Mary Ann Moon

Antipsychotic medications are associated with adverse metabolic and cardiovascular events in children and adolescents who are treated in usual-care settings.

In a retrospective cohort study, children who are treated with antipsychotics, particularly those who were also receiving antidepressants or mood stabilizers, were two to three times more likely than those not taking the drugs to develop metabolic disruption and cardiovascular abnormalities, notably obesity, type 2 diabetes, cardiomegaly, nonspecified heart disease, tachycardia, nonspecified arrhythmia, and orthostatic hypotension/ syncope, said Dr. Roger S. McIntyre of the University of Toronto and his associates.

When assessing the risk-benefit profile of this class of drugs, physicians “need to give careful consideration to possible metabolic disruptions or cardiovascular toxic effects, especially in individuals with comorbid metabolic conditions and those receiving concomitant psychotropic medications,” the investigators said.

They examined adverse events in children and adolescents who were included in the South Carolina Medicaid database in 1996–2005. In all, 4,140 patients were prescribed atypical or conventional antipsychotics (aripiprazole, ziprasidone, quetiapine, risperidone, olanzapine, haloperidol, or fluphena- zine). A random sample of 4,500 children who weren't treated with antipsychotics were controls.

The treated children and adolescents had primary diagnoses of ADHD, conduct disorder, oppositional-defiant disorder, major affective disorder, schizophrenia, and other psychotic disorders. Comorbid conditions included convulsions, CNS disorder, organic brain syndrome, severe mental retardation, substance-related disorder, and congenital heart defects. Nearly 80% of these patients were concomitantly taking antidepressants that can induce weight gain, and many were taking psychostimulants, SSRIs, and mood stabilizers.

Compared with controls, the patients who were treated with antipsychotics were more likely to develop obesity (odds ratio, 2.13), type 2 diabetes (OR, 3.23), cardiovascular conditions (OR, 2.70), and orthostatic hypotension (OR, 1.64). Girls, adolescents, and patients on combination therapy were at highest risk of these adverse effects, the authors said (Arch. Pediatr. Adolesc. Med. 2008;162:929-35).

“Of major public health concern is that, by the end of the study period, 25% of the sample had [one to three] comorbid chronic medical conditions (metabolic and cardiovascular) in addition to their psychiatric disorder,” they added. “We can speculate that the antipsychotic treatment may have predisposed or exacerbated metabolic changes subsequently leading to cardiovascular events. Other hypothetical mechanisms could be ECG changes (such as QT-interval prolongation), procoagulation effects, or direct effects on blood pressure via adrenoreceptor antagonism.

Dr. McIntyre has received research grants from, served on advisory boards of, served on speakers bureaus of, and participated in CME activities of, Eli Lilly & Co., the Stanley Medical Research Institute, the National Alliance for Research on Schizophrenia and Depression, AstraZeneca, Biovail Corp., Bristol-Myers Squibb Co., the France Foundation, GlaxoSmithKline, Janssen-Ortho Inc., Organon, Lundbeck, Pfizer Inc., Solvay/Wyeth, Shire PLC, 13CME, and Physicians Postgraduate Press Inc.

Antipsychotic medications are associated with adverse metabolic and cardiovascular events in children and adolescents who are treated in usual-care settings.

In a retrospective cohort study, children who are treated with antipsychotics, particularly those who were also receiving antidepressants or mood stabilizers, were two to three times more likely than those not taking the drugs to develop metabolic disruption and cardiovascular abnormalities, notably obesity, type 2 diabetes, cardiomegaly, nonspecified heart disease, tachycardia, nonspecified arrhythmia, and orthostatic hypotension/ syncope, said Dr. Roger S. McIntyre of the University of Toronto and his associates.

When assessing the risk-benefit profile of this class of drugs, physicians “need to give careful consideration to possible metabolic disruptions or cardiovascular toxic effects, especially in individuals with comorbid metabolic conditions and those receiving concomitant psychotropic medications,” the investigators said.

They examined adverse events in children and adolescents who were included in the South Carolina Medicaid database in 1996–2005. In all, 4,140 patients were prescribed atypical or conventional antipsychotics (aripiprazole, ziprasidone, quetiapine, risperidone, olanzapine, haloperidol, or fluphena- zine). A random sample of 4,500 children who weren't treated with antipsychotics were controls.

The treated children and adolescents had primary diagnoses of ADHD, conduct disorder, oppositional-defiant disorder, major affective disorder, schizophrenia, and other psychotic disorders. Comorbid conditions included convulsions, CNS disorder, organic brain syndrome, severe mental retardation, substance-related disorder, and congenital heart defects. Nearly 80% of these patients were concomitantly taking antidepressants that can induce weight gain, and many were taking psychostimulants, SSRIs, and mood stabilizers.

Compared with controls, the patients who were treated with antipsychotics were more likely to develop obesity (odds ratio, 2.13), type 2 diabetes (OR, 3.23), cardiovascular conditions (OR, 2.70), and orthostatic hypotension (OR, 1.64). Girls, adolescents, and patients on combination therapy were at highest risk of these adverse effects, the authors said (Arch. Pediatr. Adolesc. Med. 2008;162:929-35).

“Of major public health concern is that, by the end of the study period, 25% of the sample had [one to three] comorbid chronic medical conditions (metabolic and cardiovascular) in addition to their psychiatric disorder,” they added. “We can speculate that the antipsychotic treatment may have predisposed or exacerbated metabolic changes subsequently leading to cardiovascular events. Other hypothetical mechanisms could be ECG changes (such as QT-interval prolongation), procoagulation effects, or direct effects on blood pressure via adrenoreceptor antagonism.

Dr. McIntyre has received research grants from, served on advisory boards of, served on speakers bureaus of, and participated in CME activities of, Eli Lilly & Co., the Stanley Medical Research Institute, the National Alliance for Research on Schizophrenia and Depression, AstraZeneca, Biovail Corp., Bristol-Myers Squibb Co., the France Foundation, GlaxoSmithKline, Janssen-Ortho Inc., Organon, Lundbeck, Pfizer Inc., Solvay/Wyeth, Shire PLC, 13CME, and Physicians Postgraduate Press Inc.

Antipsychotic medications are associated with adverse metabolic and cardiovascular events in children and adolescents who are treated in usual-care settings.

In a retrospective cohort study, children who are treated with antipsychotics, particularly those who were also receiving antidepressants or mood stabilizers, were two to three times more likely than those not taking the drugs to develop metabolic disruption and cardiovascular abnormalities, notably obesity, type 2 diabetes, cardiomegaly, nonspecified heart disease, tachycardia, nonspecified arrhythmia, and orthostatic hypotension/ syncope, said Dr. Roger S. McIntyre of the University of Toronto and his associates.

When assessing the risk-benefit profile of this class of drugs, physicians “need to give careful consideration to possible metabolic disruptions or cardiovascular toxic effects, especially in individuals with comorbid metabolic conditions and those receiving concomitant psychotropic medications,” the investigators said.

They examined adverse events in children and adolescents who were included in the South Carolina Medicaid database in 1996–2005. In all, 4,140 patients were prescribed atypical or conventional antipsychotics (aripiprazole, ziprasidone, quetiapine, risperidone, olanzapine, haloperidol, or fluphena- zine). A random sample of 4,500 children who weren't treated with antipsychotics were controls.

The treated children and adolescents had primary diagnoses of ADHD, conduct disorder, oppositional-defiant disorder, major affective disorder, schizophrenia, and other psychotic disorders. Comorbid conditions included convulsions, CNS disorder, organic brain syndrome, severe mental retardation, substance-related disorder, and congenital heart defects. Nearly 80% of these patients were concomitantly taking antidepressants that can induce weight gain, and many were taking psychostimulants, SSRIs, and mood stabilizers.

Compared with controls, the patients who were treated with antipsychotics were more likely to develop obesity (odds ratio, 2.13), type 2 diabetes (OR, 3.23), cardiovascular conditions (OR, 2.70), and orthostatic hypotension (OR, 1.64). Girls, adolescents, and patients on combination therapy were at highest risk of these adverse effects, the authors said (Arch. Pediatr. Adolesc. Med. 2008;162:929-35).

“Of major public health concern is that, by the end of the study period, 25% of the sample had [one to three] comorbid chronic medical conditions (metabolic and cardiovascular) in addition to their psychiatric disorder,” they added. “We can speculate that the antipsychotic treatment may have predisposed or exacerbated metabolic changes subsequently leading to cardiovascular events. Other hypothetical mechanisms could be ECG changes (such as QT-interval prolongation), procoagulation effects, or direct effects on blood pressure via adrenoreceptor antagonism.

