Deeanna Franklin

BALTIMORE — One of the most common questions from pediatricians is when to immunize cancer patients under their care, said Dr. Patrick Brown, a pediatric oncologist at Johns Hopkins University, Baltimore.

Chemotherapy and radiation treatments leave these patients profoundly immunocompromised. Additionally, if a patient has received a bone marrow transplant (BMT), they in some ways “gain the immune system of their allogeneic donor,” he said.

“The recovery of the patient's adaptive immunity … takes a minimum of several months, and often a year,” he said. This is particularly true for those being treated for complications such as graft versus host disease (GVHD).

Dr. Brown advised against immunizing patients prior to BMT, because their immunity is completely eliminated during the week of preparation. These patients should receive no vaccinations until 6 months post BMT.

“After this, patients should be considered completely unimmunized, and therefore need to catch up,” Dr. Brown said.

Specifically, patients should get a flu shot as soon as possible after the 6 months post-BMT period, regardless of any other treatments they're receiving, and annually from then on.

Although patients normally should not receive vaccinations during intensive sessions of chemotherapy, “The exception to that is influenza. Even though it's variably effective during the intensive phases of therapy, the downside is so great, we do recommend immunizing patients with influenza vaccine even during intensive phases of therapy,” Dr. Brown stressed at a meeting on pediatric trends sponsored by Johns Hopkins University.

Other nonlive viral vaccines should begin no sooner than 12 months after BMT, and all should be given as boosters. The only exception to that advice is pneumococcal 7-valent conjugate vaccine (Prevnar), which is not recommended because of a lack of efficacy data in this patient group.

Dr. Brown noted that the meningococcal vaccine is safe and should be given to any patient who is at least 12 months post BMT and over 2 years old, particularly patients with chronic GVHD, who are at markedly increased risk of infections with encapsulated organisms such as meningococcus.

He advises waiting 2 years before immunizing patients with live vaccines such as MMR—the only live-virus vaccine shown to be safe for this patient group. The varicella vaccine is “relatively” contraindicated for this patient group because its safety profile is still unknown.

“All family members and household contacts can and should receive any and all indicated vaccinations, including live-virus vaccines,” Dr. Brown said.

Flu vaccinations are particularly encouraged, he added.

According to Dr. Brown, when it comes to nontransplant cancer therapy and the status of protective antibody titers, approximately 50% of patients will lose their hepatitis B immunity, 25% will lose their MMR immunity, 15% will lose tetanus immunity, and about 10% will lose polio immunity.

Younger patients are more likely to lose their immunity. “The rate of recovery of protective antibody titers after giving boosters post chemotherapy is very, very high,” he said.

He recommended the Web site www.curesearch.org

Providers may also go directly to www.survivorshipguidelines.org

Family members and household contacts should receive any and all indicated vaccinations. DR. BROWN

BALTIMORE — One of the most common questions from pediatricians is when to immunize cancer patients under their care, said Dr. Patrick Brown, a pediatric oncologist at Johns Hopkins University, Baltimore.

Chemotherapy and radiation treatments leave these patients profoundly immunocompromised. Additionally, if a patient has received a bone marrow transplant (BMT), they in some ways “gain the immune system of their allogeneic donor,” he said.

“The recovery of the patient's adaptive immunity … takes a minimum of several months, and often a year,” he said. This is particularly true for those being treated for complications such as graft versus host disease (GVHD).

Dr. Brown advised against immunizing patients prior to BMT, because their immunity is completely eliminated during the week of preparation. These patients should receive no vaccinations until 6 months post BMT.

“After this, patients should be considered completely unimmunized, and therefore need to catch up,” Dr. Brown said.

Specifically, patients should get a flu shot as soon as possible after the 6 months post-BMT period, regardless of any other treatments they're receiving, and annually from then on.

Although patients normally should not receive vaccinations during intensive sessions of chemotherapy, “The exception to that is influenza. Even though it's variably effective during the intensive phases of therapy, the downside is so great, we do recommend immunizing patients with influenza vaccine even during intensive phases of therapy,” Dr. Brown stressed at a meeting on pediatric trends sponsored by Johns Hopkins University.

Other nonlive viral vaccines should begin no sooner than 12 months after BMT, and all should be given as boosters. The only exception to that advice is pneumococcal 7-valent conjugate vaccine (Prevnar), which is not recommended because of a lack of efficacy data in this patient group.

Dr. Brown noted that the meningococcal vaccine is safe and should be given to any patient who is at least 12 months post BMT and over 2 years old, particularly patients with chronic GVHD, who are at markedly increased risk of infections with encapsulated organisms such as meningococcus.

He advises waiting 2 years before immunizing patients with live vaccines such as MMR—the only live-virus vaccine shown to be safe for this patient group. The varicella vaccine is “relatively” contraindicated for this patient group because its safety profile is still unknown.

“All family members and household contacts can and should receive any and all indicated vaccinations, including live-virus vaccines,” Dr. Brown said.

Flu vaccinations are particularly encouraged, he added.

According to Dr. Brown, when it comes to nontransplant cancer therapy and the status of protective antibody titers, approximately 50% of patients will lose their hepatitis B immunity, 25% will lose their MMR immunity, 15% will lose tetanus immunity, and about 10% will lose polio immunity.

Younger patients are more likely to lose their immunity. “The rate of recovery of protective antibody titers after giving boosters post chemotherapy is very, very high,” he said.

He recommended the Web site www.curesearch.org

Providers may also go directly to www.survivorshipguidelines.org

Family members and household contacts should receive any and all indicated vaccinations. DR. BROWN

BALTIMORE — One of the most common questions from pediatricians is when to immunize cancer patients under their care, said Dr. Patrick Brown, a pediatric oncologist at Johns Hopkins University, Baltimore.

Chemotherapy and radiation treatments leave these patients profoundly immunocompromised. Additionally, if a patient has received a bone marrow transplant (BMT), they in some ways “gain the immune system of their allogeneic donor,” he said.

“The recovery of the patient's adaptive immunity … takes a minimum of several months, and often a year,” he said. This is particularly true for those being treated for complications such as graft versus host disease (GVHD).

Dr. Brown advised against immunizing patients prior to BMT, because their immunity is completely eliminated during the week of preparation. These patients should receive no vaccinations until 6 months post BMT.

“After this, patients should be considered completely unimmunized, and therefore need to catch up,” Dr. Brown said.

Specifically, patients should get a flu shot as soon as possible after the 6 months post-BMT period, regardless of any other treatments they're receiving, and annually from then on.

Although patients normally should not receive vaccinations during intensive sessions of chemotherapy, “The exception to that is influenza. Even though it's variably effective during the intensive phases of therapy, the downside is so great, we do recommend immunizing patients with influenza vaccine even during intensive phases of therapy,” Dr. Brown stressed at a meeting on pediatric trends sponsored by Johns Hopkins University.

Other nonlive viral vaccines should begin no sooner than 12 months after BMT, and all should be given as boosters. The only exception to that advice is pneumococcal 7-valent conjugate vaccine (Prevnar), which is not recommended because of a lack of efficacy data in this patient group.

Dr. Brown noted that the meningococcal vaccine is safe and should be given to any patient who is at least 12 months post BMT and over 2 years old, particularly patients with chronic GVHD, who are at markedly increased risk of infections with encapsulated organisms such as meningococcus.

He advises waiting 2 years before immunizing patients with live vaccines such as MMR—the only live-virus vaccine shown to be safe for this patient group. The varicella vaccine is “relatively” contraindicated for this patient group because its safety profile is still unknown.

“All family members and household contacts can and should receive any and all indicated vaccinations, including live-virus vaccines,” Dr. Brown said.

Flu vaccinations are particularly encouraged, he added.

According to Dr. Brown, when it comes to nontransplant cancer therapy and the status of protective antibody titers, approximately 50% of patients will lose their hepatitis B immunity, 25% will lose their MMR immunity, 15% will lose tetanus immunity, and about 10% will lose polio immunity.

Younger patients are more likely to lose their immunity. “The rate of recovery of protective antibody titers after giving boosters post chemotherapy is very, very high,” he said.

He recommended the Web site www.curesearch.org

Providers may also go directly to www.survivorshipguidelines.org

Family members and household contacts should receive any and all indicated vaccinations. DR. BROWN

The 6-minute walk test is highly reproducible during trials of patients with interstitial lung disease secondary to scleroderma, but it may not be a valid outcome measurement because it correlates poorly with other standard physiologic measurements for lung functioning, reported Dr. Maya H. Buch, of the University of Michigan Scleroderma Program in Ann Arbor, and her colleagues.

In a study of 163 patients with interstitial lung disease (ILD) secondary to scleroderma (SSc), researchers had each participant perform a 6-minute walk test (6MWT). In a space without additional oxygen, they were instructed to walk back and forth in a hallway as many times as they could for 6 minutes. Participants were allowed to stop, slow down, and rest as needed. The test was stopped if patients were exhausted or experienced chest pain, leg cramps, or diaphoresis. Those with very mild or very severe lung impairment were excluded (Ann. Rheum. Dis. 2006 [Epub ahead of print]; doi:10.1136/ard.2006.054866).

The data were taken from the results of a 12-month, double-blind, placebo-controlled study that compared the drug bosentan with a placebo for the treatment of SSc-ILD. Participants came from 29 centers in 10 countries. There were 122 women and 41 men; 95 (58%) patients were classified as having diffuse SSc and the remaining 42% had limited SSc. Their mean age was 52.3 years, and the mean disease duration was 6.4 years.

When it came to the 6MWT, 152 participants had less than 15% variability between their first and second tests. Eleven patients required a third test, and there was less than 15% variability between their second and third 6MWT. Mean distance walked was 396.6 m on test one, compared with 399.5 m on test two. Mean overall distance for the two walks was 398 m, and “the mean absolute difference for an individual patient between the two walks was 20.75 m,” said Dr. Buch and her colleagues.

After the 6MWT, a rating of dyspnea was measured using a Borg scale. After walk one, the mean Borg dyspnea index was 2.75, and after walk two it was 2.79. The overall mean Borg score was 2.77, with a mean absolute difference between the assessments of 0.8. According to the researchers, the mean percentage predicted diffusing capacity was 46% and mean percentage predicted forced vital capacity (FVC) was 71%.

There was only a minimal correlation between the 6MWT and the Borg dyspnea scale. There was a weak correlation between the 6MWT and percentage predicted FVC, and the walk test did not correlate at all with mean percentage predicted diffusing capacity. Also, there was a “very weak correlation” between mean percentage predicted diffusing capacity and the Borg dyspnea scale.

“The primary finding of this study is the high intertest reproducibility of the test. We, however, failed to demonstrate correlation of the 6MWT with pulmonary function parameters. This raises the question of what exactly is being measured by the test,” commented Dr. Buch and her colleagues.

They speculated that “multiple confounding variables in the assessment of SSc-ILD” might account for the failure to establish a correlation between the 6MWT and the traditional lung function parameters.

These variables would include subtle cardiopulmonary responses and comorbidity not detected by the lung function tests. Other possibilities not related to SSc that might account for the lack of correlation include variability in FVC and interlaboratory variation in measurement of mean percentage predicted diffusing capacity.

Additionally, participants may have exhibited different psychological responses to exercise, which “could lead to either a training effect or decompensation. Separately, temporal and adaptive changes in breathing patterns could also facilitate exercise performance,” said the researchers. They concluded that further studies and greater “clarification of the relative contributions of nonpulmonary manifestations of SSc on exercise capacity” are needed before the 6MWT could be accepted as a valid assessment criterion, the investigators said.

The 6-minute walk test is highly reproducible during trials of patients with interstitial lung disease secondary to scleroderma, but it may not be a valid outcome measurement because it correlates poorly with other standard physiologic measurements for lung functioning, reported Dr. Maya H. Buch, of the University of Michigan Scleroderma Program in Ann Arbor, and her colleagues.

