept reduced CRP levels by more than 2 mg/L, a 34% reduction within 4 weeks. Weight, nutritional status, and body composition remained unchanged, indicating that the drug acted independently of these factors to improve CRP, the researchers said (Arch. Intern. Med. 2006;166:902–8). At the same time, adiponectin levels rose significantly. Adiponectin, an adipocyte-derived cytokine that has anti-inflammatory and antiatherosclerotic properties, is decreased in obese people. Etanercept also decreased the subjects' markedly high levels of fibrinogen, a clotting factor and marker of inflammation and abnormal hemostasis. The drug also tended to reduce levels of interleukin-6 levels, another indicator of inflammation. It did not affect insulin sensitivity.

Etanercept was well tolerated in these subjects. However, they had been well screened before enrollment for contraindications to the drug, known to impair immune function in some patients. “Further studies with longer duration will be necessary to determine the safety” of etanercept in people with metabolic syndrome, the investigators noted.

The findings “suggest a novel and physiologically relevant approach to improve the increased inflammatory milieu associated with abdominal obesity” and metabolic syndrome. But additional studies are needed to investigate such a hypothesis.

Etanercept, a tumor necrosis factor-α antagonist usually used to treat inflammatory arthritis, decreased C-reactive protein levels and improved other inflammatory markers in patients with metabolic syndrome, reported Dr. L. Elizabeth Bernstein and her associates at Massachusetts General Hospital and Harvard Medical School, Boston.

Etanercept interferes with tumor necrosis factor-α's ability to bind with cell receptors, blocking the inflammatory response. The investigators examined the drug's effects on C-reactive protein (CRP) and other inflammatory markers associated with cardiovascular disease in 52 men and women with metabolic syndrome.

These subjects (mean age 46 years) had either hyperinsulinemia or impaired glucose tolerance; an elevated body mass index or a high waist-hip ratio; elevated serum triglycerides or low HDL cholesterol levels; and hypertension. All the subjects had elevated CRP levels at baseline, which was likely linked to an obesity-associated activation of the tumor necrosis factor system, since none had any other known inflammatory condition.

Half the subjects were randomly assigned to receive etanercept in two 25-mg subcutaneous injections weekly for 4 weeks, and the other half received placebo injections.

Etanercept reduced CRP levels by more than 2 mg/L, a 34% reduction within 4 weeks. Weight, nutritional status, and body composition remained unchanged, indicating that the drug acted independently of these factors to improve CRP, the researchers said (Arch. Intern. Med. 2006;166:902–8). At the same time, adiponectin levels rose significantly. Adiponectin, an adipocyte-derived cytokine that has anti-inflammatory and antiatherosclerotic properties, is decreased in obese people. Etanercept also decreased the subjects' markedly high levels of fibrinogen, a clotting factor and marker of inflammation and abnormal hemostasis. The drug also tended to reduce levels of interleukin-6 levels, another indicator of inflammation. It did not affect insulin sensitivity.

Etanercept was well tolerated in these subjects. However, they had been well screened before enrollment for contraindications to the drug, known to impair immune function in some patients. “Further studies with longer duration will be necessary to determine the safety” of etanercept in people with metabolic syndrome, the investigators noted.

The findings “suggest a novel and physiologically relevant approach to improve the increased inflammatory milieu associated with abdominal obesity” and metabolic syndrome. But additional studies are needed to investigate such a hypothesis.

Pyridostigmine significantly improves standing blood pressure in patients with orthostatic hypotension, and it does so without worsening supine hypertension, reported Dr. Wolfgang Singer and his associates at the Mayo Medical Center, Rochester, Minn.

Midodrine is the only drug previously shown in a blinded trial to improve orthostatic hypotension. But midodrine and other adrenergic agonists aggravate supine hypertension, “a major problem” in these patients because their blood pressure fluctuates widely throughout the day. Adrenergic agonists also raise the risk of intracerebral hemorrhage, the investigators said.

Dr. Singer and his associates assessed the effects of pyridostigmine, an anticholinesterase agent, in a study of 58 patients with neurogenic orthostatic hypotension. The 30 men and 28 women had associated multiple system atrophy (17 patients), pure autonomic failure (15), diabetic autonomic neuropathy (11), autoimmune autonomic neuropathy (9), or unspecified neurogenic orthostatic hypotension (6).

On sequential days, the subjects took either oral placebo, 60 mg of pyridostigmine alone, pyridostigmine plus a subthreshold dose of midodrine (2.5 mg), or pyridostigmine plus low-dose midodrine (5 mg).

Pyridostigmine alone or with midodrine alleviated orthostatic hypotension, compared with placebo. The blood pressure fall upon standing was 27.2 mm Hg with pyridostigmine plus 5 mg midodrine, compared with a fall of 34.0 mm Hg for placebo.

Although the mean improvement in standing blood pressure was modest, a small increase appears to suffice in alleviating symptoms. “Symptomatic improvement in some individuals was dramatic,” the researchers said (Arch. Neurol. 2006;63:www.archneurol.com

Most patients chose to continue taking pyridostigmine. Of the 29 patients who were available for follow-up 1–2 years later, 20 (69%) were still taking it. And of those 20 patients, 17 (85%) “were extremely satisfied” with the medication and rated their orthostatic symptoms as moderately to markedly improved. Ten patients reported an increased energy level, said Dr. Singer.

Pyridostigmine significantly improves standing blood pressure in patients with orthostatic hypotension, and it does so without worsening supine hypertension, reported Dr. Wolfgang Singer and his associates at the Mayo Medical Center, Rochester, Minn.

Midodrine is the only drug previously shown in a blinded trial to improve orthostatic hypotension. But midodrine and other adrenergic agonists aggravate supine hypertension, “a major problem” in these patients because their blood pressure fluctuates widely throughout the day. Adrenergic agonists also raise the risk of intracerebral hemorrhage, the investigators said.

Dr. Singer and his associates assessed the effects of pyridostigmine, an anticholinesterase agent, in a study of 58 patients with neurogenic orthostatic hypotension. The 30 men and 28 women had associated multiple system atrophy (17 patients), pure autonomic failure (15), diabetic autonomic neuropathy (11), autoimmune autonomic neuropathy (9), or unspecified neurogenic orthostatic hypotension (6).

On sequential days, the subjects took either oral placebo, 60 mg of pyridostigmine alone, pyridostigmine plus a subthreshold dose of midodrine (2.5 mg), or pyridostigmine plus low-dose midodrine (5 mg).

Pyridostigmine alone or with midodrine alleviated orthostatic hypotension, compared with placebo. The blood pressure fall upon standing was 27.2 mm Hg with pyridostigmine plus 5 mg midodrine, compared with a fall of 34.0 mm Hg for placebo.

Although the mean improvement in standing blood pressure was modest, a small increase appears to suffice in alleviating symptoms. “Symptomatic improvement in some individuals was dramatic,” the researchers said (Arch. Neurol. 2006;63:www.archneurol.com

Most patients chose to continue taking pyridostigmine. Of the 29 patients who were available for follow-up 1–2 years later, 20 (69%) were still taking it. And of those 20 patients, 17 (85%) “were extremely satisfied” with the medication and rated their orthostatic symptoms as moderately to markedly improved. Ten patients reported an increased energy level, said Dr. Singer.