Dr. McIntyre has received research grants from, served on advisory boards of, served on speakers bureaus of, and participated in CME activities of, Eli Lilly & Co., the Stanley Medical Research Institute, the National Alliance for Research on Schizophrenia and Depression, AstraZeneca, Biovail Corp., Bristol-Myers Squibb Co., the France Foundation, GlaxoSmithKline, Janssen-Ortho Inc., Organon, Lundbeck, Pfizer Inc., Solvay/Wyeth, Shire PLC, 13CME, and Physicians Postgraduate Press Inc.

Fewer than half of Medicare patients undergoing elective percutaneous coronary intervention for stable angina had a stress test to document ischemia, according to cohort study of more than 20,000 individuals.

“Without documentation of ischemia, PCIs may have been performed in patients who would not have benefited from the procedure,” Dr. Grace A. Lin of the University of California, San Francisco, and her associates reported.

Guidelines published jointly by the American College of Cardiology, the American Heart Association, and the Society for Cardiovascular Angiography and Intervention state that in patients with stable angina any vessels to be dilated via PCI must be “associated with a moderate to severe degree of ischemia on noninvasive testing.”

Dr. Lin and her colleagues assessed the frequency of stress testing in a cohort of 23,887 Medicare patients treated throughout the United States in 2004.

Overall, only 45% of the patients underwent stress testing within 90 days prior to their elective PCI.

This proportion varied dramatically by geographic region, from 22% in some areas to 71% in others. It was unclear why such variation exists, since stress testing is widely available and there was no correlation with the volume of PCIs done in those geographic regions. This finding shows that “local practice patterns may supersede clinical guidelines and evidence from clinical trials in the decision-making process for patients with stable CAD,” the investigators said (JAMA 2008;300:1765–73).

Younger physicians and those who performed higher volumes of PCIs were less likely than were others to perform stress testing. “This suggests that physician decision making regarding PCI was influenced less by the presence of ischemia, as guidelines suggest, and more by physicians' own biases and community practice patterns,” Dr. Lin and her associates said.

Similarly, certain patient characteristics predicted the use of a stress test. Patients who had previously undergone cardiac catheterization, older patients, and those with comorbidities such as rheumatic or pulmonary disease were less likely to have stress tests. “Although these factors do increase the probability that obstructive CAD is present, evidence of ischemia (not just visualization of anatomy) is crucial in determining if the use of PCI is appropriate,” the researchers noted.

In an editorial comment accompanying this report, Dr. George A. Diamond and Dr. Sanjay Kaul of Cedars-Sinai Medical Center, Los Angeles, said “the analyses that were performed leave the clear impression that referral for PCI was influenced less by objective evidence of ischemia than by incidental factors” (JAMA 2008;300:1817–9).

Fewer than half of Medicare patients undergoing elective percutaneous coronary intervention for stable angina had a stress test to document ischemia, according to cohort study of more than 20,000 individuals.

“Without documentation of ischemia, PCIs may have been performed in patients who would not have benefited from the procedure,” Dr. Grace A. Lin of the University of California, San Francisco, and her associates reported.

Guidelines published jointly by the American College of Cardiology, the American Heart Association, and the Society for Cardiovascular Angiography and Intervention state that in patients with stable angina any vessels to be dilated via PCI must be “associated with a moderate to severe degree of ischemia on noninvasive testing.”

Dr. Lin and her colleagues assessed the frequency of stress testing in a cohort of 23,887 Medicare patients treated throughout the United States in 2004.

Overall, only 45% of the patients underwent stress testing within 90 days prior to their elective PCI.

This proportion varied dramatically by geographic region, from 22% in some areas to 71% in others. It was unclear why such variation exists, since stress testing is widely available and there was no correlation with the volume of PCIs done in those geographic regions. This finding shows that “local practice patterns may supersede clinical guidelines and evidence from clinical trials in the decision-making process for patients with stable CAD,” the investigators said (JAMA 2008;300:1765–73).

Younger physicians and those who performed higher volumes of PCIs were less likely than were others to perform stress testing. “This suggests that physician decision making regarding PCI was influenced less by the presence of ischemia, as guidelines suggest, and more by physicians' own biases and community practice patterns,” Dr. Lin and her associates said.

Similarly, certain patient characteristics predicted the use of a stress test. Patients who had previously undergone cardiac catheterization, older patients, and those with comorbidities such as rheumatic or pulmonary disease were less likely to have stress tests. “Although these factors do increase the probability that obstructive CAD is present, evidence of ischemia (not just visualization of anatomy) is crucial in determining if the use of PCI is appropriate,” the researchers noted.

In an editorial comment accompanying this report, Dr. George A. Diamond and Dr. Sanjay Kaul of Cedars-Sinai Medical Center, Los Angeles, said “the analyses that were performed leave the clear impression that referral for PCI was influenced less by objective evidence of ischemia than by incidental factors” (JAMA 2008;300:1817–9).

Fewer than half of Medicare patients undergoing elective percutaneous coronary intervention for stable angina had a stress test to document ischemia, according to cohort study of more than 20,000 individuals.

“Without documentation of ischemia, PCIs may have been performed in patients who would not have benefited from the procedure,” Dr. Grace A. Lin of the University of California, San Francisco, and her associates reported.

Guidelines published jointly by the American College of Cardiology, the American Heart Association, and the Society for Cardiovascular Angiography and Intervention state that in patients with stable angina any vessels to be dilated via PCI must be “associated with a moderate to severe degree of ischemia on noninvasive testing.”

Dr. Lin and her colleagues assessed the frequency of stress testing in a cohort of 23,887 Medicare patients treated throughout the United States in 2004.

Overall, only 45% of the patients underwent stress testing within 90 days prior to their elective PCI.

This proportion varied dramatically by geographic region, from 22% in some areas to 71% in others. It was unclear why such variation exists, since stress testing is widely available and there was no correlation with the volume of PCIs done in those geographic regions. This finding shows that “local practice patterns may supersede clinical guidelines and evidence from clinical trials in the decision-making process for patients with stable CAD,” the investigators said (JAMA 2008;300:1765–73).

Younger physicians and those who performed higher volumes of PCIs were less likely than were others to perform stress testing. “This suggests that physician decision making regarding PCI was influenced less by the presence of ischemia, as guidelines suggest, and more by physicians' own biases and community practice patterns,” Dr. Lin and her associates said.

Similarly, certain patient characteristics predicted the use of a stress test. Patients who had previously undergone cardiac catheterization, older patients, and those with comorbidities such as rheumatic or pulmonary disease were less likely to have stress tests. “Although these factors do increase the probability that obstructive CAD is present, evidence of ischemia (not just visualization of anatomy) is crucial in determining if the use of PCI is appropriate,” the researchers noted.

In an editorial comment accompanying this report, Dr. George A. Diamond and Dr. Sanjay Kaul of Cedars-Sinai Medical Center, Los Angeles, said “the analyses that were performed leave the clear impression that referral for PCI was influenced less by objective evidence of ischemia than by incidental factors” (JAMA 2008;300:1817–9).

Moderate physical activity improved cognition in people aged 50 years and older who had mild memory impairment, according to findings of a recently reported clinical trial.

The cognitive benefits of a light exercise program–the equivalent of walking for 20 minutes per day–became apparent within 6 months and persisted for an additional year after the exercise intervention was stopped, said Dr. Nicola T. Lautenschlager of the University of Melbourne, and her associates (JAMA 2008;300:1027–37).

The investigators conducted the single-site trial to test whether a 6-month home-based exercise program would help forestall dementia. Research has suggested that people who are physically active are less likely than sedentary people to develop dementia in later life. Studies also have shown that adults with mild memory impairment are more likely than those without it to develop dementia.

Dr. Lautenschlager and her colleagues assessed 170 people aged 50 and older who reported that they had memory problems but showed no dementia. In addition to this subjective memory assessment, 59 subjects were found on objective testing to have amnestic mild cognitive impairment in a single domain, 28 were found to have amnestic mild cognitive impairment in multiple domains, and 15 were found to have nonamnestic mild cognitive impairment.

A total of 85 subjects were randomly assigned to the intervention group and encouraged to perform moderate physical activity (usually walking) in three 50-minute sessions per week. The other 85 served as a control group.

The exercise intervention included a behavioral component with a workshop, a manual and workbook, and periodic newsletters and phone calls to encourage exercising. At the conclusion of the 6-month intervention, subjects in the activity group were walking about 9,000 steps per week more than were subjects in the control group, as assessed by pedometers.

The intervention group showed significantly better delayed recall, lower scores on the Clinical Dementia Rating, and better scores on the Alzheimer's Disease Assessment Scale-Cognitive subscale at 6-, 12-, and 18-month assessments, the investigators said.