In a study of 163 patients with interstitial lung disease (ILD) secondary to scleroderma (SSc), researchers had each participant perform a 6-minute walk test (6MWT). In a space without additional oxygen, they were instructed to walk back and forth in a hallway as many times as they could for 6 minutes. Participants were allowed to stop, slow down, and rest as needed. The test was stopped if patients were exhausted or experienced chest pain, leg cramps, or diaphoresis. Those with very mild or very severe lung impairment were excluded (Ann. Rheum. Dis. 2006 [Epub ahead of print]; doi:10.1136/ard.2006.054866).

The data were taken from the results of a 12-month, double-blind, placebo-controlled study that compared the drug bosentan with a placebo for the treatment of SSc-ILD. Participants came from 29 centers in 10 countries. There were 122 women and 41 men; 95 (58%) patients were classified as having diffuse SSc and the remaining 42% had limited SSc. Their mean age was 52.3 years, and the mean disease duration was 6.4 years.

When it came to the 6MWT, 152 participants had less than 15% variability between their first and second tests. Eleven patients required a third test, and there was less than 15% variability between their second and third 6MWT. Mean distance walked was 396.6 m on test one, compared with 399.5 m on test two. Mean overall distance for the two walks was 398 m, and “the mean absolute difference for an individual patient between the two walks was 20.75 m,” said Dr. Buch and her colleagues.

After the 6MWT, a rating of dyspnea was measured using a Borg scale. After walk one, the mean Borg dyspnea index was 2.75, and after walk two it was 2.79. The overall mean Borg score was 2.77, with a mean absolute difference between the assessments of 0.8. According to the researchers, the mean percentage predicted diffusing capacity was 46% and mean percentage predicted forced vital capacity (FVC) was 71%.

There was only a minimal correlation between the 6MWT and the Borg dyspnea scale. There was a weak correlation between the 6MWT and percentage predicted FVC, and the walk test did not correlate at all with mean percentage predicted diffusing capacity. Also, there was a “very weak correlation” between mean percentage predicted diffusing capacity and the Borg dyspnea scale.

“The primary finding of this study is the high intertest reproducibility of the test. We, however, failed to demonstrate correlation of the 6MWT with pulmonary function parameters. This raises the question of what exactly is being measured by the test,” commented Dr. Buch and her colleagues.

They speculated that “multiple confounding variables in the assessment of SSc-ILD” might account for the failure to establish a correlation between the 6MWT and the traditional lung function parameters.

These variables would include subtle cardiopulmonary responses and comorbidity not detected by the lung function tests. Other possibilities not related to SSc that might account for the lack of correlation include variability in FVC and interlaboratory variation in measurement of mean percentage predicted diffusing capacity.

Additionally, participants may have exhibited different psychological responses to exercise, which “could lead to either a training effect or decompensation. Separately, temporal and adaptive changes in breathing patterns could also facilitate exercise performance,” said the researchers. They concluded that further studies and greater “clarification of the relative contributions of nonpulmonary manifestations of SSc on exercise capacity” are needed before the 6MWT could be accepted as a valid assessment criterion, the investigators said.

The 6-minute walk test is highly reproducible during trials of patients with interstitial lung disease secondary to scleroderma, but it may not be a valid outcome measurement because it correlates poorly with other standard physiologic measurements for lung functioning, reported Dr. Maya H. Buch, of the University of Michigan Scleroderma Program in Ann Arbor, and her colleagues.

In a study of 163 patients with interstitial lung disease (ILD) secondary to scleroderma (SSc), researchers had each participant perform a 6-minute walk test (6MWT). In a space without additional oxygen, they were instructed to walk back and forth in a hallway as many times as they could for 6 minutes. Participants were allowed to stop, slow down, and rest as needed. The test was stopped if patients were exhausted or experienced chest pain, leg cramps, or diaphoresis. Those with very mild or very severe lung impairment were excluded (Ann. Rheum. Dis. 2006 [Epub ahead of print]; doi:10.1136/ard.2006.054866).

The data were taken from the results of a 12-month, double-blind, placebo-controlled study that compared the drug bosentan with a placebo for the treatment of SSc-ILD. Participants came from 29 centers in 10 countries. There were 122 women and 41 men; 95 (58%) patients were classified as having diffuse SSc and the remaining 42% had limited SSc. Their mean age was 52.3 years, and the mean disease duration was 6.4 years.

When it came to the 6MWT, 152 participants had less than 15% variability between their first and second tests. Eleven patients required a third test, and there was less than 15% variability between their second and third 6MWT. Mean distance walked was 396.6 m on test one, compared with 399.5 m on test two. Mean overall distance for the two walks was 398 m, and “the mean absolute difference for an individual patient between the two walks was 20.75 m,” said Dr. Buch and her colleagues.

After the 6MWT, a rating of dyspnea was measured using a Borg scale. After walk one, the mean Borg dyspnea index was 2.75, and after walk two it was 2.79. The overall mean Borg score was 2.77, with a mean absolute difference between the assessments of 0.8. According to the researchers, the mean percentage predicted diffusing capacity was 46% and mean percentage predicted forced vital capacity (FVC) was 71%.

There was only a minimal correlation between the 6MWT and the Borg dyspnea scale. There was a weak correlation between the 6MWT and percentage predicted FVC, and the walk test did not correlate at all with mean percentage predicted diffusing capacity. Also, there was a “very weak correlation” between mean percentage predicted diffusing capacity and the Borg dyspnea scale.

“The primary finding of this study is the high intertest reproducibility of the test. We, however, failed to demonstrate correlation of the 6MWT with pulmonary function parameters. This raises the question of what exactly is being measured by the test,” commented Dr. Buch and her colleagues.

They speculated that “multiple confounding variables in the assessment of SSc-ILD” might account for the failure to establish a correlation between the 6MWT and the traditional lung function parameters.

These variables would include subtle cardiopulmonary responses and comorbidity not detected by the lung function tests. Other possibilities not related to SSc that might account for the lack of correlation include variability in FVC and interlaboratory variation in measurement of mean percentage predicted diffusing capacity.

Additionally, participants may have exhibited different psychological responses to exercise, which “could lead to either a training effect or decompensation. Separately, temporal and adaptive changes in breathing patterns could also facilitate exercise performance,” said the researchers. They concluded that further studies and greater “clarification of the relative contributions of nonpulmonary manifestations of SSc on exercise capacity” are needed before the 6MWT could be accepted as a valid assessment criterion, the investigators said.

The 6-minute walk test is highly reproducible during trials of patients with interstitial lung disease secondary to scleroderma, but it may not be a valid outcome measurement because it correlates poorly with other standard physiologic measurements for lung functioning, reported Dr. Maya H. Buch, of the University of Michigan Scleroderma Program in Ann Arbor, and her colleagues.

In a study of 163 patients with interstitial lung disease (ILD) secondary to scleroderma (SSc), researchers had each participant perform a 6-minute walk test (6MWT). In a space without additional oxygen, they were instructed to walk back and forth in a hallway as many times as they could for 6 minutes. Participants were allowed to stop, slow down, and rest as needed. The test was stopped if patients were exhausted or experienced chest pain, leg cramps, or diaphoresis. Those with very mild or very severe lung impairment were excluded (Ann. Rheum. Dis. 2006 [Epub doi:10.1136/ard.2006.054866]). The data were taken from the results of a 12-month, double-blind, placebo-controlled study that compared the drug bosentan with a placebo for the treatment of SSc-ILD. Participants came from 29 centers in 10 countries. There were 122 women and 41 men; 95 (58%) patients were classified as having diffuse SSc and the remaining 42% had limited SSc. Their mean age was 52.3 years, and the mean disease duration was 6.4 years.

When it came to the 6MWT, 152 participants had less than 15% variability between their first and second tests. Eleven patients required a third test, and there was less than 15% variability between their second and third 6MWT. Mean distance walked was 396.6 m on test one, compared with 399.5 m on test two. Mean overall distance for the two walks was 398 m, and “the mean absolute difference for an individual patient between the two walks was 20.75 m,” said Dr. Buch and her colleagues.

After the 6MWT, a rating of dyspnea was measured using a Borg scale. After walk one, the mean Borg dyspnea index was 2.75, and after walk two it was 2.79. The overall mean Borg score was 2.77, with a mean absolute difference between the assessments of 0.8. According to the researchers, the mean percentage predicted diffusing capacity was 46% and mean percentage predicted forced vital capacity (FVC) was 71%.

There was only a minimal correlation between the 6MWT and the Borg dyspnea scale. There was a weak correlation between the 6MWT and percentage predicted FVC, and the walk test did not correlate at all with mean percentage predicted diffusing capacity. Also, there was a “very weak correlation” between mean percentage predicted diffusing capacity and the Borg dyspnea scale.

“The primary finding of this study is the high intertest reproducibility of the test. We, however, failed to demonstrate correlation of the 6MWT with pulmonary function parameters. This raises the question of what exactly is being measured by the test,” commented Dr. Buch and her colleagues. They speculated that “multiple confounding variables in the assessment of SSc-ILD” might account for the failure of correlation between the 6MWT and the traditional lung function parameters. These variables would include subtle cardiopulmonary responses and comorbidity not detected by the lung function tests. Other possibilities not related to SSc that might account for the lack of correlation include variability in FVC and interlaboratory variation in measurement of mean percentage predicted diffusing capacity.

Additionally, participants may have exhibited different psychological responses to exercise, which “could lead to either a training effect or decompensation. Separately, temporal and adaptive changes in breathing patterns could also facilitate exercise performance,” said the researchers. They concluded that further studies and greater “clarification of the relative contributions of nonpulmonary manifestations of SSc on exercise capacity” are needed.

The 6-minute walk test is highly reproducible during trials of patients with interstitial lung disease secondary to scleroderma, but it may not be a valid outcome measurement because it correlates poorly with other standard physiologic measurements for lung functioning, reported Dr. Maya H. Buch, of the University of Michigan Scleroderma Program in Ann Arbor, and her colleagues.

In a study of 163 patients with interstitial lung disease (ILD) secondary to scleroderma (SSc), researchers had each participant perform a 6-minute walk test (6MWT). In a space without additional oxygen, they were instructed to walk back and forth in a hallway as many times as they could for 6 minutes. Participants were allowed to stop, slow down, and rest as needed. The test was stopped if patients were exhausted or experienced chest pain, leg cramps, or diaphoresis. Those with very mild or very severe lung impairment were excluded (Ann. Rheum. Dis. 2006 [Epub doi:10.1136/ard.2006.054866]). The data were taken from the results of a 12-month, double-blind, placebo-controlled study that compared the drug bosentan with a placebo for the treatment of SSc-ILD. Participants came from 29 centers in 10 countries. There were 122 women and 41 men; 95 (58%) patients were classified as having diffuse SSc and the remaining 42% had limited SSc. Their mean age was 52.3 years, and the mean disease duration was 6.4 years.

When it came to the 6MWT, 152 participants had less than 15% variability between their first and second tests. Eleven patients required a third test, and there was less than 15% variability between their second and third 6MWT. Mean distance walked was 396.6 m on test one, compared with 399.5 m on test two. Mean overall distance for the two walks was 398 m, and “the mean absolute difference for an individual patient between the two walks was 20.75 m,” said Dr. Buch and her colleagues.

After the 6MWT, a rating of dyspnea was measured using a Borg scale. After walk one, the mean Borg dyspnea index was 2.75, and after walk two it was 2.79. The overall mean Borg score was 2.77, with a mean absolute difference between the assessments of 0.8. According to the researchers, the mean percentage predicted diffusing capacity was 46% and mean percentage predicted forced vital capacity (FVC) was 71%.

There was only a minimal correlation between the 6MWT and the Borg dyspnea scale. There was a weak correlation between the 6MWT and percentage predicted FVC, and the walk test did not correlate at all with mean percentage predicted diffusing capacity. Also, there was a “very weak correlation” between mean percentage predicted diffusing capacity and the Borg dyspnea scale.

