Mary Ann Moon

Major finding: In the community-based setting, surveillance colonoscopy is substantially overused for low-risk patients, but it is underused for those with advanced lesions, according to current guidelines.

Source of data: Subjects participating in a randomized, controlled trial of community-based cancer screening were interviewed. The participants had undergone flexible sigmoidoscopy at the time of randomization between 1993 and 2001. They had then undergone follow-up diagnostic colonoscopy within 18 months of that exam, and had been followed for at least 5 more years (median follow-up, 9 years), undergoing surveillance colonoscopy as recommended by their physicians.

Disclosures: This study was supported by the National Cancer Institute. The investigator reported no financial conflicts of interest.

In community practice, surveillance colonoscopy is substantially overused for low-risk patients, but it is underused for those with advanced lesions who need it most, Dr. Robert E. Schoen and his colleagues reported.

Interventions are needed to better align the use of surveillance colonoscopy with actual patient risk, they noted.

Survey results have suggested that primary care physicians, gastroenterologists, and surgeons all endorse surveillance colonoscopy at more frequent intervals than is recommended in guidelines.

However until now, “no studies have measured the actual use of surveillance colonoscopy on a community-wide basis, nor have they examined how surveillance is being employed in relation to prior histologic findings,” said Dr. Schoen of the University of Pittsburgh Cancer Institute and his associates.

The investigators assessed use of surveillance colonoscopy by interviewing 3,627 subjects participating in a randomized, controlled trial of community-based cancer screening. These subjects had undergone flexible sigmoidoscopy at nine regional study centers across the United States at the time of randomization between 1993 and 2001.

They had then undergone follow-up diagnostic colonoscopy within 18 months of that exam, and had been followed for at least 5 more years (median follow-up, 9 years), undergoing surveillance colonoscopy as recommended by their physicians.

The study subjects were aged 55–74 years at enrollment. In all, 60% were men, 93% were white, and nearly 70% had attended or graduated from college.

At the initial screening, 1,342 subjects had advanced adenoma, 1,022 had nonadvanced adenoma, and 1,263 had nonadenomatous findings.

Among the subjects who had no adenomas, 27% underwent surveillance colonoscopy within 5 years and 45% did so within 7 years.

A large subgroup of these subjects (70%) had no symptoms and no family history of colorectal cancer, nor had their exams been incomplete or inadequate. In other words, they had no identifiable reason for a repeat surveillance exam. Yet more than 35% of them underwent a second surveillance at a median of 3 years after the first.

Including the baseline exam, more than 90% of these subjects had three colonoscopies within a 9-year period. “This level of utilization contrasts to current guidelines, which advise that colonoscopy can be deferred for 10 years after an exam in which no adenoma is detected,” Dr. Schoen and his colleagues said.

The subjects with nonadvanced adenoma also overutilized surveillance colonoscopy. More than one-third of them had repeat exams within 4 years, when early guidelines had recommended a 5-year interval and more recent guidelines recommend a 5- to 10-year interval in such cases.

Almost all the repeat colonoscopies were performed by the same physician, by the same practice, or in the same location as the screening colonoscopy that categorized these subjects as low risk. This means that lack of communication among physicians was unlikely to be the reason for unnecessary overutilization, the investigators said.

In contrast with low-risk patients, only 31% of the subjects with advanced adenoma had a repeat colonoscopy within the recommended 3 years, and only 58% underwent surveillance within 5 years, according to the findings.

“Subjects with advanced adenoma are advised to undergo a surveillance exam within 3 years because of their increased risk for subsequent colorectal cancer, and the 3-year follow-up recommendation has been in place for many years,” the researchers noted.

It is unclear why so many of these high-risk subjects did not undergo surveillance as recommended.

In general, older patients were less likely than younger patients to have repeat colonoscopies, and Dr. Schoen and his associates initially speculated that perhaps they had a higher burden of comorbid conditions that rendered colon cancer less of a concern.

The findings from the investigation indicate that the costs of colonoscopy likely have been underestimated because estimates usually are based on “ideal” adherence to screening guidelines, and it appears that many patients undergo the procedure more often than recommended.

Major finding: In the community-based setting, surveillance colonoscopy is substantially overused for low-risk patients, but it is underused for those with advanced lesions, according to current guidelines.

Source of data: Subjects participating in a randomized, controlled trial of community-based cancer screening were interviewed. The participants had undergone flexible sigmoidoscopy at the time of randomization between 1993 and 2001. They had then undergone follow-up diagnostic colonoscopy within 18 months of that exam, and had been followed for at least 5 more years (median follow-up, 9 years), undergoing surveillance colonoscopy as recommended by their physicians.

Disclosures: This study was supported by the National Cancer Institute. The investigator reported no financial conflicts of interest.

In community practice, surveillance colonoscopy is substantially overused for low-risk patients, but it is underused for those with advanced lesions who need it most, Dr. Robert E. Schoen and his colleagues reported.

Interventions are needed to better align the use of surveillance colonoscopy with actual patient risk, they noted.

Survey results have suggested that primary care physicians, gastroenterologists, and surgeons all endorse surveillance colonoscopy at more frequent intervals than is recommended in guidelines.

However until now, “no studies have measured the actual use of surveillance colonoscopy on a community-wide basis, nor have they examined how surveillance is being employed in relation to prior histologic findings,” said Dr. Schoen of the University of Pittsburgh Cancer Institute and his associates.

The investigators assessed use of surveillance colonoscopy by interviewing 3,627 subjects participating in a randomized, controlled trial of community-based cancer screening. These subjects had undergone flexible sigmoidoscopy at nine regional study centers across the United States at the time of randomization between 1993 and 2001.

They had then undergone follow-up diagnostic colonoscopy within 18 months of that exam, and had been followed for at least 5 more years (median follow-up, 9 years), undergoing surveillance colonoscopy as recommended by their physicians.

The study subjects were aged 55–74 years at enrollment. In all, 60% were men, 93% were white, and nearly 70% had attended or graduated from college.

At the initial screening, 1,342 subjects had advanced adenoma, 1,022 had nonadvanced adenoma, and 1,263 had nonadenomatous findings.

Among the subjects who had no adenomas, 27% underwent surveillance colonoscopy within 5 years and 45% did so within 7 years.

A large subgroup of these subjects (70%) had no symptoms and no family history of colorectal cancer, nor had their exams been incomplete or inadequate. In other words, they had no identifiable reason for a repeat surveillance exam. Yet more than 35% of them underwent a second surveillance at a median of 3 years after the first.

Including the baseline exam, more than 90% of these subjects had three colonoscopies within a 9-year period. “This level of utilization contrasts to current guidelines, which advise that colonoscopy can be deferred for 10 years after an exam in which no adenoma is detected,” Dr. Schoen and his colleagues said.

The subjects with nonadvanced adenoma also overutilized surveillance colonoscopy. More than one-third of them had repeat exams within 4 years, when early guidelines had recommended a 5-year interval and more recent guidelines recommend a 5- to 10-year interval in such cases.

Almost all the repeat colonoscopies were performed by the same physician, by the same practice, or in the same location as the screening colonoscopy that categorized these subjects as low risk. This means that lack of communication among physicians was unlikely to be the reason for unnecessary overutilization, the investigators said.

In contrast with low-risk patients, only 31% of the subjects with advanced adenoma had a repeat colonoscopy within the recommended 3 years, and only 58% underwent surveillance within 5 years, according to the findings.

“Subjects with advanced adenoma are advised to undergo a surveillance exam within 3 years because of their increased risk for subsequent colorectal cancer, and the 3-year follow-up recommendation has been in place for many years,” the researchers noted.

It is unclear why so many of these high-risk subjects did not undergo surveillance as recommended.

In general, older patients were less likely than younger patients to have repeat colonoscopies, and Dr. Schoen and his associates initially speculated that perhaps they had a higher burden of comorbid conditions that rendered colon cancer less of a concern.

The findings from the investigation indicate that the costs of colonoscopy likely have been underestimated because estimates usually are based on “ideal” adherence to screening guidelines, and it appears that many patients undergo the procedure more often than recommended.

Major finding: In the community-based setting, surveillance colonoscopy is substantially overused for low-risk patients, but it is underused for those with advanced lesions, according to current guidelines.

Source of data: Subjects participating in a randomized, controlled trial of community-based cancer screening were interviewed. The participants had undergone flexible sigmoidoscopy at the time of randomization between 1993 and 2001. They had then undergone follow-up diagnostic colonoscopy within 18 months of that exam, and had been followed for at least 5 more years (median follow-up, 9 years), undergoing surveillance colonoscopy as recommended by their physicians.

Disclosures: This study was supported by the National Cancer Institute. The investigator reported no financial conflicts of interest.

In community practice, surveillance colonoscopy is substantially overused for low-risk patients, but it is underused for those with advanced lesions who need it most, Dr. Robert E. Schoen and his colleagues reported.

Interventions are needed to better align the use of surveillance colonoscopy with actual patient risk, they noted.

Survey results have suggested that primary care physicians, gastroenterologists, and surgeons all endorse surveillance colonoscopy at more frequent intervals than is recommended in guidelines.

However until now, “no studies have measured the actual use of surveillance colonoscopy on a community-wide basis, nor have they examined how surveillance is being employed in relation to prior histologic findings,” said Dr. Schoen of the University of Pittsburgh Cancer Institute and his associates.

The investigators assessed use of surveillance colonoscopy by interviewing 3,627 subjects participating in a randomized, controlled trial of community-based cancer screening. These subjects had undergone flexible sigmoidoscopy at nine regional study centers across the United States at the time of randomization between 1993 and 2001.

They had then undergone follow-up diagnostic colonoscopy within 18 months of that exam, and had been followed for at least 5 more years (median follow-up, 9 years), undergoing surveillance colonoscopy as recommended by their physicians.

The study subjects were aged 55–74 years at enrollment. In all, 60% were men, 93% were white, and nearly 70% had attended or graduated from college.

At the initial screening, 1,342 subjects had advanced adenoma, 1,022 had nonadvanced adenoma, and 1,263 had nonadenomatous findings.

Among the subjects who had no adenomas, 27% underwent surveillance colonoscopy within 5 years and 45% did so within 7 years.

A large subgroup of these subjects (70%) had no symptoms and no family history of colorectal cancer, nor had their exams been incomplete or inadequate. In other words, they had no identifiable reason for a repeat surveillance exam. Yet more than 35% of them underwent a second surveillance at a median of 3 years after the first.

Including the baseline exam, more than 90% of these subjects had three colonoscopies within a 9-year period. “This level of utilization contrasts to current guidelines, which advise that colonoscopy can be deferred for 10 years after an exam in which no adenoma is detected,” Dr. Schoen and his colleagues said.

The subjects with nonadvanced adenoma also overutilized surveillance colonoscopy. More than one-third of them had repeat exams within 4 years, when early guidelines had recommended a 5-year interval and more recent guidelines recommend a 5- to 10-year interval in such cases.