Although the average improvement on cognitive testing was “modest,” it was significant and greater than that reported with donepezil (Aricept) therapy. Even a small improvement is important “when one considers the relatively modest amount of physical activity undertaken by participants in the study,” Dr. Lautenschlager and her associates noted.

The mechanism by which physical activity improves brain function is not yet known, but it is possible that exercise improves cerebral vascular functioning and brain perfusion. Other researchers have suggested that physical activity stimulates synaptogenesis and neurogenesis, and also may preserve brain function by attenuating brain responses to stress.

In an accompanying editorial, Dr. Eric B. Larson of Group Health Center for Health Studies, Seattle, said this study, “using rigorous methods, makes the important contribution of 'proof of concept' by establishing that a relatively small dose of habitual exercise modestly improved cognition relative to placebo, and therefore has the potential to help prevent Alzheimer's disease.”

Delaying the onset of dementia, even in a small portion of the population at risk, “can produce a large absolute decline in disease prevalence because of competing sources of mortality–a patient may die of another disease before dementia can develop,” he said (JAMA 2008;300:1077–9).

“If exercise is protective and if its effects can be sustained, presumably with minimal adverse effects and costs, then it becomes an attractive option and perhaps a key strategy to help reduce cognitive morbidity in an increasingly aging society,” he said.

Moderate physical activity improved cognition in people aged 50 years and older who had mild memory impairment, according to findings of a recently reported clinical trial.

The cognitive benefits of a light exercise program–the equivalent of walking for 20 minutes per day–became apparent within 6 months and persisted for an additional year after the exercise intervention was stopped, said Dr. Nicola T. Lautenschlager of the University of Melbourne, and her associates (JAMA 2008;300:1027–37).

The investigators conducted the single-site trial to test whether a 6-month home-based exercise program would help forestall dementia. Research has suggested that people who are physically active are less likely than sedentary people to develop dementia in later life. Studies also have shown that adults with mild memory impairment are more likely than those without it to develop dementia.

Dr. Lautenschlager and her colleagues assessed 170 people aged 50 and older who reported that they had memory problems but showed no dementia. In addition to this subjective memory assessment, 59 subjects were found on objective testing to have amnestic mild cognitive impairment in a single domain, 28 were found to have amnestic mild cognitive impairment in multiple domains, and 15 were found to have nonamnestic mild cognitive impairment.

A total of 85 subjects were randomly assigned to the intervention group and encouraged to perform moderate physical activity (usually walking) in three 50-minute sessions per week. The other 85 served as a control group.

The exercise intervention included a behavioral component with a workshop, a manual and workbook, and periodic newsletters and phone calls to encourage exercising. At the conclusion of the 6-month intervention, subjects in the activity group were walking about 9,000 steps per week more than were subjects in the control group, as assessed by pedometers.

The intervention group showed significantly better delayed recall, lower scores on the Clinical Dementia Rating, and better scores on the Alzheimer's Disease Assessment Scale-Cognitive subscale at 6-, 12-, and 18-month assessments, the investigators said.

Although the average improvement on cognitive testing was “modest,” it was significant and greater than that reported with donepezil (Aricept) therapy. Even a small improvement is important “when one considers the relatively modest amount of physical activity undertaken by participants in the study,” Dr. Lautenschlager and her associates noted.

The mechanism by which physical activity improves brain function is not yet known, but it is possible that exercise improves cerebral vascular functioning and brain perfusion. Other researchers have suggested that physical activity stimulates synaptogenesis and neurogenesis, and also may preserve brain function by attenuating brain responses to stress.

In an accompanying editorial, Dr. Eric B. Larson of Group Health Center for Health Studies, Seattle, said this study, “using rigorous methods, makes the important contribution of 'proof of concept' by establishing that a relatively small dose of habitual exercise modestly improved cognition relative to placebo, and therefore has the potential to help prevent Alzheimer's disease.”

Delaying the onset of dementia, even in a small portion of the population at risk, “can produce a large absolute decline in disease prevalence because of competing sources of mortality–a patient may die of another disease before dementia can develop,” he said (JAMA 2008;300:1077–9).

“If exercise is protective and if its effects can be sustained, presumably with minimal adverse effects and costs, then it becomes an attractive option and perhaps a key strategy to help reduce cognitive morbidity in an increasingly aging society,” he said.

Moderate physical activity improved cognition in people aged 50 years and older who had mild memory impairment, according to findings of a recently reported clinical trial.

The cognitive benefits of a light exercise program–the equivalent of walking for 20 minutes per day–became apparent within 6 months and persisted for an additional year after the exercise intervention was stopped, said Dr. Nicola T. Lautenschlager of the University of Melbourne, and her associates (JAMA 2008;300:1027–37).

The investigators conducted the single-site trial to test whether a 6-month home-based exercise program would help forestall dementia. Research has suggested that people who are physically active are less likely than sedentary people to develop dementia in later life. Studies also have shown that adults with mild memory impairment are more likely than those without it to develop dementia.

Dr. Lautenschlager and her colleagues assessed 170 people aged 50 and older who reported that they had memory problems but showed no dementia. In addition to this subjective memory assessment, 59 subjects were found on objective testing to have amnestic mild cognitive impairment in a single domain, 28 were found to have amnestic mild cognitive impairment in multiple domains, and 15 were found to have nonamnestic mild cognitive impairment.

A total of 85 subjects were randomly assigned to the intervention group and encouraged to perform moderate physical activity (usually walking) in three 50-minute sessions per week. The other 85 served as a control group.

The exercise intervention included a behavioral component with a workshop, a manual and workbook, and periodic newsletters and phone calls to encourage exercising. At the conclusion of the 6-month intervention, subjects in the activity group were walking about 9,000 steps per week more than were subjects in the control group, as assessed by pedometers.

The intervention group showed significantly better delayed recall, lower scores on the Clinical Dementia Rating, and better scores on the Alzheimer's Disease Assessment Scale-Cognitive subscale at 6-, 12-, and 18-month assessments, the investigators said.

Although the average improvement on cognitive testing was “modest,” it was significant and greater than that reported with donepezil (Aricept) therapy. Even a small improvement is important “when one considers the relatively modest amount of physical activity undertaken by participants in the study,” Dr. Lautenschlager and her associates noted.

The mechanism by which physical activity improves brain function is not yet known, but it is possible that exercise improves cerebral vascular functioning and brain perfusion. Other researchers have suggested that physical activity stimulates synaptogenesis and neurogenesis, and also may preserve brain function by attenuating brain responses to stress.

In an accompanying editorial, Dr. Eric B. Larson of Group Health Center for Health Studies, Seattle, said this study, “using rigorous methods, makes the important contribution of 'proof of concept' by establishing that a relatively small dose of habitual exercise modestly improved cognition relative to placebo, and therefore has the potential to help prevent Alzheimer's disease.”

Delaying the onset of dementia, even in a small portion of the population at risk, “can produce a large absolute decline in disease prevalence because of competing sources of mortality–a patient may die of another disease before dementia can develop,” he said (JAMA 2008;300:1077–9).

“If exercise is protective and if its effects can be sustained, presumably with minimal adverse effects and costs, then it becomes an attractive option and perhaps a key strategy to help reduce cognitive morbidity in an increasingly aging society,” he said.

Antipsychotic medications are associated with adverse metabolic and cardiovascular events in children and adolescents who are treated in usual-care settings, according to a report.

In a retrospective cohort study, children who are treated with antipsychotics, particularly those who were also receiving antidepressants or mood stabilizers, were two to three times more likely than those not taking the drugs to develop metabolic disruption and cardiovascular abnormalities, notably obesity, type 2 diabetes, cardiomegaly, nonspecified heart disease, tachycardia, nonspecified arrhythmia, and orthostatic hypotension/syncope, reported Dr. Roger S. McIntyre of the University of Toronto and his associates.

When assessing the risk-benefit profile of this class of drugs, physicians “need to give careful consideration to possible metabolic disruptions or cardiovascular toxic effects, especially in individuals with comorbid metabolic conditions and those receiving concomitant psychotropic medications,” the investigators said.

They examined adverse events among children and adolescents who were included in the South Carolina Medicaid database in 1996–2005. In all, 4,140 patients were prescribed atypical or conventional antipsychotics (aripiprazole, ziprasidone, quetiapine, risperidone, olanzapine, haloperidol, or fluphenazine). A random sample of 4,500 children who were not treated with antipsychotics served as controls.