“The primary finding of this study is the high intertest reproducibility of the test. We, however, failed to demonstrate correlation of the 6MWT with pulmonary function parameters. This raises the question of what exactly is being measured by the test,” commented Dr. Buch and her colleagues. They speculated that “multiple confounding variables in the assessment of SSc-ILD” might account for the failure of correlation between the 6MWT and the traditional lung function parameters. These variables would include subtle cardiopulmonary responses and comorbidity not detected by the lung function tests. Other possibilities not related to SSc that might account for the lack of correlation include variability in FVC and interlaboratory variation in measurement of mean percentage predicted diffusing capacity.

Additionally, participants may have exhibited different psychological responses to exercise, which “could lead to either a training effect or decompensation. Separately, temporal and adaptive changes in breathing patterns could also facilitate exercise performance,” said the researchers. They concluded that further studies and greater “clarification of the relative contributions of nonpulmonary manifestations of SSc on exercise capacity” are needed.

The 6-minute walk test is highly reproducible during trials of patients with interstitial lung disease secondary to scleroderma, but it may not be a valid outcome measurement because it correlates poorly with other standard physiologic measurements for lung functioning, reported Dr. Maya H. Buch, of the University of Michigan Scleroderma Program in Ann Arbor, and her colleagues.

In a study of 163 patients with interstitial lung disease (ILD) secondary to scleroderma (SSc), researchers had each participant perform a 6-minute walk test (6MWT). In a space without additional oxygen, they were instructed to walk back and forth in a hallway as many times as they could for 6 minutes. Participants were allowed to stop, slow down, and rest as needed. The test was stopped if patients were exhausted or experienced chest pain, leg cramps, or diaphoresis. Those with very mild or very severe lung impairment were excluded (Ann. Rheum. Dis. 2006 [Epub doi:10.1136/ard.2006.054866]). The data were taken from the results of a 12-month, double-blind, placebo-controlled study that compared the drug bosentan with a placebo for the treatment of SSc-ILD. Participants came from 29 centers in 10 countries. There were 122 women and 41 men; 95 (58%) patients were classified as having diffuse SSc and the remaining 42% had limited SSc. Their mean age was 52.3 years, and the mean disease duration was 6.4 years.

When it came to the 6MWT, 152 participants had less than 15% variability between their first and second tests. Eleven patients required a third test, and there was less than 15% variability between their second and third 6MWT. Mean distance walked was 396.6 m on test one, compared with 399.5 m on test two. Mean overall distance for the two walks was 398 m, and “the mean absolute difference for an individual patient between the two walks was 20.75 m,” said Dr. Buch and her colleagues.

After the 6MWT, a rating of dyspnea was measured using a Borg scale. After walk one, the mean Borg dyspnea index was 2.75, and after walk two it was 2.79. The overall mean Borg score was 2.77, with a mean absolute difference between the assessments of 0.8. According to the researchers, the mean percentage predicted diffusing capacity was 46% and mean percentage predicted forced vital capacity (FVC) was 71%.

There was only a minimal correlation between the 6MWT and the Borg dyspnea scale. There was a weak correlation between the 6MWT and percentage predicted FVC, and the walk test did not correlate at all with mean percentage predicted diffusing capacity. Also, there was a “very weak correlation” between mean percentage predicted diffusing capacity and the Borg dyspnea scale.

“The primary finding of this study is the high intertest reproducibility of the test. We, however, failed to demonstrate correlation of the 6MWT with pulmonary function parameters. This raises the question of what exactly is being measured by the test,” commented Dr. Buch and her colleagues. They speculated that “multiple confounding variables in the assessment of SSc-ILD” might account for the failure of correlation between the 6MWT and the traditional lung function parameters. These variables would include subtle cardiopulmonary responses and comorbidity not detected by the lung function tests. Other possibilities not related to SSc that might account for the lack of correlation include variability in FVC and interlaboratory variation in measurement of mean percentage predicted diffusing capacity.

Additionally, participants may have exhibited different psychological responses to exercise, which “could lead to either a training effect or decompensation. Separately, temporal and adaptive changes in breathing patterns could also facilitate exercise performance,” said the researchers. They concluded that further studies and greater “clarification of the relative contributions of nonpulmonary manifestations of SSc on exercise capacity” are needed.

The virologic response in HIV-positive patients to highly active antiretroviral therapy has improved over the past 10 years; however, there has been no corresponding decrease in mortality, reported Dr. Margaret T. May of the University of Bristol (England) and her colleagues.

The researchers analyzed data from the Antiretroviral Treatment Cohort Collaboration, and examined 12 cohort studies.

The studies focused on characteristics of antiretroviral-naive patients at the start of highly active antiretroviral therapy (HAART) as well as their response to therapy and disease progression.

The cohort studies were conducted in Europe, the United States, and Canada, and they enrolled at least 100 patients aged 16 years or older with HIV-1 infection (median age was 36 years). The participants had started antiretroviral therapy with a combination of at least three drugs, and the median duration of follow-up was 1 year.

The medications included nucleoside reverse transcriptase inhibitors, protease inhibitors, and nonnucleoside reverse transcriptase inhibitors (NNRTIs). The severity of immunodeficiency at baseline ranged from severe to nonexistent, and viral replication ranged from undetectable to extremely high, the investigators wrote (Lancet 2006;368:451–8).

Starting with data from 1995–1996 and ending in 2002–2003, the researchers evaluated the clinical prognosis of 22,217 patients based on two primary end points: AIDS events and death from all causes.

The percentage of women infected rose from 16% in 1995–1996 to 32% in 2002–2003. In 1995–1996, 56% of patients starting HAART were presumed to have been infected via male homosexual contact, but this figure dropped to 34% by 2002–2003, while the percentage of patients infected via heterosexual contact rose from 20% in 1995–1996 to 47% in 2002–2003.

“The percentage of patients infected via injection drug use declined from 20% in 1997 to 9% in 2002–2003,” wrote Dr. May and colleagues. Fewer than 1% of patients were infected by contaminated blood, and about 9% had an unspecified mode of transmission.

The median CD4 cell count at the initiation of HAART rose from 170 cells per μL in 1995–1996 to 269 cells per μL in 1998, and decreased to about 200 cells per μL in 2002–2003. According to the researchers, most patients started on a protease inhibitor-based HAART regimen in 1995–1998, whereas from 1999 onwards, at least 40% started HAART with NNRTI-based regimens. The percentage of patients starting HAART with four or more drugs rose from 1% in 1995–1996 to 11% in 2002–2003.

In 1995–1996, 58% of patients achieved an HIV-1 RNA of 500 copies per mL or less by 6 months of treatment. By 1997, this figure increased to 73% of patients, and by 2002–2003, it was 83% of patients.

“The estimated probability of death up to 1 year after starting HAART did not differ greatly by calendar period. Compared with 1998, the adjusted hazard ratio for AIDS was 1.30 in 1997 and 1.35 in 2002–03,” Dr. May noted.

The researchers evaluated whether the rise in AIDS events (including AIDS-related deaths) in the most recent years could be attributed to an increase in the rate of tuberculosis. Their analysis demonstrated that, compared with 1998, the rise in AIDS events in 2002–2003 “is largely attributable to an increase in tuberculosis.”

“The discrepancy between the clear improvement we recorded for virological response and the apparently worsening rates of clinical progression might be related to the change in the demographic characteristics of study participants with an increasing number of patients from areas with a high incidence of tuberculosis,” the investigators wrote.

The lower CD4 cell count at the initiation of HAART in recent years was of great concern, and research showed many missed opportunities for earlier diagnosis. Expansion of screenings for AIDS would be beneficial, they concluded.

In a commentary by Dr. Gregory J. Dore and Dr. David A. Cooper of the University of New South Wales in Australia, they called for more widespread tuberculosis screenings and prophylaxis initiatives, particularly for individuals from high-prevalence regions (Lancet 2006;368:427–8). The trend toward lower CD4-lymphocyte count at the start of HAART was also a point of concern, and “might have increased the risk of immune restoration syndrome,” they said. “Undiagnosed active opportunistic infections at the start of HAART might be a further contributing factor.”

The virologic response in HIV-positive patients to highly active antiretroviral therapy has improved over the past 10 years; however, there has been no corresponding decrease in mortality, reported Dr. Margaret T. May of the University of Bristol (England) and her colleagues.

The researchers analyzed data from the Antiretroviral Treatment Cohort Collaboration, and examined 12 cohort studies.

The studies focused on characteristics of antiretroviral-naive patients at the start of highly active antiretroviral therapy (HAART) as well as their response to therapy and disease progression.

The cohort studies were conducted in Europe, the United States, and Canada, and they enrolled at least 100 patients aged 16 years or older with HIV-1 infection (median age was 36 years). The participants had started antiretroviral therapy with a combination of at least three drugs, and the median duration of follow-up was 1 year.

The medications included nucleoside reverse transcriptase inhibitors, protease inhibitors, and nonnucleoside reverse transcriptase inhibitors (NNRTIs). The severity of immunodeficiency at baseline ranged from severe to nonexistent, and viral replication ranged from undetectable to extremely high, the investigators wrote (Lancet 2006;368:451–8).

Starting with data from 1995–1996 and ending in 2002–2003, the researchers evaluated the clinical prognosis of 22,217 patients based on two primary end points: AIDS events and death from all causes.

The percentage of women infected rose from 16% in 1995–1996 to 32% in 2002–2003. In 1995–1996, 56% of patients starting HAART were presumed to have been infected via male homosexual contact, but this figure dropped to 34% by 2002–2003, while the percentage of patients infected via heterosexual contact rose from 20% in 1995–1996 to 47% in 2002–2003.

“The percentage of patients infected via injection drug use declined from 20% in 1997 to 9% in 2002–2003,” wrote Dr. May and colleagues. Fewer than 1% of patients were infected by contaminated blood, and about 9% had an unspecified mode of transmission.

The median CD4 cell count at the initiation of HAART rose from 170 cells per μL in 1995–1996 to 269 cells per μL in 1998, and decreased to about 200 cells per μL in 2002–2003. According to the researchers, most patients started on a protease inhibitor-based HAART regimen in 1995–1998, whereas from 1999 onwards, at least 40% started HAART with NNRTI-based regimens. The percentage of patients starting HAART with four or more drugs rose from 1% in 1995–1996 to 11% in 2002–2003.

In 1995–1996, 58% of patients achieved an HIV-1 RNA of 500 copies per mL or less by 6 months of treatment. By 1997, this figure increased to 73% of patients, and by 2002–2003, it was 83% of patients.

“The estimated probability of death up to 1 year after starting HAART did not differ greatly by calendar period. Compared with 1998, the adjusted hazard ratio for AIDS was 1.30 in 1997 and 1.35 in 2002–03,” Dr. May noted.

The researchers evaluated whether the rise in AIDS events (including AIDS-related deaths) in the most recent years could be attributed to an increase in the rate of tuberculosis. Their analysis demonstrated that, compared with 1998, the rise in AIDS events in 2002–2003 “is largely attributable to an increase in tuberculosis.”

“The discrepancy between the clear improvement we recorded for virological response and the apparently worsening rates of clinical progression might be related to the change in the demographic characteristics of study participants with an increasing number of patients from areas with a high incidence of tuberculosis,” the investigators wrote.

The lower CD4 cell count at the initiation of HAART in recent years was of great concern, and research showed many missed opportunities for earlier diagnosis. Expansion of screenings for AIDS would be beneficial, they concluded.

In a commentary by Dr. Gregory J. Dore and Dr. David A. Cooper of the University of New South Wales in Australia, they called for more widespread tuberculosis screenings and prophylaxis initiatives, particularly for individuals from high-prevalence regions (Lancet 2006;368:427–8). The trend toward lower CD4-lymphocyte count at the start of HAART was also a point of concern, and “might have increased the risk of immune restoration syndrome,” they said. “Undiagnosed active opportunistic infections at the start of HAART might be a further contributing factor.”

The virologic response in HIV-positive patients to highly active antiretroviral therapy has improved over the past 10 years; however, there has been no corresponding decrease in mortality, reported Dr. Margaret T. May of the University of Bristol (England) and her colleagues.

The researchers analyzed data from the Antiretroviral Treatment Cohort Collaboration, and examined 12 cohort studies.