Almost all the repeat colonoscopies were performed by the same physician, by the same practice, or in the same location as the screening colonoscopy that categorized these subjects as low risk. This means that lack of communication among physicians was unlikely to be the reason for unnecessary overutilization, the investigators said.

In contrast with low-risk patients, only 31% of the subjects with advanced adenoma had a repeat colonoscopy within the recommended 3 years, and only 58% underwent surveillance within 5 years, according to the findings.

“Subjects with advanced adenoma are advised to undergo a surveillance exam within 3 years because of their increased risk for subsequent colorectal cancer, and the 3-year follow-up recommendation has been in place for many years,” the researchers noted.

It is unclear why so many of these high-risk subjects did not undergo surveillance as recommended.

In general, older patients were less likely than younger patients to have repeat colonoscopies, and Dr. Schoen and his associates initially speculated that perhaps they had a higher burden of comorbid conditions that rendered colon cancer less of a concern.

The findings from the investigation indicate that the costs of colonoscopy likely have been underestimated because estimates usually are based on “ideal” adherence to screening guidelines, and it appears that many patients undergo the procedure more often than recommended.

Pegylated interferon alpha-2a appears to induce a significantly better sustained virologic response than interferon alpha-2b, when combined with ribavirin in patients with chronic hepatitis C, Dr. Maria Grazia Rumi and her colleagues reported.

The two interferons differ in molecular size and structure, as well as in their pharmacokinetic and pharmacodynamic profiles. Interferon alpha-2a is administered in a fixed dose, while the dose of interferon alpha-2b is calculated according to body weight. Adverse effects differ as well. Interferon alpha-2b has been associated with lower rates of anemia, while interferon alpha-2a has been associated with lower rates of depression.

These distinctions “suggest that differences [also] may exist in safety and tolerability,” wrote Dr. Rumi of the University of Milan and her associates.

Until now, there has been insufficient evidence to support choosing one of these agents over the other. Combined with ribavirin, either is considered to be a standard of care for eradicating chronic hepatitis C virus (HCV) infection. Studies that have directly compared interferon alpha-2a and interferon alpha-2b have been “limited in sample size or scope” and have arrived at disparate conclusions, the investigators said.

The new study was a randomized, head-to-head comparison of the safety and efficacy of the two drugs in 447 patients who had not received previous treatment for chronic hepatitis C. Overall, patients assigned to receive pegylated interferon alpha-2a for 48 weeks showed a higher rate of sustained virologic response (66%) than those assigned to receive interferon alpha-2b (54%).

In the subgroup of patients with the highest levels of HCV RNA, rates of sustained virologic response were 62% with interferon alpha-2a and 48% with interferon alpha-2b. Similarly, in the subgroup of patients with cirrhosis, rates of sustained virologic response were 53% and 38%, respectively.

The researchers wrote that they were surprised that their analysis did not show cirrhosis to be a predictor of treatment failure, as it has been in previous studies of interferon. However, this study was statistically underpowered to assess the role of cirrhosis as a moderator of treatment outcome, they said.

Interferon alpha-2a also achieved higher rates of sustained virologic response (48%), compared with interferon alpha-2b (32%), in the subgroup of patients who had viral type HCV-1. Similarly, interferon alpha-2a achieved higher rates of sustained virologic response (96%) than interferon alpha-2b (82%) in the subgroup of patients who had viral type HCV-2

However, the two interferon formulations achieved similar rates of sustained virologic response in patients who had HCV-3 (65% and 69%, respectively) and in those who had HCV-4 (44% and 31%, respectively).

Rapid virologic response was the strongest predictor of a sustained response, “further supporting that early suppression of HCV is of crucial importance in the therapeutic resolution of chronic hepatitis C,” they said. Dr. Rumi reported having no conflicts of interest.

Pegylated interferon alpha-2a appears to induce a significantly better sustained virologic response than interferon alpha-2b, when combined with ribavirin in patients with chronic hepatitis C, Dr. Maria Grazia Rumi and her colleagues reported.

The two interferons differ in molecular size and structure, as well as in their pharmacokinetic and pharmacodynamic profiles. Interferon alpha-2a is administered in a fixed dose, while the dose of interferon alpha-2b is calculated according to body weight. Adverse effects differ as well. Interferon alpha-2b has been associated with lower rates of anemia, while interferon alpha-2a has been associated with lower rates of depression.

These distinctions “suggest that differences [also] may exist in safety and tolerability,” wrote Dr. Rumi of the University of Milan and her associates.

Until now, there has been insufficient evidence to support choosing one of these agents over the other. Combined with ribavirin, either is considered to be a standard of care for eradicating chronic hepatitis C virus (HCV) infection. Studies that have directly compared interferon alpha-2a and interferon alpha-2b have been “limited in sample size or scope” and have arrived at disparate conclusions, the investigators said.

The new study was a randomized, head-to-head comparison of the safety and efficacy of the two drugs in 447 patients who had not received previous treatment for chronic hepatitis C. Overall, patients assigned to receive pegylated interferon alpha-2a for 48 weeks showed a higher rate of sustained virologic response (66%) than those assigned to receive interferon alpha-2b (54%).

In the subgroup of patients with the highest levels of HCV RNA, rates of sustained virologic response were 62% with interferon alpha-2a and 48% with interferon alpha-2b. Similarly, in the subgroup of patients with cirrhosis, rates of sustained virologic response were 53% and 38%, respectively.

The researchers wrote that they were surprised that their analysis did not show cirrhosis to be a predictor of treatment failure, as it has been in previous studies of interferon. However, this study was statistically underpowered to assess the role of cirrhosis as a moderator of treatment outcome, they said.

Interferon alpha-2a also achieved higher rates of sustained virologic response (48%), compared with interferon alpha-2b (32%), in the subgroup of patients who had viral type HCV-1. Similarly, interferon alpha-2a achieved higher rates of sustained virologic response (96%) than interferon alpha-2b (82%) in the subgroup of patients who had viral type HCV-2

However, the two interferon formulations achieved similar rates of sustained virologic response in patients who had HCV-3 (65% and 69%, respectively) and in those who had HCV-4 (44% and 31%, respectively).

Rapid virologic response was the strongest predictor of a sustained response, “further supporting that early suppression of HCV is of crucial importance in the therapeutic resolution of chronic hepatitis C,” they said. Dr. Rumi reported having no conflicts of interest.

Pegylated interferon alpha-2a appears to induce a significantly better sustained virologic response than interferon alpha-2b, when combined with ribavirin in patients with chronic hepatitis C, Dr. Maria Grazia Rumi and her colleagues reported.

The two interferons differ in molecular size and structure, as well as in their pharmacokinetic and pharmacodynamic profiles. Interferon alpha-2a is administered in a fixed dose, while the dose of interferon alpha-2b is calculated according to body weight. Adverse effects differ as well. Interferon alpha-2b has been associated with lower rates of anemia, while interferon alpha-2a has been associated with lower rates of depression.

These distinctions “suggest that differences [also] may exist in safety and tolerability,” wrote Dr. Rumi of the University of Milan and her associates.

Until now, there has been insufficient evidence to support choosing one of these agents over the other. Combined with ribavirin, either is considered to be a standard of care for eradicating chronic hepatitis C virus (HCV) infection. Studies that have directly compared interferon alpha-2a and interferon alpha-2b have been “limited in sample size or scope” and have arrived at disparate conclusions, the investigators said.

The new study was a randomized, head-to-head comparison of the safety and efficacy of the two drugs in 447 patients who had not received previous treatment for chronic hepatitis C. Overall, patients assigned to receive pegylated interferon alpha-2a for 48 weeks showed a higher rate of sustained virologic response (66%) than those assigned to receive interferon alpha-2b (54%).

In the subgroup of patients with the highest levels of HCV RNA, rates of sustained virologic response were 62% with interferon alpha-2a and 48% with interferon alpha-2b. Similarly, in the subgroup of patients with cirrhosis, rates of sustained virologic response were 53% and 38%, respectively.

The researchers wrote that they were surprised that their analysis did not show cirrhosis to be a predictor of treatment failure, as it has been in previous studies of interferon. However, this study was statistically underpowered to assess the role of cirrhosis as a moderator of treatment outcome, they said.

Interferon alpha-2a also achieved higher rates of sustained virologic response (48%), compared with interferon alpha-2b (32%), in the subgroup of patients who had viral type HCV-1. Similarly, interferon alpha-2a achieved higher rates of sustained virologic response (96%) than interferon alpha-2b (82%) in the subgroup of patients who had viral type HCV-2

However, the two interferon formulations achieved similar rates of sustained virologic response in patients who had HCV-3 (65% and 69%, respectively) and in those who had HCV-4 (44% and 31%, respectively).

Rapid virologic response was the strongest predictor of a sustained response, “further supporting that early suppression of HCV is of crucial importance in the therapeutic resolution of chronic hepatitis C,” they said. Dr. Rumi reported having no conflicts of interest.

The diagnosis of melanoma is delayed in Hispanic and black patients, compared with whites, and thus the mortality burden is disproportionately high in these minority populations, according to a database analysis.

“The results of our study should motivate the expansion of melanoma awareness and screening campaigns to the minority communities, which can ultimately alleviate the disparities in melanoma outcome,” said Dr. Shasa Hu of Sylvester Comprehensive Cancer Center at the University of Miami and associates.

“Research and public education efforts have focused on melanoma prevention in white populations because of their higher risk of developing melanoma.” These campaigns to improve awareness are likely the reason that survival among whites has risen from 68% in the early 1970s to 92% in recent years, they noted.

To assess long-term trends in other ethnic groups, Dr. Hu and her colleagues analyzed data from the Florida Cancer Data System (FCDS), a database that includes information dating back to 1981 on a relatively large Hispanic population. In comparison, the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database did not classify data according to the “Hispanic” designation until the late 1990s, they said.

Between 1990 and 2004, 41,072 melanoma cases with known patient ethnicity and disease stage were reported to the FCDS in three mutually exclusive categories: 39,670 cases among whites, 1,148 among white Hispanics, and 254 among black non-Hispanics.

Despite the lower incidence of melanoma among Hispanic and black patients, both minority groups were much more likely to have a delayed diagnosis than were whites. A total of 26% of black patients presented with either regional- or distant-stage melanoma, as did 18% of Hispanic patients. In contrast, only 12% of white patients presented with such advanced melanoma, the investigators said (Arch. Derm. 2009;145:1369–74).

Melanoma diagnosis improved very little over the 15-year study period among Hispanics and did not improve at all among blacks, but it improved significantly among whites.

“These results clearly suggest that public education and screening efforts have successfully reduced the burden of late-stage melanomas in white non-Hispanics but have not reached other populations who already have disproportionately greater burden from late-stage melanoma,” Dr. Hu and her associates said.

No financial conflicts of interest were reported.

