Mary Ann Moon

Women who have placental syndromes are at high risk for premature cardiovascular disease, particularly if there is associated fetal compromise, according to Dr. Joel G. Ray, of the University of Toronto, and his associates.

The level of cardiovascular risk that is conferred by a placental syndrome—preeclampsia, gestational hypertension, placental abruption, or placental infarction—is comparable with that of such conventional risk factors as hypertension, obesity, diabetes, and dyslipidemia.

“We believe that maternal placental syndrome should be considered an additional risk factor for cardiovascular disease in women, especially when the woman's fetus is adversely affected,” Dr. Ray, of the division of obstetrics and gynecology at the university, and his associates said (Lancet 2005;366:1797–803).

They assessed cardiovascular outcomes in a population-based study of Ontario residents who gave birth between 1990 and 2004. The mean maternal age at delivery was 28 years. Of the 1,026,265 subjects, 75,380 (7%) were diagnosed as having a placental syndrome.

After a mean of 8.7 years' follow-up, cardiovascular events occurred in more than twice as many women with placental syndromes as in women without placental syndromes, irrespective of the presence of potential confounders such as diabetes.

The rate of events was 500/million person-years among those with placental syndromes, compared with 200/million in those without placental syndromes.

The women's mean age was 38 years at the time of the first cardiovascular event. These included coronary, cerebrovascular, or peripheral artery events, or the need for a revascularization procedure.

The risk for cardiovascular events was even higher if the placental syndromes led to fetal growth restriction or intrauterine fetal death. It was higher still in women who had preexisting cardiovascular risk factors when they became pregnant, such as smoking or various features of the metabolic syndrome.

The findings do not imply that placental disorders cause cardiovascular events to occur in the near future, the investigators cautioned.

“Rather, a more plausible explanation relates to a woman's abnormal metabolic milieu that predates her pregnancy and continues after delivery. This chronic state of dysmetabolism might create an inhospitable environment during the development of the placental spiral arteries, which can adversely affect fetal health, while negatively affecting the large arteries of a woman's heart, brain, and extremities over a broader period of time,” researchers noted.

Physicians “should try to ensure that women are a healthy weight before they enter their reproductive years.” This should reduce their risk for placental syndromes and fetal compromise as well as for cardiovascular disease, Dr. Ray and his associates said.

It remains unknown whether women who have had placental syndromes might be able to lower their risk of premature cardiovascular disease by making lifestyle modifications, they added.

Women who have placental syndromes are at high risk for premature cardiovascular disease, particularly if there is associated fetal compromise, according to Dr. Joel G. Ray, of the University of Toronto, and his associates.

The level of cardiovascular risk that is conferred by a placental syndrome—preeclampsia, gestational hypertension, placental abruption, or placental infarction—is comparable with that of such conventional risk factors as hypertension, obesity, diabetes, and dyslipidemia.

“We believe that maternal placental syndrome should be considered an additional risk factor for cardiovascular disease in women, especially when the woman's fetus is adversely affected,” Dr. Ray, of the division of obstetrics and gynecology at the university, and his associates said (Lancet 2005;366:1797–803).

They assessed cardiovascular outcomes in a population-based study of Ontario residents who gave birth between 1990 and 2004. The mean maternal age at delivery was 28 years. Of the 1,026,265 subjects, 75,380 (7%) were diagnosed as having a placental syndrome.

After a mean of 8.7 years' follow-up, cardiovascular events occurred in more than twice as many women with placental syndromes as in women without placental syndromes, irrespective of the presence of potential confounders such as diabetes.

The rate of events was 500/million person-years among those with placental syndromes, compared with 200/million in those without placental syndromes.

The women's mean age was 38 years at the time of the first cardiovascular event. These included coronary, cerebrovascular, or peripheral artery events, or the need for a revascularization procedure.

The risk for cardiovascular events was even higher if the placental syndromes led to fetal growth restriction or intrauterine fetal death. It was higher still in women who had preexisting cardiovascular risk factors when they became pregnant, such as smoking or various features of the metabolic syndrome.

The findings do not imply that placental disorders cause cardiovascular events to occur in the near future, the investigators cautioned.

“Rather, a more plausible explanation relates to a woman's abnormal metabolic milieu that predates her pregnancy and continues after delivery. This chronic state of dysmetabolism might create an inhospitable environment during the development of the placental spiral arteries, which can adversely affect fetal health, while negatively affecting the large arteries of a woman's heart, brain, and extremities over a broader period of time,” researchers noted.

Physicians “should try to ensure that women are a healthy weight before they enter their reproductive years.” This should reduce their risk for placental syndromes and fetal compromise as well as for cardiovascular disease, Dr. Ray and his associates said.

It remains unknown whether women who have had placental syndromes might be able to lower their risk of premature cardiovascular disease by making lifestyle modifications, they added.

Women who have placental syndromes are at high risk for premature cardiovascular disease, particularly if there is associated fetal compromise, according to Dr. Joel G. Ray, of the University of Toronto, and his associates.

The level of cardiovascular risk that is conferred by a placental syndrome—preeclampsia, gestational hypertension, placental abruption, or placental infarction—is comparable with that of such conventional risk factors as hypertension, obesity, diabetes, and dyslipidemia.

“We believe that maternal placental syndrome should be considered an additional risk factor for cardiovascular disease in women, especially when the woman's fetus is adversely affected,” Dr. Ray, of the division of obstetrics and gynecology at the university, and his associates said (Lancet 2005;366:1797–803).

They assessed cardiovascular outcomes in a population-based study of Ontario residents who gave birth between 1990 and 2004. The mean maternal age at delivery was 28 years. Of the 1,026,265 subjects, 75,380 (7%) were diagnosed as having a placental syndrome.

After a mean of 8.7 years' follow-up, cardiovascular events occurred in more than twice as many women with placental syndromes as in women without placental syndromes, irrespective of the presence of potential confounders such as diabetes.

The rate of events was 500/million person-years among those with placental syndromes, compared with 200/million in those without placental syndromes.

The women's mean age was 38 years at the time of the first cardiovascular event. These included coronary, cerebrovascular, or peripheral artery events, or the need for a revascularization procedure.

The risk for cardiovascular events was even higher if the placental syndromes led to fetal growth restriction or intrauterine fetal death. It was higher still in women who had preexisting cardiovascular risk factors when they became pregnant, such as smoking or various features of the metabolic syndrome.

The findings do not imply that placental disorders cause cardiovascular events to occur in the near future, the investigators cautioned.

“Rather, a more plausible explanation relates to a woman's abnormal metabolic milieu that predates her pregnancy and continues after delivery. This chronic state of dysmetabolism might create an inhospitable environment during the development of the placental spiral arteries, which can adversely affect fetal health, while negatively affecting the large arteries of a woman's heart, brain, and extremities over a broader period of time,” researchers noted.

Physicians “should try to ensure that women are a healthy weight before they enter their reproductive years.” This should reduce their risk for placental syndromes and fetal compromise as well as for cardiovascular disease, Dr. Ray and his associates said.

It remains unknown whether women who have had placental syndromes might be able to lower their risk of premature cardiovascular disease by making lifestyle modifications, they added.

Plasma concentration of apolipoprotein B is a slightly better predictor of coronary heart disease than is non-HDL cholesterol and a much better predictor than is LDL cholesterol, reported Dr. Tobias Pischon of the Harvard School of Public Health, Boston, and his associates.

This finding is sure to add to the controversy over which lipid measurement is the best for assessing both coronary risk and treatment efficacy. According to current National Cholesterol Education Program guidelines, LDL cholesterol is recommended as the primary target for lipid-lowering therapy, HDL cholesterol is considered a secondary treatment target, and apolipoprotein B (apoB) is not considered a target at all, the investigators said.

In the first large prospective study to directly compare these three measures, apoB was the best predictor of coronary heart disease (CHD) risk (Circulation 2005;112:3375–83). The researchers used a database of more than 51,000 male health professionals who had been followed every 2 years since 1986 to identify 243 subjects who had developed CHD during a 6-year study period and 496 matched control subjects who had not developed the disease. The baseline level of apoB was the strongest predictor of CHD, with a relative risk of 2.98. The concentration of non-HDL cholesterol also was strongly predictive, with a relative risk of 2.75, and the LDL cholesterol level was predictive but less so, with a relative risk of 2.07.

“The practical application of our findings,” the investigators wrote, would be to switch from assessing LDL and non-HDL cholesterol in screening and treatment of CHD to assessing apoB instead. However, the cost of such a switch relative to the potential improvement in risk assessment “needs to be further evaluated,” they said.

Plasma concentration of apolipoprotein B is a slightly better predictor of coronary heart disease than is non-HDL cholesterol and a much better predictor than is LDL cholesterol, reported Dr. Tobias Pischon of the Harvard School of Public Health, Boston, and his associates.

This finding is sure to add to the controversy over which lipid measurement is the best for assessing both coronary risk and treatment efficacy. According to current National Cholesterol Education Program guidelines, LDL cholesterol is recommended as the primary target for lipid-lowering therapy, HDL cholesterol is considered a secondary treatment target, and apolipoprotein B (apoB) is not considered a target at all, the investigators said.