The treated children and adolescents had primary diagnoses of ADHD, conduct disorder, oppositional-defiant disorder, major affective disorder, schizophrenia, and other psychotic disorders. Comorbid conditions included convulsions, CNS disorder, organic brain syndrome, severe mental retardation, substance-related disorder, and congenital heart defects. Nearly 80% of these patients were concomitantly taking antidepressants that can induce weight gain, and many were taking psychostimulants, SSRIs, and mood stabilizers.

Compared with controls, the patients who were treated with antipsychotics were more likely to develop obesity (odds ratio, 2.13), type 2 diabetes (OR, 3.23), cardiovascular conditions (OR, 2.70), and orthostatic hypotension (OR, 1.64). Girls, adolescents, and patients on combination therapy were at highest risk of these adverse effects, Dr. McIntyre and his associates said (Arch. Pediatr. Adolesc. Med. 2008;162:929–35).

“Of major public health concern is that, by the end of the study period, 25% of the sample had [one to three] comorbid chronic medical conditions (metabolic and cardiovascular) in addition to their psychiatric disorder,” they added.

“We can speculate that the antipsychotic treatment may have predisposed or exacerbated metabolic changes subsequently leading to cardiovascular events. Other hypothetical mechanisms could be ECG changes (such as QT-interval prolongation), procoagulation effects, or direct effects on blood pressure via adrenoreceptor antagonism,” the investigators noted.

The study findings show that “psychiatric and primary care practitioners need to familiarize themselves with the potential for cardiometabolic toxic effects associated with antipsychotics in pediatric populations, and use them sparingly in children displaying early-onset risk factors,” Dr. McIntyre and his colleagues said.

Dr. McIntyre has received research grants from, served on advisory boards of, served on speakers bureaus of, and participated in CME activities of Eli Lilly & Co., the Stanley Medical Research Institute, the National Alliance for Research on Schizophrenia and Depression, AstraZeneca, Biovail Corp., Bristol-Myers Squibb Co., the France Foundation, GlaxoSmithKline, Janssen-Ortho Inc., Organon, Lundbeck, Pfizer Inc., Solvay/Wyeth, Shire PLC, 13CME, and Physicians Postgraduate Press Inc.

Antipsychotic medications are associated with adverse metabolic and cardiovascular events in children and adolescents who are treated in usual-care settings, according to a report.

In a retrospective cohort study, children who are treated with antipsychotics, particularly those who were also receiving antidepressants or mood stabilizers, were two to three times more likely than those not taking the drugs to develop metabolic disruption and cardiovascular abnormalities, notably obesity, type 2 diabetes, cardiomegaly, nonspecified heart disease, tachycardia, nonspecified arrhythmia, and orthostatic hypotension/syncope, reported Dr. Roger S. McIntyre of the University of Toronto and his associates.

When assessing the risk-benefit profile of this class of drugs, physicians “need to give careful consideration to possible metabolic disruptions or cardiovascular toxic effects, especially in individuals with comorbid metabolic conditions and those receiving concomitant psychotropic medications,” the investigators said.

They examined adverse events among children and adolescents who were included in the South Carolina Medicaid database in 1996–2005. In all, 4,140 patients were prescribed atypical or conventional antipsychotics (aripiprazole, ziprasidone, quetiapine, risperidone, olanzapine, haloperidol, or fluphenazine). A random sample of 4,500 children who were not treated with antipsychotics served as controls.

The treated children and adolescents had primary diagnoses of ADHD, conduct disorder, oppositional-defiant disorder, major affective disorder, schizophrenia, and other psychotic disorders. Comorbid conditions included convulsions, CNS disorder, organic brain syndrome, severe mental retardation, substance-related disorder, and congenital heart defects. Nearly 80% of these patients were concomitantly taking antidepressants that can induce weight gain, and many were taking psychostimulants, SSRIs, and mood stabilizers.

Compared with controls, the patients who were treated with antipsychotics were more likely to develop obesity (odds ratio, 2.13), type 2 diabetes (OR, 3.23), cardiovascular conditions (OR, 2.70), and orthostatic hypotension (OR, 1.64). Girls, adolescents, and patients on combination therapy were at highest risk of these adverse effects, Dr. McIntyre and his associates said (Arch. Pediatr. Adolesc. Med. 2008;162:929–35).

“Of major public health concern is that, by the end of the study period, 25% of the sample had [one to three] comorbid chronic medical conditions (metabolic and cardiovascular) in addition to their psychiatric disorder,” they added.

“We can speculate that the antipsychotic treatment may have predisposed or exacerbated metabolic changes subsequently leading to cardiovascular events. Other hypothetical mechanisms could be ECG changes (such as QT-interval prolongation), procoagulation effects, or direct effects on blood pressure via adrenoreceptor antagonism,” the investigators noted.

The study findings show that “psychiatric and primary care practitioners need to familiarize themselves with the potential for cardiometabolic toxic effects associated with antipsychotics in pediatric populations, and use them sparingly in children displaying early-onset risk factors,” Dr. McIntyre and his colleagues said.

Dr. McIntyre has received research grants from, served on advisory boards of, served on speakers bureaus of, and participated in CME activities of Eli Lilly & Co., the Stanley Medical Research Institute, the National Alliance for Research on Schizophrenia and Depression, AstraZeneca, Biovail Corp., Bristol-Myers Squibb Co., the France Foundation, GlaxoSmithKline, Janssen-Ortho Inc., Organon, Lundbeck, Pfizer Inc., Solvay/Wyeth, Shire PLC, 13CME, and Physicians Postgraduate Press Inc.

Antipsychotic medications are associated with adverse metabolic and cardiovascular events in children and adolescents who are treated in usual-care settings, according to a report.

In a retrospective cohort study, children who are treated with antipsychotics, particularly those who were also receiving antidepressants or mood stabilizers, were two to three times more likely than those not taking the drugs to develop metabolic disruption and cardiovascular abnormalities, notably obesity, type 2 diabetes, cardiomegaly, nonspecified heart disease, tachycardia, nonspecified arrhythmia, and orthostatic hypotension/syncope, reported Dr. Roger S. McIntyre of the University of Toronto and his associates.

When assessing the risk-benefit profile of this class of drugs, physicians “need to give careful consideration to possible metabolic disruptions or cardiovascular toxic effects, especially in individuals with comorbid metabolic conditions and those receiving concomitant psychotropic medications,” the investigators said.

They examined adverse events among children and adolescents who were included in the South Carolina Medicaid database in 1996–2005. In all, 4,140 patients were prescribed atypical or conventional antipsychotics (aripiprazole, ziprasidone, quetiapine, risperidone, olanzapine, haloperidol, or fluphenazine). A random sample of 4,500 children who were not treated with antipsychotics served as controls.

The treated children and adolescents had primary diagnoses of ADHD, conduct disorder, oppositional-defiant disorder, major affective disorder, schizophrenia, and other psychotic disorders. Comorbid conditions included convulsions, CNS disorder, organic brain syndrome, severe mental retardation, substance-related disorder, and congenital heart defects. Nearly 80% of these patients were concomitantly taking antidepressants that can induce weight gain, and many were taking psychostimulants, SSRIs, and mood stabilizers.

Compared with controls, the patients who were treated with antipsychotics were more likely to develop obesity (odds ratio, 2.13), type 2 diabetes (OR, 3.23), cardiovascular conditions (OR, 2.70), and orthostatic hypotension (OR, 1.64). Girls, adolescents, and patients on combination therapy were at highest risk of these adverse effects, Dr. McIntyre and his associates said (Arch. Pediatr. Adolesc. Med. 2008;162:929–35).

“Of major public health concern is that, by the end of the study period, 25% of the sample had [one to three] comorbid chronic medical conditions (metabolic and cardiovascular) in addition to their psychiatric disorder,” they added.

“We can speculate that the antipsychotic treatment may have predisposed or exacerbated metabolic changes subsequently leading to cardiovascular events. Other hypothetical mechanisms could be ECG changes (such as QT-interval prolongation), procoagulation effects, or direct effects on blood pressure via adrenoreceptor antagonism,” the investigators noted.

The study findings show that “psychiatric and primary care practitioners need to familiarize themselves with the potential for cardiometabolic toxic effects associated with antipsychotics in pediatric populations, and use them sparingly in children displaying early-onset risk factors,” Dr. McIntyre and his colleagues said.

Dr. McIntyre has received research grants from, served on advisory boards of, served on speakers bureaus of, and participated in CME activities of Eli Lilly & Co., the Stanley Medical Research Institute, the National Alliance for Research on Schizophrenia and Depression, AstraZeneca, Biovail Corp., Bristol-Myers Squibb Co., the France Foundation, GlaxoSmithKline, Janssen-Ortho Inc., Organon, Lundbeck, Pfizer Inc., Solvay/Wyeth, Shire PLC, 13CME, and Physicians Postgraduate Press Inc.