The diagnosis of melanoma is delayed in Hispanic and black patients, compared with whites, and thus the mortality burden is disproportionately high in these minority populations, according to a database analysis.

“The results of our study should motivate the expansion of melanoma awareness and screening campaigns to the minority communities, which can ultimately alleviate the disparities in melanoma outcome,” said Dr. Shasa Hu of Sylvester Comprehensive Cancer Center at the University of Miami and associates.

“Research and public education efforts have focused on melanoma prevention in white populations because of their higher risk of developing melanoma.” These campaigns to improve awareness are likely the reason that survival among whites has risen from 68% in the early 1970s to 92% in recent years, they noted.

To assess long-term trends in other ethnic groups, Dr. Hu and her colleagues analyzed data from the Florida Cancer Data System (FCDS), a database that includes information dating back to 1981 on a relatively large Hispanic population. In comparison, the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database did not classify data according to the “Hispanic” designation until the late 1990s, they said.

Between 1990 and 2004, 41,072 melanoma cases with known patient ethnicity and disease stage were reported to the FCDS in three mutually exclusive categories: 39,670 cases among whites, 1,148 among white Hispanics, and 254 among black non-Hispanics.

Despite the lower incidence of melanoma among Hispanic and black patients, both minority groups were much more likely to have a delayed diagnosis than were whites. A total of 26% of black patients presented with either regional- or distant-stage melanoma, as did 18% of Hispanic patients. In contrast, only 12% of white patients presented with such advanced melanoma, the investigators said (Arch. Derm. 2009;145:1369–74).

Melanoma diagnosis improved very little over the 15-year study period among Hispanics and did not improve at all among blacks, but it improved significantly among whites.

“These results clearly suggest that public education and screening efforts have successfully reduced the burden of late-stage melanomas in white non-Hispanics but have not reached other populations who already have disproportionately greater burden from late-stage melanoma,” Dr. Hu and her associates said.

No financial conflicts of interest were reported.

The diagnosis of melanoma is delayed in Hispanic and black patients, compared with whites, and thus the mortality burden is disproportionately high in these minority populations, according to a database analysis.

“The results of our study should motivate the expansion of melanoma awareness and screening campaigns to the minority communities, which can ultimately alleviate the disparities in melanoma outcome,” said Dr. Shasa Hu of Sylvester Comprehensive Cancer Center at the University of Miami and associates.

“Research and public education efforts have focused on melanoma prevention in white populations because of their higher risk of developing melanoma.” These campaigns to improve awareness are likely the reason that survival among whites has risen from 68% in the early 1970s to 92% in recent years, they noted.

To assess long-term trends in other ethnic groups, Dr. Hu and her colleagues analyzed data from the Florida Cancer Data System (FCDS), a database that includes information dating back to 1981 on a relatively large Hispanic population. In comparison, the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database did not classify data according to the “Hispanic” designation until the late 1990s, they said.

Between 1990 and 2004, 41,072 melanoma cases with known patient ethnicity and disease stage were reported to the FCDS in three mutually exclusive categories: 39,670 cases among whites, 1,148 among white Hispanics, and 254 among black non-Hispanics.

Despite the lower incidence of melanoma among Hispanic and black patients, both minority groups were much more likely to have a delayed diagnosis than were whites. A total of 26% of black patients presented with either regional- or distant-stage melanoma, as did 18% of Hispanic patients. In contrast, only 12% of white patients presented with such advanced melanoma, the investigators said (Arch. Derm. 2009;145:1369–74).

Melanoma diagnosis improved very little over the 15-year study period among Hispanics and did not improve at all among blacks, but it improved significantly among whites.

“These results clearly suggest that public education and screening efforts have successfully reduced the burden of late-stage melanomas in white non-Hispanics but have not reached other populations who already have disproportionately greater burden from late-stage melanoma,” Dr. Hu and her associates said.

No financial conflicts of interest were reported.

Intensive medical therapy for asymptomatic carotid stenosis has decreased the risk of stroke to such a degree that it has marginalized the benefits of revascularization in most patients, according to a new study.

Intensive medical therapy, widely adopted after 2003, has cut the rate of microemboli to less than 4% and markedly reduced cardiovascular events, particularly stroke, in patients with asymptomatic carotid stenosis. It therefore should be considered the treatment of choice for this patient population, said Dr. J. David Spence of the Stroke Prevention and Atherosclerosis Research Centre, London, Ont., and his associates.

Their conclusion was based on the results of their study that assessed the relative benefits of carotid revascularization using data from a clinical trial documenting microemboli on transcranial Doppler imaging.

“We think that revascularization should be considered only for the rare patients with microemboli.” These patients are at higher risk for cardiovascular events, so the benefit of carotid revascularization may outweigh the risks of the procedure in these cases, they noted.

The investigators assessed 468 patients with asymptomatic carotid stenosis. Subjects who were assessed between Jan. 1, 2000, and Dec. 31, 2002 (199 patients), were taking the less intensive medical therapy recommended at that time, whereas those assessed between Jan. 1, 2003, and July 30, 2007 (269 patients), were taking the more aggressive medical therapy that is prevalent now. Patients in each group had a mean age of about 70 years. Since 2003, 34% of patients were female, compared with 42% before 2003.

The rate of microemboli was 12.6% before 2003, significantly higher than the 3.7% rate after 2003. Concomitantly, plasma lipid profiles steadily improved and the rate of carotid artery plaque progression markedly declined. More importantly, the rate of cardiovascular events dropped from 17.6% before 2003 to 5.2% afterward, Dr. Spence and his associates reported (Arch. Neurol. 2010;67[doi:10.1001/archneurol.2009.289]).

Patients who were assessed in 2003 or later were significantly more likely to be taking statins, angiotensin-converting enzyme inhibitors, and clopidogrel at the time of their baseline transcranial Doppler embolus detection than were those who were assessed before 2003.

The study was funded by grants from the Heart and Stroke Foundation of Ontario and by donations to the Stroke Prevention and Atherosclerosis Research Centre. No financial conflicts of interest were reported.

Intensive medical therapy for asymptomatic carotid stenosis has decreased the risk of stroke to such a degree that it has marginalized the benefits of revascularization in most patients, according to a new study.

Intensive medical therapy, widely adopted after 2003, has cut the rate of microemboli to less than 4% and markedly reduced cardiovascular events, particularly stroke, in patients with asymptomatic carotid stenosis. It therefore should be considered the treatment of choice for this patient population, said Dr. J. David Spence of the Stroke Prevention and Atherosclerosis Research Centre, London, Ont., and his associates.

Their conclusion was based on the results of their study that assessed the relative benefits of carotid revascularization using data from a clinical trial documenting microemboli on transcranial Doppler imaging.

“We think that revascularization should be considered only for the rare patients with microemboli.” These patients are at higher risk for cardiovascular events, so the benefit of carotid revascularization may outweigh the risks of the procedure in these cases, they noted.

The investigators assessed 468 patients with asymptomatic carotid stenosis. Subjects who were assessed between Jan. 1, 2000, and Dec. 31, 2002 (199 patients), were taking the less intensive medical therapy recommended at that time, whereas those assessed between Jan. 1, 2003, and July 30, 2007 (269 patients), were taking the more aggressive medical therapy that is prevalent now. Patients in each group had a mean age of about 70 years. Since 2003, 34% of patients were female, compared with 42% before 2003.

The rate of microemboli was 12.6% before 2003, significantly higher than the 3.7% rate after 2003. Concomitantly, plasma lipid profiles steadily improved and the rate of carotid artery plaque progression markedly declined. More importantly, the rate of cardiovascular events dropped from 17.6% before 2003 to 5.2% afterward, Dr. Spence and his associates reported (Arch. Neurol. 2010;67[doi:10.1001/archneurol.2009.289]).

Patients who were assessed in 2003 or later were significantly more likely to be taking statins, angiotensin-converting enzyme inhibitors, and clopidogrel at the time of their baseline transcranial Doppler embolus detection than were those who were assessed before 2003.

The study was funded by grants from the Heart and Stroke Foundation of Ontario and by donations to the Stroke Prevention and Atherosclerosis Research Centre. No financial conflicts of interest were reported.

Intensive medical therapy for asymptomatic carotid stenosis has decreased the risk of stroke to such a degree that it has marginalized the benefits of revascularization in most patients, according to a new study.

Intensive medical therapy, widely adopted after 2003, has cut the rate of microemboli to less than 4% and markedly reduced cardiovascular events, particularly stroke, in patients with asymptomatic carotid stenosis. It therefore should be considered the treatment of choice for this patient population, said Dr. J. David Spence of the Stroke Prevention and Atherosclerosis Research Centre, London, Ont., and his associates.

Their conclusion was based on the results of their study that assessed the relative benefits of carotid revascularization using data from a clinical trial documenting microemboli on transcranial Doppler imaging.

“We think that revascularization should be considered only for the rare patients with microemboli.” These patients are at higher risk for cardiovascular events, so the benefit of carotid revascularization may outweigh the risks of the procedure in these cases, they noted.

The investigators assessed 468 patients with asymptomatic carotid stenosis. Subjects who were assessed between Jan. 1, 2000, and Dec. 31, 2002 (199 patients), were taking the less intensive medical therapy recommended at that time, whereas those assessed between Jan. 1, 2003, and July 30, 2007 (269 patients), were taking the more aggressive medical therapy that is prevalent now. Patients in each group had a mean age of about 70 years. Since 2003, 34% of patients were female, compared with 42% before 2003.

The rate of microemboli was 12.6% before 2003, significantly higher than the 3.7% rate after 2003. Concomitantly, plasma lipid profiles steadily improved and the rate of carotid artery plaque progression markedly declined. More importantly, the rate of cardiovascular events dropped from 17.6% before 2003 to 5.2% afterward, Dr. Spence and his associates reported (Arch. Neurol. 2010;67[doi:10.1001/archneurol.2009.289]).

Patients who were assessed in 2003 or later were significantly more likely to be taking statins, angiotensin-converting enzyme inhibitors, and clopidogrel at the time of their baseline transcranial Doppler embolus detection than were those who were assessed before 2003.

The study was funded by grants from the Heart and Stroke Foundation of Ontario and by donations to the Stroke Prevention and Atherosclerosis Research Centre. No financial conflicts of interest were reported.

In some patients who die at very old age, the brain might show the classic pathologic features of Alzheimer's disease even though the patient did not exhibit dementia, according George M. Savva, Ph.D., of the University of Cambridge, and his associates.

The Cognitive Function and Ageing Study (CFAS) “confirms earlier reports of considerable overlap in the burden of neuropathological features of Alzheimer's disease between groups of the oldest old persons with dementia and those without dementia,” said Dr. Savva.