In the first large prospective study to directly compare these three measures, apoB was the best predictor of coronary heart disease (CHD) risk (Circulation 2005;112:3375–83). The researchers used a database of more than 51,000 male health professionals who had been followed every 2 years since 1986 to identify 243 subjects who had developed CHD during a 6-year study period and 496 matched control subjects who had not developed the disease. The baseline level of apoB was the strongest predictor of CHD, with a relative risk of 2.98. The concentration of non-HDL cholesterol also was strongly predictive, with a relative risk of 2.75, and the LDL cholesterol level was predictive but less so, with a relative risk of 2.07.

“The practical application of our findings,” the investigators wrote, would be to switch from assessing LDL and non-HDL cholesterol in screening and treatment of CHD to assessing apoB instead. However, the cost of such a switch relative to the potential improvement in risk assessment “needs to be further evaluated,” they said.

Plasma concentration of apolipoprotein B is a slightly better predictor of coronary heart disease than is non-HDL cholesterol and a much better predictor than is LDL cholesterol, reported Dr. Tobias Pischon of the Harvard School of Public Health, Boston, and his associates.

This finding is sure to add to the controversy over which lipid measurement is the best for assessing both coronary risk and treatment efficacy. According to current National Cholesterol Education Program guidelines, LDL cholesterol is recommended as the primary target for lipid-lowering therapy, HDL cholesterol is considered a secondary treatment target, and apolipoprotein B (apoB) is not considered a target at all, the investigators said.

In the first large prospective study to directly compare these three measures, apoB was the best predictor of coronary heart disease (CHD) risk (Circulation 2005;112:3375–83). The researchers used a database of more than 51,000 male health professionals who had been followed every 2 years since 1986 to identify 243 subjects who had developed CHD during a 6-year study period and 496 matched control subjects who had not developed the disease. The baseline level of apoB was the strongest predictor of CHD, with a relative risk of 2.98. The concentration of non-HDL cholesterol also was strongly predictive, with a relative risk of 2.75, and the LDL cholesterol level was predictive but less so, with a relative risk of 2.07.

“The practical application of our findings,” the investigators wrote, would be to switch from assessing LDL and non-HDL cholesterol in screening and treatment of CHD to assessing apoB instead. However, the cost of such a switch relative to the potential improvement in risk assessment “needs to be further evaluated,” they said.

Fiber Not a Factor in Colorectal Cancer

Dietary fiber intake showed no effect on the risk of colorectal cancer in an analysis that pooled data from 13 prospective cohort studies, reported Dr. Yikyung Park of Harvard School of Public Health, Boston, and associates.

Each of the 13 studies that Dr. Park and associates identified for their analysis included at least 50 cases of colorectal cancer and adequately assessed dietary fiber intake. The pooled data yielded over 7,300,000 person-years of follow-up (6–20 years of follow-up across the studies), and included incident colorectal cancer cases in 2,776 men and 5,305 women. The analysis had a level of statistical power such that “a substantial effect of fiber is unlikely to have been missed,” the investigators said (JAMA 2005;294:2849–57).

The pooled analysis was undertaken because the results of many epidemiologic studies and randomized clinical trials have been conflicting, and there is still much debate over whether dietary fiber decreases colorectal cancer risk.

The initial, age-adjusted analysis showed a significant link between fiber and reduced colorectal cancer risk, with the highest levels of intake associated with a 16% lower risk than the lowest fiber intakes. However, after the data were adjusted for potential confounders including nondietary factors, milk and red meat intake, and alcohol consumption, “only a nonsignificant weak inverse association was found,” they said. In addition, dietary fiber showed no effect on cancer risk when the data were categorized by subjects' body mass index or by specific food sources of fiber.

COX-2 Inhibitors vs. NSAIDs for Safety

Cyclooxygenase-2 inhibitors were found to be no safer than nonselective NSAIDs in averting adverse gastrointestinal events in a large observational study conducted in the United Kingdom.

The finding is important “given that enhanced gastrointestinal safety has been one of the main justifications for these drugs,” wrote Dr. Julia Hippisley-Cox and her associates at the University of Nottingham (England). The COX-2 inhibitors were developed to relieve pain without inducing the GI side effects common with NSAIDs, but data on their long-term safety are lacking.

The researchers calculated the risk of GI events in patients who took these prescription pain relievers between 2000 and 2004. After reviewing the medical records in a database of more than 7 million patients treated at general practices throughout England, Scotland, and Wales, the investigators identified 9,407 who had an adverse GI event and matched them with more than 88,000 controls who had no such events (BMJ 2005;331:1310–6).

Patients with GI events were more likely to have taken either prescription NSAIDs (odds ratio 1.69) or prescription COX-2 inhibitors (odds ratio 1.89) than were control subjects.

The researchers also found that the concomitant use of ulcer-healing drugs reduces the GI risks of COX-2 inhibitors, which suggests “that there is some risk to protect against.” Taken together, these results indicate that COX-2 inhibitors “may not be as safe as originally thought,” the authors said.

Insulin and Pancreatic Cancer Risk

Both high insulin concentrations and insulin resistance appear to be associated with increased risk of pancreatic cancer, reported Rachael Z. Stolzenberg-Solomon, Ph.D., of the National Cancer Institute, Rockville, Md., and her associates.

In a large study of pancreatic cancer in male smokers, men who self-reported that they had diabetes had a twofold increase in risk for the malignancy. The investigators used the same patient population to further examine the issue, assessing whether fasting serum insulin concentrations predicted development of pancreatic cancer.

The subjects included more than 29,000 Finnish men ages 50–69 years at study entry (1985–1988). Baseline serum insulin and glucose levels were analyzed in 169 men who developed pancreatic cancer during a mean of 16 years of follow-up and in 400 randomly selected participants without pancreatic cancer who served as controls.

After the data were adjusted for age, years of smoking, and body mass index, the risk for pancreatic cancer was found to rise as insulin levels increased and as the degree of insulin resistance worsened. Subjects with established diabetes and the highest insulin levels were at twice the risk for pancreatic cancer as controls, the investigators said (JAMA 2005;294:2872–8).

Although researchers have noted an association between diabetes and pancreatic cancer for some time, it is unclear whether diabetes somehow contributes to carcinogenesis in the pancreas or is instead a result of subclinical pancreatic malignancy. In this study, Dr. Stolzenberg-Solomon and her associates included only cases of pancreatic cancer that developed 5 years or more after serum samples were collected.

Fiber Not a Factor in Colorectal Cancer

Dietary fiber intake showed no effect on the risk of colorectal cancer in an analysis that pooled data from 13 prospective cohort studies, reported Dr. Yikyung Park of Harvard School of Public Health, Boston, and associates.

Each of the 13 studies that Dr. Park and associates identified for their analysis included at least 50 cases of colorectal cancer and adequately assessed dietary fiber intake. The pooled data yielded over 7,300,000 person-years of follow-up (6–20 years of follow-up across the studies), and included incident colorectal cancer cases in 2,776 men and 5,305 women. The analysis had a level of statistical power such that “a substantial effect of fiber is unlikely to have been missed,” the investigators said (JAMA 2005;294:2849–57).

The pooled analysis was undertaken because the results of many epidemiologic studies and randomized clinical trials have been conflicting, and there is still much debate over whether dietary fiber decreases colorectal cancer risk.

The initial, age-adjusted analysis showed a significant link between fiber and reduced colorectal cancer risk, with the highest levels of intake associated with a 16% lower risk than the lowest fiber intakes. However, after the data were adjusted for potential confounders including nondietary factors, milk and red meat intake, and alcohol consumption, “only a nonsignificant weak inverse association was found,” they said. In addition, dietary fiber showed no effect on cancer risk when the data were categorized by subjects' body mass index or by specific food sources of fiber.

COX-2 Inhibitors vs. NSAIDs for Safety

Cyclooxygenase-2 inhibitors were found to be no safer than nonselective NSAIDs in averting adverse gastrointestinal events in a large observational study conducted in the United Kingdom.

The finding is important “given that enhanced gastrointestinal safety has been one of the main justifications for these drugs,” wrote Dr. Julia Hippisley-Cox and her associates at the University of Nottingham (England). The COX-2 inhibitors were developed to relieve pain without inducing the GI side effects common with NSAIDs, but data on their long-term safety are lacking.

The researchers calculated the risk of GI events in patients who took these prescription pain relievers between 2000 and 2004. After reviewing the medical records in a database of more than 7 million patients treated at general practices throughout England, Scotland, and Wales, the investigators identified 9,407 who had an adverse GI event and matched them with more than 88,000 controls who had no such events (BMJ 2005;331:1310–6).

Patients with GI events were more likely to have taken either prescription NSAIDs (odds ratio 1.69) or prescription COX-2 inhibitors (odds ratio 1.89) than were control subjects.

The researchers also found that the concomitant use of ulcer-healing drugs reduces the GI risks of COX-2 inhibitors, which suggests “that there is some risk to protect against.” Taken together, these results indicate that COX-2 inhibitors “may not be as safe as originally thought,” the authors said.

Insulin and Pancreatic Cancer Risk

Both high insulin concentrations and insulin resistance appear to be associated with increased risk of pancreatic cancer, reported Rachael Z. Stolzenberg-Solomon, Ph.D., of the National Cancer Institute, Rockville, Md., and her associates.

In a large study of pancreatic cancer in male smokers, men who self-reported that they had diabetes had a twofold increase in risk for the malignancy. The investigators used the same patient population to further examine the issue, assessing whether fasting serum insulin concentrations predicted development of pancreatic cancer.