The studies focused on characteristics of antiretroviral-naive patients at the start of highly active antiretroviral therapy (HAART) as well as their response to therapy and disease progression.

The cohort studies were conducted in Europe, the United States, and Canada, and they enrolled at least 100 patients aged 16 years or older with HIV-1 infection (median age was 36 years). The participants had started antiretroviral therapy with a combination of at least three drugs, and the median duration of follow-up was 1 year.

The medications included nucleoside reverse transcriptase inhibitors, protease inhibitors, and nonnucleoside reverse transcriptase inhibitors (NNRTIs). The severity of immunodeficiency at baseline ranged from severe to nonexistent, and viral replication ranged from undetectable to extremely high, the investigators wrote (Lancet 2006;368:451–8).

Starting with data from 1995–1996 and ending in 2002–2003, the researchers evaluated the clinical prognosis of 22,217 patients based on two primary end points: AIDS events and death from all causes.

The percentage of women infected rose from 16% in 1995–1996 to 32% in 2002–2003. In 1995–1996, 56% of patients starting HAART were presumed to have been infected via male homosexual contact, but this figure dropped to 34% by 2002–2003, while the percentage of patients infected via heterosexual contact rose from 20% in 1995–1996 to 47% in 2002–2003.

“The percentage of patients infected via injection drug use declined from 20% in 1997 to 9% in 2002–2003,” wrote Dr. May and colleagues. Fewer than 1% of patients were infected by contaminated blood, and about 9% had an unspecified mode of transmission.

The median CD4 cell count at the initiation of HAART rose from 170 cells per μL in 1995–1996 to 269 cells per μL in 1998, and decreased to about 200 cells per μL in 2002–2003. According to the researchers, most patients started on a protease inhibitor-based HAART regimen in 1995–1998, whereas from 1999 onwards, at least 40% started HAART with NNRTI-based regimens. The percentage of patients starting HAART with four or more drugs rose from 1% in 1995–1996 to 11% in 2002–2003.

In 1995–1996, 58% of patients achieved an HIV-1 RNA of 500 copies per mL or less by 6 months of treatment. By 1997, this figure increased to 73% of patients, and by 2002–2003, it was 83% of patients.

“The estimated probability of death up to 1 year after starting HAART did not differ greatly by calendar period. Compared with 1998, the adjusted hazard ratio for AIDS was 1.30 in 1997 and 1.35 in 2002–03,” Dr. May noted.

The researchers evaluated whether the rise in AIDS events (including AIDS-related deaths) in the most recent years could be attributed to an increase in the rate of tuberculosis. Their analysis demonstrated that, compared with 1998, the rise in AIDS events in 2002–2003 “is largely attributable to an increase in tuberculosis.”

“The discrepancy between the clear improvement we recorded for virological response and the apparently worsening rates of clinical progression might be related to the change in the demographic characteristics of study participants with an increasing number of patients from areas with a high incidence of tuberculosis,” the investigators wrote.

The lower CD4 cell count at the initiation of HAART in recent years was of great concern, and research showed many missed opportunities for earlier diagnosis. Expansion of screenings for AIDS would be beneficial, they concluded.

In a commentary by Dr. Gregory J. Dore and Dr. David A. Cooper of the University of New South Wales in Australia, they called for more widespread tuberculosis screenings and prophylaxis initiatives, particularly for individuals from high-prevalence regions (Lancet 2006;368:427–8). The trend toward lower CD4-lymphocyte count at the start of HAART was also a point of concern, and “might have increased the risk of immune restoration syndrome,” they said. “Undiagnosed active opportunistic infections at the start of HAART might be a further contributing factor.”

A simple and inexpensive laboratory test that measures thrombin generation can be used to identify venous thromboembolism patients at low risk of recurrence—those who are unlikely to benefit from indefinite anticoagulant treatments, reported Dr. Gregor Hron of the Medical University of Vienna, and his colleagues.

In the Austrian Study on Recurrent Venous Thromboembolism (AUREC), an ongoing prospective cohort study that enrolled 914 patients between 1992 and 2005, those patients without recurrent VTE were found to have significantly lower peak thrombin generation than patients with VTE recurrence, according to the researchers.

The mean patient age at first venous thromboembolism (VTE) was 47 years, and 55% of the patients were women.

Deep vein thrombosis was found in 55% of patients, and 46% had a pulmonary embolism. Patients with both conditions were classified as having pulmonary embolism.

The mean duration of oral anticoagulant therapy in the patients studied was 8 months, with a mean observation time after therapy was discontinued of 47 months.

According to Dr. Hron and colleagues, patients were enrolled after discontinuation of vitamin K antagonist therapy. “For measurement of peak thrombin generation, blood was collected at a median of 13 months after discontinuation of anticoagulant therapy. Patients were seen at 3-month intervals and every 6 months thereafter,” they said (JAMA 2006;296:397–402).

The researchers analyzed thrombin generation with an assay kit called Technothrombin TGA (Technoclone GmbH, Vienna) using a computer-controlled microplate reader and specially adapted software.

“Patients with a first spontaneous VTE and peak thrombin generation of less than 400 nm after discontinuation of vitamin K antagonists have a low risk of recurrence,” said the researchers. Their likelihood of recurrence “was as low as 7% after 4 years,” according to Dr. Hron and his colleagues.

When compared with those with higher levels, patients with peak thrombin generation less than 400 nm had a 60% lower risk of recurrence, and this group represented the majority of the total patient population.

When underlying coagulation factors were assessed, 242 (27%) patients were found heterozygous for the factor V Leiden mutation, and 18 (2%) were homozygous. The mean factor VIII level was 166 IU/dL and mean factor IX level was 119 IU/dL. The number of patients with the prothrombin G20210A mutation was 63 (7%).

Overall, VTE was seen to recur in 100 patients (11%)—69 men and 31 women—with deep vein thrombosis in 58 patients and pulmonary embolism in 42 patients. Those patients with recurrent VTE had higher concentrations of factor VIII levels (173 IU/dL vs. 165 IU/dL), and factor IX levels (127 IU/dL vs. 118 IU/dL). These patients also had a shorter observation period (32 months vs. 48 months) and were older (50 years vs. 47 years).

The factor V Leiden polymorphism was detected in 38% of patients with recurrence and in 27% of patients without recurrence. Nine patients with recurrence and 54 patients without recurrence showed the presence of factor II G20210A. Women and carriers of factor II G20210A had higher peak thrombin generation than men and patients without the mutation. There was no difference in peak thrombin generation in patients with or without factor V Leiden, or those patients with or without high factor VIII.

By the end of the study, a total of 194 of the original 914 patients were excluded for various medical reasons such as cancer, arterial disease or atrial fibrillation, or death, or were lost to follow-up.

“Using a simple and commercially available laboratory method developed to measure thrombin generation, we were able to identify patients in whom the long-term risk of recurrent VTE is almost negligible. Considering the incidence rates of severe or fatal hemorrhage related to anticoagulant therapy and the case-fatality rate of recurrent VTE, patients with low peak thrombin generation (less than 400 nm) would almost certainly not benefit from indefinite anticoagulant therapy,” concluded the researchers.

A simple and inexpensive laboratory test that measures thrombin generation can be used to identify venous thromboembolism patients at low risk of recurrence—those who are unlikely to benefit from indefinite anticoagulant treatments, reported Dr. Gregor Hron of the Medical University of Vienna, and his colleagues.

In the Austrian Study on Recurrent Venous Thromboembolism (AUREC), an ongoing prospective cohort study that enrolled 914 patients between 1992 and 2005, those patients without recurrent VTE were found to have significantly lower peak thrombin generation than patients with VTE recurrence, according to the researchers.

The mean patient age at first venous thromboembolism (VTE) was 47 years, and 55% of the patients were women.

Deep vein thrombosis was found in 55% of patients, and 46% had a pulmonary embolism. Patients with both conditions were classified as having pulmonary embolism.

The mean duration of oral anticoagulant therapy in the patients studied was 8 months, with a mean observation time after therapy was discontinued of 47 months.

According to Dr. Hron and colleagues, patients were enrolled after discontinuation of vitamin K antagonist therapy. “For measurement of peak thrombin generation, blood was collected at a median of 13 months after discontinuation of anticoagulant therapy. Patients were seen at 3-month intervals and every 6 months thereafter,” they said (JAMA 2006;296:397–402).

The researchers analyzed thrombin generation with an assay kit called Technothrombin TGA (Technoclone GmbH, Vienna) using a computer-controlled microplate reader and specially adapted software.

“Patients with a first spontaneous VTE and peak thrombin generation of less than 400 nm after discontinuation of vitamin K antagonists have a low risk of recurrence,” said the researchers. Their likelihood of recurrence “was as low as 7% after 4 years,” according to Dr. Hron and his colleagues.

When compared with those with higher levels, patients with peak thrombin generation less than 400 nm had a 60% lower risk of recurrence, and this group represented the majority of the total patient population.

When underlying coagulation factors were assessed, 242 (27%) patients were found heterozygous for the factor V Leiden mutation, and 18 (2%) were homozygous. The mean factor VIII level was 166 IU/dL and mean factor IX level was 119 IU/dL. The number of patients with the prothrombin G20210A mutation was 63 (7%).

Overall, VTE was seen to recur in 100 patients (11%)—69 men and 31 women—with deep vein thrombosis in 58 patients and pulmonary embolism in 42 patients. Those patients with recurrent VTE had higher concentrations of factor VIII levels (173 IU/dL vs. 165 IU/dL), and factor IX levels (127 IU/dL vs. 118 IU/dL). These patients also had a shorter observation period (32 months vs. 48 months) and were older (50 years vs. 47 years).

The factor V Leiden polymorphism was detected in 38% of patients with recurrence and in 27% of patients without recurrence. Nine patients with recurrence and 54 patients without recurrence showed the presence of factor II G20210A. Women and carriers of factor II G20210A had higher peak thrombin generation than men and patients without the mutation. There was no difference in peak thrombin generation in patients with or without factor V Leiden, or those patients with or without high factor VIII.

By the end of the study, a total of 194 of the original 914 patients were excluded for various medical reasons such as cancer, arterial disease or atrial fibrillation, or death, or were lost to follow-up.

“Using a simple and commercially available laboratory method developed to measure thrombin generation, we were able to identify patients in whom the long-term risk of recurrent VTE is almost negligible. Considering the incidence rates of severe or fatal hemorrhage related to anticoagulant therapy and the case-fatality rate of recurrent VTE, patients with low peak thrombin generation (less than 400 nm) would almost certainly not benefit from indefinite anticoagulant therapy,” concluded the researchers.

A simple and inexpensive laboratory test that measures thrombin generation can be used to identify venous thromboembolism patients at low risk of recurrence—those who are unlikely to benefit from indefinite anticoagulant treatments, reported Dr. Gregor Hron of the Medical University of Vienna, and his colleagues.

In the Austrian Study on Recurrent Venous Thromboembolism (AUREC), an ongoing prospective cohort study that enrolled 914 patients between 1992 and 2005, those patients without recurrent VTE were found to have significantly lower peak thrombin generation than patients with VTE recurrence, according to the researchers.

The mean patient age at first venous thromboembolism (VTE) was 47 years, and 55% of the patients were women.

Deep vein thrombosis was found in 55% of patients, and 46% had a pulmonary embolism. Patients with both conditions were classified as having pulmonary embolism.

The mean duration of oral anticoagulant therapy in the patients studied was 8 months, with a mean observation time after therapy was discontinued of 47 months.

According to Dr. Hron and colleagues, patients were enrolled after discontinuation of vitamin K antagonist therapy. “For measurement of peak thrombin generation, blood was collected at a median of 13 months after discontinuation of anticoagulant therapy. Patients were seen at 3-month intervals and every 6 months thereafter,” they said (JAMA 2006;296:397–402).

The researchers analyzed thrombin generation with an assay kit called Technothrombin TGA (Technoclone GmbH, Vienna) using a computer-controlled microplate reader and specially adapted software.