Pyridostigmine significantly improves standing blood pressure in patients with orthostatic hypotension, and it does so without worsening supine hypertension, reported Dr. Wolfgang Singer and his associates at the Mayo Medical Center, Rochester, Minn.

Midodrine is the only drug previously shown in a blinded trial to improve orthostatic hypotension. But midodrine and other adrenergic agonists aggravate supine hypertension, “a major problem” in these patients because their blood pressure fluctuates widely throughout the day. Adrenergic agonists also raise the risk of intracerebral hemorrhage, the investigators said.

Dr. Singer and his associates assessed the effects of pyridostigmine, an anticholinesterase agent, in a study of 58 patients with neurogenic orthostatic hypotension. The 30 men and 28 women had associated multiple system atrophy (17 patients), pure autonomic failure (15), diabetic autonomic neuropathy (11), autoimmune autonomic neuropathy (9), or unspecified neurogenic orthostatic hypotension (6).

On sequential days, the subjects took either oral placebo, 60 mg of pyridostigmine alone, pyridostigmine plus a subthreshold dose of midodrine (2.5 mg), or pyridostigmine plus low-dose midodrine (5 mg).

Pyridostigmine alone or with midodrine alleviated orthostatic hypotension, compared with placebo. The blood pressure fall upon standing was 27.2 mm Hg with pyridostigmine plus 5 mg midodrine, compared with a fall of 34.0 mm Hg for placebo.

Although the mean improvement in standing blood pressure was modest, a small increase appears to suffice in alleviating symptoms. “Symptomatic improvement in some individuals was dramatic,” the researchers said (Arch. Neurol. 2006;63:www.archneurol.com

Most patients chose to continue taking pyridostigmine. Of the 29 patients who were available for follow-up 1–2 years later, 20 (69%) were still taking it. And of those 20 patients, 17 (85%) “were extremely satisfied” with the medication and rated their orthostatic symptoms as moderately to markedly improved. Ten patients reported an increased energy level, said Dr. Singer.

At all levels of socioeconomic status, Americans are much less healthy than their British counterparts, reported James Banks, Ph.D., of University College, London, and his associates.

In both countries, people with the highest levels of education and income are the healthiest, while those of low education and income are the unhealthiest. But the overall differences in health status between the two countries is so profound that the wealthiest Americans have comparable rates of diabetes and heart disease to people at the lowest levels of education and income in England.

Dr. Banks and his associates compared rates of seven major diagnoses among populations of comparable socioeconomic positions in nationally representative samples from the United States and England. To minimize the effects of racial and age differences between the populations, they restricted their study to only non-Hispanic white men and women aged 55–64 years.

The analysis included health-related data on 2,097 Americans and 5,526 British subjects. All were interviewed in 2002 and underwent physical examinations that included laboratory tests to verify their self-report of conditions such as diabetes.

Overall, Americans were more likely to have diabetes, hypertension, heart disease, a history of myocardial infarction or stroke, lung disease, and cancer than British subjects.

Diabetes prevalence was twice as high in the United States (13%) as it was in England (6%), the rate of hypertension was nearly 9% higher, and the rate of heart disease was almost 6% higher, the investigators said (JAMA 2006;295:2037–45).

Regarding markers of future cardiovascular risk, 40% of Americans had high levels of C-reactive protein and 24% had high levels of fibrinogen, compared with 30% and 10%, respectively, among the British participants. Similarly, only 28% of Americans had heart-healthy levels of HDL cholesterol, compared with 44% of the European comparison group. The study was not designed to explain the reasons underlying the large discrepancy in health status between England and the United States, and the investigators did not offer any potential explanations. However, they were able to rule out possible causes.

The discrepancy was not because of differences between the two populations in major risk factors. Smoking status was remarkably similar between the two countries. And although obesity was much more common in Americans, while heavy drinking was much more common in England, “very little of the overall between-country differences in health conditions are due to differences in … behavioral risk factors,” the researchers noted.

Nor did differences in access to health care account for the wide gap in health status. The British participants may have nationalized health care, but most of the Americans in the survey had full insurance coverage. “Health insurance cannot be the central reason for the better health outcomes in England because the top [socioeconomic] tier of the U.S. population have close to universal access but their health outcomes are often worse than those of their English counterparts,” Dr. Banks and his associates said.

ELSEVIER GLOBAL MEDICAL NEWS

At all levels of socioeconomic status, Americans are much less healthy than their British counterparts, reported James Banks, Ph.D., of University College, London, and his associates.

In both countries, people with the highest levels of education and income are the healthiest, while those of low education and income are the unhealthiest. But the overall differences in health status between the two countries is so profound that the wealthiest Americans have comparable rates of diabetes and heart disease to people at the lowest levels of education and income in England.

Dr. Banks and his associates compared rates of seven major diagnoses among populations of comparable socioeconomic positions in nationally representative samples from the United States and England. To minimize the effects of racial and age differences between the populations, they restricted their study to only non-Hispanic white men and women aged 55–64 years.

The analysis included health-related data on 2,097 Americans and 5,526 British subjects. All were interviewed in 2002 and underwent physical examinations that included laboratory tests to verify their self-report of conditions such as diabetes.

Overall, Americans were more likely to have diabetes, hypertension, heart disease, a history of myocardial infarction or stroke, lung disease, and cancer than British subjects.

Diabetes prevalence was twice as high in the United States (13%) as it was in England (6%), the rate of hypertension was nearly 9% higher, and the rate of heart disease was almost 6% higher, the investigators said (JAMA 2006;295:2037–45).

Regarding markers of future cardiovascular risk, 40% of Americans had high levels of C-reactive protein and 24% had high levels of fibrinogen, compared with 30% and 10%, respectively, among the British participants. Similarly, only 28% of Americans had heart-healthy levels of HDL cholesterol, compared with 44% of the European comparison group. The study was not designed to explain the reasons underlying the large discrepancy in health status between England and the United States, and the investigators did not offer any potential explanations. However, they were able to rule out possible causes.

The discrepancy was not because of differences between the two populations in major risk factors. Smoking status was remarkably similar between the two countries. And although obesity was much more common in Americans, while heavy drinking was much more common in England, “very little of the overall between-country differences in health conditions are due to differences in … behavioral risk factors,” the researchers noted.

Nor did differences in access to health care account for the wide gap in health status. The British participants may have nationalized health care, but most of the Americans in the survey had full insurance coverage. “Health insurance cannot be the central reason for the better health outcomes in England because the top [socioeconomic] tier of the U.S. population have close to universal access but their health outcomes are often worse than those of their English counterparts,” Dr. Banks and his associates said.

ELSEVIER GLOBAL MEDICAL NEWS

At all levels of socioeconomic status, Americans are much less healthy than their British counterparts, reported James Banks, Ph.D., of University College, London, and his associates.

In both countries, people with the highest levels of education and income are the healthiest, while those of low education and income are the unhealthiest. But the overall differences in health status between the two countries is so profound that the wealthiest Americans have comparable rates of diabetes and heart disease to people at the lowest levels of education and income in England.

Dr. Banks and his associates compared rates of seven major diagnoses among populations of comparable socioeconomic positions in nationally representative samples from the United States and England. To minimize the effects of racial and age differences between the populations, they restricted their study to only non-Hispanic white men and women aged 55–64 years.

The analysis included health-related data on 2,097 Americans and 5,526 British subjects. All were interviewed in 2002 and underwent physical examinations that included laboratory tests to verify their self-report of conditions such as diabetes.