The subjects included more than 29,000 Finnish men ages 50–69 years at study entry (1985–1988). Baseline serum insulin and glucose levels were analyzed in 169 men who developed pancreatic cancer during a mean of 16 years of follow-up and in 400 randomly selected participants without pancreatic cancer who served as controls.

After the data were adjusted for age, years of smoking, and body mass index, the risk for pancreatic cancer was found to rise as insulin levels increased and as the degree of insulin resistance worsened. Subjects with established diabetes and the highest insulin levels were at twice the risk for pancreatic cancer as controls, the investigators said (JAMA 2005;294:2872–8).

Although researchers have noted an association between diabetes and pancreatic cancer for some time, it is unclear whether diabetes somehow contributes to carcinogenesis in the pancreas or is instead a result of subclinical pancreatic malignancy. In this study, Dr. Stolzenberg-Solomon and her associates included only cases of pancreatic cancer that developed 5 years or more after serum samples were collected.

Fiber Not a Factor in Colorectal Cancer

Dietary fiber intake showed no effect on the risk of colorectal cancer in an analysis that pooled data from 13 prospective cohort studies, reported Dr. Yikyung Park of Harvard School of Public Health, Boston, and associates.

Each of the 13 studies that Dr. Park and associates identified for their analysis included at least 50 cases of colorectal cancer and adequately assessed dietary fiber intake. The pooled data yielded over 7,300,000 person-years of follow-up (6–20 years of follow-up across the studies), and included incident colorectal cancer cases in 2,776 men and 5,305 women. The analysis had a level of statistical power such that “a substantial effect of fiber is unlikely to have been missed,” the investigators said (JAMA 2005;294:2849–57).

The pooled analysis was undertaken because the results of many epidemiologic studies and randomized clinical trials have been conflicting, and there is still much debate over whether dietary fiber decreases colorectal cancer risk.

The initial, age-adjusted analysis showed a significant link between fiber and reduced colorectal cancer risk, with the highest levels of intake associated with a 16% lower risk than the lowest fiber intakes. However, after the data were adjusted for potential confounders including nondietary factors, milk and red meat intake, and alcohol consumption, “only a nonsignificant weak inverse association was found,” they said. In addition, dietary fiber showed no effect on cancer risk when the data were categorized by subjects' body mass index or by specific food sources of fiber.

COX-2 Inhibitors vs. NSAIDs for Safety

Cyclooxygenase-2 inhibitors were found to be no safer than nonselective NSAIDs in averting adverse gastrointestinal events in a large observational study conducted in the United Kingdom.

The finding is important “given that enhanced gastrointestinal safety has been one of the main justifications for these drugs,” wrote Dr. Julia Hippisley-Cox and her associates at the University of Nottingham (England). The COX-2 inhibitors were developed to relieve pain without inducing the GI side effects common with NSAIDs, but data on their long-term safety are lacking.

The researchers calculated the risk of GI events in patients who took these prescription pain relievers between 2000 and 2004. After reviewing the medical records in a database of more than 7 million patients treated at general practices throughout England, Scotland, and Wales, the investigators identified 9,407 who had an adverse GI event and matched them with more than 88,000 controls who had no such events (BMJ 2005;331:1310–6).

Patients with GI events were more likely to have taken either prescription NSAIDs (odds ratio 1.69) or prescription COX-2 inhibitors (odds ratio 1.89) than were control subjects.

The researchers also found that the concomitant use of ulcer-healing drugs reduces the GI risks of COX-2 inhibitors, which suggests “that there is some risk to protect against.” Taken together, these results indicate that COX-2 inhibitors “may not be as safe as originally thought,” the authors said.

Insulin and Pancreatic Cancer Risk

Both high insulin concentrations and insulin resistance appear to be associated with increased risk of pancreatic cancer, reported Rachael Z. Stolzenberg-Solomon, Ph.D., of the National Cancer Institute, Rockville, Md., and her associates.

In a large study of pancreatic cancer in male smokers, men who self-reported that they had diabetes had a twofold increase in risk for the malignancy. The investigators used the same patient population to further examine the issue, assessing whether fasting serum insulin concentrations predicted development of pancreatic cancer.

The subjects included more than 29,000 Finnish men ages 50–69 years at study entry (1985–1988). Baseline serum insulin and glucose levels were analyzed in 169 men who developed pancreatic cancer during a mean of 16 years of follow-up and in 400 randomly selected participants without pancreatic cancer who served as controls.

After the data were adjusted for age, years of smoking, and body mass index, the risk for pancreatic cancer was found to rise as insulin levels increased and as the degree of insulin resistance worsened. Subjects with established diabetes and the highest insulin levels were at twice the risk for pancreatic cancer as controls, the investigators said (JAMA 2005;294:2872–8).

Although researchers have noted an association between diabetes and pancreatic cancer for some time, it is unclear whether diabetes somehow contributes to carcinogenesis in the pancreas or is instead a result of subclinical pancreatic malignancy. In this study, Dr. Stolzenberg-Solomon and her associates included only cases of pancreatic cancer that developed 5 years or more after serum samples were collected.

Elderly patients with subclinical hypothyroidism have a higher rate of congestive heart failure than do those who are euthyroid, according to Dr. Nicolas Rodondi of the University of California, San Francisco, and his associates.

Overt hypothyroidism is known to be associated with cardiovascular disease (CVD), but studies evaluating a possible link between subclinical hypothyroidism and CVD have produced conflicting results. Dr. Rodondi and his associates conducted what they described as the first prospective study to assess the risk of heart failure (HF) events in subjects with subclinical hypothyroidism.

The investigators assessed thyrotropin levels in 2,730 men and women aged 70–79 years who were participating in a large cohort study of aging. The subjects were followed for 4 years to determine whether these hormone levels were related to HF or other cardiovascular disease events.

A total of 338 subjects (12.4%) were found to have subclinical hypothyroidism, defined as an elevated level of thyrotropin and a normal level of free thyroxine (T₄). During follow-up, 178 subjects had HF events (Arch. Intern. Med. 2005;165:2460–6).

Subjects with moderately to severely elevated thyrotropin levels (7.0 mIU/L or greater) had more HF events (35 per 1,000 person-years) than did those who were euthyroid (17 per 1,000 person-years). Each standard deviation increase of 4.0 mIU/L was associated with a 30% increase in HF events.

This link was stronger among subjects known to have previous HF events. The rate of recurrent HF events was seven times higher in those with subclinical hypothyroidism than in those who were euthyroid.

In contrast, subjects with mildly elevated thyrotropin (4.5–6.9 mIU/L) did not have higher HF event rates. Subclinical hypothyroidism was not found to be associated with other coronary heart disease events, stroke, peripheral arterial disease, CVD-related mortality, or total mortality.

These results suggest that further study is warranted to determine whether subclinical hypothyroidism causes heart failure or worsens existing heart failure, Dr. Rodondi and his associates said.

In an editorial that accompanied the article, Dr. Lawrence M. Crapo of Santa Clara Valley Medical Center, San Jose, Calif., noted these findings “certainly support the idea that the treatment of severe subclinical hypothyroidism with levothyroxine in patients younger than 80 years may be beneficial, but this remains to be proved in a randomized prospective therapeutic trial.”

The results further indicate that patients with mild hypothyroidism probably would not benefit from levothyroxine treatment, Dr. Crapo said (Arch. Intern. Med. 2005;165:2451–2).

Elderly patients with subclinical hypothyroidism have a higher rate of congestive heart failure than do those who are euthyroid, according to Dr. Nicolas Rodondi of the University of California, San Francisco, and his associates.

Overt hypothyroidism is known to be associated with cardiovascular disease (CVD), but studies evaluating a possible link between subclinical hypothyroidism and CVD have produced conflicting results. Dr. Rodondi and his associates conducted what they described as the first prospective study to assess the risk of heart failure (HF) events in subjects with subclinical hypothyroidism.

The investigators assessed thyrotropin levels in 2,730 men and women aged 70–79 years who were participating in a large cohort study of aging. The subjects were followed for 4 years to determine whether these hormone levels were related to HF or other cardiovascular disease events.

A total of 338 subjects (12.4%) were found to have subclinical hypothyroidism, defined as an elevated level of thyrotropin and a normal level of free thyroxine (T₄). During follow-up, 178 subjects had HF events (Arch. Intern. Med. 2005;165:2460–6).

Subjects with moderately to severely elevated thyrotropin levels (7.0 mIU/L or greater) had more HF events (35 per 1,000 person-years) than did those who were euthyroid (17 per 1,000 person-years). Each standard deviation increase of 4.0 mIU/L was associated with a 30% increase in HF events.

This link was stronger among subjects known to have previous HF events. The rate of recurrent HF events was seven times higher in those with subclinical hypothyroidism than in those who were euthyroid.

In contrast, subjects with mildly elevated thyrotropin (4.5–6.9 mIU/L) did not have higher HF event rates. Subclinical hypothyroidism was not found to be associated with other coronary heart disease events, stroke, peripheral arterial disease, CVD-related mortality, or total mortality.

These results suggest that further study is warranted to determine whether subclinical hypothyroidism causes heart failure or worsens existing heart failure, Dr. Rodondi and his associates said.

In an editorial that accompanied the article, Dr. Lawrence M. Crapo of Santa Clara Valley Medical Center, San Jose, Calif., noted these findings “certainly support the idea that the treatment of severe subclinical hypothyroidism with levothyroxine in patients younger than 80 years may be beneficial, but this remains to be proved in a randomized prospective therapeutic trial.”