“Patients with a first spontaneous VTE and peak thrombin generation of less than 400 nm after discontinuation of vitamin K antagonists have a low risk of recurrence,” said the researchers. Their likelihood of recurrence “was as low as 7% after 4 years,” according to Dr. Hron and his colleagues.

When compared with those with higher levels, patients with peak thrombin generation less than 400 nm had a 60% lower risk of recurrence, and this group represented the majority of the total patient population.

When underlying coagulation factors were assessed, 242 (27%) patients were found heterozygous for the factor V Leiden mutation, and 18 (2%) were homozygous. The mean factor VIII level was 166 IU/dL and mean factor IX level was 119 IU/dL. The number of patients with the prothrombin G20210A mutation was 63 (7%).

Overall, VTE was seen to recur in 100 patients (11%)—69 men and 31 women—with deep vein thrombosis in 58 patients and pulmonary embolism in 42 patients. Those patients with recurrent VTE had higher concentrations of factor VIII levels (173 IU/dL vs. 165 IU/dL), and factor IX levels (127 IU/dL vs. 118 IU/dL). These patients also had a shorter observation period (32 months vs. 48 months) and were older (50 years vs. 47 years).

The factor V Leiden polymorphism was detected in 38% of patients with recurrence and in 27% of patients without recurrence. Nine patients with recurrence and 54 patients without recurrence showed the presence of factor II G20210A. Women and carriers of factor II G20210A had higher peak thrombin generation than men and patients without the mutation. There was no difference in peak thrombin generation in patients with or without factor V Leiden, or those patients with or without high factor VIII.

By the end of the study, a total of 194 of the original 914 patients were excluded for various medical reasons such as cancer, arterial disease or atrial fibrillation, or death, or were lost to follow-up.

“Using a simple and commercially available laboratory method developed to measure thrombin generation, we were able to identify patients in whom the long-term risk of recurrent VTE is almost negligible. Considering the incidence rates of severe or fatal hemorrhage related to anticoagulant therapy and the case-fatality rate of recurrent VTE, patients with low peak thrombin generation (less than 400 nm) would almost certainly not benefit from indefinite anticoagulant therapy,” concluded the researchers.

Low testosterone levels increase susceptibility to anemia, but may not be a sufficient causal factor for anemia in the elderly, reported Dr. Luigi Ferrucci of the National Institute on Aging, Bethesda, Md., and his colleagues.

The researchers evaluated data from the Italian InCHIANTI study, which enrolled 396 men and 509 women.

At baseline, 365 men did not have anemia, were a mean age of 74 years, and had a mean total testosterone level of 438 ng/dL.

Using the World Health Organization criteria, the investigators defined anemia as hemoglobin levels below 12 g/dL for women and 13 g/dL for men. Participants with “explained” anemia had one or more potential causes, and those with “unexplained” anemia had normal serum iron and no vitamin B12 or folate deficiencies.

Eleven men had explained anemia and a mean total testosterone of 355 ng/dL. Another 20 had unexplained anemia and a mean total testosterone of 332 ng/dL.

At baseline, 452 women did not have anemia, were a mean age of 64 years, and had a mean total testosterone of 64 ng/dL. Thirty-one had explained anemia and a mean total testosterone of 54 ng/dL; 26 had unexplained anemia and a mean total testosterone of 52 ng/dL (Arch. Intern. Med. 2006;166:1380–8).

Bioavailable testosterone level declined with age. Men in the lowest total and bioavailable testosterone level quartiles were 5.4 times and 13.1 times more likely, respectively, to be anemic than men in the highest quartiles. Women in the lowest bioavailable testosterone level quartile were 3.4 times more likely to have anemia than women in the highest quartile.

For a longitudinal analysis, 274 men and 337 women without anemia at baseline were reevaluated 3 years later; 23 men (8.4%) and 26 women (7.7%) had developed anemia.

Total testosterone levels were not significantly associated with anemia, but bioavailable testosterone was. Men and women in the lowest level quartiles were 4.7 and 4.4 times more likely, respectively, to develop anemia, compared with those in the higher level quartiles.

Low testosterone levels increase susceptibility to anemia, but may not be a sufficient causal factor for anemia in the elderly, reported Dr. Luigi Ferrucci of the National Institute on Aging, Bethesda, Md., and his colleagues.

The researchers evaluated data from the Italian InCHIANTI study, which enrolled 396 men and 509 women.

At baseline, 365 men did not have anemia, were a mean age of 74 years, and had a mean total testosterone level of 438 ng/dL.

Using the World Health Organization criteria, the investigators defined anemia as hemoglobin levels below 12 g/dL for women and 13 g/dL for men. Participants with “explained” anemia had one or more potential causes, and those with “unexplained” anemia had normal serum iron and no vitamin B12 or folate deficiencies.

Eleven men had explained anemia and a mean total testosterone of 355 ng/dL. Another 20 had unexplained anemia and a mean total testosterone of 332 ng/dL.

At baseline, 452 women did not have anemia, were a mean age of 64 years, and had a mean total testosterone of 64 ng/dL. Thirty-one had explained anemia and a mean total testosterone of 54 ng/dL; 26 had unexplained anemia and a mean total testosterone of 52 ng/dL (Arch. Intern. Med. 2006;166:1380–8).

Bioavailable testosterone level declined with age. Men in the lowest total and bioavailable testosterone level quartiles were 5.4 times and 13.1 times more likely, respectively, to be anemic than men in the highest quartiles. Women in the lowest bioavailable testosterone level quartile were 3.4 times more likely to have anemia than women in the highest quartile.

For a longitudinal analysis, 274 men and 337 women without anemia at baseline were reevaluated 3 years later; 23 men (8.4%) and 26 women (7.7%) had developed anemia.

Total testosterone levels were not significantly associated with anemia, but bioavailable testosterone was. Men and women in the lowest level quartiles were 4.7 and 4.4 times more likely, respectively, to develop anemia, compared with those in the higher level quartiles.

Low testosterone levels increase susceptibility to anemia, but may not be a sufficient causal factor for anemia in the elderly, reported Dr. Luigi Ferrucci of the National Institute on Aging, Bethesda, Md., and his colleagues.

The researchers evaluated data from the Italian InCHIANTI study, which enrolled 396 men and 509 women.

At baseline, 365 men did not have anemia, were a mean age of 74 years, and had a mean total testosterone level of 438 ng/dL.

Using the World Health Organization criteria, the investigators defined anemia as hemoglobin levels below 12 g/dL for women and 13 g/dL for men. Participants with “explained” anemia had one or more potential causes, and those with “unexplained” anemia had normal serum iron and no vitamin B12 or folate deficiencies.

Eleven men had explained anemia and a mean total testosterone of 355 ng/dL. Another 20 had unexplained anemia and a mean total testosterone of 332 ng/dL.

At baseline, 452 women did not have anemia, were a mean age of 64 years, and had a mean total testosterone of 64 ng/dL. Thirty-one had explained anemia and a mean total testosterone of 54 ng/dL; 26 had unexplained anemia and a mean total testosterone of 52 ng/dL (Arch. Intern. Med. 2006;166:1380–8).

Bioavailable testosterone level declined with age. Men in the lowest total and bioavailable testosterone level quartiles were 5.4 times and 13.1 times more likely, respectively, to be anemic than men in the highest quartiles. Women in the lowest bioavailable testosterone level quartile were 3.4 times more likely to have anemia than women in the highest quartile.

For a longitudinal analysis, 274 men and 337 women without anemia at baseline were reevaluated 3 years later; 23 men (8.4%) and 26 women (7.7%) had developed anemia.

Total testosterone levels were not significantly associated with anemia, but bioavailable testosterone was. Men and women in the lowest level quartiles were 4.7 and 4.4 times more likely, respectively, to develop anemia, compared with those in the higher level quartiles.

Etanercept provided 4-year clinical efficacy in patients with polyarticular-course juvenile rheumatoid arthritis, and was well tolerated without an increase in the rate of serious infection, reported Dr. Daniel J. Lovell and colleagues.

The researchers had previously conducted a randomized, open-label trial that found that clinical efficacy could be sustained for at least 2 years. From this initial group of 69 patients, Dr. Lovell and colleagues enrolled 58 patients in a multicenter, open-label extension study to assess etanercept's long-term efficacy and safety (Arthritis Rheum. 2006;54:1987–94).

The study group had a mean age of 10 years, of which 39 (67%) were female. Five participants (9%) had pauciarticular JRA, 34 (59%) had polyarticular JRA, and 19 (33%) had systemic JRA. The mean duration of their disease was 5.9 years; 100% had previously used methotrexate (MTX), 97% had used NSAIDs, and 38% had previously used corticosteroids with a mean dose of 5.7 mg/day. At year 4, 32 of the 58 patients remained, with a similar demographic composition, disease history, and previous use of JRA therapies.

Dr. Lovell, of Cincinnati Children's Hospital Medical Center, and his colleagues calculated infection safety data from all 69 patients enrolled in the original study and the long-term extension. Results showed that eight patients (12%) “had serious infections, for a rate of 0.04 infections per patient-year. The exposure-adjusted rates of serious infection did not increase over time with continuing etanercept treatment,” the researchers reported.

When it came to long-term efficacy, data from the 58 patients in the extension study were assessed. Patient assessment of pain, on a 0–10 scale, was a median of 3.6 at baseline, 0.3 at 1 year, and 0.9 by the 4th year. The physician's global assessment on a 0–10 scale was a median 6.5 at baseline, 2.0 at 1 year, and 1.0 at year 4.

For total joints with active disease, the median at baseline was 28.5, 2.5 at 1 year, and 2.0 at 4 years. When participants scored the number of joints experiencing limitation of motion and painful/tender joints, it was a median of 9 at baseline, and 0 at both the 1-year and 4-year marks. The articular severity score for participants was a median 88 at baseline, 25 at year 1, and 18 at year 4.

By the second year of the extension study, 8 (17%) of the 47 remaining patients were receiving MTX at a mean dose of 13.4 mg/week, and by the 4th year 13 of 38 patients (34%) were receiving MTX at a mean dose of 15.8 mg/week. According to the researchers, 23 (40%) of the 58 patients were taking low-dose steroids at the start of the extension study, but 70% of these patients discontinued steroid use, while another 4 participants decreased their dosages. From the original 58 participants in the extension study, 6 withdrew due to lack of efficacy.

“Patients with JRA showed sustained improvements in disease activity measures in this extension study. ACR Pediatric 30 scores observed at year 1 were sustained through year 4 of treatment with etanercept,” said Dr. Lovell. Adding MTX to the treatment regimen may have contributed to the sustained improvements.

“Overall, etanercept offers significant clinical benefit with an acceptable safety profile,” the investigators concluded.

Etanercept provided 4-year clinical efficacy in patients with polyarticular-course juvenile rheumatoid arthritis, and was well tolerated without an increase in the rate of serious infection, reported Dr. Daniel J. Lovell and colleagues.

The researchers had previously conducted a randomized, open-label trial that found that clinical efficacy could be sustained for at least 2 years. From this initial group of 69 patients, Dr. Lovell and colleagues enrolled 58 patients in a multicenter, open-label extension study to assess etanercept's long-term efficacy and safety (Arthritis Rheum. 2006;54:1987–94).

The study group had a mean age of 10 years, of which 39 (67%) were female. Five participants (9%) had pauciarticular JRA, 34 (59%) had polyarticular JRA, and 19 (33%) had systemic JRA. The mean duration of their disease was 5.9 years; 100% had previously used methotrexate (MTX), 97% had used NSAIDs, and 38% had previously used corticosteroids with a mean dose of 5.7 mg/day. At year 4, 32 of the 58 patients remained, with a similar demographic composition, disease history, and previous use of JRA therapies.

Dr. Lovell, of Cincinnati Children's Hospital Medical Center, and his colleagues calculated infection safety data from all 69 patients enrolled in the original study and the long-term extension. Results showed that eight patients (12%) “had serious infections, for a rate of 0.04 infections per patient-year. The exposure-adjusted rates of serious infection did not increase over time with continuing etanercept treatment,” the researchers reported.