Overall, Americans were more likely to have diabetes, hypertension, heart disease, a history of myocardial infarction or stroke, lung disease, and cancer than British subjects.

Diabetes prevalence was twice as high in the United States (13%) as it was in England (6%), the rate of hypertension was nearly 9% higher, and the rate of heart disease was almost 6% higher, the investigators said (JAMA 2006;295:2037–45).

Regarding markers of future cardiovascular risk, 40% of Americans had high levels of C-reactive protein and 24% had high levels of fibrinogen, compared with 30% and 10%, respectively, among the British participants. Similarly, only 28% of Americans had heart-healthy levels of HDL cholesterol, compared with 44% of the European comparison group. The study was not designed to explain the reasons underlying the large discrepancy in health status between England and the United States, and the investigators did not offer any potential explanations. However, they were able to rule out possible causes.

The discrepancy was not because of differences between the two populations in major risk factors. Smoking status was remarkably similar between the two countries. And although obesity was much more common in Americans, while heavy drinking was much more common in England, “very little of the overall between-country differences in health conditions are due to differences in … behavioral risk factors,” the researchers noted.

Nor did differences in access to health care account for the wide gap in health status. The British participants may have nationalized health care, but most of the Americans in the survey had full insurance coverage. “Health insurance cannot be the central reason for the better health outcomes in England because the top [socioeconomic] tier of the U.S. population have close to universal access but their health outcomes are often worse than those of their English counterparts,” Dr. Banks and his associates said.

ELSEVIER GLOBAL MEDICAL NEWS

People with kidney disease have a somewhat different symptom profile when they present with acute myocardial infarction than those without kidney disease, reported Dr. Jonathan Sosnov of Tufts-New England Medical Center, Boston, and his associates.

More patients with kidney disease die from cardiovascular causes than from any other cause. “Accurate and rapid diagnosis of MI in these high-risk patients might decrease their risk for subsequent morbidity and mortality by providing definitive treatment in a more timely manner,” the investigators said.

They reviewed data from a large, ongoing prospective epidemiologic study of MI to examine whether kidney disease might alter the symptom profile of MI, much as diabetes recently has been shown to do. They analyzed the medical records of 4,482 patients hospitalized for MI at 11 medical centers in the Worcester, Mass., area in 1997, 1999, 2001, and 2003.

Patients with kidney disease were significantly less likely to report chest pain as their chief complaint. Only 44% presented with chest pain, compared with 72% of patients without kidney disease, Dr. Sosnov and his associates said (Am. J. Kidney Dis. 2006;47:378–84). Similarly, patients with kidney disease were significantly less likely to complain of arm pain, numbness or tingling in the arm or hand, shoulder pain, jaw pain, or neck pain.

Patients with kidney disease were significantly more likely to report shortness of breath as their chief complaint. A total of 26% presented with shortness of breath, compared with only 10% of patients without kidney disease.

The reasons for these differences in presentation remain unknown and “need to be explored further, given the high incidence of [acute myocardial infarction] in patients with kidney disease,” the researchers said.

“To the best of our knowledge, this is the first report to describe how kidney disease may impact on the symptoms” of acute MI, they added.

ELSEVIER GLOBAL MEDICAL NEWS

People with kidney disease have a somewhat different symptom profile when they present with acute myocardial infarction than those without kidney disease, reported Dr. Jonathan Sosnov of Tufts-New England Medical Center, Boston, and his associates.

More patients with kidney disease die from cardiovascular causes than from any other cause. “Accurate and rapid diagnosis of MI in these high-risk patients might decrease their risk for subsequent morbidity and mortality by providing definitive treatment in a more timely manner,” the investigators said.

They reviewed data from a large, ongoing prospective epidemiologic study of MI to examine whether kidney disease might alter the symptom profile of MI, much as diabetes recently has been shown to do. They analyzed the medical records of 4,482 patients hospitalized for MI at 11 medical centers in the Worcester, Mass., area in 1997, 1999, 2001, and 2003.

Patients with kidney disease were significantly less likely to report chest pain as their chief complaint. Only 44% presented with chest pain, compared with 72% of patients without kidney disease, Dr. Sosnov and his associates said (Am. J. Kidney Dis. 2006;47:378–84). Similarly, patients with kidney disease were significantly less likely to complain of arm pain, numbness or tingling in the arm or hand, shoulder pain, jaw pain, or neck pain.

Patients with kidney disease were significantly more likely to report shortness of breath as their chief complaint. A total of 26% presented with shortness of breath, compared with only 10% of patients without kidney disease.

The reasons for these differences in presentation remain unknown and “need to be explored further, given the high incidence of [acute myocardial infarction] in patients with kidney disease,” the researchers said.

“To the best of our knowledge, this is the first report to describe how kidney disease may impact on the symptoms” of acute MI, they added.

ELSEVIER GLOBAL MEDICAL NEWS

People with kidney disease have a somewhat different symptom profile when they present with acute myocardial infarction than those without kidney disease, reported Dr. Jonathan Sosnov of Tufts-New England Medical Center, Boston, and his associates.

More patients with kidney disease die from cardiovascular causes than from any other cause. “Accurate and rapid diagnosis of MI in these high-risk patients might decrease their risk for subsequent morbidity and mortality by providing definitive treatment in a more timely manner,” the investigators said.

They reviewed data from a large, ongoing prospective epidemiologic study of MI to examine whether kidney disease might alter the symptom profile of MI, much as diabetes recently has been shown to do. They analyzed the medical records of 4,482 patients hospitalized for MI at 11 medical centers in the Worcester, Mass., area in 1997, 1999, 2001, and 2003.

Patients with kidney disease were significantly less likely to report chest pain as their chief complaint. Only 44% presented with chest pain, compared with 72% of patients without kidney disease, Dr. Sosnov and his associates said (Am. J. Kidney Dis. 2006;47:378–84). Similarly, patients with kidney disease were significantly less likely to complain of arm pain, numbness or tingling in the arm or hand, shoulder pain, jaw pain, or neck pain.

Patients with kidney disease were significantly more likely to report shortness of breath as their chief complaint. A total of 26% presented with shortness of breath, compared with only 10% of patients without kidney disease.

The reasons for these differences in presentation remain unknown and “need to be explored further, given the high incidence of [acute myocardial infarction] in patients with kidney disease,” the researchers said.

“To the best of our knowledge, this is the first report to describe how kidney disease may impact on the symptoms” of acute MI, they added.

ELSEVIER GLOBAL MEDICAL NEWS

People with prehypertension and hypertension can make and sustain multiple lifestyle modifications, controlling their blood pressure and perhaps reducing their risk for many chronic diseases, according to Patricia J. Elmer, Ph.D., of Kaiser Permanente Northwest's center for health research, Portland, Ore., and her associates.

They reported the results at 18-month follow-up of a randomized, multicenter study of middle-aged people. The study, funded by the National Heart, Lung, and Blood Institute, enrolled 810 subjects across the country with a systolic blood pressure of 120–159 mm Hg and a diastolic blood pressure of 80–95 mm Hg.

Almost all participants were overweight or obese, 62% were women, and 34% were African American.

One subject group (268 people) received a behavioral intervention including advice to lose at least 15 pounds, perform at least 180 minutes per week of moderate-intensity physical activity, consume no more than 100 mmol per day of sodium, and drink no more than 1–2 alcoholic drinks per day.