The results further indicate that patients with mild hypothyroidism probably would not benefit from levothyroxine treatment, Dr. Crapo said (Arch. Intern. Med. 2005;165:2451–2).

Elderly patients with subclinical hypothyroidism have a higher rate of congestive heart failure than do those who are euthyroid, according to Dr. Nicolas Rodondi of the University of California, San Francisco, and his associates.

Overt hypothyroidism is known to be associated with cardiovascular disease (CVD), but studies evaluating a possible link between subclinical hypothyroidism and CVD have produced conflicting results. Dr. Rodondi and his associates conducted what they described as the first prospective study to assess the risk of heart failure (HF) events in subjects with subclinical hypothyroidism.

The investigators assessed thyrotropin levels in 2,730 men and women aged 70–79 years who were participating in a large cohort study of aging. The subjects were followed for 4 years to determine whether these hormone levels were related to HF or other cardiovascular disease events.

A total of 338 subjects (12.4%) were found to have subclinical hypothyroidism, defined as an elevated level of thyrotropin and a normal level of free thyroxine (T₄). During follow-up, 178 subjects had HF events (Arch. Intern. Med. 2005;165:2460–6).

Subjects with moderately to severely elevated thyrotropin levels (7.0 mIU/L or greater) had more HF events (35 per 1,000 person-years) than did those who were euthyroid (17 per 1,000 person-years). Each standard deviation increase of 4.0 mIU/L was associated with a 30% increase in HF events.

This link was stronger among subjects known to have previous HF events. The rate of recurrent HF events was seven times higher in those with subclinical hypothyroidism than in those who were euthyroid.

In contrast, subjects with mildly elevated thyrotropin (4.5–6.9 mIU/L) did not have higher HF event rates. Subclinical hypothyroidism was not found to be associated with other coronary heart disease events, stroke, peripheral arterial disease, CVD-related mortality, or total mortality.

These results suggest that further study is warranted to determine whether subclinical hypothyroidism causes heart failure or worsens existing heart failure, Dr. Rodondi and his associates said.

In an editorial that accompanied the article, Dr. Lawrence M. Crapo of Santa Clara Valley Medical Center, San Jose, Calif., noted these findings “certainly support the idea that the treatment of severe subclinical hypothyroidism with levothyroxine in patients younger than 80 years may be beneficial, but this remains to be proved in a randomized prospective therapeutic trial.”

The results further indicate that patients with mild hypothyroidism probably would not benefit from levothyroxine treatment, Dr. Crapo said (Arch. Intern. Med. 2005;165:2451–2).

High-risk patients with acute coronary syndromes remain likely candidates for further cardiovascular events and death at 1-year follow-up despite receiving aggressive intervention, according to Kenneth W. Mahaffey, M.D., and his associates.

The short-term (30-day) results of the Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial were widely reported in 2004. The study involved more than 10,000 patients with acute coronary syndromes (ACS) treated in 12 countries, who were randomly assigned to receive either low-molecular-weight heparin (enoxaparin) or unfractionated heparin, and who were also treated with an early invasive management strategy.

More than 70% of the patients underwent percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery. Most (92%) also received aspirin, clopidogrel (54%), β-blockers (85%), ACE inhibitors (73%), and/or statins (81%), according to the discretion of their clinicians.

The SYNERGY investigators continued their follow-up and reported their long-term results. At the 6-month and 1-year marks, these patients remained at high risk for recurrent cardiovascular complications and death.

“Overall, nearly 18% died or experienced nonfatal MI [at] 6 months of follow-up, and 7% died by 1-year follow-up, despite aggressive coronary revascularization and high use of evidence-based therapies at the time of hospital discharge,” the researchers said (JAMA 2005;294:2594–600).

Outcomes were even worse for the highest-risk patients, defined as those aged 60 years or older, those with elevated levels of cardiac biomarkers, and those with adverse ECG changes. Among such patients, 21% had either died or sustained a nonfatal MI within 6 months of their initial ACS, and 10% had died within 1 year.

“These rates of morbidity and mortality are higher than those reported in virtually all contemporary non-ST-segment elevation ACS trials,” reported Dr. Mahaffey, of Duke Clinical Research Institute, Durham, N.C., and his associates.

“It is clear that patients with an ACS event with high-risk baseline features are at substantial risk for adverse cardiac events over time,” they noted.

Researchers found that the two anticoagulants performed equally well in the long term, as they had in the short term. There were no significant differences between patients who received enoxaparin and those who received unfractionated heparin in rates of hospital readmission (18% and 19.0%, respectively) or death (7.7% and 7.3%).

Stroke was a rare occurrence in both treatment groups, affecting 1.5% of those given enoxaparin and 1.6% of those given unfractionated heparin, the researchers reported.

High-risk patients with acute coronary syndromes remain likely candidates for further cardiovascular events and death at 1-year follow-up despite receiving aggressive intervention, according to Kenneth W. Mahaffey, M.D., and his associates.

The short-term (30-day) results of the Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial were widely reported in 2004. The study involved more than 10,000 patients with acute coronary syndromes (ACS) treated in 12 countries, who were randomly assigned to receive either low-molecular-weight heparin (enoxaparin) or unfractionated heparin, and who were also treated with an early invasive management strategy.

More than 70% of the patients underwent percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery. Most (92%) also received aspirin, clopidogrel (54%), β-blockers (85%), ACE inhibitors (73%), and/or statins (81%), according to the discretion of their clinicians.

The SYNERGY investigators continued their follow-up and reported their long-term results. At the 6-month and 1-year marks, these patients remained at high risk for recurrent cardiovascular complications and death.

“Overall, nearly 18% died or experienced nonfatal MI [at] 6 months of follow-up, and 7% died by 1-year follow-up, despite aggressive coronary revascularization and high use of evidence-based therapies at the time of hospital discharge,” the researchers said (JAMA 2005;294:2594–600).

Outcomes were even worse for the highest-risk patients, defined as those aged 60 years or older, those with elevated levels of cardiac biomarkers, and those with adverse ECG changes. Among such patients, 21% had either died or sustained a nonfatal MI within 6 months of their initial ACS, and 10% had died within 1 year.

“These rates of morbidity and mortality are higher than those reported in virtually all contemporary non-ST-segment elevation ACS trials,” reported Dr. Mahaffey, of Duke Clinical Research Institute, Durham, N.C., and his associates.

“It is clear that patients with an ACS event with high-risk baseline features are at substantial risk for adverse cardiac events over time,” they noted.

Researchers found that the two anticoagulants performed equally well in the long term, as they had in the short term. There were no significant differences between patients who received enoxaparin and those who received unfractionated heparin in rates of hospital readmission (18% and 19.0%, respectively) or death (7.7% and 7.3%).

Stroke was a rare occurrence in both treatment groups, affecting 1.5% of those given enoxaparin and 1.6% of those given unfractionated heparin, the researchers reported.

High-risk patients with acute coronary syndromes remain likely candidates for further cardiovascular events and death at 1-year follow-up despite receiving aggressive intervention, according to Kenneth W. Mahaffey, M.D., and his associates.

The short-term (30-day) results of the Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial were widely reported in 2004. The study involved more than 10,000 patients with acute coronary syndromes (ACS) treated in 12 countries, who were randomly assigned to receive either low-molecular-weight heparin (enoxaparin) or unfractionated heparin, and who were also treated with an early invasive management strategy.

More than 70% of the patients underwent percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery. Most (92%) also received aspirin, clopidogrel (54%), β-blockers (85%), ACE inhibitors (73%), and/or statins (81%), according to the discretion of their clinicians.

The SYNERGY investigators continued their follow-up and reported their long-term results. At the 6-month and 1-year marks, these patients remained at high risk for recurrent cardiovascular complications and death.

“Overall, nearly 18% died or experienced nonfatal MI [at] 6 months of follow-up, and 7% died by 1-year follow-up, despite aggressive coronary revascularization and high use of evidence-based therapies at the time of hospital discharge,” the researchers said (JAMA 2005;294:2594–600).

Outcomes were even worse for the highest-risk patients, defined as those aged 60 years or older, those with elevated levels of cardiac biomarkers, and those with adverse ECG changes. Among such patients, 21% had either died or sustained a nonfatal MI within 6 months of their initial ACS, and 10% had died within 1 year.

“These rates of morbidity and mortality are higher than those reported in virtually all contemporary non-ST-segment elevation ACS trials,” reported Dr. Mahaffey, of Duke Clinical Research Institute, Durham, N.C., and his associates.

“It is clear that patients with an ACS event with high-risk baseline features are at substantial risk for adverse cardiac events over time,” they noted.

Researchers found that the two anticoagulants performed equally well in the long term, as they had in the short term. There were no significant differences between patients who received enoxaparin and those who received unfractionated heparin in rates of hospital readmission (18% and 19.0%, respectively) or death (7.7% and 7.3%).

Stroke was a rare occurrence in both treatment groups, affecting 1.5% of those given enoxaparin and 1.6% of those given unfractionated heparin, the researchers reported.

Elderly patients with subclinical hypothyroidism have a higher rate of congestive heart failure than do those who are euthyroid, according to Dr. Nicolas Rodondi, of the University of California, San Francisco, and associates.

Overt hypothyroidism is known to be associated with cardiovascular disease (CVD), but studies evaluating a possible link between subclinical hypothyroidism and CVD have produced conflicting results. Dr. Rodondi and his associates conducted what they described as the first prospective study to assess the risk of congestive heart failure (CHF) events in subjects with subclinical hypothyroidism.