When it came to long-term efficacy, data from the 58 patients in the extension study were assessed. Patient assessment of pain, on a 0–10 scale, was a median of 3.6 at baseline, 0.3 at 1 year, and 0.9 by the 4th year. The physician's global assessment on a 0–10 scale was a median 6.5 at baseline, 2.0 at 1 year, and 1.0 at year 4.

For total joints with active disease, the median at baseline was 28.5, 2.5 at 1 year, and 2.0 at 4 years. When participants scored the number of joints experiencing limitation of motion and painful/tender joints, it was a median of 9 at baseline, and 0 at both the 1-year and 4-year marks. The articular severity score for participants was a median 88 at baseline, 25 at year 1, and 18 at year 4.

By the second year of the extension study, 8 (17%) of the 47 remaining patients were receiving MTX at a mean dose of 13.4 mg/week, and by the 4th year 13 of 38 patients (34%) were receiving MTX at a mean dose of 15.8 mg/week. According to the researchers, 23 (40%) of the 58 patients were taking low-dose steroids at the start of the extension study, but 70% of these patients discontinued steroid use, while another 4 participants decreased their dosages. From the original 58 participants in the extension study, 6 withdrew due to lack of efficacy.

“Patients with JRA showed sustained improvements in disease activity measures in this extension study. ACR Pediatric 30 scores observed at year 1 were sustained through year 4 of treatment with etanercept,” said Dr. Lovell. Adding MTX to the treatment regimen may have contributed to the sustained improvements.

“Overall, etanercept offers significant clinical benefit with an acceptable safety profile,” the investigators concluded.

Etanercept provided 4-year clinical efficacy in patients with polyarticular-course juvenile rheumatoid arthritis, and was well tolerated without an increase in the rate of serious infection, reported Dr. Daniel J. Lovell and colleagues.

The researchers had previously conducted a randomized, open-label trial that found that clinical efficacy could be sustained for at least 2 years. From this initial group of 69 patients, Dr. Lovell and colleagues enrolled 58 patients in a multicenter, open-label extension study to assess etanercept's long-term efficacy and safety (Arthritis Rheum. 2006;54:1987–94).

The study group had a mean age of 10 years, of which 39 (67%) were female. Five participants (9%) had pauciarticular JRA, 34 (59%) had polyarticular JRA, and 19 (33%) had systemic JRA. The mean duration of their disease was 5.9 years; 100% had previously used methotrexate (MTX), 97% had used NSAIDs, and 38% had previously used corticosteroids with a mean dose of 5.7 mg/day. At year 4, 32 of the 58 patients remained, with a similar demographic composition, disease history, and previous use of JRA therapies.

Dr. Lovell, of Cincinnati Children's Hospital Medical Center, and his colleagues calculated infection safety data from all 69 patients enrolled in the original study and the long-term extension. Results showed that eight patients (12%) “had serious infections, for a rate of 0.04 infections per patient-year. The exposure-adjusted rates of serious infection did not increase over time with continuing etanercept treatment,” the researchers reported.

When it came to long-term efficacy, data from the 58 patients in the extension study were assessed. Patient assessment of pain, on a 0–10 scale, was a median of 3.6 at baseline, 0.3 at 1 year, and 0.9 by the 4th year. The physician's global assessment on a 0–10 scale was a median 6.5 at baseline, 2.0 at 1 year, and 1.0 at year 4.

For total joints with active disease, the median at baseline was 28.5, 2.5 at 1 year, and 2.0 at 4 years. When participants scored the number of joints experiencing limitation of motion and painful/tender joints, it was a median of 9 at baseline, and 0 at both the 1-year and 4-year marks. The articular severity score for participants was a median 88 at baseline, 25 at year 1, and 18 at year 4.

By the second year of the extension study, 8 (17%) of the 47 remaining patients were receiving MTX at a mean dose of 13.4 mg/week, and by the 4th year 13 of 38 patients (34%) were receiving MTX at a mean dose of 15.8 mg/week. According to the researchers, 23 (40%) of the 58 patients were taking low-dose steroids at the start of the extension study, but 70% of these patients discontinued steroid use, while another 4 participants decreased their dosages. From the original 58 participants in the extension study, 6 withdrew due to lack of efficacy.

“Patients with JRA showed sustained improvements in disease activity measures in this extension study. ACR Pediatric 30 scores observed at year 1 were sustained through year 4 of treatment with etanercept,” said Dr. Lovell. Adding MTX to the treatment regimen may have contributed to the sustained improvements.

“Overall, etanercept offers significant clinical benefit with an acceptable safety profile,” the investigators concluded.

Raloxifene did not significantly increase the risk of coronary events in women with coronary heart disease or those at high risk for the disease in a randomized study of more than 10,000 postmenopausal women.

In addition, treatment with raloxifene for a median of 5 years decreased the risk of invasive breast cancer and vertebral fractures but increased the risks of venous thromboembolic events and fatal stroke, study investigators reported.

Dr. Elizabeth Barrett-Connor of the University of California, San Diego, and her colleagues concluded that when considering the use of raloxifene in a postmenopausal woman, clinicians should “weigh the benefits and risks against the availability of alternative interventions” (N. Engl. J. Med. 2006;355:125–37).

In an accompanying editorial, Marcia L. Stefanick, Ph.D., agreed with that conclusion, but noted that, for postmenopausal women similar to those in the study who have or are at increased risk of coronary heart disease (CHD), the modest benefits offered by raloxifene as a breast cancer prophylaxis “do not seem to justify the risks.”

“For now, there is no magic bullet that can reduce the risks of major health problems related to estrogens and aging without introducing other potentially serious health concerns,” said Dr. Stefanick of Stanford (Calif.) University (N. Engl. J. Med. 2006;355:190–2).

The Raloxifene Use for the Heart study, an international, multicenter, randomized, double-blind, placebo-controlled trial, was conducted to determine of the effect of the drug on clinical coronary events. The study was supported by Eli Lilly, maker of raloxifene (marketed as Evista).

A total of 10,101 postmenopausal women were enrolled from June 1998 through August 2000. The participants were at least 1 year post menopause and had established CHD or were at increased risk for CHD.

A total of 5,057 participants were randomized to receive 60 mg of oral raloxifene daily, and 5,044 were randomized to placebo.

The median duration of follow-up was 5.6 years; 80% of those in the raloxifene group and 79% in the placebo group completed the study.

Both groups had similar baseline characteristics, “except that the raloxifene group had a slightly higher cardiovascular risk score and a higher proportion of women reporting coronary artery bypass grafting,” the researchers said.

In both groups, the mean age was 68 years.

There was no significant difference between the raloxifene and placebo groups in the study's combined coronary end point of death from coronary causes, nonfatal myocardial infarction, or hospitalization for an acute coronary syndrome other than myocardial infarction (533 events vs. 553 events, hazard ratio of 0.95).

Raloxifene, a nonsteroidal selective estrogen-receptor modulator, reduced the incidence of invasive breast cancer (hazard ratio, 0.56), another primary outcome in the study.

The researchers attributed this finding “to a reduction in estrogen-receptor-positive invasive breast cancer.

The absolute risk reduction per 1,000 women treated with raloxifene for 1 year was 1.2 cases of invasive breast cancer and 1.2 cases of estrogen-receptor-positive invasive breast cancer.”

There was no significant difference between the two groups in the incidence of estrogen-receptor-negative invasive breast cancer.

The overall stroke rate, a secondary outcome, did not differ between groups, but the incidence of fatal stroke was 49% higher in the raloxifene group, compared with the placebo group (59 events vs. 39 events); the absolute risk increase was 0.7 per 1,000 woman-years.

The incidence of venous thromboembolic events was 44% higher in the raloxifene group, compared with placebo (103 events vs. 71 events); the absolute risk increase was 1.2 per 1,000 woman-years.

However, the raloxifene group also showed a 33% lower incidence of all breast cancers, with an absolute risk reduction of 0.9 per 1,000 woman-years.

Raloxifene users also had a 35% lower incidence of clinical vertebral fractures; their absolute risk reduction was 1.3 per 1,000 woman-years.

The raloxifene group also had a lower rate of death from noncardiovascular causes (188 events vs. 231 events in the placebo group), but there was no significant difference between groups in death from any cause or overall death from cardiovascular causes.

In addition, participants in the placebo group showed an increase of 3.6% in low-density lipoprotein (LDL) cholesterol and a 0.9% increase in high-density lipoprotein (HDL) cholesterol, compared with a 4.4% decrease in LDL cholesterol and a 2.3% increase in HDL cholesterol for raloxifene users.

Raloxifene did not significantly increase the risk of coronary events in women with coronary heart disease or those at high risk for the disease in a randomized study of more than 10,000 postmenopausal women.

In addition, treatment with raloxifene for a median of 5 years decreased the risk of invasive breast cancer and vertebral fractures but increased the risks of venous thromboembolic events and fatal stroke, study investigators reported.

Dr. Elizabeth Barrett-Connor of the University of California, San Diego, and her colleagues concluded that when considering the use of raloxifene in a postmenopausal woman, clinicians should “weigh the benefits and risks against the availability of alternative interventions” (N. Engl. J. Med. 2006;355:125–37).

In an accompanying editorial, Marcia L. Stefanick, Ph.D., agreed with that conclusion, but noted that, for postmenopausal women similar to those in the study who have or are at increased risk of coronary heart disease (CHD), the modest benefits offered by raloxifene as a breast cancer prophylaxis “do not seem to justify the risks.”

“For now, there is no magic bullet that can reduce the risks of major health problems related to estrogens and aging without introducing other potentially serious health concerns,” said Dr. Stefanick of Stanford (Calif.) University (N. Engl. J. Med. 2006;355:190–2).

The Raloxifene Use for the Heart study, an international, multicenter, randomized, double-blind, placebo-controlled trial, was conducted to determine of the effect of the drug on clinical coronary events. The study was supported by Eli Lilly, maker of raloxifene (marketed as Evista).

A total of 10,101 postmenopausal women were enrolled from June 1998 through August 2000. The participants were at least 1 year post menopause and had established CHD or were at increased risk for CHD.

A total of 5,057 participants were randomized to receive 60 mg of oral raloxifene daily, and 5,044 were randomized to placebo.

The median duration of follow-up was 5.6 years; 80% of those in the raloxifene group and 79% in the placebo group completed the study.

Both groups had similar baseline characteristics, “except that the raloxifene group had a slightly higher cardiovascular risk score and a higher proportion of women reporting coronary artery bypass grafting,” the researchers said.

In both groups, the mean age was 68 years.

There was no significant difference between the raloxifene and placebo groups in the study's combined coronary end point of death from coronary causes, nonfatal myocardial infarction, or hospitalization for an acute coronary syndrome other than myocardial infarction (533 events vs. 553 events, hazard ratio of 0.95).

Raloxifene, a nonsteroidal selective estrogen-receptor modulator, reduced the incidence of invasive breast cancer (hazard ratio, 0.56), another primary outcome in the study.

The researchers attributed this finding “to a reduction in estrogen-receptor-positive invasive breast cancer.

The absolute risk reduction per 1,000 women treated with raloxifene for 1 year was 1.2 cases of invasive breast cancer and 1.2 cases of estrogen-receptor-positive invasive breast cancer.”

There was no significant difference between the two groups in the incidence of estrogen-receptor-negative invasive breast cancer.

The overall stroke rate, a secondary outcome, did not differ between groups, but the incidence of fatal stroke was 49% higher in the raloxifene group, compared with the placebo group (59 events vs. 39 events); the absolute risk increase was 0.7 per 1,000 woman-years.

The incidence of venous thromboembolic events was 44% higher in the raloxifene group, compared with placebo (103 events vs. 71 events); the absolute risk increase was 1.2 per 1,000 woman-years.

However, the raloxifene group also showed a 33% lower incidence of all breast cancers, with an absolute risk reduction of 0.9 per 1,000 woman-years.

Raloxifene users also had a 35% lower incidence of clinical vertebral fractures; their absolute risk reduction was 1.3 per 1,000 woman-years.

The raloxifene group also had a lower rate of death from noncardiovascular causes (188 events vs. 231 events in the placebo group), but there was no significant difference between groups in death from any cause or overall death from cardiovascular causes.