For patients at average risk for colorectal cancer whose initial screening colonoscopy reveals no abnormalities, an interval of 5 years or longer before the next exam appears to be safe.

The 5-year risk of colorectal cancer in such patients is extremely low, and the risk of advanced neoplasms also is low—findings that “provide support for rescreening after an interval of 5 years or longer,” said Dr. Thomas F. Imperiale, professor of medicine, Indiana University, Indianapolis, and his associates.

They studied 1,256 middle-aged people at average risk for colorectal cancer who had undergone initial screening colonoscopy with 36 gastroenterologists in Indiana between 1995 and 2000. A total of 1,057 subjects had no polyps, and 199 had only hyperplastic polyps at that time.

No cancers were discovered 5 years later at follow-up colonoscopy at a mean age of 57 years. But 201 subjects (16%) had neoplastic polyps at rescreening, including 16 (1.3%) with advanced neoplasms. These results are similar to those of previous studies of rescreening among people with normal findings on baseline colonoscopy, the researchers said (N. Engl. J. Med. 2008;359:1218–24).

In an editorial, Dr. Robert H. Fletcher, professor emeritus at Harvard Medical School, Boston, said that even though intervals of 5–10 years between screenings have been recommended, “in clinical practice, intervals between colonoscopic examinations have apparently not reflected the evidence. In a survey, endoscopists in the United States said they performed follow-up colonoscopies at substantially shorter intervals than those recommended by expert groups. Perhaps with stronger evidence that longer intervals are safe, practicing endoscopists will be persuaded to extend the time between colonoscopic examinations,” Dr. Fletcher said (N. Engl. J. Med. 2008;359:1285–7).

Dr. Imperiale's study involved employees, retirees, and dependents of Eli Lilly & Co. The study was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases, and no potential conflict of interest was noted. Dr. Fletcher reports serving as a paid consultant for Exact Sciences.

For patients at average risk for colorectal cancer whose initial screening colonoscopy reveals no abnormalities, an interval of 5 years or longer before the next exam appears to be safe.

The 5-year risk of colorectal cancer in such patients is extremely low, and the risk of advanced neoplasms also is low—findings that “provide support for rescreening after an interval of 5 years or longer,” said Dr. Thomas F. Imperiale, professor of medicine, Indiana University, Indianapolis, and his associates.

They studied 1,256 middle-aged people at average risk for colorectal cancer who had undergone initial screening colonoscopy with 36 gastroenterologists in Indiana between 1995 and 2000. A total of 1,057 subjects had no polyps, and 199 had only hyperplastic polyps at that time.

No cancers were discovered 5 years later at follow-up colonoscopy at a mean age of 57 years. But 201 subjects (16%) had neoplastic polyps at rescreening, including 16 (1.3%) with advanced neoplasms. These results are similar to those of previous studies of rescreening among people with normal findings on baseline colonoscopy, the researchers said (N. Engl. J. Med. 2008;359:1218–24).

In an editorial, Dr. Robert H. Fletcher, professor emeritus at Harvard Medical School, Boston, said that even though intervals of 5–10 years between screenings have been recommended, “in clinical practice, intervals between colonoscopic examinations have apparently not reflected the evidence. In a survey, endoscopists in the United States said they performed follow-up colonoscopies at substantially shorter intervals than those recommended by expert groups. Perhaps with stronger evidence that longer intervals are safe, practicing endoscopists will be persuaded to extend the time between colonoscopic examinations,” Dr. Fletcher said (N. Engl. J. Med. 2008;359:1285–7).

Dr. Imperiale's study involved employees, retirees, and dependents of Eli Lilly & Co. The study was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases, and no potential conflict of interest was noted. Dr. Fletcher reports serving as a paid consultant for Exact Sciences.

For patients at average risk for colorectal cancer whose initial screening colonoscopy reveals no abnormalities, an interval of 5 years or longer before the next exam appears to be safe.

The 5-year risk of colorectal cancer in such patients is extremely low, and the risk of advanced neoplasms also is low—findings that “provide support for rescreening after an interval of 5 years or longer,” said Dr. Thomas F. Imperiale, professor of medicine, Indiana University, Indianapolis, and his associates.

They studied 1,256 middle-aged people at average risk for colorectal cancer who had undergone initial screening colonoscopy with 36 gastroenterologists in Indiana between 1995 and 2000. A total of 1,057 subjects had no polyps, and 199 had only hyperplastic polyps at that time.

No cancers were discovered 5 years later at follow-up colonoscopy at a mean age of 57 years. But 201 subjects (16%) had neoplastic polyps at rescreening, including 16 (1.3%) with advanced neoplasms. These results are similar to those of previous studies of rescreening among people with normal findings on baseline colonoscopy, the researchers said (N. Engl. J. Med. 2008;359:1218–24).

In an editorial, Dr. Robert H. Fletcher, professor emeritus at Harvard Medical School, Boston, said that even though intervals of 5–10 years between screenings have been recommended, “in clinical practice, intervals between colonoscopic examinations have apparently not reflected the evidence. In a survey, endoscopists in the United States said they performed follow-up colonoscopies at substantially shorter intervals than those recommended by expert groups. Perhaps with stronger evidence that longer intervals are safe, practicing endoscopists will be persuaded to extend the time between colonoscopic examinations,” Dr. Fletcher said (N. Engl. J. Med. 2008;359:1285–7).

Dr. Imperiale's study involved employees, retirees, and dependents of Eli Lilly & Co. The study was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases, and no potential conflict of interest was noted. Dr. Fletcher reports serving as a paid consultant for Exact Sciences.

For patients at average risk for colorectal cancer whose initial screening colonoscopy reveals no abnormalities, an interval of 5 years or longer before the next exam appears to be safe.

The 5-year risk of colorectal cancer in such patients is extremely low, and the risk of advanced neoplasms also is low—findings that “provide support for rescreening after an interval of 5 years or longer,” said Dr. Thomas F. Imperiale of the Indiana University, Indianapolis, and his associates.

The investigators determined the incidences of any neoplasia and of advanced neoplasia at 5-year rescreening colonoscopy in a population of 1,256 middle-age people at average risk for colorectal cancer. The study subjects had undergone initial screening colonoscopy with 36 gastroenterologists at seven clinical centers in Indiana between 1995 and 2000. A total of 1,057 subjects had no polyps, and 199 had only hyperplastic polyps at that time.

Five years later, they underwent follow-up colonoscopy at a mean age of 57 years. No cancers were discovered.

However, 201 subjects (16%) had neoplastic polyps at rescreening. Sixteen subjects (1.3%) had advanced neoplasms at rescreening. These results are similar to those of previous studies of interval rescreening among people with normal findings on baseline colonoscopy (N. Engl. J. Med. 2008;359:1218-24).

In an editorial comment, Dr. Robert H. Fletcher, professor emeritus at Harvard Medical School, Boston, said that even though intervals of 5–10 years between screenings have been recommended, “in clinical practice, intervals between colonoscopic examinations have apparently not reflected the evidence.

“In a survey, endoscopists in the United States said they performed follow-up colonoscopies at substantially shorter intervals than those recommended by expert groups,” Dr. Fletcher said (N. Engl. J. Med. 2008;359:1285-7).

The study was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases, and no potential conflict of interest was noted. Dr. Fletcher reports serving as a paid consultant for Exact Sciences.

For patients at average risk for colorectal cancer whose initial screening colonoscopy reveals no abnormalities, an interval of 5 years or longer before the next exam appears to be safe.

The 5-year risk of colorectal cancer in such patients is extremely low, and the risk of advanced neoplasms also is low—findings that “provide support for rescreening after an interval of 5 years or longer,” said Dr. Thomas F. Imperiale of the Indiana University, Indianapolis, and his associates.

The investigators determined the incidences of any neoplasia and of advanced neoplasia at 5-year rescreening colonoscopy in a population of 1,256 middle-age people at average risk for colorectal cancer. The study subjects had undergone initial screening colonoscopy with 36 gastroenterologists at seven clinical centers in Indiana between 1995 and 2000. A total of 1,057 subjects had no polyps, and 199 had only hyperplastic polyps at that time.

Five years later, they underwent follow-up colonoscopy at a mean age of 57 years. No cancers were discovered.

However, 201 subjects (16%) had neoplastic polyps at rescreening. Sixteen subjects (1.3%) had advanced neoplasms at rescreening. These results are similar to those of previous studies of interval rescreening among people with normal findings on baseline colonoscopy (N. Engl. J. Med. 2008;359:1218-24).

In an editorial comment, Dr. Robert H. Fletcher, professor emeritus at Harvard Medical School, Boston, said that even though intervals of 5–10 years between screenings have been recommended, “in clinical practice, intervals between colonoscopic examinations have apparently not reflected the evidence.