The investigators assessed thyrotropin levels in 2,730 men and women aged 70-79 years who were participating in a large cohort study of aging. The subjects were followed for 4 years to determine whether these hormone levels were related to CHF or other cardiovascular disease events.

A total of 338 subjects (12.4%) were found to have subclinical hypothyroidism, defined as an elevated level of thyrotropin and a normal level of free thyroxine (T4). During follow-up, 178 subjects had CHF events (Arch. Intern. Med. 2005;165:2460-6).

Subjects with moderately to severely elevated thyrotropin levels (7.0 mIU/L or greater) had more CHF events (35.0 per 1,000 person-years) than did those who were euthyroid (16.5 per 1,000 person-years). Each standard deviation increase of 4.0 mIU/L was associated with a 30% increase in CHF events.

This link was even stronger among subjects known to have had previous CHF events. The rate of recurrent CHF events was seven times higher in those with subclinical hypothyroidism than in those who were euthyroid.

In contrast, subjects with mildly elevated thyrotropin (4.5-6.9 mIU/L) did not have higher rates of CHF events. Subclinical hypothyroidism was not found to be associated with other coronary heart disease events, stroke, peripheral arterial disease, CVD-related mortality, or total mortality.

In an editorial accompanying this report, Dr. Lawrence M. Crapo, of Santa Clara Valley Medical Center, San Jose, Calif., noted that these findings “certainly support the idea that the treatment of severe subclinical hypothyroidism with levothyroxine in patients younger than 80 years may be beneficial, but this remains to be proved in a randomized prospective therapeutic trial.”

The results further indicate that patients with mild hypothyroidism probably would not benefit from such treatment, Dr. Crapo said (Arch. Intern. Med. 2005;165:2451-2).

Elderly patients with subclinical hypothyroidism have a higher rate of congestive heart failure than do those who are euthyroid, according to Dr. Nicolas Rodondi, of the University of California, San Francisco, and associates.

Overt hypothyroidism is known to be associated with cardiovascular disease (CVD), but studies evaluating a possible link between subclinical hypothyroidism and CVD have produced conflicting results. Dr. Rodondi and his associates conducted what they described as the first prospective study to assess the risk of congestive heart failure (CHF) events in subjects with subclinical hypothyroidism.

The investigators assessed thyrotropin levels in 2,730 men and women aged 70-79 years who were participating in a large cohort study of aging. The subjects were followed for 4 years to determine whether these hormone levels were related to CHF or other cardiovascular disease events.

A total of 338 subjects (12.4%) were found to have subclinical hypothyroidism, defined as an elevated level of thyrotropin and a normal level of free thyroxine (T4). During follow-up, 178 subjects had CHF events (Arch. Intern. Med. 2005;165:2460-6).

Subjects with moderately to severely elevated thyrotropin levels (7.0 mIU/L or greater) had more CHF events (35.0 per 1,000 person-years) than did those who were euthyroid (16.5 per 1,000 person-years). Each standard deviation increase of 4.0 mIU/L was associated with a 30% increase in CHF events.

This link was even stronger among subjects known to have had previous CHF events. The rate of recurrent CHF events was seven times higher in those with subclinical hypothyroidism than in those who were euthyroid.

In contrast, subjects with mildly elevated thyrotropin (4.5-6.9 mIU/L) did not have higher rates of CHF events. Subclinical hypothyroidism was not found to be associated with other coronary heart disease events, stroke, peripheral arterial disease, CVD-related mortality, or total mortality.

In an editorial accompanying this report, Dr. Lawrence M. Crapo, of Santa Clara Valley Medical Center, San Jose, Calif., noted that these findings “certainly support the idea that the treatment of severe subclinical hypothyroidism with levothyroxine in patients younger than 80 years may be beneficial, but this remains to be proved in a randomized prospective therapeutic trial.”

The results further indicate that patients with mild hypothyroidism probably would not benefit from such treatment, Dr. Crapo said (Arch. Intern. Med. 2005;165:2451-2).

Elderly patients with subclinical hypothyroidism have a higher rate of congestive heart failure than do those who are euthyroid, according to Dr. Nicolas Rodondi, of the University of California, San Francisco, and associates.

Overt hypothyroidism is known to be associated with cardiovascular disease (CVD), but studies evaluating a possible link between subclinical hypothyroidism and CVD have produced conflicting results. Dr. Rodondi and his associates conducted what they described as the first prospective study to assess the risk of congestive heart failure (CHF) events in subjects with subclinical hypothyroidism.

The investigators assessed thyrotropin levels in 2,730 men and women aged 70-79 years who were participating in a large cohort study of aging. The subjects were followed for 4 years to determine whether these hormone levels were related to CHF or other cardiovascular disease events.

A total of 338 subjects (12.4%) were found to have subclinical hypothyroidism, defined as an elevated level of thyrotropin and a normal level of free thyroxine (T4). During follow-up, 178 subjects had CHF events (Arch. Intern. Med. 2005;165:2460-6).

Subjects with moderately to severely elevated thyrotropin levels (7.0 mIU/L or greater) had more CHF events (35.0 per 1,000 person-years) than did those who were euthyroid (16.5 per 1,000 person-years). Each standard deviation increase of 4.0 mIU/L was associated with a 30% increase in CHF events.

This link was even stronger among subjects known to have had previous CHF events. The rate of recurrent CHF events was seven times higher in those with subclinical hypothyroidism than in those who were euthyroid.

In contrast, subjects with mildly elevated thyrotropin (4.5-6.9 mIU/L) did not have higher rates of CHF events. Subclinical hypothyroidism was not found to be associated with other coronary heart disease events, stroke, peripheral arterial disease, CVD-related mortality, or total mortality.

In an editorial accompanying this report, Dr. Lawrence M. Crapo, of Santa Clara Valley Medical Center, San Jose, Calif., noted that these findings “certainly support the idea that the treatment of severe subclinical hypothyroidism with levothyroxine in patients younger than 80 years may be beneficial, but this remains to be proved in a randomized prospective therapeutic trial.”

The results further indicate that patients with mild hypothyroidism probably would not benefit from such treatment, Dr. Crapo said (Arch. Intern. Med. 2005;165:2451-2).

Testosterone replacement improved the quality of life for men with Alzheimer's disease and low serum testosterone levels in a small preliminary study, reported Po H. Lu, PsyD., and associates at the University of California, Los Angeles, David Geffen School of Medicine.

Testosterone therapy has been shown to improve mood, muscle mass, strength, bone density, libido, and certain cognitive functions in hypogonadal men who are otherwise healthy, but this is the first study to report that testosterone may exert positive effects in Alzheimer's disease (AD), the researchers said (Arch. Neurol. 2006;63:1–9).

They assessed testosterone's effects on a variety of cognitive, behavioral, mood, and quality of life (QOL) measures in 16 men with mild to moderate AD and 22 healthy elderly men who served as control subjects. The study subjects were randomly assigned to apply either testosterone patches (7 patients and 10 controls) or placebo patches (9 patients and 12 controls) every day for 6 months.

Five of the AD patients and six of the control subjects were hypogonadal at baseline, with serum testosterone levels below 298 ng/dL.

As a group, AD patients who received testosterone showed a significantly better QOL, as assessed by their caregivers using the 13-item Quality of Life-Alzheimer's Disease scale, than AD patients who received placebo. This effect occurred because the testosterone recipients showed a nonsignificant trend toward improved QOL over the 6-month study period, while the placebo group showed significant declines.

Similarly, the AD patients who received testosterone showed either greater improvement or less decline in three measures of visual-spatial cognitive functioning, compared with the AD placebo group and the control groups.

Both the improved QOL and the improved cognitive functioning were correlated with increased serum testosterone levels.

Two AD patients and four control subjects withdrew from the study because of adverse effects, including skin rash at the testosterone patch application site. None of the AD patients who received testosterone showed more aggression or agitation than placebo subjects, and caregivers did not observe any marked changes in patients' sexual behavior.

Testosterone replacement improved the quality of life for men with Alzheimer's disease and low serum testosterone levels in a small preliminary study, reported Po H. Lu, PsyD., and associates at the University of California, Los Angeles, David Geffen School of Medicine.

Testosterone therapy has been shown to improve mood, muscle mass, strength, bone density, libido, and certain cognitive functions in hypogonadal men who are otherwise healthy, but this is the first study to report that testosterone may exert positive effects in Alzheimer's disease (AD), the researchers said (Arch. Neurol. 2006;63:1–9).

They assessed testosterone's effects on a variety of cognitive, behavioral, mood, and quality of life (QOL) measures in 16 men with mild to moderate AD and 22 healthy elderly men who served as control subjects. The study subjects were randomly assigned to apply either testosterone patches (7 patients and 10 controls) or placebo patches (9 patients and 12 controls) every day for 6 months.

Five of the AD patients and six of the control subjects were hypogonadal at baseline, with serum testosterone levels below 298 ng/dL.

As a group, AD patients who received testosterone showed a significantly better QOL, as assessed by their caregivers using the 13-item Quality of Life-Alzheimer's Disease scale, than AD patients who received placebo. This effect occurred because the testosterone recipients showed a nonsignificant trend toward improved QOL over the 6-month study period, while the placebo group showed significant declines.