The brain donors were subjects who had participated in the CFAS when they were aged 70–100 years, undergoing periodic evaluations for dementia with the Mini-Mental State Examination, the Geriatric Mental State Examination, and interviews. A subgroup of 426 subjects donated their brains to the study upon their deaths. In all, 243 had a diagnosis of dementia at the time of death; the rest had been determined to be free of dementia.

The prevalence of moderate or severe neuritic plaques and of neurofibrillary tangles rose with increasing age at death, even in those who had not had dementia. In contrast, the prevalence of cortical atrophy corresponded with dementia diagnoses, the investigators said (N. Engl. J. Med. 2009;360:2302–9).

“Neuropathological validation of the diagnosis of Alzheimer's disease, based on confirmation of the presence of these changes, has a different meaning in the oldest old, because the same burden of pathological features may be found in persons who do not have dementia,” wrote Dr. Savva and his colleagues who reported no relevant conflicts of interest.

In some patients who die at very old age, the brain might show the classic pathologic features of Alzheimer's disease even though the patient did not exhibit dementia, according George M. Savva, Ph.D., of the University of Cambridge, and his associates.

The Cognitive Function and Ageing Study (CFAS) “confirms earlier reports of considerable overlap in the burden of neuropathological features of Alzheimer's disease between groups of the oldest old persons with dementia and those without dementia,” said Dr. Savva.

The brain donors were subjects who had participated in the CFAS when they were aged 70–100 years, undergoing periodic evaluations for dementia with the Mini-Mental State Examination, the Geriatric Mental State Examination, and interviews. A subgroup of 426 subjects donated their brains to the study upon their deaths. In all, 243 had a diagnosis of dementia at the time of death; the rest had been determined to be free of dementia.

The prevalence of moderate or severe neuritic plaques and of neurofibrillary tangles rose with increasing age at death, even in those who had not had dementia. In contrast, the prevalence of cortical atrophy corresponded with dementia diagnoses, the investigators said (N. Engl. J. Med. 2009;360:2302–9).

“Neuropathological validation of the diagnosis of Alzheimer's disease, based on confirmation of the presence of these changes, has a different meaning in the oldest old, because the same burden of pathological features may be found in persons who do not have dementia,” wrote Dr. Savva and his colleagues who reported no relevant conflicts of interest.

In some patients who die at very old age, the brain might show the classic pathologic features of Alzheimer's disease even though the patient did not exhibit dementia, according George M. Savva, Ph.D., of the University of Cambridge, and his associates.

The Cognitive Function and Ageing Study (CFAS) “confirms earlier reports of considerable overlap in the burden of neuropathological features of Alzheimer's disease between groups of the oldest old persons with dementia and those without dementia,” said Dr. Savva.

The brain donors were subjects who had participated in the CFAS when they were aged 70–100 years, undergoing periodic evaluations for dementia with the Mini-Mental State Examination, the Geriatric Mental State Examination, and interviews. A subgroup of 426 subjects donated their brains to the study upon their deaths. In all, 243 had a diagnosis of dementia at the time of death; the rest had been determined to be free of dementia.

The prevalence of moderate or severe neuritic plaques and of neurofibrillary tangles rose with increasing age at death, even in those who had not had dementia. In contrast, the prevalence of cortical atrophy corresponded with dementia diagnoses, the investigators said (N. Engl. J. Med. 2009;360:2302–9).

“Neuropathological validation of the diagnosis of Alzheimer's disease, based on confirmation of the presence of these changes, has a different meaning in the oldest old, because the same burden of pathological features may be found in persons who do not have dementia,” wrote Dr. Savva and his colleagues who reported no relevant conflicts of interest.

Children and adolescents rapidly gain substantial weight on a short course of the atypical antipsychotic medications aripiprazole, olanzapine, quetiapine, and risperidone, according to a report in the JAMA.

Up to 36% of patients in a study of 272 children and adolescents transitioned to overweight or obese status within 11 weeks, and many showed significant abnormalities in lipid profiles and metabolic measures, said Dr. Christoph U. Correll of Zucker Hillside Hospital, Glen Oaks, N.Y., and his associates.

The researchers investigated the cardiometabolic effects of atypical antipsychotic agents because they are “commonly and increasingly prescribed to children and adolescents in the United States as first-line treatment for psychotic disorders, bipolar disorder,” and a widening variety of nonpsychotic mental disorders.

Yet, they have been linked to weight gain, hypertension, lipid abnormalities, and glucose abnormalities that are a particular concern during development “because they predict adult obesity, the metabolic syndrome, cardiovascular morbidity, and malignancy,” the researchers wrote.

Until now, investigators have been unable to tease out the cardiometabolic effects of atypical antipsychotics in children because the agents have only been studied in subjects already exposed to a variety of other antipsychotic medications.

In an editorial accompanying the report, Dr. Christopher K. Varley and Dr. Jon McClellan of Seattle Children's Hospital said, “the development of clinically significant hyperlipidemias and insulin resistance after only 12 weeks of treatment portends severe long-term metabolic and cardiovascular sequelae.

“These results challenge the widespread use of atypical antipsychotic medications in youth.”

When first introduced, atypicals were widely touted as more effective and safer than older neuroleptic agents, which eased the physician reticence about prescribing these medications for young patients, they wrote. Before this, traditional antipsychotic medications were far less commonly prescribed for disruptive behavioral disorders, they noted (JAMA 2009;302:1811–2). Much of the data supporting the use of these agents have been provided by industry-sponsored research. “Medical treatment should be dictated by empirical data rather than by anecdote, assumptions, or marketing strategies,” they commented.

Dr. Correll and his colleagues assessed patients aged 4–19 years who were naive to previous antipsychotic therapy and were participating in a cohort study of pediatric psychotic, mood, or aggressive spectrum disorders.

For comparison, they assessed a control group of 15 similar participants who either refused or immediately discontinued atypical antipsychotic agents.

After a median of 11 weeks, all four drugs were associated with weight gain: an average of 8.5 kg for the 45 patients taking olanzapine, 6.1 kg for the 36 patients taking quetiapine, 5.3 kg for the 135 patients taking risperidone, and 4.4 kg for the 41 patients taking aripiprazole.

All the drugs significantly increased fat mass and waist circumference. In all, 10%–36% of patients, depending on which agent they were taking, gained enough weight to shift into overweight or obese status.

Lipid and metabolic abnormalities were not consistent across all four medications. Olanzapine and quetiapine significantly worsened total cholesterol, triglyceride, non-HDL cholesterol, and other lipid measures, while risperidone significantly raised triglycerides. Quetiapine and olanzapine raised the rates of hyperglycemia and metabolic syndrome.

Olanzapine in particular had the largest weight effects, “and also significantly worsened all glucose and lipid parameters, except HDL cholesterol, which is more related to physical activity,” the investigators said (JAMA 2009;302:1765–73).

In contrast, the control group showed no such changes, indicating that these alterations could not be attributed to the psychiatric disorder itself or to other aspects of treatment.

“In view of poor physical health outcomes and suboptimal metabolic monitoring in the severely mentally ill, the benefits of second-generation antipsychotic medication must be balanced against their cardiometabolic risks through a careful assessment of the indications for their use, consideration of lower-risk alternatives, and proactive adverse effect monitoring and management,” the authors said.

Vitals

Major Finding: More than half of the active treatment subjects gained more than 7% of total body weight after a median of 11 weeks.

Data Source: Cohort of 272 children/adolescents being treated with atypical antipsychotics.

Disclosures: Dr. Correll reported being a consultant or receiving honoraria from and serving on the speakers bureau of numerous pharmaceutical companies, including makers of some of the drugs studied. Dr. Varley and Dr. McClellan reported no disclosures.

Children and adolescents rapidly gain substantial weight on a short course of the atypical antipsychotic medications aripiprazole, olanzapine, quetiapine, and risperidone, according to a report in the JAMA.

Up to 36% of patients in a study of 272 children and adolescents transitioned to overweight or obese status within 11 weeks, and many showed significant abnormalities in lipid profiles and metabolic measures, said Dr. Christoph U. Correll of Zucker Hillside Hospital, Glen Oaks, N.Y., and his associates.

The researchers investigated the cardiometabolic effects of atypical antipsychotic agents because they are “commonly and increasingly prescribed to children and adolescents in the United States as first-line treatment for psychotic disorders, bipolar disorder,” and a widening variety of nonpsychotic mental disorders.

Yet, they have been linked to weight gain, hypertension, lipid abnormalities, and glucose abnormalities that are a particular concern during development “because they predict adult obesity, the metabolic syndrome, cardiovascular morbidity, and malignancy,” the researchers wrote.

Until now, investigators have been unable to tease out the cardiometabolic effects of atypical antipsychotics in children because the agents have only been studied in subjects already exposed to a variety of other antipsychotic medications.

In an editorial accompanying the report, Dr. Christopher K. Varley and Dr. Jon McClellan of Seattle Children's Hospital said, “the development of clinically significant hyperlipidemias and insulin resistance after only 12 weeks of treatment portends severe long-term metabolic and cardiovascular sequelae.

“These results challenge the widespread use of atypical antipsychotic medications in youth.”

When first introduced, atypicals were widely touted as more effective and safer than older neuroleptic agents, which eased the physician reticence about prescribing these medications for young patients, they wrote. Before this, traditional antipsychotic medications were far less commonly prescribed for disruptive behavioral disorders, they noted (JAMA 2009;302:1811–2). Much of the data supporting the use of these agents have been provided by industry-sponsored research. “Medical treatment should be dictated by empirical data rather than by anecdote, assumptions, or marketing strategies,” they commented.

Dr. Correll and his colleagues assessed patients aged 4–19 years who were naive to previous antipsychotic therapy and were participating in a cohort study of pediatric psychotic, mood, or aggressive spectrum disorders.

For comparison, they assessed a control group of 15 similar participants who either refused or immediately discontinued atypical antipsychotic agents.

After a median of 11 weeks, all four drugs were associated with weight gain: an average of 8.5 kg for the 45 patients taking olanzapine, 6.1 kg for the 36 patients taking quetiapine, 5.3 kg for the 135 patients taking risperidone, and 4.4 kg for the 41 patients taking aripiprazole.

All the drugs significantly increased fat mass and waist circumference. In all, 10%–36% of patients, depending on which agent they were taking, gained enough weight to shift into overweight or obese status.

Lipid and metabolic abnormalities were not consistent across all four medications. Olanzapine and quetiapine significantly worsened total cholesterol, triglyceride, non-HDL cholesterol, and other lipid measures, while risperidone significantly raised triglycerides. Quetiapine and olanzapine raised the rates of hyperglycemia and metabolic syndrome.

Olanzapine in particular had the largest weight effects, “and also significantly worsened all glucose and lipid parameters, except HDL cholesterol, which is more related to physical activity,” the investigators said (JAMA 2009;302:1765–73).

In contrast, the control group showed no such changes, indicating that these alterations could not be attributed to the psychiatric disorder itself or to other aspects of treatment.