“In a survey, endoscopists in the United States said they performed follow-up colonoscopies at substantially shorter intervals than those recommended by expert groups,” Dr. Fletcher said (N. Engl. J. Med. 2008;359:1285-7).

The study was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases, and no potential conflict of interest was noted. Dr. Fletcher reports serving as a paid consultant for Exact Sciences.

For patients at average risk for colorectal cancer whose initial screening colonoscopy reveals no abnormalities, an interval of 5 years or longer before the next exam appears to be safe.

The 5-year risk of colorectal cancer in such patients is extremely low, and the risk of advanced neoplasms also is low—findings that “provide support for rescreening after an interval of 5 years or longer,” said Dr. Thomas F. Imperiale of the Indiana University, Indianapolis, and his associates.

The investigators determined the incidences of any neoplasia and of advanced neoplasia at 5-year rescreening colonoscopy in a population of 1,256 middle-age people at average risk for colorectal cancer. The study subjects had undergone initial screening colonoscopy with 36 gastroenterologists at seven clinical centers in Indiana between 1995 and 2000. A total of 1,057 subjects had no polyps, and 199 had only hyperplastic polyps at that time.

Five years later, they underwent follow-up colonoscopy at a mean age of 57 years. No cancers were discovered.

However, 201 subjects (16%) had neoplastic polyps at rescreening. Sixteen subjects (1.3%) had advanced neoplasms at rescreening. These results are similar to those of previous studies of interval rescreening among people with normal findings on baseline colonoscopy (N. Engl. J. Med. 2008;359:1218-24).

In an editorial comment, Dr. Robert H. Fletcher, professor emeritus at Harvard Medical School, Boston, said that even though intervals of 5–10 years between screenings have been recommended, “in clinical practice, intervals between colonoscopic examinations have apparently not reflected the evidence.

“In a survey, endoscopists in the United States said they performed follow-up colonoscopies at substantially shorter intervals than those recommended by expert groups,” Dr. Fletcher said (N. Engl. J. Med. 2008;359:1285-7).

The study was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases, and no potential conflict of interest was noted. Dr. Fletcher reports serving as a paid consultant for Exact Sciences.

An estimated 25% of women in the United States have pelvic floor disorders including urinary incontinence, pelvic organ prolapse, and fecal incontinence, according to national survey results.

The prevalence of these disorders rises with increasing age and parity, so that as many as one-third of older women may be affected, said Dr. Ingrid Nygaard of the University of Utah, Salt Lake City, and associates.

The results are based on responses of a nationally representative sample of 1,961 nonpregnant women aged 20 years and older, included in the 2005–2006 National Health and Nutrition Examination Survey. The survey is conducted by the Centers for Disease Control and Prevention. Until now, no national survey has assessed the prevalence of moderate to severe pelvic floor disorders in these patients. Only moderate to severe symptoms were included in this analysis: at least weekly urinary leakage or leakage of substantial urinary volumes; at least monthly leakage of solid, liquid, or mucous stool; and/or seeing or feeling a bulge or “something falling out” in the vaginal area.

Overall, 24% of women reported at least one such symptom. Approximately 16% reported urinary incontinence, 9% reported fecal incontinence, and 3% reported pelvic organ prolapse, the investigators said (JAMA 2008;300:1311-6). Participants were interviewed in their homes and then were given standardized physical examinations in a mobile examination center.

The proportion of affected women rose with age. The prevalence was approximately 10% among women in their 20s and 30s, 27% among those in their 40s and 50s, 37% among women in their 60s and 70s, and 50% among women aged 80 years and older.

Women with more body mass and higher parity were more likely to have pelvic floor disorders than were women of less body mass and lower parity.

These prevalences are likely to be underestimates because the analysis excluded women who already had been treated for pelvic floor disorders. The analysis also used conservative definitions of leakage. Moreover, physical examination of a study subset showed that the prevalence of physically diagnosed pelvic organ prolapse was greater than that diagnosed by symptoms only.

The study findings indicate that as the population of older women increases, “the national burden related to pelvic floor disorders in terms of health care costs, lost productivity, and decreased quality of life will be substantial,” Dr. Nygaard and her associates noted.

This study was funded by a variety of grants from public institutions.

An estimated 25% of women in the United States have pelvic floor disorders including urinary incontinence, pelvic organ prolapse, and fecal incontinence, according to national survey results.

The prevalence of these disorders rises with increasing age and parity, so that as many as one-third of older women may be affected, said Dr. Ingrid Nygaard of the University of Utah, Salt Lake City, and associates.

The results are based on responses of a nationally representative sample of 1,961 nonpregnant women aged 20 years and older, included in the 2005–2006 National Health and Nutrition Examination Survey. The survey is conducted by the Centers for Disease Control and Prevention. Until now, no national survey has assessed the prevalence of moderate to severe pelvic floor disorders in these patients. Only moderate to severe symptoms were included in this analysis: at least weekly urinary leakage or leakage of substantial urinary volumes; at least monthly leakage of solid, liquid, or mucous stool; and/or seeing or feeling a bulge or “something falling out” in the vaginal area.

Overall, 24% of women reported at least one such symptom. Approximately 16% reported urinary incontinence, 9% reported fecal incontinence, and 3% reported pelvic organ prolapse, the investigators said (JAMA 2008;300:1311-6). Participants were interviewed in their homes and then were given standardized physical examinations in a mobile examination center.

The proportion of affected women rose with age. The prevalence was approximately 10% among women in their 20s and 30s, 27% among those in their 40s and 50s, 37% among women in their 60s and 70s, and 50% among women aged 80 years and older.

Women with more body mass and higher parity were more likely to have pelvic floor disorders than were women of less body mass and lower parity.

These prevalences are likely to be underestimates because the analysis excluded women who already had been treated for pelvic floor disorders. The analysis also used conservative definitions of leakage. Moreover, physical examination of a study subset showed that the prevalence of physically diagnosed pelvic organ prolapse was greater than that diagnosed by symptoms only.

The study findings indicate that as the population of older women increases, “the national burden related to pelvic floor disorders in terms of health care costs, lost productivity, and decreased quality of life will be substantial,” Dr. Nygaard and her associates noted.

This study was funded by a variety of grants from public institutions.

An estimated 25% of women in the United States have pelvic floor disorders including urinary incontinence, pelvic organ prolapse, and fecal incontinence, according to national survey results.

The prevalence of these disorders rises with increasing age and parity, so that as many as one-third of older women may be affected, said Dr. Ingrid Nygaard of the University of Utah, Salt Lake City, and associates.

The results are based on responses of a nationally representative sample of 1,961 nonpregnant women aged 20 years and older, included in the 2005–2006 National Health and Nutrition Examination Survey. The survey is conducted by the Centers for Disease Control and Prevention. Until now, no national survey has assessed the prevalence of moderate to severe pelvic floor disorders in these patients. Only moderate to severe symptoms were included in this analysis: at least weekly urinary leakage or leakage of substantial urinary volumes; at least monthly leakage of solid, liquid, or mucous stool; and/or seeing or feeling a bulge or “something falling out” in the vaginal area.

Overall, 24% of women reported at least one such symptom. Approximately 16% reported urinary incontinence, 9% reported fecal incontinence, and 3% reported pelvic organ prolapse, the investigators said (JAMA 2008;300:1311-6). Participants were interviewed in their homes and then were given standardized physical examinations in a mobile examination center.

The proportion of affected women rose with age. The prevalence was approximately 10% among women in their 20s and 30s, 27% among those in their 40s and 50s, 37% among women in their 60s and 70s, and 50% among women aged 80 years and older.

Women with more body mass and higher parity were more likely to have pelvic floor disorders than were women of less body mass and lower parity.

These prevalences are likely to be underestimates because the analysis excluded women who already had been treated for pelvic floor disorders. The analysis also used conservative definitions of leakage. Moreover, physical examination of a study subset showed that the prevalence of physically diagnosed pelvic organ prolapse was greater than that diagnosed by symptoms only.

The study findings indicate that as the population of older women increases, “the national burden related to pelvic floor disorders in terms of health care costs, lost productivity, and decreased quality of life will be substantial,” Dr. Nygaard and her associates noted.

This study was funded by a variety of grants from public institutions.

Both continuous positive airway pressure (CPAP) and noninvasive intermittent positive-pressure ventilation (NIPPV) yield earlier resolution of dyspnea, respiratory distress, and metabolic abnormalities than does standard oxygen therapy in patients hospitalized with acute cardiogenic pulmonary edema, according to a report.