Similarly, the AD patients who received testosterone showed either greater improvement or less decline in three measures of visual-spatial cognitive functioning, compared with the AD placebo group and the control groups.

Both the improved QOL and the improved cognitive functioning were correlated with increased serum testosterone levels.

Two AD patients and four control subjects withdrew from the study because of adverse effects, including skin rash at the testosterone patch application site. None of the AD patients who received testosterone showed more aggression or agitation than placebo subjects, and caregivers did not observe any marked changes in patients' sexual behavior.

Testosterone replacement improved the quality of life for men with Alzheimer's disease and low serum testosterone levels in a small preliminary study, reported Po H. Lu, PsyD., and associates at the University of California, Los Angeles, David Geffen School of Medicine.

Testosterone therapy has been shown to improve mood, muscle mass, strength, bone density, libido, and certain cognitive functions in hypogonadal men who are otherwise healthy, but this is the first study to report that testosterone may exert positive effects in Alzheimer's disease (AD), the researchers said (Arch. Neurol. 2006;63:1–9).

They assessed testosterone's effects on a variety of cognitive, behavioral, mood, and quality of life (QOL) measures in 16 men with mild to moderate AD and 22 healthy elderly men who served as control subjects. The study subjects were randomly assigned to apply either testosterone patches (7 patients and 10 controls) or placebo patches (9 patients and 12 controls) every day for 6 months.

Five of the AD patients and six of the control subjects were hypogonadal at baseline, with serum testosterone levels below 298 ng/dL.

As a group, AD patients who received testosterone showed a significantly better QOL, as assessed by their caregivers using the 13-item Quality of Life-Alzheimer's Disease scale, than AD patients who received placebo. This effect occurred because the testosterone recipients showed a nonsignificant trend toward improved QOL over the 6-month study period, while the placebo group showed significant declines.

Similarly, the AD patients who received testosterone showed either greater improvement or less decline in three measures of visual-spatial cognitive functioning, compared with the AD placebo group and the control groups.

Both the improved QOL and the improved cognitive functioning were correlated with increased serum testosterone levels.

Two AD patients and four control subjects withdrew from the study because of adverse effects, including skin rash at the testosterone patch application site. None of the AD patients who received testosterone showed more aggression or agitation than placebo subjects, and caregivers did not observe any marked changes in patients' sexual behavior.

Regular administration of acetaminophen raises levels of general activity, social interaction, engagement with media such as television or magazines, and worklike activity in elderly patients with moderate to severe dementia, reported John T. Chibnall, Ph.D., of St. Louis University School of Medicine, and his associates.

Regular dosing with the analgesic presumably addresses untreated pain in these patients, who often cannot report pain and who have a high prevalence of comorbidities, including arthritis, fractures, and diabetes, which can generate significant pain, the researchers said.

Their study findings imply that untreated pain inhibits dementia patients' active engagement with the environment and promotes their withdrawal, Dr. Chibnall, a professor of psychiatry at the university, and his associates added (J. Am. Geriatr. Soc. 2005;53:1921–9).

The researchers evaluated behavioral changes in 25 elderly (mean age 85.9 years) nursing home residents with moderate to severe dementia during an 8-week study. The subjects had Alzheimer's disease, degenerative dementia, or multi-infarct dementia and had resided in nursing homes for a mean of 35 months. All had moderate to severe cognitive decline and impairment in the activities of daily living.

The subjects were given either two 500 mg tablets of acetaminophen or two placebo tablets at mealtimes every day for 4 weeks, then switched to the other treatment for 4 weeks, following a 1-week washout period between the two phases.

Their behavior was evaluated under both conditions using the Dementia Care Mapping (DCM) tool, in which trained “mappers” observed patients for 5 hours between 9 a.m. and 2 p.m., when subjects were likely to be most active. At 5-minute intervals, the observers quantified a wide range of behaviors across 24 domains such as direct or passive social involvement, creative activities, exercise, listening to music, and eating.

The subjects also were evaluated using the Cohen-Mansfield Agitation Inventory (CMAI), a 29-item scale in which nursing home personnel assessed how often the patients had displayed a variety of agitated behaviors during the preceding 2 weeks.

With acetaminophen, subjects clearly showed higher levels of general activity, spent more time in direct social interactions and in engagement with media, and participated more in worklike activity. They also spent significantly less time alone in their rooms.

However, subjects also spent more time in passive social involvement, more time talking to themselves or to imaginary others, and slightly more time experiencing unattended distress while on acetaminophen.

Agitation did not decrease, and the use of both routine and as-needed psychotropic medications did not decrease, while the subjects were taking acetaminophen. However, the levels of agitation and the frequency of agitated behaviors were quite low in this study, which may have confounded the results. Similarly, the use of psychotropic drugs was quite low overall, leaving little room for the intervention to show an effect, the researchers noted.

Overall, the results support the contention that pain dampens dementia patients' activity and restricts their engagement with the environment, while prophylactic treatment of that pain reverses these effects.

Regular administration of acetaminophen raises levels of general activity, social interaction, engagement with media such as television or magazines, and worklike activity in elderly patients with moderate to severe dementia, reported John T. Chibnall, Ph.D., of St. Louis University School of Medicine, and his associates.

Regular dosing with the analgesic presumably addresses untreated pain in these patients, who often cannot report pain and who have a high prevalence of comorbidities, including arthritis, fractures, and diabetes, which can generate significant pain, the researchers said.

Their study findings imply that untreated pain inhibits dementia patients' active engagement with the environment and promotes their withdrawal, Dr. Chibnall, a professor of psychiatry at the university, and his associates added (J. Am. Geriatr. Soc. 2005;53:1921–9).

The researchers evaluated behavioral changes in 25 elderly (mean age 85.9 years) nursing home residents with moderate to severe dementia during an 8-week study. The subjects had Alzheimer's disease, degenerative dementia, or multi-infarct dementia and had resided in nursing homes for a mean of 35 months. All had moderate to severe cognitive decline and impairment in the activities of daily living.

The subjects were given either two 500 mg tablets of acetaminophen or two placebo tablets at mealtimes every day for 4 weeks, then switched to the other treatment for 4 weeks, following a 1-week washout period between the two phases.

Their behavior was evaluated under both conditions using the Dementia Care Mapping (DCM) tool, in which trained “mappers” observed patients for 5 hours between 9 a.m. and 2 p.m., when subjects were likely to be most active. At 5-minute intervals, the observers quantified a wide range of behaviors across 24 domains such as direct or passive social involvement, creative activities, exercise, listening to music, and eating.

The subjects also were evaluated using the Cohen-Mansfield Agitation Inventory (CMAI), a 29-item scale in which nursing home personnel assessed how often the patients had displayed a variety of agitated behaviors during the preceding 2 weeks.

With acetaminophen, subjects clearly showed higher levels of general activity, spent more time in direct social interactions and in engagement with media, and participated more in worklike activity. They also spent significantly less time alone in their rooms.

However, subjects also spent more time in passive social involvement, more time talking to themselves or to imaginary others, and slightly more time experiencing unattended distress while on acetaminophen.

Agitation did not decrease, and the use of both routine and as-needed psychotropic medications did not decrease, while the subjects were taking acetaminophen. However, the levels of agitation and the frequency of agitated behaviors were quite low in this study, which may have confounded the results. Similarly, the use of psychotropic drugs was quite low overall, leaving little room for the intervention to show an effect, the researchers noted.

Overall, the results support the contention that pain dampens dementia patients' activity and restricts their engagement with the environment, while prophylactic treatment of that pain reverses these effects.

Regular administration of acetaminophen raises levels of general activity, social interaction, engagement with media such as television or magazines, and worklike activity in elderly patients with moderate to severe dementia, reported John T. Chibnall, Ph.D., of St. Louis University School of Medicine, and his associates.

Regular dosing with the analgesic presumably addresses untreated pain in these patients, who often cannot report pain and who have a high prevalence of comorbidities, including arthritis, fractures, and diabetes, which can generate significant pain, the researchers said.

Their study findings imply that untreated pain inhibits dementia patients' active engagement with the environment and promotes their withdrawal, Dr. Chibnall, a professor of psychiatry at the university, and his associates added (J. Am. Geriatr. Soc. 2005;53:1921–9).

The researchers evaluated behavioral changes in 25 elderly (mean age 85.9 years) nursing home residents with moderate to severe dementia during an 8-week study. The subjects had Alzheimer's disease, degenerative dementia, or multi-infarct dementia and had resided in nursing homes for a mean of 35 months. All had moderate to severe cognitive decline and impairment in the activities of daily living.

The subjects were given either two 500 mg tablets of acetaminophen or two placebo tablets at mealtimes every day for 4 weeks, then switched to the other treatment for 4 weeks, following a 1-week washout period between the two phases.

Their behavior was evaluated under both conditions using the Dementia Care Mapping (DCM) tool, in which trained “mappers” observed patients for 5 hours between 9 a.m. and 2 p.m., when subjects were likely to be most active. At 5-minute intervals, the observers quantified a wide range of behaviors across 24 domains such as direct or passive social involvement, creative activities, exercise, listening to music, and eating.

The subjects also were evaluated using the Cohen-Mansfield Agitation Inventory (CMAI), a 29-item scale in which nursing home personnel assessed how often the patients had displayed a variety of agitated behaviors during the preceding 2 weeks.

With acetaminophen, subjects clearly showed higher levels of general activity, spent more time in direct social interactions and in engagement with media, and participated more in worklike activity. They also spent significantly less time alone in their rooms.