A second group (269 subjects) received the same behavioral intervention plus additional advice to follow the DASH (Dietary Approaches to Stop Hypertension) diet, increasing their consumption of fruits, vegetables, and low-fat dairy products and decreasing their intake of total fat and saturated fat.

Both intervention groups kept food diaries, monitored their calorie and sodium intakes, and recorded minutes of physical activity.

In both groups, the subjects attended 14 group and 4 individual counseling sessions for the first 6 months, then attended monthly group sessions supplemented with 3 individual counseling sessions for the following 12 months. At these sessions, counseling focused on self-monitoring, reinforcement, and problem-solving, and it also promoted social support and individual motivation.

The third group of study subjects (273 people) received only advice rather than a behavioral intervention. They attended a 30-minute individual session at enrollment in the study and another 6 months later, at which they were counseled to lose weight, reduce sodium intake, increase physical activity, and eat a heart-healthy diet.

At 18 months, the prevalence of mild hypertension had decreased in all three groups, from a high of 36%–38% at baseline to 32% in the advice-only group to 24% in the behavioral intervention group instructed in established, guideline-recommended lifestyle changes; and to 22% in the behavioral intervention group instructed in those changes plus the DASH diet. This result compares favorably with the degree of blood pressure control reported for drug therapy in community-based studies, the investigators said (Ann. Intern. Med. 2006;144:485–95).

None of the subjects had normal blood pressure at baseline, but at 18 months the rates of normal blood pressure were 18%, 24%, and 24% in these three groups, respectively.

Fitness, as measured by heart rate on treadmill testing, improved in all three groups. Subjects in all groups also lost weight, but the mean weight loss was significantly greater in the two behavioral intervention groups than in the advice-only group. Subjects in both intervention groups reduced their intake of sodium and fat; those in the DASH diet group also significantly increased their intake of fruits, vegetables, dairy products, and important nutrients such as fiber, folate, and minerals—all of which “may reduce the risk for chronic disease,” Dr. Elmer and her associates said.

Adherence to these lifestyle modifications decreased between 6 and 18 months, with “recidivism” in weight loss, sodium intake, and potassium intake. However, subjects in the two intervention groups still maintained about a 4% weight loss at 18 months. This “modest” reduction “should be viewed in the context of public health goals that emphasize the prevention of additional weight gain, rather than weight loss, because of the well-documented difficulties of sustaining weight loss,” the researchers said.

They noted that randomized controlled trials typically recruit highly motivated volunteers, so the results of this trial may not be generalizable to the overall population.

People with prehypertension and hypertension can make and sustain multiple lifestyle modifications, controlling their blood pressure and perhaps reducing their risk for many chronic diseases, according to Patricia J. Elmer, Ph.D., of Kaiser Permanente Northwest's center for health research, Portland, Ore., and her associates.

They reported the results at 18-month follow-up of a randomized, multicenter study of middle-aged people. The study, funded by the National Heart, Lung, and Blood Institute, enrolled 810 subjects across the country with a systolic blood pressure of 120–159 mm Hg and a diastolic blood pressure of 80–95 mm Hg.

Almost all participants were overweight or obese, 62% were women, and 34% were African American.

One subject group (268 people) received a behavioral intervention including advice to lose at least 15 pounds, perform at least 180 minutes per week of moderate-intensity physical activity, consume no more than 100 mmol per day of sodium, and drink no more than 1–2 alcoholic drinks per day.

A second group (269 subjects) received the same behavioral intervention plus additional advice to follow the DASH (Dietary Approaches to Stop Hypertension) diet, increasing their consumption of fruits, vegetables, and low-fat dairy products and decreasing their intake of total fat and saturated fat.

Both intervention groups kept food diaries, monitored their calorie and sodium intakes, and recorded minutes of physical activity.

In both groups, the subjects attended 14 group and 4 individual counseling sessions for the first 6 months, then attended monthly group sessions supplemented with 3 individual counseling sessions for the following 12 months. At these sessions, counseling focused on self-monitoring, reinforcement, and problem-solving, and it also promoted social support and individual motivation.

The third group of study subjects (273 people) received only advice rather than a behavioral intervention. They attended a 30-minute individual session at enrollment in the study and another 6 months later, at which they were counseled to lose weight, reduce sodium intake, increase physical activity, and eat a heart-healthy diet.

At 18 months, the prevalence of mild hypertension had decreased in all three groups, from a high of 36%–38% at baseline to 32% in the advice-only group to 24% in the behavioral intervention group instructed in established, guideline-recommended lifestyle changes; and to 22% in the behavioral intervention group instructed in those changes plus the DASH diet. This result compares favorably with the degree of blood pressure control reported for drug therapy in community-based studies, the investigators said (Ann. Intern. Med. 2006;144:485–95).

None of the subjects had normal blood pressure at baseline, but at 18 months the rates of normal blood pressure were 18%, 24%, and 24% in these three groups, respectively.

Fitness, as measured by heart rate on treadmill testing, improved in all three groups. Subjects in all groups also lost weight, but the mean weight loss was significantly greater in the two behavioral intervention groups than in the advice-only group. Subjects in both intervention groups reduced their intake of sodium and fat; those in the DASH diet group also significantly increased their intake of fruits, vegetables, dairy products, and important nutrients such as fiber, folate, and minerals—all of which “may reduce the risk for chronic disease,” Dr. Elmer and her associates said.

Adherence to these lifestyle modifications decreased between 6 and 18 months, with “recidivism” in weight loss, sodium intake, and potassium intake. However, subjects in the two intervention groups still maintained about a 4% weight loss at 18 months. This “modest” reduction “should be viewed in the context of public health goals that emphasize the prevention of additional weight gain, rather than weight loss, because of the well-documented difficulties of sustaining weight loss,” the researchers said.

They noted that randomized controlled trials typically recruit highly motivated volunteers, so the results of this trial may not be generalizable to the overall population.

People with prehypertension and hypertension can make and sustain multiple lifestyle modifications, controlling their blood pressure and perhaps reducing their risk for many chronic diseases, according to Patricia J. Elmer, Ph.D., of Kaiser Permanente Northwest's center for health research, Portland, Ore., and her associates.

They reported the results at 18-month follow-up of a randomized, multicenter study of middle-aged people. The study, funded by the National Heart, Lung, and Blood Institute, enrolled 810 subjects across the country with a systolic blood pressure of 120–159 mm Hg and a diastolic blood pressure of 80–95 mm Hg.

Almost all participants were overweight or obese, 62% were women, and 34% were African American.

One subject group (268 people) received a behavioral intervention including advice to lose at least 15 pounds, perform at least 180 minutes per week of moderate-intensity physical activity, consume no more than 100 mmol per day of sodium, and drink no more than 1–2 alcoholic drinks per day.

A second group (269 subjects) received the same behavioral intervention plus additional advice to follow the DASH (Dietary Approaches to Stop Hypertension) diet, increasing their consumption of fruits, vegetables, and low-fat dairy products and decreasing their intake of total fat and saturated fat.

Both intervention groups kept food diaries, monitored their calorie and sodium intakes, and recorded minutes of physical activity.

In both groups, the subjects attended 14 group and 4 individual counseling sessions for the first 6 months, then attended monthly group sessions supplemented with 3 individual counseling sessions for the following 12 months. At these sessions, counseling focused on self-monitoring, reinforcement, and problem-solving, and it also promoted social support and individual motivation.