However, those treatments did not affect short-term mortality, the primary objective of the Cardiogenic Pulmonary Oedema (3CPO) trial.

Nonetheless, because of the clinical improvements, “We recommend that CPAP or NIPPV be considered as adjunctive therapy in patients with acute cardiogenic pulmonary edema who have severe respiratory distress or whose condition does not improve with pharmacologic therapy,” said Dr. Alasdair Gray of the Royal Infirmary of Edinburgh and his associates.

CPAP maintains the same positive airway pressure support throughout the respiratory cycle; NIPPV raises airway pressure more during inspiration than expiration. Both methods, which deliver oxygen through a face mask, have shown benefit in case series or small trials that have been conducted primarily at single centers. “Therefore, it is uncertain whether these results are either generalizable or robust,” Dr. Gray and his colleagues noted.

3CPO was a large, randomized, controlled trial in 26 emergency departments throughout the United Kingdom that compared the two techniques against standard oxygen therapy and against each other. A total of 367 patients were randomly assigned to standard oxygen therapy, 346 to CPAP, and 356 to NIPPV.

The mean patient age was 78 years, and subjects had marked tachycardia, tachypnea, hypertension, acidosis, and hypercapnia.

Both CPAP and NIPPV yielded greater reductions in dyspnea, heart rate, acidosis, and hypercapnia than did standard oxygen therapy, and the two methods performed similarly, the investigators said (N. Engl. J. Med. 2008;359:142-51).

Standard oxygen therapy was associated with a greater rate of failure due to respiratory distress, while both CPAP and NIPPV were associated with higher rates of noncompletion due to patient discomfort.

There were similar rates of tracheal intubation, admission to the critical care unit, and myocardial infarction among the three groups.

Unfortunately, there were no significant differences among the three groups in the primary end point of 7-day mortality, which was 9.5% with CPAP and NIPPV and 9.8% with standard oxygen therapy. The rates of 30-day mortality also were not significantly different (16.4% with CPAP and NIPPV vs 15.2% with oxygen).

Thus, early improvements in symptoms and surrogate measures of disease severity did not translate into improved short-term or long-term mortality for the two new techniques.

Previous trials have indicated that the physiologic improvements seen with noninvasive ventilation caused a reduced use of tracheal intubation, but this benefit was not observed in this study, Dr. Gray and his associates said.

Both continuous positive airway pressure (CPAP) and noninvasive intermittent positive-pressure ventilation (NIPPV) yield earlier resolution of dyspnea, respiratory distress, and metabolic abnormalities than does standard oxygen therapy in patients hospitalized with acute cardiogenic pulmonary edema, according to a report.

However, those treatments did not affect short-term mortality, the primary objective of the Cardiogenic Pulmonary Oedema (3CPO) trial.

Nonetheless, because of the clinical improvements, “We recommend that CPAP or NIPPV be considered as adjunctive therapy in patients with acute cardiogenic pulmonary edema who have severe respiratory distress or whose condition does not improve with pharmacologic therapy,” said Dr. Alasdair Gray of the Royal Infirmary of Edinburgh and his associates.

CPAP maintains the same positive airway pressure support throughout the respiratory cycle; NIPPV raises airway pressure more during inspiration than expiration. Both methods, which deliver oxygen through a face mask, have shown benefit in case series or small trials that have been conducted primarily at single centers. “Therefore, it is uncertain whether these results are either generalizable or robust,” Dr. Gray and his colleagues noted.

3CPO was a large, randomized, controlled trial in 26 emergency departments throughout the United Kingdom that compared the two techniques against standard oxygen therapy and against each other. A total of 367 patients were randomly assigned to standard oxygen therapy, 346 to CPAP, and 356 to NIPPV.

The mean patient age was 78 years, and subjects had marked tachycardia, tachypnea, hypertension, acidosis, and hypercapnia.

Both CPAP and NIPPV yielded greater reductions in dyspnea, heart rate, acidosis, and hypercapnia than did standard oxygen therapy, and the two methods performed similarly, the investigators said (N. Engl. J. Med. 2008;359:142-51).

Standard oxygen therapy was associated with a greater rate of failure due to respiratory distress, while both CPAP and NIPPV were associated with higher rates of noncompletion due to patient discomfort.

There were similar rates of tracheal intubation, admission to the critical care unit, and myocardial infarction among the three groups.

Unfortunately, there were no significant differences among the three groups in the primary end point of 7-day mortality, which was 9.5% with CPAP and NIPPV and 9.8% with standard oxygen therapy. The rates of 30-day mortality also were not significantly different (16.4% with CPAP and NIPPV vs 15.2% with oxygen).

Thus, early improvements in symptoms and surrogate measures of disease severity did not translate into improved short-term or long-term mortality for the two new techniques.

Previous trials have indicated that the physiologic improvements seen with noninvasive ventilation caused a reduced use of tracheal intubation, but this benefit was not observed in this study, Dr. Gray and his associates said.

Both continuous positive airway pressure (CPAP) and noninvasive intermittent positive-pressure ventilation (NIPPV) yield earlier resolution of dyspnea, respiratory distress, and metabolic abnormalities than does standard oxygen therapy in patients hospitalized with acute cardiogenic pulmonary edema, according to a report.

However, those treatments did not affect short-term mortality, the primary objective of the Cardiogenic Pulmonary Oedema (3CPO) trial.

Nonetheless, because of the clinical improvements, “We recommend that CPAP or NIPPV be considered as adjunctive therapy in patients with acute cardiogenic pulmonary edema who have severe respiratory distress or whose condition does not improve with pharmacologic therapy,” said Dr. Alasdair Gray of the Royal Infirmary of Edinburgh and his associates.

CPAP maintains the same positive airway pressure support throughout the respiratory cycle; NIPPV raises airway pressure more during inspiration than expiration. Both methods, which deliver oxygen through a face mask, have shown benefit in case series or small trials that have been conducted primarily at single centers. “Therefore, it is uncertain whether these results are either generalizable or robust,” Dr. Gray and his colleagues noted.

3CPO was a large, randomized, controlled trial in 26 emergency departments throughout the United Kingdom that compared the two techniques against standard oxygen therapy and against each other. A total of 367 patients were randomly assigned to standard oxygen therapy, 346 to CPAP, and 356 to NIPPV.

The mean patient age was 78 years, and subjects had marked tachycardia, tachypnea, hypertension, acidosis, and hypercapnia.

Both CPAP and NIPPV yielded greater reductions in dyspnea, heart rate, acidosis, and hypercapnia than did standard oxygen therapy, and the two methods performed similarly, the investigators said (N. Engl. J. Med. 2008;359:142-51).

Standard oxygen therapy was associated with a greater rate of failure due to respiratory distress, while both CPAP and NIPPV were associated with higher rates of noncompletion due to patient discomfort.

There were similar rates of tracheal intubation, admission to the critical care unit, and myocardial infarction among the three groups.

Unfortunately, there were no significant differences among the three groups in the primary end point of 7-day mortality, which was 9.5% with CPAP and NIPPV and 9.8% with standard oxygen therapy. The rates of 30-day mortality also were not significantly different (16.4% with CPAP and NIPPV vs 15.2% with oxygen).

Thus, early improvements in symptoms and surrogate measures of disease severity did not translate into improved short-term or long-term mortality for the two new techniques.

Previous trials have indicated that the physiologic improvements seen with noninvasive ventilation caused a reduced use of tracheal intubation, but this benefit was not observed in this study, Dr. Gray and his associates said.

Two gene variants were found to confer risk for obesity, but that risk was offset by an intensely physical lifestyle in a study of an Amish community.

The findings suggest that in people genetically predisposed to obesity, high levels of physical activity can blunt that predisposition, said Evadnie Rampersaud, Ph.D., of the University of Maryland, Baltimore, and her associates. They performed DNA analysis of blood samples from an Old Order Amish population in Pennsylvania. The 704 subjects had also provided an objective measurement of physical activity by wearing an activity monitor for 1 week.

Members of the order eschew many modern conveniences and their daily lives tend to be physically demanding. Their mean age was 44 years. Prevalence of overweight was 54% and of obesity, 10%, in men; and 64% and 30%, respectively, in women.

The researchers analyzed 92 single-nucleotide polymorphisms (SNPs) located in an interval that spanned the FTO (fat mass and obesity-associated) gene and found two that significantly correlated with obesity. One of these, the A allele for rs1861868, was already known to confer a predisposition for obesity. The second SNP, the C allele of rs1477196, has not been associated with obesity before, they said (Arch. Intern. Med. 2008;168:1791–7).

When the subjects were stratified by level of physical activity, these variants were significantly associated with greater body mass index only in the 361 subjects with low levels of physical activity. High levels of physical activity in the remaining subjects seemed to blunt the association between the two alleles and obesity.