However, subjects also spent more time in passive social involvement, more time talking to themselves or to imaginary others, and slightly more time experiencing unattended distress while on acetaminophen.

Agitation did not decrease, and the use of both routine and as-needed psychotropic medications did not decrease, while the subjects were taking acetaminophen. However, the levels of agitation and the frequency of agitated behaviors were quite low in this study, which may have confounded the results. Similarly, the use of psychotropic drugs was quite low overall, leaving little room for the intervention to show an effect, the researchers noted.

Overall, the results support the contention that pain dampens dementia patients' activity and restricts their engagement with the environment, while prophylactic treatment of that pain reverses these effects.

Imaging Agent Tied to Complications

Palatin Technologies, manufacturer of NeutroSpec, is voluntarily suspending U.S. sales and marketing of the radiodiagnostic agent, according to a public health advisory issued by the Food and Drug Administration. The action was taken “pending review of reported and serious life-threatening adverse events associated with use of the product,” the FDA said.

NeutroSpec [Technetium (99m Tc) fanolesomab], a murine IgM monoclonal antibody labeled with technetium, is approved for scintigraphic imaging of patients 5 years of age or older with equivocal signs and symptoms of appendicitis.

Two deaths attributed to cardiopulmonary failure within 30 minutes of injection have been reported, as have serious events including cardiac arrest, hypoxia, dyspnea, and hypotension. Most of the adverse events occurred within minutes of injection and required patient resuscitation with fluids, vasopressors, and oxygen. Most of the reports involved patients receiving NeutroSpec for unapproved indications, but “some patients who received the drug for [diagnosis of appendicitis] developed reactions of a similar nature,” the FDA said.

The FDA advisory recommended that health care providers discontinue use of NeutroSpec and contact the manufacturer about returning existing stocks.

Any patient given NeutroSpec despite the warning should be closely monitored for at least 1 hour, with access to resuscitation equipment and trained personnel. Patients with underlying cardiopulmonary conditions may be at higher risk for serious complications, the FDA said.

Adverse events can be reported to the manufacturer or directly to the FDA MedWatch reporting system by calling 800-332-1088 or by faxing 800-332-0178.

Blacks Have Worse Outcomes After ACS

Black patients with acute coronary syndrome face worse angina, physical impairment, and quality of life 1 year later than their white counterparts, reported Dr. John Spertus of Mid America Heart Institute of Saint Luke's Hospital, Kansas City, Mo., and his associates.

Researchers have documented racial disparities in ACS treatment and have found that these disparities have little impact on mortality outcomes. But no studies have assessed racial differences in symptoms, function, or quality of life after ACS treatment, Dr. Spertus and his associates said (J. Am. Coll. Cardiol. 2005:46:1838-44).

They evaluated outcomes using a database on nearly 11,000 consecutive patients treated at two Kansas City hospitals in 2001-2002. At 1-year follow-up, black ACS patients were 46% more likely than whites to have residual angina, and they had more frequent bouts of angina. Blacks also had poorer physical function and worse quality of life than did whites; 52% of blacks reported some degree of limitation, compared with only 29% of whites.

As in previous studies, black patients were much less likely than white patients to undergo primary or secondary percutaneous coronary intervention, to undergo diagnostic angiography, or to have bypass surgery. Yet these treatment disparities did not fully account for the racial differences in outcomes. “Other factors in the care of patients between discharge and 1 year may be responsible,” the investigators noted.

Until further research addresses underlying causes, “greater surveillance of the health status of black patients appears warranted so that those who are symptomatic, physically limited, or suffering a significant impairment in their quality of life can be identified and reevaluated for further treatment options,” they added.

HCM Diagnosed Later in Women

Hypertrophic cardiomyopathy is diagnosed later in women than in men, and is more likely to progress to severe, disabling symptoms or death, reported Dr. Iacopo Olivotto of Azienda Ospedaliera Universitaria Careggi, Florence, Italy, and associates.

Both findings “underscore the importance of heightened suspicion for HCM in women,” the researchers said (J. Am. Coll. Cardiol. 2005;46:480-7).

They assessed disease progression over an average of 6 years in 969 consecutive patients treated for HCM at three medical centers in Italy and the United States. The 393 women were an average of 9 years older than the 576 men at diagnosis. Nearly 60% of the women had severe symptoms, including exertional dyspnea, chest pain, and syncope, compared with fewer than 40% of the men. Women were more likely to have left ventricular outflow obstruction, possibly because of the smaller dimensions of their left ventricular cavities.

Treatment was equivalent for men and women once diagnosed, but women were much more likely to show symptomatic progression and to die from heart failure or embolic stroke. This was due in part to the delay in diagnosis and treatment, but the data suggest that some other, as yet unknown, mechanism related to female gender may make women more prone to HCM progression, the researchers said.

Imaging Agent Tied to Complications

Palatin Technologies, manufacturer of NeutroSpec, is voluntarily suspending U.S. sales and marketing of the radiodiagnostic agent, according to a public health advisory issued by the Food and Drug Administration. The action was taken “pending review of reported and serious life-threatening adverse events associated with use of the product,” the FDA said.

NeutroSpec [Technetium (99m Tc) fanolesomab], a murine IgM monoclonal antibody labeled with technetium, is approved for scintigraphic imaging of patients 5 years of age or older with equivocal signs and symptoms of appendicitis.

Two deaths attributed to cardiopulmonary failure within 30 minutes of injection have been reported, as have serious events including cardiac arrest, hypoxia, dyspnea, and hypotension. Most of the adverse events occurred within minutes of injection and required patient resuscitation with fluids, vasopressors, and oxygen. Most of the reports involved patients receiving NeutroSpec for unapproved indications, but “some patients who received the drug for [diagnosis of appendicitis] developed reactions of a similar nature,” the FDA said.

The FDA advisory recommended that health care providers discontinue use of NeutroSpec and contact the manufacturer about returning existing stocks.

Any patient given NeutroSpec despite the warning should be closely monitored for at least 1 hour, with access to resuscitation equipment and trained personnel. Patients with underlying cardiopulmonary conditions may be at higher risk for serious complications, the FDA said.

Adverse events can be reported to the manufacturer or directly to the FDA MedWatch reporting system by calling 800-332-1088 or by faxing 800-332-0178.

Blacks Have Worse Outcomes After ACS

Black patients with acute coronary syndrome face worse angina, physical impairment, and quality of life 1 year later than their white counterparts, reported Dr. John Spertus of Mid America Heart Institute of Saint Luke's Hospital, Kansas City, Mo., and his associates.

Researchers have documented racial disparities in ACS treatment and have found that these disparities have little impact on mortality outcomes. But no studies have assessed racial differences in symptoms, function, or quality of life after ACS treatment, Dr. Spertus and his associates said (J. Am. Coll. Cardiol. 2005:46:1838-44).

They evaluated outcomes using a database on nearly 11,000 consecutive patients treated at two Kansas City hospitals in 2001-2002. At 1-year follow-up, black ACS patients were 46% more likely than whites to have residual angina, and they had more frequent bouts of angina. Blacks also had poorer physical function and worse quality of life than did whites; 52% of blacks reported some degree of limitation, compared with only 29% of whites.

As in previous studies, black patients were much less likely than white patients to undergo primary or secondary percutaneous coronary intervention, to undergo diagnostic angiography, or to have bypass surgery. Yet these treatment disparities did not fully account for the racial differences in outcomes. “Other factors in the care of patients between discharge and 1 year may be responsible,” the investigators noted.

Until further research addresses underlying causes, “greater surveillance of the health status of black patients appears warranted so that those who are symptomatic, physically limited, or suffering a significant impairment in their quality of life can be identified and reevaluated for further treatment options,” they added.

HCM Diagnosed Later in Women

Hypertrophic cardiomyopathy is diagnosed later in women than in men, and is more likely to progress to severe, disabling symptoms or death, reported Dr. Iacopo Olivotto of Azienda Ospedaliera Universitaria Careggi, Florence, Italy, and associates.

Both findings “underscore the importance of heightened suspicion for HCM in women,” the researchers said (J. Am. Coll. Cardiol. 2005;46:480-7).

They assessed disease progression over an average of 6 years in 969 consecutive patients treated for HCM at three medical centers in Italy and the United States. The 393 women were an average of 9 years older than the 576 men at diagnosis. Nearly 60% of the women had severe symptoms, including exertional dyspnea, chest pain, and syncope, compared with fewer than 40% of the men. Women were more likely to have left ventricular outflow obstruction, possibly because of the smaller dimensions of their left ventricular cavities.

Treatment was equivalent for men and women once diagnosed, but women were much more likely to show symptomatic progression and to die from heart failure or embolic stroke. This was due in part to the delay in diagnosis and treatment, but the data suggest that some other, as yet unknown, mechanism related to female gender may make women more prone to HCM progression, the researchers said.

Imaging Agent Tied to Complications

Palatin Technologies, manufacturer of NeutroSpec, is voluntarily suspending U.S. sales and marketing of the radiodiagnostic agent, according to a public health advisory issued by the Food and Drug Administration. The action was taken “pending review of reported and serious life-threatening adverse events associated with use of the product,” the FDA said.

NeutroSpec [Technetium (99m Tc) fanolesomab], a murine IgM monoclonal antibody labeled with technetium, is approved for scintigraphic imaging of patients 5 years of age or older with equivocal signs and symptoms of appendicitis.