In addition, participants in the placebo group showed an increase of 3.6% in low-density lipoprotein (LDL) cholesterol and a 0.9% increase in high-density lipoprotein (HDL) cholesterol, compared with a 4.4% decrease in LDL cholesterol and a 2.3% increase in HDL cholesterol for raloxifene users.

Raloxifene did not significantly increase the risk of coronary events in women with coronary heart disease or those at high risk for the disease in a randomized study of more than 10,000 postmenopausal women.

In addition, treatment with raloxifene for a median of 5 years decreased the risk of invasive breast cancer and vertebral fractures but increased the risks of venous thromboembolic events and fatal stroke, study investigators reported.

Dr. Elizabeth Barrett-Connor of the University of California, San Diego, and her colleagues concluded that when considering the use of raloxifene in a postmenopausal woman, clinicians should “weigh the benefits and risks against the availability of alternative interventions” (N. Engl. J. Med. 2006;355:125–37).

In an accompanying editorial, Marcia L. Stefanick, Ph.D., agreed with that conclusion, but noted that, for postmenopausal women similar to those in the study who have or are at increased risk of coronary heart disease (CHD), the modest benefits offered by raloxifene as a breast cancer prophylaxis “do not seem to justify the risks.”

“For now, there is no magic bullet that can reduce the risks of major health problems related to estrogens and aging without introducing other potentially serious health concerns,” said Dr. Stefanick of Stanford (Calif.) University (N. Engl. J. Med. 2006;355:190–2).

The Raloxifene Use for the Heart study, an international, multicenter, randomized, double-blind, placebo-controlled trial, was conducted to determine of the effect of the drug on clinical coronary events. The study was supported by Eli Lilly, maker of raloxifene (marketed as Evista).

A total of 10,101 postmenopausal women were enrolled from June 1998 through August 2000. The participants were at least 1 year post menopause and had established CHD or were at increased risk for CHD.

A total of 5,057 participants were randomized to receive 60 mg of oral raloxifene daily, and 5,044 were randomized to placebo.

The median duration of follow-up was 5.6 years; 80% of those in the raloxifene group and 79% in the placebo group completed the study.

Both groups had similar baseline characteristics, “except that the raloxifene group had a slightly higher cardiovascular risk score and a higher proportion of women reporting coronary artery bypass grafting,” the researchers said.

In both groups, the mean age was 68 years.

There was no significant difference between the raloxifene and placebo groups in the study's combined coronary end point of death from coronary causes, nonfatal myocardial infarction, or hospitalization for an acute coronary syndrome other than myocardial infarction (533 events vs. 553 events, hazard ratio of 0.95).

Raloxifene, a nonsteroidal selective estrogen-receptor modulator, reduced the incidence of invasive breast cancer (hazard ratio, 0.56), another primary outcome in the study.

The researchers attributed this finding “to a reduction in estrogen-receptor-positive invasive breast cancer.

The absolute risk reduction per 1,000 women treated with raloxifene for 1 year was 1.2 cases of invasive breast cancer and 1.2 cases of estrogen-receptor-positive invasive breast cancer.”

There was no significant difference between the two groups in the incidence of estrogen-receptor-negative invasive breast cancer.

The overall stroke rate, a secondary outcome, did not differ between groups, but the incidence of fatal stroke was 49% higher in the raloxifene group, compared with the placebo group (59 events vs. 39 events); the absolute risk increase was 0.7 per 1,000 woman-years.

The incidence of venous thromboembolic events was 44% higher in the raloxifene group, compared with placebo (103 events vs. 71 events); the absolute risk increase was 1.2 per 1,000 woman-years.

However, the raloxifene group also showed a 33% lower incidence of all breast cancers, with an absolute risk reduction of 0.9 per 1,000 woman-years.

Raloxifene users also had a 35% lower incidence of clinical vertebral fractures; their absolute risk reduction was 1.3 per 1,000 woman-years.

The raloxifene group also had a lower rate of death from noncardiovascular causes (188 events vs. 231 events in the placebo group), but there was no significant difference between groups in death from any cause or overall death from cardiovascular causes.

In addition, participants in the placebo group showed an increase of 3.6% in low-density lipoprotein (LDL) cholesterol and a 0.9% increase in high-density lipoprotein (HDL) cholesterol, compared with a 4.4% decrease in LDL cholesterol and a 2.3% increase in HDL cholesterol for raloxifene users.

BALTIMORE — From the outside, pediatric oncology treatment may look like a puzzling maze for patients, their families, and even primary care providers.

“One question that tends to come up is, 'How exactly is that black box of pediatric oncology organized?' From the pediatrician's perspective, often it's hard to know who are the best people to get in touch with to get the best information,” said Dr. Patrick Brown, of the pediatric oncology department at Johns Hopkins University, Baltimore.

At his institution, a pediatric oncology fellow is usually designated as the first contact for a referred patient, and this fellow “is at the center of delivering care.

“The fellow works closely with the attending on service at the time. Together this pair will become the primary oncology team for the patient,” he said at a meeting on pediatric trends sponsored by Johns Hopkins University. This team devises a treatment plan that's carried out by a larger team of pediatric residents and physician extenders. Another important component is the multidisciplinary team, composed of surgeons, radiology oncologists, bone marrow transplant specialists, pediatric ICU staff, nurses, and social workers—all working closely with the fellow.

Each patient is assigned a primary team of oncologists who have longitudinal responsibility for the patient's care. “These providers are your primary point of contact. You should be hearing from either the attending or the fellow while the patient is being treated, and you should know how to get in touch with one or both of these individuals,” he said.

As with all good relationships, communication is a two-way street, and Dr. Brown suggested pediatricians initially try to refer patients to a medical center that can offer a multidisciplinary approach. While it's not necessary that a center be a transplant center, he urged physicians “to find a place that's a member of a clinical trials network for children with cancer. It's been documented over the years that children with cancer who are treated within the context of clinical trials have better outcomes.”

The pediatrician plays a key role in communicating many of the elements of the diagnosis, prognosis, and treatment plan to the child, parents, and any siblings and—most importantly—offers them emotional support. The pediatrician also provides essential background information on the patient to the oncology team.

Dr. Brown stressed it is the job of the oncologist to “open lines of communication with the pediatrician early and sustain them.

“We recognize the diagnosis of cancer is almost always the unexpected result of a series of rational diagnostic procedures, and that true cases where cues have been missed that cause a delay in diagnosis and negatively impact prognosis are exceedingly rare,” he said. While it often seems to parents that something should have been picked up earlier, “we do everything we can to dissuade them of that notion, because in the vast majority of cases that is not true. I think it's our job to help the parents understand that and to help you understand that.”

During treatment the oncology team takes responsibility for all medical issues, including primary care issues, but they may ask a pediatrician for assistance with blood work, referrals, and urgent care matters, especially for patients who live far from the cancer treatment center or for patients who are in “lower-intensity phases of therapy or on maintenance therapy,” he noted. In turn, oncologists should update pediatricians on all major events, such as complications or relapses.

After a patient is treated, the pediatrician should be given a comprehensive treatment summary by the oncologist. “It should not be something that's done over the telephone. This should be a document in your hand that you can refer to and put in your patient's chart,” said Dr. Brown. This document should contain information on the location of the cancer, its stage, and any relapses. It should include information on chemotherapy and radiation treatments (“you should know where and at what dose”), surgeries and the extent of resection, bone marrow transplants (autologous or allogeneic), any investigational treatments used, complications, and adverse reactions or allergies.

“It's very important to know what chemotherapy agents patients have received,” he said.

For example, anthracycline carries a risk for cardiac toxicity, while use of high or low doses of methotrexate or cytarabine should be noted because the particular doses of these agents significantly affect the risk of certain long-term complications.

The oncologist should detail the risk of relapse and the risk of secondary malignancies. Relapse and the timing of relapse are very disease specific. “If a patient comes back to you after having received treatment for Burkitt's lymphoma and they're a year out from completion of therapy, the chances are excellent that they're not going to relapse … compared with a patient with a low-grade brain tumor, for example, where it is actually relatively common for the duration of remission prior to relapse to be fairly extended,” Dr. Brown said.

The pediatrician should be involved in any major changes in the goals of care, specifically a switch to end-of-life and palliative care, and of course should be immediately notified of a patient's death. “It's at that point that I think the pediatrician should be reinvolved in a significant way,” he said. This provides further emotional support for the family, reinforces the therapeutic relationship, and assists in psychosocial screening. The pediatrician's involvement at this stage also is often particularly helpful for surviving siblings.

BALTIMORE — From the outside, pediatric oncology treatment may look like a puzzling maze for patients, their families, and even primary care providers.

“One question that tends to come up is, 'How exactly is that black box of pediatric oncology organized?' From the pediatrician's perspective, often it's hard to know who are the best people to get in touch with to get the best information,” said Dr. Patrick Brown, of the pediatric oncology department at Johns Hopkins University, Baltimore.

At his institution, a pediatric oncology fellow is usually designated as the first contact for a referred patient, and this fellow “is at the center of delivering care.

“The fellow works closely with the attending on service at the time. Together this pair will become the primary oncology team for the patient,” he said at a meeting on pediatric trends sponsored by Johns Hopkins University. This team devises a treatment plan that's carried out by a larger team of pediatric residents and physician extenders. Another important component is the multidisciplinary team, composed of surgeons, radiology oncologists, bone marrow transplant specialists, pediatric ICU staff, nurses, and social workers—all working closely with the fellow.

Each patient is assigned a primary team of oncologists who have longitudinal responsibility for the patient's care. “These providers are your primary point of contact. You should be hearing from either the attending or the fellow while the patient is being treated, and you should know how to get in touch with one or both of these individuals,” he said.

As with all good relationships, communication is a two-way street, and Dr. Brown suggested pediatricians initially try to refer patients to a medical center that can offer a multidisciplinary approach. While it's not necessary that a center be a transplant center, he urged physicians “to find a place that's a member of a clinical trials network for children with cancer. It's been documented over the years that children with cancer who are treated within the context of clinical trials have better outcomes.”

The pediatrician plays a key role in communicating many of the elements of the diagnosis, prognosis, and treatment plan to the child, parents, and any siblings and—most importantly—offers them emotional support. The pediatrician also provides essential background information on the patient to the oncology team.

Dr. Brown stressed it is the job of the oncologist to “open lines of communication with the pediatrician early and sustain them.

“We recognize the diagnosis of cancer is almost always the unexpected result of a series of rational diagnostic procedures, and that true cases where cues have been missed that cause a delay in diagnosis and negatively impact prognosis are exceedingly rare,” he said. While it often seems to parents that something should have been picked up earlier, “we do everything we can to dissuade them of that notion, because in the vast majority of cases that is not true. I think it's our job to help the parents understand that and to help you understand that.”

During treatment the oncology team takes responsibility for all medical issues, including primary care issues, but they may ask a pediatrician for assistance with blood work, referrals, and urgent care matters, especially for patients who live far from the cancer treatment center or for patients who are in “lower-intensity phases of therapy or on maintenance therapy,” he noted. In turn, oncologists should update pediatricians on all major events, such as complications or relapses.

After a patient is treated, the pediatrician should be given a comprehensive treatment summary by the oncologist. “It should not be something that's done over the telephone. This should be a document in your hand that you can refer to and put in your patient's chart,” said Dr. Brown. This document should contain information on the location of the cancer, its stage, and any relapses. It should include information on chemotherapy and radiation treatments (“you should know where and at what dose”), surgeries and the extent of resection, bone marrow transplants (autologous or allogeneic), any investigational treatments used, complications, and adverse reactions or allergies.

“It's very important to know what chemotherapy agents patients have received,” he said.

For example, anthracycline carries a risk for cardiac toxicity, while use of high or low doses of methotrexate or cytarabine should be noted because the particular doses of these agents significantly affect the risk of certain long-term complications.