The third group of study subjects (273 people) received only advice rather than a behavioral intervention. They attended a 30-minute individual session at enrollment in the study and another 6 months later, at which they were counseled to lose weight, reduce sodium intake, increase physical activity, and eat a heart-healthy diet.

At 18 months, the prevalence of mild hypertension had decreased in all three groups, from a high of 36%–38% at baseline to 32% in the advice-only group to 24% in the behavioral intervention group instructed in established, guideline-recommended lifestyle changes; and to 22% in the behavioral intervention group instructed in those changes plus the DASH diet. This result compares favorably with the degree of blood pressure control reported for drug therapy in community-based studies, the investigators said (Ann. Intern. Med. 2006;144:485–95).

None of the subjects had normal blood pressure at baseline, but at 18 months the rates of normal blood pressure were 18%, 24%, and 24% in these three groups, respectively.

Fitness, as measured by heart rate on treadmill testing, improved in all three groups. Subjects in all groups also lost weight, but the mean weight loss was significantly greater in the two behavioral intervention groups than in the advice-only group. Subjects in both intervention groups reduced their intake of sodium and fat; those in the DASH diet group also significantly increased their intake of fruits, vegetables, dairy products, and important nutrients such as fiber, folate, and minerals—all of which “may reduce the risk for chronic disease,” Dr. Elmer and her associates said.

Adherence to these lifestyle modifications decreased between 6 and 18 months, with “recidivism” in weight loss, sodium intake, and potassium intake. However, subjects in the two intervention groups still maintained about a 4% weight loss at 18 months. This “modest” reduction “should be viewed in the context of public health goals that emphasize the prevention of additional weight gain, rather than weight loss, because of the well-documented difficulties of sustaining weight loss,” the researchers said.

They noted that randomized controlled trials typically recruit highly motivated volunteers, so the results of this trial may not be generalizable to the overall population.

Three additional cases of Guillain-Barré syndrome related to the Menactra MCV4 meningococcal conjugate vaccine have been reported, according to the Centers for Disease Control and Prevention, Atlanta.

Even with these additional cases, the incidence of this adverse effect does not exceed the incidence that might be expected to occur by chance alone, so the CDC has not changed its recommendations regarding the vaccine. However, the timing of the onset of Guillain-Barré syndrome (GBS) within 2–5 weeks of vaccination “is still a concern,” so monitoring continues and controlled clinical trials are planned, the CDC said.

Clinicians are advised to share information about the CDC investigation with adolescents and parents before administering the vaccine. Fact sheets for patients and for health-care workers are available at www.cdc.gov

The CDC alerted physicians to a possible association between the Menactra MCV4 vaccine and GBS in October 2005, based on five cases in teenagers that were reported to the Vaccine Adverse Events Reporting System. The vaccine manufacturer, Sanofi Pasteur Inc., and the Food and Drug Administration updated the package insert, listing previous GBS as a new contraindication to the vaccine and warning clinicians of a possible temporal relation with GBS. At that time the CDC and the FDA also advised clinicians to report any cases of GBS occurring in patients who had received the vaccine. As of February 2006, three additional cases had been reported to VAERS and confirmed.

GBS, a serious neurologic disorder involving demyelination of the peripheral nerves, is characterized by numbness or tingling in the feet or hands which often progresses to the legs and arms and is accompanied by muscle weakness or paralysis and loss of deep tendon reflexes.

The CDC provided details on two of the three newly reported cases that occurred since October 2005. Both involved teenage males who were hospitalized and treated with intravenous immunoglobulin. Both patients recovered fully (MMWR 2006;55:364–6).

The third case is undergoing detailed clinical investigation but meets the provisional case definition for GBS, the CDC said.

The CDC continues to advise that people with a history of GBS should not be vaccinated with the Menactra MCV4 vaccine unless they are at high risk for meningococcal disease. The vaccine is still recommended for others at risk, including first-year college students, military recruits, travelers, scientists who are exposed to meningitis, patients with anatomic or functional asplenia, and patients with terminal complement deficiency. Also, in February 2005, the Advisory Committee on Immunization Practices recommended routine vaccination of adolescents at the preadolescent health-care visit (at ages 11–12 years). For persons not previously vaccinated, the committee recommended vaccination before high-school entry (at approximately 15 years of age).

To report adverse events related to the MCV4 or any vaccine, clinicians should go to www.vaers.hhs.gov

Three additional cases of Guillain-Barré syndrome related to the Menactra MCV4 meningococcal conjugate vaccine have been reported, according to the Centers for Disease Control and Prevention, Atlanta.

Even with these additional cases, the incidence of this adverse effect does not exceed the incidence that might be expected to occur by chance alone, so the CDC has not changed its recommendations regarding the vaccine. However, the timing of the onset of Guillain-Barré syndrome (GBS) within 2–5 weeks of vaccination “is still a concern,” so monitoring continues and controlled clinical trials are planned, the CDC said.

Clinicians are advised to share information about the CDC investigation with adolescents and parents before administering the vaccine. Fact sheets for patients and for health-care workers are available at www.cdc.gov

The CDC alerted physicians to a possible association between the Menactra MCV4 vaccine and GBS in October 2005, based on five cases in teenagers that were reported to the Vaccine Adverse Events Reporting System. The vaccine manufacturer, Sanofi Pasteur Inc., and the Food and Drug Administration updated the package insert, listing previous GBS as a new contraindication to the vaccine and warning clinicians of a possible temporal relation with GBS. At that time the CDC and the FDA also advised clinicians to report any cases of GBS occurring in patients who had received the vaccine. As of February 2006, three additional cases had been reported to VAERS and confirmed.

GBS, a serious neurologic disorder involving demyelination of the peripheral nerves, is characterized by numbness or tingling in the feet or hands which often progresses to the legs and arms and is accompanied by muscle weakness or paralysis and loss of deep tendon reflexes.

The CDC provided details on two of the three newly reported cases that occurred since October 2005. Both involved teenage males who were hospitalized and treated with intravenous immunoglobulin. Both patients recovered fully (MMWR 2006;55:364–6).

The third case is undergoing detailed clinical investigation but meets the provisional case definition for GBS, the CDC said.

The CDC continues to advise that people with a history of GBS should not be vaccinated with the Menactra MCV4 vaccine unless they are at high risk for meningococcal disease. The vaccine is still recommended for others at risk, including first-year college students, military recruits, travelers, scientists who are exposed to meningitis, patients with anatomic or functional asplenia, and patients with terminal complement deficiency. Also, in February 2005, the Advisory Committee on Immunization Practices recommended routine vaccination of adolescents at the preadolescent health-care visit (at ages 11–12 years). For persons not previously vaccinated, the committee recommended vaccination before high-school entry (at approximately 15 years of age).

To report adverse events related to the MCV4 or any vaccine, clinicians should go to www.vaers.hhs.gov

Three additional cases of Guillain-Barré syndrome related to the Menactra MCV4 meningococcal conjugate vaccine have been reported, according to the Centers for Disease Control and Prevention, Atlanta.

Even with these additional cases, the incidence of this adverse effect does not exceed the incidence that might be expected to occur by chance alone, so the CDC has not changed its recommendations regarding the vaccine. However, the timing of the onset of Guillain-Barré syndrome (GBS) within 2–5 weeks of vaccination “is still a concern,” so monitoring continues and controlled clinical trials are planned, the CDC said.