Two deaths attributed to cardiopulmonary failure within 30 minutes of injection have been reported, as have serious events including cardiac arrest, hypoxia, dyspnea, and hypotension. Most of the adverse events occurred within minutes of injection and required patient resuscitation with fluids, vasopressors, and oxygen. Most of the reports involved patients receiving NeutroSpec for unapproved indications, but “some patients who received the drug for [diagnosis of appendicitis] developed reactions of a similar nature,” the FDA said.

The FDA advisory recommended that health care providers discontinue use of NeutroSpec and contact the manufacturer about returning existing stocks.

Any patient given NeutroSpec despite the warning should be closely monitored for at least 1 hour, with access to resuscitation equipment and trained personnel. Patients with underlying cardiopulmonary conditions may be at higher risk for serious complications, the FDA said.

Adverse events can be reported to the manufacturer or directly to the FDA MedWatch reporting system by calling 800-332-1088 or by faxing 800-332-0178.

Blacks Have Worse Outcomes After ACS

Black patients with acute coronary syndrome face worse angina, physical impairment, and quality of life 1 year later than their white counterparts, reported Dr. John Spertus of Mid America Heart Institute of Saint Luke's Hospital, Kansas City, Mo., and his associates.

Researchers have documented racial disparities in ACS treatment and have found that these disparities have little impact on mortality outcomes. But no studies have assessed racial differences in symptoms, function, or quality of life after ACS treatment, Dr. Spertus and his associates said (J. Am. Coll. Cardiol. 2005:46:1838-44).

They evaluated outcomes using a database on nearly 11,000 consecutive patients treated at two Kansas City hospitals in 2001-2002. At 1-year follow-up, black ACS patients were 46% more likely than whites to have residual angina, and they had more frequent bouts of angina. Blacks also had poorer physical function and worse quality of life than did whites; 52% of blacks reported some degree of limitation, compared with only 29% of whites.

As in previous studies, black patients were much less likely than white patients to undergo primary or secondary percutaneous coronary intervention, to undergo diagnostic angiography, or to have bypass surgery. Yet these treatment disparities did not fully account for the racial differences in outcomes. “Other factors in the care of patients between discharge and 1 year may be responsible,” the investigators noted.

Until further research addresses underlying causes, “greater surveillance of the health status of black patients appears warranted so that those who are symptomatic, physically limited, or suffering a significant impairment in their quality of life can be identified and reevaluated for further treatment options,” they added.

HCM Diagnosed Later in Women

Hypertrophic cardiomyopathy is diagnosed later in women than in men, and is more likely to progress to severe, disabling symptoms or death, reported Dr. Iacopo Olivotto of Azienda Ospedaliera Universitaria Careggi, Florence, Italy, and associates.

Both findings “underscore the importance of heightened suspicion for HCM in women,” the researchers said (J. Am. Coll. Cardiol. 2005;46:480-7).

They assessed disease progression over an average of 6 years in 969 consecutive patients treated for HCM at three medical centers in Italy and the United States. The 393 women were an average of 9 years older than the 576 men at diagnosis. Nearly 60% of the women had severe symptoms, including exertional dyspnea, chest pain, and syncope, compared with fewer than 40% of the men. Women were more likely to have left ventricular outflow obstruction, possibly because of the smaller dimensions of their left ventricular cavities.

Treatment was equivalent for men and women once diagnosed, but women were much more likely to show symptomatic progression and to die from heart failure or embolic stroke. This was due in part to the delay in diagnosis and treatment, but the data suggest that some other, as yet unknown, mechanism related to female gender may make women more prone to HCM progression, the researchers said.

Vitamin D sufficiency appears to be more important for bone health than is high calcium intake, according to Laufey Steingrimsdottir, Ph.D., of the Public Health Institute of Iceland, Reykjavik, and associates.

Both nutrients are known to influence calcium homeostasis, but the relative contributions of each haven't been studied before, they said (JAMA 2005:294:2336–41).

Although ideal intakes of these two nutrients “need to be further defined in more elaborate studies, there is already sufficient evidence from numerous studies for physicians” to further emphasize the vital importance of vitamin D to bone health, Dr. Steingrimsdottir and associates said.

Physicians should recommend vitamin D supplements for the general public “when sun exposure and dietary sources are insufficient,” they added.

The researchers assessed the relative importance of calcium intake and serum levels of 25-hydroxy vitamin D for maintaining calcium homeostasis in a study of 944 healthy white residents of Iceland. The 491 women and 453 men, aged 30–85 years.

Most Icelanders take vitamin supplements or cod liver oil to supply vitamin D because there isn't sufficient sunshine there throughout the year for adequate biosynthesis of vitamin D. Most also have a relatively high calcium intake, chiefly through the consumption of dairy products. In this study, the mean intake of both vitamin D and calcium were well above recommended levels in all age groups, although there was great variation in both.

Vitamin D status was found to ensure ideal values for serum parathyroid hormone, even when calcium intake was not sufficient to maintain those PTH levels.

In addition, mean serum ionized calcium levels, a more precise marker of calcium homeostasis and thus of bone health, were dependent on serum 25-hydroxyvitamin D levels, but not on calcium intake.

“Although sufficient intake of both nutrients is certainly important, our study indicates that as long as vitamin D status is secured by vitamin D supplements or sufficient sunshine, calcium intake levels of more than 800 mg [per day] may be unnecessary for maintaining calcium homeostasis,” the investigators noted, adding that high calcium intake levels “may have other beneficial effects not addressed in this study,” such as possibly protecting the gut lumen against polyp formation.

Vitamin D sufficiency appears to be more important for bone health than is high calcium intake, according to Laufey Steingrimsdottir, Ph.D., of the Public Health Institute of Iceland, Reykjavik, and associates.

Both nutrients are known to influence calcium homeostasis, but the relative contributions of each haven't been studied before, they said (JAMA 2005:294:2336–41).

Although ideal intakes of these two nutrients “need to be further defined in more elaborate studies, there is already sufficient evidence from numerous studies for physicians” to further emphasize the vital importance of vitamin D to bone health, Dr. Steingrimsdottir and associates said.

Physicians should recommend vitamin D supplements for the general public “when sun exposure and dietary sources are insufficient,” they added.

The researchers assessed the relative importance of calcium intake and serum levels of 25-hydroxy vitamin D for maintaining calcium homeostasis in a study of 944 healthy white residents of Iceland. The 491 women and 453 men, aged 30–85 years.

Most Icelanders take vitamin supplements or cod liver oil to supply vitamin D because there isn't sufficient sunshine there throughout the year for adequate biosynthesis of vitamin D. Most also have a relatively high calcium intake, chiefly through the consumption of dairy products. In this study, the mean intake of both vitamin D and calcium were well above recommended levels in all age groups, although there was great variation in both.

Vitamin D status was found to ensure ideal values for serum parathyroid hormone, even when calcium intake was not sufficient to maintain those PTH levels.

In addition, mean serum ionized calcium levels, a more precise marker of calcium homeostasis and thus of bone health, were dependent on serum 25-hydroxyvitamin D levels, but not on calcium intake.

“Although sufficient intake of both nutrients is certainly important, our study indicates that as long as vitamin D status is secured by vitamin D supplements or sufficient sunshine, calcium intake levels of more than 800 mg [per day] may be unnecessary for maintaining calcium homeostasis,” the investigators noted, adding that high calcium intake levels “may have other beneficial effects not addressed in this study,” such as possibly protecting the gut lumen against polyp formation.

Vitamin D sufficiency appears to be more important for bone health than is high calcium intake, according to Laufey Steingrimsdottir, Ph.D., of the Public Health Institute of Iceland, Reykjavik, and associates.

Both nutrients are known to influence calcium homeostasis, but the relative contributions of each haven't been studied before, they said (JAMA 2005:294:2336–41).

Although ideal intakes of these two nutrients “need to be further defined in more elaborate studies, there is already sufficient evidence from numerous studies for physicians” to further emphasize the vital importance of vitamin D to bone health, Dr. Steingrimsdottir and associates said.

Physicians should recommend vitamin D supplements for the general public “when sun exposure and dietary sources are insufficient,” they added.

The researchers assessed the relative importance of calcium intake and serum levels of 25-hydroxy vitamin D for maintaining calcium homeostasis in a study of 944 healthy white residents of Iceland. The 491 women and 453 men, aged 30–85 years.

Most Icelanders take vitamin supplements or cod liver oil to supply vitamin D because there isn't sufficient sunshine there throughout the year for adequate biosynthesis of vitamin D. Most also have a relatively high calcium intake, chiefly through the consumption of dairy products. In this study, the mean intake of both vitamin D and calcium were well above recommended levels in all age groups, although there was great variation in both.

Vitamin D status was found to ensure ideal values for serum parathyroid hormone, even when calcium intake was not sufficient to maintain those PTH levels.

In addition, mean serum ionized calcium levels, a more precise marker of calcium homeostasis and thus of bone health, were dependent on serum 25-hydroxyvitamin D levels, but not on calcium intake.

“Although sufficient intake of both nutrients is certainly important, our study indicates that as long as vitamin D status is secured by vitamin D supplements or sufficient sunshine, calcium intake levels of more than 800 mg [per day] may be unnecessary for maintaining calcium homeostasis,” the investigators noted, adding that high calcium intake levels “may have other beneficial effects not addressed in this study,” such as possibly protecting the gut lumen against polyp formation.