“In view of poor physical health outcomes and suboptimal metabolic monitoring in the severely mentally ill, the benefits of second-generation antipsychotic medication must be balanced against their cardiometabolic risks through a careful assessment of the indications for their use, consideration of lower-risk alternatives, and proactive adverse effect monitoring and management,” the authors said.

Vitals

Major Finding: More than half of the active treatment subjects gained more than 7% of total body weight after a median of 11 weeks.

Data Source: Cohort of 272 children/adolescents being treated with atypical antipsychotics.

Disclosures: Dr. Correll reported being a consultant or receiving honoraria from and serving on the speakers bureau of numerous pharmaceutical companies, including makers of some of the drugs studied. Dr. Varley and Dr. McClellan reported no disclosures.

Children and adolescents rapidly gain substantial weight on a short course of the atypical antipsychotic medications aripiprazole, olanzapine, quetiapine, and risperidone, according to a report in the JAMA.

Up to 36% of patients in a study of 272 children and adolescents transitioned to overweight or obese status within 11 weeks, and many showed significant abnormalities in lipid profiles and metabolic measures, said Dr. Christoph U. Correll of Zucker Hillside Hospital, Glen Oaks, N.Y., and his associates.

The researchers investigated the cardiometabolic effects of atypical antipsychotic agents because they are “commonly and increasingly prescribed to children and adolescents in the United States as first-line treatment for psychotic disorders, bipolar disorder,” and a widening variety of nonpsychotic mental disorders.

Yet, they have been linked to weight gain, hypertension, lipid abnormalities, and glucose abnormalities that are a particular concern during development “because they predict adult obesity, the metabolic syndrome, cardiovascular morbidity, and malignancy,” the researchers wrote.

Until now, investigators have been unable to tease out the cardiometabolic effects of atypical antipsychotics in children because the agents have only been studied in subjects already exposed to a variety of other antipsychotic medications.

In an editorial accompanying the report, Dr. Christopher K. Varley and Dr. Jon McClellan of Seattle Children's Hospital said, “the development of clinically significant hyperlipidemias and insulin resistance after only 12 weeks of treatment portends severe long-term metabolic and cardiovascular sequelae.

“These results challenge the widespread use of atypical antipsychotic medications in youth.”

When first introduced, atypicals were widely touted as more effective and safer than older neuroleptic agents, which eased the physician reticence about prescribing these medications for young patients, they wrote. Before this, traditional antipsychotic medications were far less commonly prescribed for disruptive behavioral disorders, they noted (JAMA 2009;302:1811–2). Much of the data supporting the use of these agents have been provided by industry-sponsored research. “Medical treatment should be dictated by empirical data rather than by anecdote, assumptions, or marketing strategies,” they commented.

Dr. Correll and his colleagues assessed patients aged 4–19 years who were naive to previous antipsychotic therapy and were participating in a cohort study of pediatric psychotic, mood, or aggressive spectrum disorders.

For comparison, they assessed a control group of 15 similar participants who either refused or immediately discontinued atypical antipsychotic agents.

After a median of 11 weeks, all four drugs were associated with weight gain: an average of 8.5 kg for the 45 patients taking olanzapine, 6.1 kg for the 36 patients taking quetiapine, 5.3 kg for the 135 patients taking risperidone, and 4.4 kg for the 41 patients taking aripiprazole.

All the drugs significantly increased fat mass and waist circumference. In all, 10%–36% of patients, depending on which agent they were taking, gained enough weight to shift into overweight or obese status.

Lipid and metabolic abnormalities were not consistent across all four medications. Olanzapine and quetiapine significantly worsened total cholesterol, triglyceride, non-HDL cholesterol, and other lipid measures, while risperidone significantly raised triglycerides. Quetiapine and olanzapine raised the rates of hyperglycemia and metabolic syndrome.

Olanzapine in particular had the largest weight effects, “and also significantly worsened all glucose and lipid parameters, except HDL cholesterol, which is more related to physical activity,” the investigators said (JAMA 2009;302:1765–73).

In contrast, the control group showed no such changes, indicating that these alterations could not be attributed to the psychiatric disorder itself or to other aspects of treatment.

“In view of poor physical health outcomes and suboptimal metabolic monitoring in the severely mentally ill, the benefits of second-generation antipsychotic medication must be balanced against their cardiometabolic risks through a careful assessment of the indications for their use, consideration of lower-risk alternatives, and proactive adverse effect monitoring and management,” the authors said.

Vitals

Major Finding: More than half of the active treatment subjects gained more than 7% of total body weight after a median of 11 weeks.

Data Source: Cohort of 272 children/adolescents being treated with atypical antipsychotics.

Disclosures: Dr. Correll reported being a consultant or receiving honoraria from and serving on the speakers bureau of numerous pharmaceutical companies, including makers of some of the drugs studied. Dr. Varley and Dr. McClellan reported no disclosures.

Intravenous drugs given as part of advanced cardiac life support failed to improve long-term survival in the first randomized, controlled trial to test outcomes of this nearly universal procedure, according to a report published in JAMA.

Intravenous epinephrine, atropine, and/or amiodarone are given in almost every case of out-of-hospital cardiac arrest in Western nations, but the use of intravenous epinephrine in this setting is based almost entirely on preclinical evidence.

“Because there are no randomized, controlled studies showing improved survival to hospital discharge with any drugs routinely administered during CPR [cardiopulmonary resuscitation], we concluded such a study was warranted,” said Dr. Theresa M. Olasveengen and her associates at Oslo University Hospital.

They assessed 851 patients who required an ambulance for out-of-hospital cardiac arrest between May 2003 and April 2008.

The study subjects were randomly assigned to receive standard advanced cardiac life support, which included intravenous drug administration (418 patients) or advanced cardiac life support without any intravenous drugs (433 patients).

Initially, short-term survival was better with the IV drugs (40%) than without them (25%), and more patients in the intravenous-drug group (30%) than in the no-intravenous-drug group (20%) survived to ICU admission.

However, this early benefit quickly dissipated, and survival to hospital discharge—the primary outcome measure of this trial—was not significantly different between patients who received intravenous drugs (10.5%) and those who did not (9.2%).

The rates of survival with favorable neurologic outcomes also were not significantly different, at 9.8% for the intravenous-drug group and 8.1% for the no-intravenous-drug group, the investigators reported (JAMA 2009;302:2222–9).

In both groups, most patients who died in hospital after initial resuscitation had severe cerebral damage.

It may be that intravenous drug administration represents “unproductive resuscitation of patients whose vital organ injury makes them unlikely candidates for long-term survival,” the researchers wrote.

“If present pharmacological interventions only facilitate cardiac resuscitation in patients who will ultimately experience irreversible cerebral damage, this may cause an additional burden on already overburdened ICUs,” said Dr. Olasveengen and her colleagues.

One encouraging finding was that for the highly trained paramedics in this study, administering intravenous drugs did not interfere with delivery of CPR. Some critics of drug administration have questioned whether the time-consuming and potentially distracting actions of establishing intravenous access and prepping and administering the drugs may detract from delivery of high-quality CPR, they said.

This study was limited in that it was a single-center trial and its results may not be applicable to other emergency medical systems that have different training, infrastructure, treatment protocols, or quality of CPR.

But the findings do justify undertaking larger trials of the issue, and show that it would not be unethical to withhold intravenous drugs for such a trial, they added.

Dr. Olasveengen reported receiving speakers fees from Medtronic Inc. and research support from Laerdal Medical Corp.

Intravenous drugs given as part of advanced cardiac life support failed to improve long-term survival in the first randomized, controlled trial to test outcomes of this nearly universal procedure, according to a report published in JAMA.

Intravenous epinephrine, atropine, and/or amiodarone are given in almost every case of out-of-hospital cardiac arrest in Western nations, but the use of intravenous epinephrine in this setting is based almost entirely on preclinical evidence.

“Because there are no randomized, controlled studies showing improved survival to hospital discharge with any drugs routinely administered during CPR [cardiopulmonary resuscitation], we concluded such a study was warranted,” said Dr. Theresa M. Olasveengen and her associates at Oslo University Hospital.

They assessed 851 patients who required an ambulance for out-of-hospital cardiac arrest between May 2003 and April 2008.

The study subjects were randomly assigned to receive standard advanced cardiac life support, which included intravenous drug administration (418 patients) or advanced cardiac life support without any intravenous drugs (433 patients).

Initially, short-term survival was better with the IV drugs (40%) than without them (25%), and more patients in the intravenous-drug group (30%) than in the no-intravenous-drug group (20%) survived to ICU admission.

However, this early benefit quickly dissipated, and survival to hospital discharge—the primary outcome measure of this trial—was not significantly different between patients who received intravenous drugs (10.5%) and those who did not (9.2%).

The rates of survival with favorable neurologic outcomes also were not significantly different, at 9.8% for the intravenous-drug group and 8.1% for the no-intravenous-drug group, the investigators reported (JAMA 2009;302:2222–9).

In both groups, most patients who died in hospital after initial resuscitation had severe cerebral damage.

It may be that intravenous drug administration represents “unproductive resuscitation of patients whose vital organ injury makes them unlikely candidates for long-term survival,” the researchers wrote.

“If present pharmacological interventions only facilitate cardiac resuscitation in patients who will ultimately experience irreversible cerebral damage, this may cause an additional burden on already overburdened ICUs,” said Dr. Olasveengen and her colleagues.

One encouraging finding was that for the highly trained paramedics in this study, administering intravenous drugs did not interfere with delivery of CPR. Some critics of drug administration have questioned whether the time-consuming and potentially distracting actions of establishing intravenous access and prepping and administering the drugs may detract from delivery of high-quality CPR, they said.

This study was limited in that it was a single-center trial and its results may not be applicable to other emergency medical systems that have different training, infrastructure, treatment protocols, or quality of CPR.

But the findings do justify undertaking larger trials of the issue, and show that it would not be unethical to withhold intravenous drugs for such a trial, they added.

Dr. Olasveengen reported receiving speakers fees from Medtronic Inc. and research support from Laerdal Medical Corp.

Intravenous drugs given as part of advanced cardiac life support failed to improve long-term survival in the first randomized, controlled trial to test outcomes of this nearly universal procedure, according to a report published in JAMA.

Intravenous epinephrine, atropine, and/or amiodarone are given in almost every case of out-of-hospital cardiac arrest in Western nations, but the use of intravenous epinephrine in this setting is based almost entirely on preclinical evidence.

“Because there are no randomized, controlled studies showing improved survival to hospital discharge with any drugs routinely administered during CPR [cardiopulmonary resuscitation], we concluded such a study was warranted,” said Dr. Theresa M. Olasveengen and her associates at Oslo University Hospital.

They assessed 851 patients who required an ambulance for out-of-hospital cardiac arrest between May 2003 and April 2008.

The study subjects were randomly assigned to receive standard advanced cardiac life support, which included intravenous drug administration (418 patients) or advanced cardiac life support without any intravenous drugs (433 patients).