Clinicians are advised to share information about the CDC investigation with adolescents and parents before administering the vaccine. Fact sheets for patients and for health-care workers are available at www.cdc.gov

The CDC alerted physicians to a possible association between the Menactra MCV4 vaccine and GBS in October 2005, based on five cases in teenagers that were reported to the Vaccine Adverse Events Reporting System. The vaccine manufacturer, Sanofi Pasteur Inc., and the Food and Drug Administration updated the package insert, listing previous GBS as a new contraindication to the vaccine and warning clinicians of a possible temporal relation with GBS. At that time the CDC and the FDA also advised clinicians to report any cases of GBS occurring in patients who had received the vaccine. As of February 2006, three additional cases had been reported to VAERS and confirmed.

GBS, a serious neurologic disorder involving demyelination of the peripheral nerves, is characterized by numbness or tingling in the feet or hands which often progresses to the legs and arms and is accompanied by muscle weakness or paralysis and loss of deep tendon reflexes.

The CDC provided details on two of the three newly reported cases that occurred since October 2005. Both involved teenage males who were hospitalized and treated with intravenous immunoglobulin. Both patients recovered fully (MMWR 2006;55:364–6).

The third case is undergoing detailed clinical investigation but meets the provisional case definition for GBS, the CDC said.

The CDC continues to advise that people with a history of GBS should not be vaccinated with the Menactra MCV4 vaccine unless they are at high risk for meningococcal disease. The vaccine is still recommended for others at risk, including first-year college students, military recruits, travelers, scientists who are exposed to meningitis, patients with anatomic or functional asplenia, and patients with terminal complement deficiency. Also, in February 2005, the Advisory Committee on Immunization Practices recommended routine vaccination of adolescents at the preadolescent health-care visit (at ages 11–12 years). For persons not previously vaccinated, the committee recommended vaccination before high-school entry (at approximately 15 years of age).

To report adverse events related to the MCV4 or any vaccine, clinicians should go to www.vaers.hhs.gov

Women beginning menopause are more likely to develop new-onset major depression than are women the same age who are not yet making the transition to menopause, reported Dr. Lee S. Cohen and his associates in the Harvard Study of Moods and Cycles.

A cross-sectional sample of 460 women aged 36–45 years was prospectively followed every 6 months for 59–92 months. A total of 326 of the women entered menopause during the study, said Dr. Cohen and his associates at Harvard Medical School, Massachusetts General Hospital, and Brigham and Women's Hospital, all in Boston. None of the women had a history of major depression.

The rate of new-onset major depression was 16.6% in the menopausal women, compared with 9.5% in those who had not yet entered menopause, after the data had been adjusted to account for age at study enrollment and history of negative life events (Arch. Gen. Psychiatry 2006;63:385–90).

This correlation between onset of depression and transition to menopause was noted both in women who used hormone therapy and in those who did not.

New-onset depression was more likely to develop in women who reported vasomotor symptoms than in those who did not. Hot flushes may disrupt sleep “enough to adversely affect daytime functioning and to impact quality of life,” the investigators said. Alternatively, “abrupt changes in neuromodulatory function and/or in reproductive-hormone levels could contribute to the constellation of mood and vasomotor symptoms.”

Women beginning menopause are more likely to develop new-onset major depression than are women the same age who are not yet making the transition to menopause, reported Dr. Lee S. Cohen and his associates in the Harvard Study of Moods and Cycles.

A cross-sectional sample of 460 women aged 36–45 years was prospectively followed every 6 months for 59–92 months. A total of 326 of the women entered menopause during the study, said Dr. Cohen and his associates at Harvard Medical School, Massachusetts General Hospital, and Brigham and Women's Hospital, all in Boston. None of the women had a history of major depression.

The rate of new-onset major depression was 16.6% in the menopausal women, compared with 9.5% in those who had not yet entered menopause, after the data had been adjusted to account for age at study enrollment and history of negative life events (Arch. Gen. Psychiatry 2006;63:385–90).

This correlation between onset of depression and transition to menopause was noted both in women who used hormone therapy and in those who did not.

New-onset depression was more likely to develop in women who reported vasomotor symptoms than in those who did not. Hot flushes may disrupt sleep “enough to adversely affect daytime functioning and to impact quality of life,” the investigators said. Alternatively, “abrupt changes in neuromodulatory function and/or in reproductive-hormone levels could contribute to the constellation of mood and vasomotor symptoms.”

Women beginning menopause are more likely to develop new-onset major depression than are women the same age who are not yet making the transition to menopause, reported Dr. Lee S. Cohen and his associates in the Harvard Study of Moods and Cycles.

A cross-sectional sample of 460 women aged 36–45 years was prospectively followed every 6 months for 59–92 months. A total of 326 of the women entered menopause during the study, said Dr. Cohen and his associates at Harvard Medical School, Massachusetts General Hospital, and Brigham and Women's Hospital, all in Boston. None of the women had a history of major depression.

The rate of new-onset major depression was 16.6% in the menopausal women, compared with 9.5% in those who had not yet entered menopause, after the data had been adjusted to account for age at study enrollment and history of negative life events (Arch. Gen. Psychiatry 2006;63:385–90).

This correlation between onset of depression and transition to menopause was noted both in women who used hormone therapy and in those who did not.

New-onset depression was more likely to develop in women who reported vasomotor symptoms than in those who did not. Hot flushes may disrupt sleep “enough to adversely affect daytime functioning and to impact quality of life,” the investigators said. Alternatively, “abrupt changes in neuromodulatory function and/or in reproductive-hormone levels could contribute to the constellation of mood and vasomotor symptoms.”

The “changing hormonal milieu” of menopause is strongly associated with new-onset major depression as well as depressive symptoms in women with no history of mood disturbance, reported Ellen W. Freeman, Ph.D., of the departments of ob.gyn. and psychiatry at the University of Pennsylvania, Philadelphia, and her associates.

Women are significantly more likely to develop a depressive disorder when their levels of estradiol fluctuate, levels of FSH and LH increase, and levels of inhibin B decrease, as happens during the transition to menopause. It appears that the hormonal changes characteristic of ovarian aging produce “destabilizing effects” that contribute to depression, Dr. Freeman and her associates in the Penn Ovarian Aging Study commented.

This finding should make a substantial contribution to what has been only “limited evidence” in the literature about mood symptoms in the perimenopausal years. “Whether mood symptoms increase in the perimenopausal years and whether the occurrence of depressed mood is independently associated with ovarian changes or is secondary to vasomotor or other bothersome symptoms” has been controversial, they noted.

Dr. Freeman and her associates examined the issue by assessing fluctuations in reproductive hormone levels in 231 premenopausal women aged 35–47 years at baseline who were followed for 8 years. During that interval, 43% of the women entered the transition to menopause.

Hormone assays were conducted in 10 assessment periods, with the first 6 at 8-month intervals. Blood samples were collected at the start of menstrual cycles, and subjects also were interviewed concerning their overall health, demographic factors, and menopausal symptoms. Depressive symptoms were assessed using the CES-D (Center for Epidemiological Studies-Depression) scale, and either the PRIME-MD (Primary Care Evaluation of Mental Disorders) or the PHQ (Patient Health Questionnaire) was used to detect major depressive disorder.