The oncologist should detail the risk of relapse and the risk of secondary malignancies. Relapse and the timing of relapse are very disease specific. “If a patient comes back to you after having received treatment for Burkitt's lymphoma and they're a year out from completion of therapy, the chances are excellent that they're not going to relapse … compared with a patient with a low-grade brain tumor, for example, where it is actually relatively common for the duration of remission prior to relapse to be fairly extended,” Dr. Brown said.

The pediatrician should be involved in any major changes in the goals of care, specifically a switch to end-of-life and palliative care, and of course should be immediately notified of a patient's death. “It's at that point that I think the pediatrician should be reinvolved in a significant way,” he said. This provides further emotional support for the family, reinforces the therapeutic relationship, and assists in psychosocial screening. The pediatrician's involvement at this stage also is often particularly helpful for surviving siblings.

BALTIMORE — From the outside, pediatric oncology treatment may look like a puzzling maze for patients, their families, and even primary care providers.

“One question that tends to come up is, 'How exactly is that black box of pediatric oncology organized?' From the pediatrician's perspective, often it's hard to know who are the best people to get in touch with to get the best information,” said Dr. Patrick Brown, of the pediatric oncology department at Johns Hopkins University, Baltimore.

At his institution, a pediatric oncology fellow is usually designated as the first contact for a referred patient, and this fellow “is at the center of delivering care.

“The fellow works closely with the attending on service at the time. Together this pair will become the primary oncology team for the patient,” he said at a meeting on pediatric trends sponsored by Johns Hopkins University. This team devises a treatment plan that's carried out by a larger team of pediatric residents and physician extenders. Another important component is the multidisciplinary team, composed of surgeons, radiology oncologists, bone marrow transplant specialists, pediatric ICU staff, nurses, and social workers—all working closely with the fellow.

Each patient is assigned a primary team of oncologists who have longitudinal responsibility for the patient's care. “These providers are your primary point of contact. You should be hearing from either the attending or the fellow while the patient is being treated, and you should know how to get in touch with one or both of these individuals,” he said.

As with all good relationships, communication is a two-way street, and Dr. Brown suggested pediatricians initially try to refer patients to a medical center that can offer a multidisciplinary approach. While it's not necessary that a center be a transplant center, he urged physicians “to find a place that's a member of a clinical trials network for children with cancer. It's been documented over the years that children with cancer who are treated within the context of clinical trials have better outcomes.”

The pediatrician plays a key role in communicating many of the elements of the diagnosis, prognosis, and treatment plan to the child, parents, and any siblings and—most importantly—offers them emotional support. The pediatrician also provides essential background information on the patient to the oncology team.

Dr. Brown stressed it is the job of the oncologist to “open lines of communication with the pediatrician early and sustain them.

“We recognize the diagnosis of cancer is almost always the unexpected result of a series of rational diagnostic procedures, and that true cases where cues have been missed that cause a delay in diagnosis and negatively impact prognosis are exceedingly rare,” he said. While it often seems to parents that something should have been picked up earlier, “we do everything we can to dissuade them of that notion, because in the vast majority of cases that is not true. I think it's our job to help the parents understand that and to help you understand that.”

During treatment the oncology team takes responsibility for all medical issues, including primary care issues, but they may ask a pediatrician for assistance with blood work, referrals, and urgent care matters, especially for patients who live far from the cancer treatment center or for patients who are in “lower-intensity phases of therapy or on maintenance therapy,” he noted. In turn, oncologists should update pediatricians on all major events, such as complications or relapses.

After a patient is treated, the pediatrician should be given a comprehensive treatment summary by the oncologist. “It should not be something that's done over the telephone. This should be a document in your hand that you can refer to and put in your patient's chart,” said Dr. Brown. This document should contain information on the location of the cancer, its stage, and any relapses. It should include information on chemotherapy and radiation treatments (“you should know where and at what dose”), surgeries and the extent of resection, bone marrow transplants (autologous or allogeneic), any investigational treatments used, complications, and adverse reactions or allergies.

“It's very important to know what chemotherapy agents patients have received,” he said.

For example, anthracycline carries a risk for cardiac toxicity, while use of high or low doses of methotrexate or cytarabine should be noted because the particular doses of these agents significantly affect the risk of certain long-term complications.

The oncologist should detail the risk of relapse and the risk of secondary malignancies. Relapse and the timing of relapse are very disease specific. “If a patient comes back to you after having received treatment for Burkitt's lymphoma and they're a year out from completion of therapy, the chances are excellent that they're not going to relapse … compared with a patient with a low-grade brain tumor, for example, where it is actually relatively common for the duration of remission prior to relapse to be fairly extended,” Dr. Brown said.

The pediatrician should be involved in any major changes in the goals of care, specifically a switch to end-of-life and palliative care, and of course should be immediately notified of a patient's death. “It's at that point that I think the pediatrician should be reinvolved in a significant way,” he said. This provides further emotional support for the family, reinforces the therapeutic relationship, and assists in psychosocial screening. The pediatrician's involvement at this stage also is often particularly helpful for surviving siblings.

Sudden cardiac death due to physical exertion is extremely rare in women, and the small increase in risk can be minimized through regular exercise, reported Dr. William Whang of Massachusetts General Hospital, Boston, and his colleagues.

They used prospective data from the Nurses' Health Study cohort of female nurses (mean age 53 years in 1986) to analyze cases of sudden cardiac death.

Starting in 1986, study questionnaires asked participants about the average time spent per week doing such activities as walking briskly, jogging, running, biking, swimming, playing tennis or squash, and participating in aerobics or other sports, as well as yard work and housework. In 1992, information was also gathered on average time spent doing lower-intensity exercises, such as yoga. Exercise intensity was based on self-assessments of time spent doing moderate to vigorous exercise (JAMA 2006;295:1399–403).

There were 288 sudden cardiac deaths among the 84,888 women who completed the 1980 questionnaire. “Of these, only nine deaths (3.1%) occurred during an episode of moderate to vigorous exertion, and only three of these occurred during activities that would be considered exercise,” the researchers wrote.

These nine deaths happened during yard work, swimming, physical therapy, housework, and shoveling snow, among participants who reported exercising at moderate to vigorous intensity at least 4 hours per week.

Among participants who did not report any moderate to vigorous exercise on a weekly basis, there were 74 sudden cardiac deaths. There were 46 deaths among those exercising at this intensity for 0–1.9 hr/week, and 28 deaths among participants exercising 2–3.9 hr/week.

The relative risk (RR) of exertion-related sudden cardiac death during moderate to vigorous exertion was calculated to be “modestly elevated” at 2.38. However, this “transient” elevation in risk was no longer significant for women reporting 2 or more hours per week of moderate to vigorous exertion—they had an RR of 1.49. Women with 2 or fewer hours per week of exertion had an RR of 8.98, and women who exercised 4 or more hours per week had an RR of 0.41.

Even after controlling for factors such as age, smoking status, body mass index, and menopausal status, the researchers said this trend persisted.

Data from the Physician's Health Study (N. Engl. J. Med. 2000;343:1355–61) showed that the relative risk for men during an episode of vigorous exertion was about 19-fold higher, at 44.9, compared with the risk observed during moderate to vigorous exertion in the Nurses' Health Study cohort (RR, 2.38).

“Part of this difference could be due to the inclusion of moderate exertion in our exercise measure,” Dr. Whang and colleagues wrote. They noted, however, that a similar gender difference was found in previous, smaller studies.

Sudden cardiac death due to physical exertion is extremely rare in women, and the small increase in risk can be minimized through regular exercise, reported Dr. William Whang of Massachusetts General Hospital, Boston, and his colleagues.

They used prospective data from the Nurses' Health Study cohort of female nurses (mean age 53 years in 1986) to analyze cases of sudden cardiac death.

Starting in 1986, study questionnaires asked participants about the average time spent per week doing such activities as walking briskly, jogging, running, biking, swimming, playing tennis or squash, and participating in aerobics or other sports, as well as yard work and housework. In 1992, information was also gathered on average time spent doing lower-intensity exercises, such as yoga. Exercise intensity was based on self-assessments of time spent doing moderate to vigorous exercise (JAMA 2006;295:1399–403).

There were 288 sudden cardiac deaths among the 84,888 women who completed the 1980 questionnaire. “Of these, only nine deaths (3.1%) occurred during an episode of moderate to vigorous exertion, and only three of these occurred during activities that would be considered exercise,” the researchers wrote.

These nine deaths happened during yard work, swimming, physical therapy, housework, and shoveling snow, among participants who reported exercising at moderate to vigorous intensity at least 4 hours per week.

Among participants who did not report any moderate to vigorous exercise on a weekly basis, there were 74 sudden cardiac deaths. There were 46 deaths among those exercising at this intensity for 0–1.9 hr/week, and 28 deaths among participants exercising 2–3.9 hr/week.

The relative risk (RR) of exertion-related sudden cardiac death during moderate to vigorous exertion was calculated to be “modestly elevated” at 2.38. However, this “transient” elevation in risk was no longer significant for women reporting 2 or more hours per week of moderate to vigorous exertion—they had an RR of 1.49. Women with 2 or fewer hours per week of exertion had an RR of 8.98, and women who exercised 4 or more hours per week had an RR of 0.41.

Even after controlling for factors such as age, smoking status, body mass index, and menopausal status, the researchers said this trend persisted.

Data from the Physician's Health Study (N. Engl. J. Med. 2000;343:1355–61) showed that the relative risk for men during an episode of vigorous exertion was about 19-fold higher, at 44.9, compared with the risk observed during moderate to vigorous exertion in the Nurses' Health Study cohort (RR, 2.38).

“Part of this difference could be due to the inclusion of moderate exertion in our exercise measure,” Dr. Whang and colleagues wrote. They noted, however, that a similar gender difference was found in previous, smaller studies.

Sudden cardiac death due to physical exertion is extremely rare in women, and the small increase in risk can be minimized through regular exercise, reported Dr. William Whang of Massachusetts General Hospital, Boston, and his colleagues.

They used prospective data from the Nurses' Health Study cohort of female nurses (mean age 53 years in 1986) to analyze cases of sudden cardiac death.

Starting in 1986, study questionnaires asked participants about the average time spent per week doing such activities as walking briskly, jogging, running, biking, swimming, playing tennis or squash, and participating in aerobics or other sports, as well as yard work and housework. In 1992, information was also gathered on average time spent doing lower-intensity exercises, such as yoga. Exercise intensity was based on self-assessments of time spent doing moderate to vigorous exercise (JAMA 2006;295:1399–403).

There were 288 sudden cardiac deaths among the 84,888 women who completed the 1980 questionnaire. “Of these, only nine deaths (3.1%) occurred during an episode of moderate to vigorous exertion, and only three of these occurred during activities that would be considered exercise,” the researchers wrote.

These nine deaths happened during yard work, swimming, physical therapy, housework, and shoveling snow, among participants who reported exercising at moderate to vigorous intensity at least 4 hours per week.

Among participants who did not report any moderate to vigorous exercise on a weekly basis, there were 74 sudden cardiac deaths. There were 46 deaths among those exercising at this intensity for 0–1.9 hr/week, and 28 deaths among participants exercising 2–3.9 hr/week.

The relative risk (RR) of exertion-related sudden cardiac death during moderate to vigorous exertion was calculated to be “modestly elevated” at 2.38. However, this “transient” elevation in risk was no longer significant for women reporting 2 or more hours per week of moderate to vigorous exertion—they had an RR of 1.49. Women with 2 or fewer hours per week of exertion had an RR of 8.98, and women who exercised 4 or more hours per week had an RR of 0.41.

Even after controlling for factors such as age, smoking status, body mass index, and menopausal status, the researchers said this trend persisted.

Data from the Physician's Health Study (N. Engl. J. Med. 2000;343:1355–61) showed that the relative risk for men during an episode of vigorous exertion was about 19-fold higher, at 44.9, compared with the risk observed during moderate to vigorous exertion in the Nurses' Health Study cohort (RR, 2.38).

“Part of this difference could be due to the inclusion of moderate exertion in our exercise measure,” Dr. Whang and colleagues wrote. They noted, however, that a similar gender difference was found in previous, smaller studies.