Initially, short-term survival was better with the IV drugs (40%) than without them (25%), and more patients in the intravenous-drug group (30%) than in the no-intravenous-drug group (20%) survived to ICU admission.

However, this early benefit quickly dissipated, and survival to hospital discharge—the primary outcome measure of this trial—was not significantly different between patients who received intravenous drugs (10.5%) and those who did not (9.2%).

The rates of survival with favorable neurologic outcomes also were not significantly different, at 9.8% for the intravenous-drug group and 8.1% for the no-intravenous-drug group, the investigators reported (JAMA 2009;302:2222–9).

In both groups, most patients who died in hospital after initial resuscitation had severe cerebral damage.

It may be that intravenous drug administration represents “unproductive resuscitation of patients whose vital organ injury makes them unlikely candidates for long-term survival,” the researchers wrote.

“If present pharmacological interventions only facilitate cardiac resuscitation in patients who will ultimately experience irreversible cerebral damage, this may cause an additional burden on already overburdened ICUs,” said Dr. Olasveengen and her colleagues.

One encouraging finding was that for the highly trained paramedics in this study, administering intravenous drugs did not interfere with delivery of CPR. Some critics of drug administration have questioned whether the time-consuming and potentially distracting actions of establishing intravenous access and prepping and administering the drugs may detract from delivery of high-quality CPR, they said.

This study was limited in that it was a single-center trial and its results may not be applicable to other emergency medical systems that have different training, infrastructure, treatment protocols, or quality of CPR.

But the findings do justify undertaking larger trials of the issue, and show that it would not be unethical to withhold intravenous drugs for such a trial, they added.

Dr. Olasveengen reported receiving speakers fees from Medtronic Inc. and research support from Laerdal Medical Corp.

Intensive medical therapy for asymptomatic carotid stenosis has decreased the risk of stroke to such a degree that it has marginalized the benefits of revascularization in most patients, according to a study published online December 14 in the Archives of Neurology.

Intensive medical therapy, widely adopted after 2003, has cut the rate of microemboli to less than 4% and markedly reduced cardiovascular events, particularly stroke, in patients with asymptomatic carotid stenosis. It therefore should be considered the treatment of choice for this patient population, said Dr. J. David Spence of the Stroke Prevention and Atherosclerosis Research Centre, London, Ont., and his associates.

Their conclusion was based on the results of their study that assessed the relative benefits of carotid revascularization using data from a clinical trial documenting microemboli on transcranial Doppler imaging.

“We think that revascularization should be considered only for the rare patients with microemboli.” These patients are at higher risk for cardiovascular events, so the benefit of carotid revascularization may outweigh the risks of the procedure in these cases, they noted.

The investigators assessed 468 patients with asymptomatic carotid stenosis. Subjects who were assessed between Jan. 1, 2000 and Dec. 31, 2002 (199 patients) were taking the less intensive medical therapy recommended at that time, whereas those assessed between Jan. 1, 2003 and July 30, 2007 (269 patients) were taking the more aggressive medical therapy that is prevalent now. Patients in each group had a mean age of about 70 years. Since 2003, 34% of patients were female, compared with 42% before 2003.

The rate of microemboli was 12.6% before 2003, significantly higher than the 3.7% rate after 2003. Concomitantly, plasma lipid profiles steadily improved and the rate of carotid artery plaque progression markedly declined. More importantly, the rate of cardiovascular events dropped from 17.6% before 2003 to 5.2% afterward, Dr. Spence and his associates reported (Arch. Neurol. 2010;67 [doi:10.1001/archneurol.2009.289

Patients who were assessed in 2003 or later were significantly more likely to be taking statins, angiotensin-converting enzyme inhibitors, and clopidogrel at the time of their baseline transcranial Doppler embolus detection than were those who were assessed before.

Within 2 years of follow-up, 32% of the patients with microemboli died, developed stroke or MI, or required carotid endarterectomy because their carotid stenosis became symptomatic. In comparison, these adverse events occurred in 9% of patients without microemboli.

The investigators adjusted each comparison for age, sex, smoking, systolic blood pressure, cholesterol, and cholesterol to high-density lipoprotein ratio.

“Our findings indicate that with more intensive medical therapy, the stroke risk in asymptomatic carotid stenosis and therefore the potential benefit of revascularization have markedly declined,” the researchers said.

The study was funded by grants from the Heart and Stroke Foundation of Ontario and by donations to the Stroke Prevention and Atherosclerosis Research Centre. No financial conflicts of interest were reported.

Intensive medical therapy for asymptomatic carotid stenosis has decreased the risk of stroke to such a degree that it has marginalized the benefits of revascularization in most patients, according to a study published online December 14 in the Archives of Neurology.

Intensive medical therapy, widely adopted after 2003, has cut the rate of microemboli to less than 4% and markedly reduced cardiovascular events, particularly stroke, in patients with asymptomatic carotid stenosis. It therefore should be considered the treatment of choice for this patient population, said Dr. J. David Spence of the Stroke Prevention and Atherosclerosis Research Centre, London, Ont., and his associates.

Their conclusion was based on the results of their study that assessed the relative benefits of carotid revascularization using data from a clinical trial documenting microemboli on transcranial Doppler imaging.

“We think that revascularization should be considered only for the rare patients with microemboli.” These patients are at higher risk for cardiovascular events, so the benefit of carotid revascularization may outweigh the risks of the procedure in these cases, they noted.

The investigators assessed 468 patients with asymptomatic carotid stenosis. Subjects who were assessed between Jan. 1, 2000 and Dec. 31, 2002 (199 patients) were taking the less intensive medical therapy recommended at that time, whereas those assessed between Jan. 1, 2003 and July 30, 2007 (269 patients) were taking the more aggressive medical therapy that is prevalent now. Patients in each group had a mean age of about 70 years. Since 2003, 34% of patients were female, compared with 42% before 2003.

The rate of microemboli was 12.6% before 2003, significantly higher than the 3.7% rate after 2003. Concomitantly, plasma lipid profiles steadily improved and the rate of carotid artery plaque progression markedly declined. More importantly, the rate of cardiovascular events dropped from 17.6% before 2003 to 5.2% afterward, Dr. Spence and his associates reported (Arch. Neurol. 2010;67 [doi:10.1001/archneurol.2009.289

Patients who were assessed in 2003 or later were significantly more likely to be taking statins, angiotensin-converting enzyme inhibitors, and clopidogrel at the time of their baseline transcranial Doppler embolus detection than were those who were assessed before.

Within 2 years of follow-up, 32% of the patients with microemboli died, developed stroke or MI, or required carotid endarterectomy because their carotid stenosis became symptomatic. In comparison, these adverse events occurred in 9% of patients without microemboli.

The investigators adjusted each comparison for age, sex, smoking, systolic blood pressure, cholesterol, and cholesterol to high-density lipoprotein ratio.

“Our findings indicate that with more intensive medical therapy, the stroke risk in asymptomatic carotid stenosis and therefore the potential benefit of revascularization have markedly declined,” the researchers said.

The study was funded by grants from the Heart and Stroke Foundation of Ontario and by donations to the Stroke Prevention and Atherosclerosis Research Centre. No financial conflicts of interest were reported.

Intensive medical therapy for asymptomatic carotid stenosis has decreased the risk of stroke to such a degree that it has marginalized the benefits of revascularization in most patients, according to a study published online December 14 in the Archives of Neurology.

Intensive medical therapy, widely adopted after 2003, has cut the rate of microemboli to less than 4% and markedly reduced cardiovascular events, particularly stroke, in patients with asymptomatic carotid stenosis. It therefore should be considered the treatment of choice for this patient population, said Dr. J. David Spence of the Stroke Prevention and Atherosclerosis Research Centre, London, Ont., and his associates.

Their conclusion was based on the results of their study that assessed the relative benefits of carotid revascularization using data from a clinical trial documenting microemboli on transcranial Doppler imaging.

“We think that revascularization should be considered only for the rare patients with microemboli.” These patients are at higher risk for cardiovascular events, so the benefit of carotid revascularization may outweigh the risks of the procedure in these cases, they noted.

The investigators assessed 468 patients with asymptomatic carotid stenosis. Subjects who were assessed between Jan. 1, 2000 and Dec. 31, 2002 (199 patients) were taking the less intensive medical therapy recommended at that time, whereas those assessed between Jan. 1, 2003 and July 30, 2007 (269 patients) were taking the more aggressive medical therapy that is prevalent now. Patients in each group had a mean age of about 70 years. Since 2003, 34% of patients were female, compared with 42% before 2003.

The rate of microemboli was 12.6% before 2003, significantly higher than the 3.7% rate after 2003. Concomitantly, plasma lipid profiles steadily improved and the rate of carotid artery plaque progression markedly declined. More importantly, the rate of cardiovascular events dropped from 17.6% before 2003 to 5.2% afterward, Dr. Spence and his associates reported (Arch. Neurol. 2010;67 [doi:10.1001/archneurol.2009.289

Patients who were assessed in 2003 or later were significantly more likely to be taking statins, angiotensin-converting enzyme inhibitors, and clopidogrel at the time of their baseline transcranial Doppler embolus detection than were those who were assessed before.

Within 2 years of follow-up, 32% of the patients with microemboli died, developed stroke or MI, or required carotid endarterectomy because their carotid stenosis became symptomatic. In comparison, these adverse events occurred in 9% of patients without microemboli.

The investigators adjusted each comparison for age, sex, smoking, systolic blood pressure, cholesterol, and cholesterol to high-density lipoprotein ratio.

“Our findings indicate that with more intensive medical therapy, the stroke risk in asymptomatic carotid stenosis and therefore the potential benefit of revascularization have markedly declined,” the researchers said.

The study was funded by grants from the Heart and Stroke Foundation of Ontario and by donations to the Stroke Prevention and Atherosclerosis Research Centre. No financial conflicts of interest were reported.

A variation in the MMP12 gene appears to be associated with beneficial pulmonary effects in children who have asthma and in adults who smoke, particularly smokers with chronic obstructive pulmonary disease, according to a study in more than 8,000 patients.

“Our results suggest that variants of MMP12 are determinants of the level of lung function in subjects who are at risk for airflow obstruction,” said Dr. Gary M. Hunninghake of Brigham and Women's Hospital, Boston, and his associates.

The investigators tested for an association between single nucleotide polymorphisms (SNPs) in the MMP12 gene and lung function as assessed by forced expiratory volume in 1 second (FEV₁) in cohorts participating in seven clinical trials. The MMP12 gene encodes matrix metalloproteinase 12, which is produced by macrophages, “the predominant cell type that patrols the lower airspaces under normal conditions and the main inflammatory cell type that is recruited with smoking,” the investigators noted.