Of the 231 women, 116 (50%) had depressive symptoms on the CES-D during follow-up and 59 (26%) had depressive disorders on the PRIME-MD or PHQ; 26 had major depressive disorder and 33 had other depressive disorders (Arch. Gen. Psychiatry 2006;63:375–82).

Changes in individual women's levels of FSH, LH, and inhibin B were significantly associated with depressive symptoms and with major depression. Similarly, variability in a woman's mean levels of estradiol, FSH, and LH also were linked to depression and depressive symptoms.

After the data were adjusted for several other depression risk factors, including change in employment status or marital status, the researchers found that a woman was, on average, more than five times “more likely to be in menopausal transition at the time of reporting high [depression] scores than she was before the onset of depressive symptoms.”

The “strongest risk factor for the new onset of diagnosed depressive disorders was the increased variability of estradiol [around the woman's own mean levels] at the time of the diagnosed disorder,” Dr. Freeman and her associates said.

The “changing hormonal milieu” of menopause is strongly associated with new-onset major depression as well as depressive symptoms in women with no history of mood disturbance, reported Ellen W. Freeman, Ph.D., of the departments of ob.gyn. and psychiatry at the University of Pennsylvania, Philadelphia, and her associates.

Women are significantly more likely to develop a depressive disorder when their levels of estradiol fluctuate, levels of FSH and LH increase, and levels of inhibin B decrease, as happens during the transition to menopause. It appears that the hormonal changes characteristic of ovarian aging produce “destabilizing effects” that contribute to depression, Dr. Freeman and her associates in the Penn Ovarian Aging Study commented.

This finding should make a substantial contribution to what has been only “limited evidence” in the literature about mood symptoms in the perimenopausal years. “Whether mood symptoms increase in the perimenopausal years and whether the occurrence of depressed mood is independently associated with ovarian changes or is secondary to vasomotor or other bothersome symptoms” has been controversial, they noted.

Dr. Freeman and her associates examined the issue by assessing fluctuations in reproductive hormone levels in 231 premenopausal women aged 35–47 years at baseline who were followed for 8 years. During that interval, 43% of the women entered the transition to menopause.

Hormone assays were conducted in 10 assessment periods, with the first 6 at 8-month intervals. Blood samples were collected at the start of menstrual cycles, and subjects also were interviewed concerning their overall health, demographic factors, and menopausal symptoms. Depressive symptoms were assessed using the CES-D (Center for Epidemiological Studies-Depression) scale, and either the PRIME-MD (Primary Care Evaluation of Mental Disorders) or the PHQ (Patient Health Questionnaire) was used to detect major depressive disorder.

Of the 231 women, 116 (50%) had depressive symptoms on the CES-D during follow-up and 59 (26%) had depressive disorders on the PRIME-MD or PHQ; 26 had major depressive disorder and 33 had other depressive disorders (Arch. Gen. Psychiatry 2006;63:375–82).

Changes in individual women's levels of FSH, LH, and inhibin B were significantly associated with depressive symptoms and with major depression. Similarly, variability in a woman's mean levels of estradiol, FSH, and LH also were linked to depression and depressive symptoms.

After the data were adjusted for several other depression risk factors, including change in employment status or marital status, the researchers found that a woman was, on average, more than five times “more likely to be in menopausal transition at the time of reporting high [depression] scores than she was before the onset of depressive symptoms.”

The “strongest risk factor for the new onset of diagnosed depressive disorders was the increased variability of estradiol [around the woman's own mean levels] at the time of the diagnosed disorder,” Dr. Freeman and her associates said.

The “changing hormonal milieu” of menopause is strongly associated with new-onset major depression as well as depressive symptoms in women with no history of mood disturbance, reported Ellen W. Freeman, Ph.D., of the departments of ob.gyn. and psychiatry at the University of Pennsylvania, Philadelphia, and her associates.

Women are significantly more likely to develop a depressive disorder when their levels of estradiol fluctuate, levels of FSH and LH increase, and levels of inhibin B decrease, as happens during the transition to menopause. It appears that the hormonal changes characteristic of ovarian aging produce “destabilizing effects” that contribute to depression, Dr. Freeman and her associates in the Penn Ovarian Aging Study commented.

This finding should make a substantial contribution to what has been only “limited evidence” in the literature about mood symptoms in the perimenopausal years. “Whether mood symptoms increase in the perimenopausal years and whether the occurrence of depressed mood is independently associated with ovarian changes or is secondary to vasomotor or other bothersome symptoms” has been controversial, they noted.

Dr. Freeman and her associates examined the issue by assessing fluctuations in reproductive hormone levels in 231 premenopausal women aged 35–47 years at baseline who were followed for 8 years. During that interval, 43% of the women entered the transition to menopause.

Hormone assays were conducted in 10 assessment periods, with the first 6 at 8-month intervals. Blood samples were collected at the start of menstrual cycles, and subjects also were interviewed concerning their overall health, demographic factors, and menopausal symptoms. Depressive symptoms were assessed using the CES-D (Center for Epidemiological Studies-Depression) scale, and either the PRIME-MD (Primary Care Evaluation of Mental Disorders) or the PHQ (Patient Health Questionnaire) was used to detect major depressive disorder.

Of the 231 women, 116 (50%) had depressive symptoms on the CES-D during follow-up and 59 (26%) had depressive disorders on the PRIME-MD or PHQ; 26 had major depressive disorder and 33 had other depressive disorders (Arch. Gen. Psychiatry 2006;63:375–82).

Changes in individual women's levels of FSH, LH, and inhibin B were significantly associated with depressive symptoms and with major depression. Similarly, variability in a woman's mean levels of estradiol, FSH, and LH also were linked to depression and depressive symptoms.

After the data were adjusted for several other depression risk factors, including change in employment status or marital status, the researchers found that a woman was, on average, more than five times “more likely to be in menopausal transition at the time of reporting high [depression] scores than she was before the onset of depressive symptoms.”

The “strongest risk factor for the new onset of diagnosed depressive disorders was the increased variability of estradiol [around the woman's own mean levels] at the time of the diagnosed disorder,” Dr. Freeman and her associates said.

Unopposed estrogen therapy in postmenopausal women who have undergone hysterectomy does not appear to raise the risk of breast cancer, in clear contrast to the significant rise in breast cancers among postmenopausal women with intact uteri who take estrogen plus medroxyprogesterone.

However, conjugated equine estrogen (CEE) therapy alone does increase the number of abnormal mammograms requiring follow-up, which includes aspiration and biopsy as well as the attendant emotional and economic costs of each, according to Marcia L. Stefanick, Ph.D., and her associates in the Women's Health Initiative (WHI) study.

The decision to use CEE in postmenopausal women without a uterus, therefore, “should continue to be based on careful consideration of potential risks and benefits for a given individual,” said Dr. Stefanick, a professor of medicine in the prevention research center at Stanford (Calif.) University, and her WHI associates.

The portion of the WHI study that addressed estrogen-only therapy involved 10,739 postmenopausal women aged 50–79 years who had undergone prior hysterectomy and were treated at 40 clinical centers across the United States between 1993 and 1998. The women were randomly assigned to receive either 0.625 mg of CEE (Premarin) or a placebo and were assessed at 6-month intervals.

The study was terminated early in 2004 because interim analysis showed that CEE raised stroke risk without reducing the risk of coronary heart disease. But preliminary analysis of the results up to that date also showed that compared with women taking placebo, those taking CEE had fewer breast cancers. This finding of a possible protective effect prompted an updated analysis, and the WHI investigators now report the results on 237 invasive and 55 in situ breast cancers that developed by the date that subjects were instructed to stop taking their study pills (JAMA 2006;295:1647–57).