Mean activity levels in the high-activity group were about 900 kcal greater than those in the low-activity group, corresponding to about 3–4 hours of moderately intensive daily activity.

Two gene variants were found to confer risk for obesity, but that risk was offset by an intensely physical lifestyle in a study of an Amish community.

The findings suggest that in people genetically predisposed to obesity, high levels of physical activity can blunt that predisposition, said Evadnie Rampersaud, Ph.D., of the University of Maryland, Baltimore, and her associates. They performed DNA analysis of blood samples from an Old Order Amish population in Pennsylvania. The 704 subjects had also provided an objective measurement of physical activity by wearing an activity monitor for 1 week.

Members of the order eschew many modern conveniences and their daily lives tend to be physically demanding. Their mean age was 44 years. Prevalence of overweight was 54% and of obesity, 10%, in men; and 64% and 30%, respectively, in women.

The researchers analyzed 92 single-nucleotide polymorphisms (SNPs) located in an interval that spanned the FTO (fat mass and obesity-associated) gene and found two that significantly correlated with obesity. One of these, the A allele for rs1861868, was already known to confer a predisposition for obesity. The second SNP, the C allele of rs1477196, has not been associated with obesity before, they said (Arch. Intern. Med. 2008;168:1791–7).

When the subjects were stratified by level of physical activity, these variants were significantly associated with greater body mass index only in the 361 subjects with low levels of physical activity. High levels of physical activity in the remaining subjects seemed to blunt the association between the two alleles and obesity.

Mean activity levels in the high-activity group were about 900 kcal greater than those in the low-activity group, corresponding to about 3–4 hours of moderately intensive daily activity.

Two gene variants were found to confer risk for obesity, but that risk was offset by an intensely physical lifestyle in a study of an Amish community.

The findings suggest that in people genetically predisposed to obesity, high levels of physical activity can blunt that predisposition, said Evadnie Rampersaud, Ph.D., of the University of Maryland, Baltimore, and her associates. They performed DNA analysis of blood samples from an Old Order Amish population in Pennsylvania. The 704 subjects had also provided an objective measurement of physical activity by wearing an activity monitor for 1 week.

Members of the order eschew many modern conveniences and their daily lives tend to be physically demanding. Their mean age was 44 years. Prevalence of overweight was 54% and of obesity, 10%, in men; and 64% and 30%, respectively, in women.

The researchers analyzed 92 single-nucleotide polymorphisms (SNPs) located in an interval that spanned the FTO (fat mass and obesity-associated) gene and found two that significantly correlated with obesity. One of these, the A allele for rs1861868, was already known to confer a predisposition for obesity. The second SNP, the C allele of rs1477196, has not been associated with obesity before, they said (Arch. Intern. Med. 2008;168:1791–7).

When the subjects were stratified by level of physical activity, these variants were significantly associated with greater body mass index only in the 361 subjects with low levels of physical activity. High levels of physical activity in the remaining subjects seemed to blunt the association between the two alleles and obesity.

Mean activity levels in the high-activity group were about 900 kcal greater than those in the low-activity group, corresponding to about 3–4 hours of moderately intensive daily activity.

Mortality rates of people infected with HIV now approach those of the general population, at least for the first 5 years of the infection, according to a large multinational study.

The gap in mortality rates between people with HIV infection and the general population has narrowed every year since the introduction of highly active antiretroviral therapy (HAART) in 1996, the study investigators reported.

This represents a 94% reduction in excess mortality in recent years, as compared with the time before HAART was available.

However, there still appears to be an excess in mortality as the duration of HIV infection increases.

To compare mortality rates, the investigators used a large data set comprising 21 separate cohorts of HIV-infected subjects whose dates of seroconversion (defined as development of serum antibodies as a result of infection) had been pinned down relatively precisely.

These cohorts included 16,534 subjects who were followed for up to 23 years in 10 European countries, Australia, and Canada.

A total of 2,571 of the subjects had died as of the end of 2006, compared with an estimated 235 deaths that would be expected in a matched cohort of individuals from the general population.

The excess in mortality was most marked during the pre-HAART time period and declined dramatically from 1996 onward, said the investigators, led by Krishnan Bhaskaran of the Medical Research Council Clinical Trials Unit, London.

By the end of the study period in 2006, “there was no evidence of any excess mortality to 5 years from seroconversion in any age group,” Mr. Bhaskaran and his associates reported (JAMA 2008;300:51–9).

However, some excess mortality was still evident as the duration of HIV infection in the subjects lengthened to 10 years or more.

“It is likely that, even with current standards of HIV management, some long-term excess mortality would remain because problems of toxicity, resistance, and therapy adherence are likely to increase with time receiving HAART,” they noted.

Mortality was four times as high among subjects who acquired HIV through intravenous drug use than among those who acquired it through sexual contact.

This difference in mortality likely reflects the fact that intravenous drug users are at higher risk than nonusers for mental health-related illness and coinfections, and often have poorer access to and adherence to treatment, the investigators added.

Mortality rates of people infected with HIV now approach those of the general population, at least for the first 5 years of the infection, according to a large multinational study.

The gap in mortality rates between people with HIV infection and the general population has narrowed every year since the introduction of highly active antiretroviral therapy (HAART) in 1996, the study investigators reported.

This represents a 94% reduction in excess mortality in recent years, as compared with the time before HAART was available.

However, there still appears to be an excess in mortality as the duration of HIV infection increases.

To compare mortality rates, the investigators used a large data set comprising 21 separate cohorts of HIV-infected subjects whose dates of seroconversion (defined as development of serum antibodies as a result of infection) had been pinned down relatively precisely.

These cohorts included 16,534 subjects who were followed for up to 23 years in 10 European countries, Australia, and Canada.

A total of 2,571 of the subjects had died as of the end of 2006, compared with an estimated 235 deaths that would be expected in a matched cohort of individuals from the general population.

The excess in mortality was most marked during the pre-HAART time period and declined dramatically from 1996 onward, said the investigators, led by Krishnan Bhaskaran of the Medical Research Council Clinical Trials Unit, London.

By the end of the study period in 2006, “there was no evidence of any excess mortality to 5 years from seroconversion in any age group,” Mr. Bhaskaran and his associates reported (JAMA 2008;300:51–9).

However, some excess mortality was still evident as the duration of HIV infection in the subjects lengthened to 10 years or more.

“It is likely that, even with current standards of HIV management, some long-term excess mortality would remain because problems of toxicity, resistance, and therapy adherence are likely to increase with time receiving HAART,” they noted.

Mortality was four times as high among subjects who acquired HIV through intravenous drug use than among those who acquired it through sexual contact.

This difference in mortality likely reflects the fact that intravenous drug users are at higher risk than nonusers for mental health-related illness and coinfections, and often have poorer access to and adherence to treatment, the investigators added.

Mortality rates of people infected with HIV now approach those of the general population, at least for the first 5 years of the infection, according to a large multinational study.

The gap in mortality rates between people with HIV infection and the general population has narrowed every year since the introduction of highly active antiretroviral therapy (HAART) in 1996, the study investigators reported.

This represents a 94% reduction in excess mortality in recent years, as compared with the time before HAART was available.

However, there still appears to be an excess in mortality as the duration of HIV infection increases.

To compare mortality rates, the investigators used a large data set comprising 21 separate cohorts of HIV-infected subjects whose dates of seroconversion (defined as development of serum antibodies as a result of infection) had been pinned down relatively precisely.

These cohorts included 16,534 subjects who were followed for up to 23 years in 10 European countries, Australia, and Canada.

A total of 2,571 of the subjects had died as of the end of 2006, compared with an estimated 235 deaths that would be expected in a matched cohort of individuals from the general population.

The excess in mortality was most marked during the pre-HAART time period and declined dramatically from 1996 onward, said the investigators, led by Krishnan Bhaskaran of the Medical Research Council Clinical Trials Unit, London.

By the end of the study period in 2006, “there was no evidence of any excess mortality to 5 years from seroconversion in any age group,” Mr. Bhaskaran and his associates reported (JAMA 2008;300:51–9).

However, some excess mortality was still evident as the duration of HIV infection in the subjects lengthened to 10 years or more.

“It is likely that, even with current standards of HIV management, some long-term excess mortality would remain because problems of toxicity, resistance, and therapy adherence are likely to increase with time receiving HAART,” they noted.

Mortality was four times as high among subjects who acquired HIV through intravenous drug use than among those who acquired it through sexual contact.

This difference in mortality likely reflects the fact that intravenous drug users are at higher risk than nonusers for mental health-related illness and coinfections, and often have poorer access to and adherence to treatment, the investigators added.