The researchers first found that the minor allele of SNP rs2276109 in the MMP12 gene was significantly associated with increased FEV₁ in children with asthma (but not nonasthmatic children) who were subjects in the Genetics of Asthma in Costa Rica Study. They then found the same link between the SNP and increased FEV₁ among children taking budesonide—but not among those who were not taking budesonide—in the Childhood Asthma Management Program. The same link between the SNP and increased FEV₁ existed among children with asthma (but not nonasthmatic children) in the BAMSE (Children, Allergy, Milieu, Stockholm, Epidemiological Survey) study.

Dr. Hunninghake and his colleagues then tested for the same association in adults who were subjects in the Boston Early-Onset COPD Study, the Lovelace Smokers Cohort, and the Normative Aging Study. The researchers found that the same SNP variation was associated with improved lung function in adults who were current or former smokers, but not in nonsmokers.

Finally, the investigators found that the same MMP12 variant appeared to protect patients at risk for COPD against the disease in those same three adult cohorts. The absence of the SNP rs2276109 was associated with a 54% increase in the risk of the onset of COPD and a population attributable risk of COPD of 28%.

The findings support the so-called “Dutch hypothesis,” which states that asthma and COPD are different manifestations of a single disease entity and suggests that as-yet unknown genetic variants may underlie both asthma and COPD, the authors said (N. Engl. J. Med. 2009; 361 [doi:10.1056/NEJMoa0904006

Most previous studies of genetic associations in pulmonary function have relied on a single cohort, the authors noted. “A strength of our study is that it included the analysis of multiple measurements of pulmonary function in a large number of subjects—more than 20,000 FEV₁ measurements in more than 8,300 subjects.”

“Evidence is accumulating that asthma and COPD share common pathogenetic pathways,” noted Dr. Guy G. Brusselle of Ghent (Belgium) University Hospital, in an editorial. The study “adds to the accumulating evidence that several mechanisms may lead to the development of COPD” (N. Engl. J. Med. 2009;361 [doi:10.1056/NEJMe0919626

The new study has several strengths, Dr. Brusselle noted. Those strengths include the inclusion of seven cohorts with more than 8,300 subjects; the replication of an association between the SNP and FEV₁ both in adult smokers and children with asthma; and the researchers' ability to repeat the analyses after stratification for asthma status and smoking status.

Disclosures: Dr. Hunninghake reported no conflicts of interest relevant to the study. His associates reported receiving support from AstraZeneca Pharmaceuticals, Merck & Co., Johnson & Johnson, Golden Helix, Novartis, GlaxoSmithKline, Sandvik, Sepracor, Genentech, and Phadia AB.

A variation in the MMP12 gene appears to be associated with beneficial pulmonary effects in children who have asthma and in adults who smoke, particularly smokers with chronic obstructive pulmonary disease, according to a study in more than 8,000 patients.

“Our results suggest that variants of MMP12 are determinants of the level of lung function in subjects who are at risk for airflow obstruction,” said Dr. Gary M. Hunninghake of Brigham and Women's Hospital, Boston, and his associates.

The investigators tested for an association between single nucleotide polymorphisms (SNPs) in the MMP12 gene and lung function as assessed by forced expiratory volume in 1 second (FEV₁) in cohorts participating in seven clinical trials. The MMP12 gene encodes matrix metalloproteinase 12, which is produced by macrophages, “the predominant cell type that patrols the lower airspaces under normal conditions and the main inflammatory cell type that is recruited with smoking,” the investigators noted.

The researchers first found that the minor allele of SNP rs2276109 in the MMP12 gene was significantly associated with increased FEV₁ in children with asthma (but not nonasthmatic children) who were subjects in the Genetics of Asthma in Costa Rica Study. They then found the same link between the SNP and increased FEV₁ among children taking budesonide—but not among those who were not taking budesonide—in the Childhood Asthma Management Program. The same link between the SNP and increased FEV₁ existed among children with asthma (but not nonasthmatic children) in the BAMSE (Children, Allergy, Milieu, Stockholm, Epidemiological Survey) study.

Dr. Hunninghake and his colleagues then tested for the same association in adults who were subjects in the Boston Early-Onset COPD Study, the Lovelace Smokers Cohort, and the Normative Aging Study. The researchers found that the same SNP variation was associated with improved lung function in adults who were current or former smokers, but not in nonsmokers.

Finally, the investigators found that the same MMP12 variant appeared to protect patients at risk for COPD against the disease in those same three adult cohorts. The absence of the SNP rs2276109 was associated with a 54% increase in the risk of the onset of COPD and a population attributable risk of COPD of 28%.

The findings support the so-called “Dutch hypothesis,” which states that asthma and COPD are different manifestations of a single disease entity and suggests that as-yet unknown genetic variants may underlie both asthma and COPD, the authors said (N. Engl. J. Med. 2009; 361 [doi:10.1056/NEJMoa0904006

Most previous studies of genetic associations in pulmonary function have relied on a single cohort, the authors noted. “A strength of our study is that it included the analysis of multiple measurements of pulmonary function in a large number of subjects—more than 20,000 FEV₁ measurements in more than 8,300 subjects.”

“Evidence is accumulating that asthma and COPD share common pathogenetic pathways,” noted Dr. Guy G. Brusselle of Ghent (Belgium) University Hospital, in an editorial. The study “adds to the accumulating evidence that several mechanisms may lead to the development of COPD” (N. Engl. J. Med. 2009;361 [doi:10.1056/NEJMe0919626

The new study has several strengths, Dr. Brusselle noted. Those strengths include the inclusion of seven cohorts with more than 8,300 subjects; the replication of an association between the SNP and FEV₁ both in adult smokers and children with asthma; and the researchers' ability to repeat the analyses after stratification for asthma status and smoking status.

Disclosures: Dr. Hunninghake reported no conflicts of interest relevant to the study. His associates reported receiving support from AstraZeneca Pharmaceuticals, Merck & Co., Johnson & Johnson, Golden Helix, Novartis, GlaxoSmithKline, Sandvik, Sepracor, Genentech, and Phadia AB.

A variation in the MMP12 gene appears to be associated with beneficial pulmonary effects in children who have asthma and in adults who smoke, particularly smokers with chronic obstructive pulmonary disease, according to a study in more than 8,000 patients.

“Our results suggest that variants of MMP12 are determinants of the level of lung function in subjects who are at risk for airflow obstruction,” said Dr. Gary M. Hunninghake of Brigham and Women's Hospital, Boston, and his associates.

The investigators tested for an association between single nucleotide polymorphisms (SNPs) in the MMP12 gene and lung function as assessed by forced expiratory volume in 1 second (FEV₁) in cohorts participating in seven clinical trials. The MMP12 gene encodes matrix metalloproteinase 12, which is produced by macrophages, “the predominant cell type that patrols the lower airspaces under normal conditions and the main inflammatory cell type that is recruited with smoking,” the investigators noted.

The researchers first found that the minor allele of SNP rs2276109 in the MMP12 gene was significantly associated with increased FEV₁ in children with asthma (but not nonasthmatic children) who were subjects in the Genetics of Asthma in Costa Rica Study. They then found the same link between the SNP and increased FEV₁ among children taking budesonide—but not among those who were not taking budesonide—in the Childhood Asthma Management Program. The same link between the SNP and increased FEV₁ existed among children with asthma (but not nonasthmatic children) in the BAMSE (Children, Allergy, Milieu, Stockholm, Epidemiological Survey) study.

Dr. Hunninghake and his colleagues then tested for the same association in adults who were subjects in the Boston Early-Onset COPD Study, the Lovelace Smokers Cohort, and the Normative Aging Study. The researchers found that the same SNP variation was associated with improved lung function in adults who were current or former smokers, but not in nonsmokers.

Finally, the investigators found that the same MMP12 variant appeared to protect patients at risk for COPD against the disease in those same three adult cohorts. The absence of the SNP rs2276109 was associated with a 54% increase in the risk of the onset of COPD and a population attributable risk of COPD of 28%.

The findings support the so-called “Dutch hypothesis,” which states that asthma and COPD are different manifestations of a single disease entity and suggests that as-yet unknown genetic variants may underlie both asthma and COPD, the authors said (N. Engl. J. Med. 2009; 361 [doi:10.1056/NEJMoa0904006

Most previous studies of genetic associations in pulmonary function have relied on a single cohort, the authors noted. “A strength of our study is that it included the analysis of multiple measurements of pulmonary function in a large number of subjects—more than 20,000 FEV₁ measurements in more than 8,300 subjects.”

“Evidence is accumulating that asthma and COPD share common pathogenetic pathways,” noted Dr. Guy G. Brusselle of Ghent (Belgium) University Hospital, in an editorial. The study “adds to the accumulating evidence that several mechanisms may lead to the development of COPD” (N. Engl. J. Med. 2009;361 [doi:10.1056/NEJMe0919626

The new study has several strengths, Dr. Brusselle noted. Those strengths include the inclusion of seven cohorts with more than 8,300 subjects; the replication of an association between the SNP and FEV₁ both in adult smokers and children with asthma; and the researchers' ability to repeat the analyses after stratification for asthma status and smoking status.

Disclosures: Dr. Hunninghake reported no conflicts of interest relevant to the study. His associates reported receiving support from AstraZeneca Pharmaceuticals, Merck & Co., Johnson & Johnson, Golden Helix, Novartis, GlaxoSmithKline, Sandvik, Sepracor, Genentech, and Phadia AB.

Children and adolescents rapidly gain substantial weight on a short course of the atypical antipsychotic medications aripiprazole, olanzapine, quetiapine, and risperidone, according to researchers.

Up to 36% of patients in a study of 272 children and adolescents transitioned to overweight or obese status within 11 weeks, and many showed significant abnormalities in lipid profiles and metabolic measures, said Dr. Christoph U. Correll of Zucker Hillside Hospital, Glen Oaks, N.Y., and his associates.

They studied the cardiometabolic effects of atypical antipsychotic agents because they are “commonly and increasingly prescribed to children and adolescents in the United States as first-line treatment for psychotic disorders, bipolar disorder,” and a widening variety of nonpsychotic mental disorders.

Yet they have been linked to weight gain, hypertension, lipid abnormalities, and glucose abnormalities that are a particular concern during development “because they predict adult obesity, the metabolic syndrome, cardiovascular morbidity, and malignancy,” the researchers wrote.

Until now, investigators have been unable to tease out the cardiometabolic effects of atypical antipsychotics in children because the agents have been studied only in subjects already exposed to a variety of other antipsychotic medications.

In an editorial accompanying the report, Dr. Christopher K. Varley and Dr. Jon McClellan of Seattle Children's Hospital observed that “the development of clinically significant hyperlipidemias and insulin resistance after only 12 weeks of treatment portends severe long-term metabolic and cardiovascular sequelae.”

These results “challenge the widespread use of atypical antipsychotic medications in youth,” they added.