In an intention-to-treat analysis, there were nonsignificant reductions in invasive breast cancers and total breast cancers among women taking CEE only, compared with those taking placebo. There was no effect on in situ disease. Further analysis showed that the number of advanced cancers was comparable between the two groups of patients, but there were fewer cases of localized disease in the CEE group.

“In the completed trial database, the invasive breast cancer incidence did not differ significantly between the CEE group and the placebo group,” investigators said.

After 1 year of therapy, the percentage of abnormal mammograms was “substantially higher” in the CEE group (9.2%) than in the placebo group (5.5%). This pattern held constant for each year thereafter, for a cumulative rate of 36.2% in the CEE group and 28.1% in the placebo group.

By the end of the study, women in the CEE group had undergone 198 biopsies or aspirations that yielded negative findings, Dr. Stefanick and her associates noted.

The percentage of mammograms showing “suspicious” rather than simply abnormal findings was similar for both groups, as was the percentage of mammograms that were highly suggestive of malignancy. In contrast to these findings, the results of the CEE plus progesterone portion of the WHI trial showed a definite increase in invasive breast cancers with combined therapy, as well as a definite increase in mammograms deemed “suspicious” or “highly suggestive of malignancy,” they noted.

After 1 year, 9.2% of the women on estrogen and 5.5% in the placebo group had abnormal mammograms. DR. STEFANICK

Unopposed estrogen therapy in postmenopausal women who have undergone hysterectomy does not appear to raise the risk of breast cancer, in clear contrast to the significant rise in breast cancers among postmenopausal women with intact uteri who take estrogen plus medroxyprogesterone.

However, conjugated equine estrogen (CEE) therapy alone does increase the number of abnormal mammograms requiring follow-up, which includes aspiration and biopsy as well as the attendant emotional and economic costs of each, according to Marcia L. Stefanick, Ph.D., and her associates in the Women's Health Initiative (WHI) study.

The decision to use CEE in postmenopausal women without a uterus, therefore, “should continue to be based on careful consideration of potential risks and benefits for a given individual,” said Dr. Stefanick, a professor of medicine in the prevention research center at Stanford (Calif.) University, and her WHI associates.

The portion of the WHI study that addressed estrogen-only therapy involved 10,739 postmenopausal women aged 50–79 years who had undergone prior hysterectomy and were treated at 40 clinical centers across the United States between 1993 and 1998. The women were randomly assigned to receive either 0.625 mg of CEE (Premarin) or a placebo and were assessed at 6-month intervals.

The study was terminated early in 2004 because interim analysis showed that CEE raised stroke risk without reducing the risk of coronary heart disease. But preliminary analysis of the results up to that date also showed that compared with women taking placebo, those taking CEE had fewer breast cancers. This finding of a possible protective effect prompted an updated analysis, and the WHI investigators now report the results on 237 invasive and 55 in situ breast cancers that developed by the date that subjects were instructed to stop taking their study pills (JAMA 2006;295:1647–57).

In an intention-to-treat analysis, there were nonsignificant reductions in invasive breast cancers and total breast cancers among women taking CEE only, compared with those taking placebo. There was no effect on in situ disease. Further analysis showed that the number of advanced cancers was comparable between the two groups of patients, but there were fewer cases of localized disease in the CEE group.

“In the completed trial database, the invasive breast cancer incidence did not differ significantly between the CEE group and the placebo group,” investigators said.

After 1 year of therapy, the percentage of abnormal mammograms was “substantially higher” in the CEE group (9.2%) than in the placebo group (5.5%). This pattern held constant for each year thereafter, for a cumulative rate of 36.2% in the CEE group and 28.1% in the placebo group.

By the end of the study, women in the CEE group had undergone 198 biopsies or aspirations that yielded negative findings, Dr. Stefanick and her associates noted.

The percentage of mammograms showing “suspicious” rather than simply abnormal findings was similar for both groups, as was the percentage of mammograms that were highly suggestive of malignancy. In contrast to these findings, the results of the CEE plus progesterone portion of the WHI trial showed a definite increase in invasive breast cancers with combined therapy, as well as a definite increase in mammograms deemed “suspicious” or “highly suggestive of malignancy,” they noted.

After 1 year, 9.2% of the women on estrogen and 5.5% in the placebo group had abnormal mammograms. DR. STEFANICK

Unopposed estrogen therapy in postmenopausal women who have undergone hysterectomy does not appear to raise the risk of breast cancer, in clear contrast to the significant rise in breast cancers among postmenopausal women with intact uteri who take estrogen plus medroxyprogesterone.

However, conjugated equine estrogen (CEE) therapy alone does increase the number of abnormal mammograms requiring follow-up, which includes aspiration and biopsy as well as the attendant emotional and economic costs of each, according to Marcia L. Stefanick, Ph.D., and her associates in the Women's Health Initiative (WHI) study.

The decision to use CEE in postmenopausal women without a uterus, therefore, “should continue to be based on careful consideration of potential risks and benefits for a given individual,” said Dr. Stefanick, a professor of medicine in the prevention research center at Stanford (Calif.) University, and her WHI associates.

The portion of the WHI study that addressed estrogen-only therapy involved 10,739 postmenopausal women aged 50–79 years who had undergone prior hysterectomy and were treated at 40 clinical centers across the United States between 1993 and 1998. The women were randomly assigned to receive either 0.625 mg of CEE (Premarin) or a placebo and were assessed at 6-month intervals.

The study was terminated early in 2004 because interim analysis showed that CEE raised stroke risk without reducing the risk of coronary heart disease. But preliminary analysis of the results up to that date also showed that compared with women taking placebo, those taking CEE had fewer breast cancers. This finding of a possible protective effect prompted an updated analysis, and the WHI investigators now report the results on 237 invasive and 55 in situ breast cancers that developed by the date that subjects were instructed to stop taking their study pills (JAMA 2006;295:1647–57).

In an intention-to-treat analysis, there were nonsignificant reductions in invasive breast cancers and total breast cancers among women taking CEE only, compared with those taking placebo. There was no effect on in situ disease. Further analysis showed that the number of advanced cancers was comparable between the two groups of patients, but there were fewer cases of localized disease in the CEE group.

“In the completed trial database, the invasive breast cancer incidence did not differ significantly between the CEE group and the placebo group,” investigators said.

After 1 year of therapy, the percentage of abnormal mammograms was “substantially higher” in the CEE group (9.2%) than in the placebo group (5.5%). This pattern held constant for each year thereafter, for a cumulative rate of 36.2% in the CEE group and 28.1% in the placebo group.

By the end of the study, women in the CEE group had undergone 198 biopsies or aspirations that yielded negative findings, Dr. Stefanick and her associates noted.

The percentage of mammograms showing “suspicious” rather than simply abnormal findings was similar for both groups, as was the percentage of mammograms that were highly suggestive of malignancy. In contrast to these findings, the results of the CEE plus progesterone portion of the WHI trial showed a definite increase in invasive breast cancers with combined therapy, as well as a definite increase in mammograms deemed “suspicious” or “highly suggestive of malignancy,” they noted.

After 1 year, 9.2% of the women on estrogen and 5.5% in the placebo group had abnormal mammograms. DR. STEFANICK