When first introduced, atypicals were widely touted as more effective and safer than older neuroleptic agents, which eased physician reticence about prescribing these medications for young patients, they wrote. Before this, traditional antipsychotic medications were far less commonly prescribed for disruptive behavioral disorders (JAMA 2009;302:1811-2).

Much of the data supporting the use of these agents has been provided by industry-sponsored research. “Medical treatment should be dictated by empirical data rather than by anecdote, assumptions, or marketing strategies,” they wrote.

Dr. Correll and his colleagues assessed patients aged 4-19 years who were naive to previous antipsychotic therapy and were participating in a cohort study of pediatric psychotic, mood, or aggressive spectrum disorders. For comparison, they assessed a control group of 15 similar participants who either refused or immediately discontinued atypical antipsychotic agents.

After a median of 11 weeks, all four drugs were associated with weight gain: an average of 8.5 kg for the 45 patients on olanzapine, 6.1 kg for the 36 patients on quetiapine, 5.3 kg for the 135 patients on risperidone, and 4.4 kg for the 41 patients on aripiprazole. More than half the children gained more than 7% of their total body weight.

All the drugs significantly increased fat mass and waist circumference. In all, 10%-36% of patients, depending on which agent they were taking, gained enough weight to shift into overweight or obese status.

Lipid and metabolic abnormalities were not consistent across all four medications. Olanzapine and quetiapine significantly worsened total cholesterol, triglyceride, non–HDL cholesterol, and other lipid measures, while risperidone significantly raised triglycerides. Quetiapine and olanzapine raised the rates of hyperglycemia and metabolic syndrome.

Olanzapine in particular had the largest weight effects, “and also significantly worsened all glucose and lipid parameters, except HDL cholesterol, which is more related to physical activity,” the investigators said (JAMA 2009;302:1765-73).

In contrast, the control group showed no such changes, indicating that these alterations could not be attributed to the psychiatric disorder itself or to other aspects of treatment.

“In view of poor physical health outcomes and suboptimal metabolic monitoring in the severely mentally ill, the benefits of second-generation antipsychotic medications must be balanced against their cardiometabolic risks through a careful assessment of the indications for their use, consideration of lower-risk alternatives, and proactive adverse effect monitoring and management,” Dr. Correll and his associates said.

Dr. Correll reported being a consultant or receiving honoraria from AstraZeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly & Co., Intra-Cellular Therapeutics, Medicure, OrthoMcNeill-Janssen, Otsuka, Organon, Pfizer, Schering-Plough, Solvay, Supernus, Vanda, and Wyeth, and serving on the speakers bureau of AstraZeneca, Bristol-Myers Squibb/Otsuka, and Pfizer.

Dr. Varley and Dr. McClellan reported no conflicts.

Children and adolescents rapidly gain substantial weight on a short course of the atypical antipsychotic medications aripiprazole, olanzapine, quetiapine, and risperidone, according to researchers.

Up to 36% of patients in a study of 272 children and adolescents transitioned to overweight or obese status within 11 weeks, and many showed significant abnormalities in lipid profiles and metabolic measures, said Dr. Christoph U. Correll of Zucker Hillside Hospital, Glen Oaks, N.Y., and his associates.

They studied the cardiometabolic effects of atypical antipsychotic agents because they are “commonly and increasingly prescribed to children and adolescents in the United States as first-line treatment for psychotic disorders, bipolar disorder,” and a widening variety of nonpsychotic mental disorders.

Yet they have been linked to weight gain, hypertension, lipid abnormalities, and glucose abnormalities that are a particular concern during development “because they predict adult obesity, the metabolic syndrome, cardiovascular morbidity, and malignancy,” the researchers wrote.

Until now, investigators have been unable to tease out the cardiometabolic effects of atypical antipsychotics in children because the agents have been studied only in subjects already exposed to a variety of other antipsychotic medications.

In an editorial accompanying the report, Dr. Christopher K. Varley and Dr. Jon McClellan of Seattle Children's Hospital observed that “the development of clinically significant hyperlipidemias and insulin resistance after only 12 weeks of treatment portends severe long-term metabolic and cardiovascular sequelae.”

These results “challenge the widespread use of atypical antipsychotic medications in youth,” they added.

When first introduced, atypicals were widely touted as more effective and safer than older neuroleptic agents, which eased physician reticence about prescribing these medications for young patients, they wrote. Before this, traditional antipsychotic medications were far less commonly prescribed for disruptive behavioral disorders (JAMA 2009;302:1811-2).

Much of the data supporting the use of these agents has been provided by industry-sponsored research. “Medical treatment should be dictated by empirical data rather than by anecdote, assumptions, or marketing strategies,” they wrote.

Dr. Correll and his colleagues assessed patients aged 4-19 years who were naive to previous antipsychotic therapy and were participating in a cohort study of pediatric psychotic, mood, or aggressive spectrum disorders. For comparison, they assessed a control group of 15 similar participants who either refused or immediately discontinued atypical antipsychotic agents.

After a median of 11 weeks, all four drugs were associated with weight gain: an average of 8.5 kg for the 45 patients on olanzapine, 6.1 kg for the 36 patients on quetiapine, 5.3 kg for the 135 patients on risperidone, and 4.4 kg for the 41 patients on aripiprazole. More than half the children gained more than 7% of their total body weight.

All the drugs significantly increased fat mass and waist circumference. In all, 10%-36% of patients, depending on which agent they were taking, gained enough weight to shift into overweight or obese status.

Lipid and metabolic abnormalities were not consistent across all four medications. Olanzapine and quetiapine significantly worsened total cholesterol, triglyceride, non–HDL cholesterol, and other lipid measures, while risperidone significantly raised triglycerides. Quetiapine and olanzapine raised the rates of hyperglycemia and metabolic syndrome.

Olanzapine in particular had the largest weight effects, “and also significantly worsened all glucose and lipid parameters, except HDL cholesterol, which is more related to physical activity,” the investigators said (JAMA 2009;302:1765-73).

In contrast, the control group showed no such changes, indicating that these alterations could not be attributed to the psychiatric disorder itself or to other aspects of treatment.

“In view of poor physical health outcomes and suboptimal metabolic monitoring in the severely mentally ill, the benefits of second-generation antipsychotic medications must be balanced against their cardiometabolic risks through a careful assessment of the indications for their use, consideration of lower-risk alternatives, and proactive adverse effect monitoring and management,” Dr. Correll and his associates said.

Dr. Correll reported being a consultant or receiving honoraria from AstraZeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly & Co., Intra-Cellular Therapeutics, Medicure, OrthoMcNeill-Janssen, Otsuka, Organon, Pfizer, Schering-Plough, Solvay, Supernus, Vanda, and Wyeth, and serving on the speakers bureau of AstraZeneca, Bristol-Myers Squibb/Otsuka, and Pfizer.

Dr. Varley and Dr. McClellan reported no conflicts.

Children and adolescents rapidly gain substantial weight on a short course of the atypical antipsychotic medications aripiprazole, olanzapine, quetiapine, and risperidone, according to researchers.

Up to 36% of patients in a study of 272 children and adolescents transitioned to overweight or obese status within 11 weeks, and many showed significant abnormalities in lipid profiles and metabolic measures, said Dr. Christoph U. Correll of Zucker Hillside Hospital, Glen Oaks, N.Y., and his associates.

They studied the cardiometabolic effects of atypical antipsychotic agents because they are “commonly and increasingly prescribed to children and adolescents in the United States as first-line treatment for psychotic disorders, bipolar disorder,” and a widening variety of nonpsychotic mental disorders.

Yet they have been linked to weight gain, hypertension, lipid abnormalities, and glucose abnormalities that are a particular concern during development “because they predict adult obesity, the metabolic syndrome, cardiovascular morbidity, and malignancy,” the researchers wrote.

Until now, investigators have been unable to tease out the cardiometabolic effects of atypical antipsychotics in children because the agents have been studied only in subjects already exposed to a variety of other antipsychotic medications.

In an editorial accompanying the report, Dr. Christopher K. Varley and Dr. Jon McClellan of Seattle Children's Hospital observed that “the development of clinically significant hyperlipidemias and insulin resistance after only 12 weeks of treatment portends severe long-term metabolic and cardiovascular sequelae.”

These results “challenge the widespread use of atypical antipsychotic medications in youth,” they added.

When first introduced, atypicals were widely touted as more effective and safer than older neuroleptic agents, which eased physician reticence about prescribing these medications for young patients, they wrote. Before this, traditional antipsychotic medications were far less commonly prescribed for disruptive behavioral disorders (JAMA 2009;302:1811-2).

Much of the data supporting the use of these agents has been provided by industry-sponsored research. “Medical treatment should be dictated by empirical data rather than by anecdote, assumptions, or marketing strategies,” they wrote.

Dr. Correll and his colleagues assessed patients aged 4-19 years who were naive to previous antipsychotic therapy and were participating in a cohort study of pediatric psychotic, mood, or aggressive spectrum disorders. For comparison, they assessed a control group of 15 similar participants who either refused or immediately discontinued atypical antipsychotic agents.

After a median of 11 weeks, all four drugs were associated with weight gain: an average of 8.5 kg for the 45 patients on olanzapine, 6.1 kg for the 36 patients on quetiapine, 5.3 kg for the 135 patients on risperidone, and 4.4 kg for the 41 patients on aripiprazole. More than half the children gained more than 7% of their total body weight.

All the drugs significantly increased fat mass and waist circumference. In all, 10%-36% of patients, depending on which agent they were taking, gained enough weight to shift into overweight or obese status.

Lipid and metabolic abnormalities were not consistent across all four medications. Olanzapine and quetiapine significantly worsened total cholesterol, triglyceride, non–HDL cholesterol, and other lipid measures, while risperidone significantly raised triglycerides. Quetiapine and olanzapine raised the rates of hyperglycemia and metabolic syndrome.

Olanzapine in particular had the largest weight effects, “and also significantly worsened all glucose and lipid parameters, except HDL cholesterol, which is more related to physical activity,” the investigators said (JAMA 2009;302:1765-73).

In contrast, the control group showed no such changes, indicating that these alterations could not be attributed to the psychiatric disorder itself or to other aspects of treatment.

“In view of poor physical health outcomes and suboptimal metabolic monitoring in the severely mentally ill, the benefits of second-generation antipsychotic medications must be balanced against their cardiometabolic risks through a careful assessment of the indications for their use, consideration of lower-risk alternatives, and proactive adverse effect monitoring and management,” Dr. Correll and his associates said.

Dr. Correll reported being a consultant or receiving honoraria from AstraZeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly & Co., Intra-Cellular Therapeutics, Medicure, OrthoMcNeill-Janssen, Otsuka, Organon, Pfizer, Schering-Plough, Solvay, Supernus, Vanda, and Wyeth, and serving on the speakers bureau of AstraZeneca, Bristol-Myers Squibb/Otsuka, and Pfizer.

Dr. Varley and Dr. McClellan reported no conflicts.