Mary Ann Moon

The angiotensin-receptor blocker irbesartan lowered blood pressure modestly but did not reduce cardiovascular events in a study of patients with atrial fibrillation, in the randomized, controlled ACTIVE-I trial reported in the March 10 issue of the New England Journal of Medicine.

Contrary to the study hypothesis, "Among patients with atrial fibrillation, most of whom had well-controlled hypertension and 60% of whom were receiving an ACE inhibitor, the addition of irbesartan did not reduce the risk of death from cardiovascular causes, stroke, or myocardial infarction, or this composite outcome plus hospitalization for heart failure," said Dr. Salim Yusuf of McMaster University and the David Braley Cardiac, Vascular, and Stroke Research Institute at Hamilton (Ont.) Health Sciences, and his associates.

Previous research showed that lowering blood pressure cuts the risk of stroke and heart failure in patients without atrial fibrillation, but no such effect has yet been demonstrated in AF. "We hypothesized that an ARB may prevent cardiovascular events and enhance the maintenance of sinus rhythm in patients with intermittent AF by reducing BP and by special effects related to blockade of the renin-angiotensin-aldosterone system," wrote Dr. Yusuf and his associates in the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE I).

The trial, funded by Bristol-Myers Squibb and Sanofi-Aventis, involved 9,016 AF patients (mean age 70 years) who were randomly assigned to receive once-daily oral irbesartan (4,518 subjects) or a matching placebo (4,498 subjects) and were followed for a mean of 4 years.

Mean blood pressure declined by 6.8/4.5 mm Hg in subjects who received irbesartan, compared with 3.9/2.6 mm Hg, respectively, in the placebo group.

Despite this modest effect, the rate of the first coprimary outcome – a composite of stroke, MI, or death from vascular causes – was identical in both groups, at 5.4% per 100 patient-years. The rate of the second coprimary outcome – the first composite plus hospitalization for heart failure – also was not significantly different, at 7.3% and 7.7% per 100 patient-years with irbesartan and placebo, respectively.

"The only component of the coprimary outcome that showed a nominally significant reduction with irbesartan was a first hospitalization for heart failure," the investigators noted (N. Engl. J. Med. 2011;364:928-38).

There was a nonsignificant numerical trend toward fewer strokes, transient ischemic attacks, and cases of systemic emboli with active treatment.

A subgroup of 1,730 patients who had been in sinus rhythm at baseline were followed for recurrence of AF. Irbesartan had no effect on recurrence in these patients.

"An important observation in ACTIVE I was that hospitalizations for heart failure were more common than stroke in this population of patients with AF, and both increased the risk of death by a factor of 4. This finding suggests that preventing heart failure is as important as preventing strokes in this population," Dr. Yusuf and his colleagues said.

More subjects in the irbesartan group (127 patients) than in the placebo group (64 patients) discontinued their medication because of hypotension. Renal dysfunction leading to drug discontinuation also was more common with irbesartan (43 patients) than placebo (24 patients). In addition, four patients taking irbesartan required dialysis, while none of those taking placebo did.

ACTIVE-I was funded by Bristol-Myers Squibb and Sanofi-Aventis, which in partnership distribute irbesartan (Avapro). Dr. Yusuf is a consultant to those companies and to AstraZeneca and Boehringer-Ingelheim. Other investigators also reported ties to pharmaceutical companies.

The angiotensin-receptor blocker irbesartan lowered blood pressure modestly but did not reduce cardiovascular events in a study of patients with atrial fibrillation, in the randomized, controlled ACTIVE-I trial reported in the March 10 issue of the New England Journal of Medicine.

Contrary to the study hypothesis, "Among patients with atrial fibrillation, most of whom had well-controlled hypertension and 60% of whom were receiving an ACE inhibitor, the addition of irbesartan did not reduce the risk of death from cardiovascular causes, stroke, or myocardial infarction, or this composite outcome plus hospitalization for heart failure," said Dr. Salim Yusuf of McMaster University and the David Braley Cardiac, Vascular, and Stroke Research Institute at Hamilton (Ont.) Health Sciences, and his associates.

Previous research showed that lowering blood pressure cuts the risk of stroke and heart failure in patients without atrial fibrillation, but no such effect has yet been demonstrated in AF. "We hypothesized that an ARB may prevent cardiovascular events and enhance the maintenance of sinus rhythm in patients with intermittent AF by reducing BP and by special effects related to blockade of the renin-angiotensin-aldosterone system," wrote Dr. Yusuf and his associates in the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE I).

The trial, funded by Bristol-Myers Squibb and Sanofi-Aventis, involved 9,016 AF patients (mean age 70 years) who were randomly assigned to receive once-daily oral irbesartan (4,518 subjects) or a matching placebo (4,498 subjects) and were followed for a mean of 4 years.

Mean blood pressure declined by 6.8/4.5 mm Hg in subjects who received irbesartan, compared with 3.9/2.6 mm Hg, respectively, in the placebo group.

Despite this modest effect, the rate of the first coprimary outcome – a composite of stroke, MI, or death from vascular causes – was identical in both groups, at 5.4% per 100 patient-years. The rate of the second coprimary outcome – the first composite plus hospitalization for heart failure – also was not significantly different, at 7.3% and 7.7% per 100 patient-years with irbesartan and placebo, respectively.

"The only component of the coprimary outcome that showed a nominally significant reduction with irbesartan was a first hospitalization for heart failure," the investigators noted (N. Engl. J. Med. 2011;364:928-38).

There was a nonsignificant numerical trend toward fewer strokes, transient ischemic attacks, and cases of systemic emboli with active treatment.

A subgroup of 1,730 patients who had been in sinus rhythm at baseline were followed for recurrence of AF. Irbesartan had no effect on recurrence in these patients.

"An important observation in ACTIVE I was that hospitalizations for heart failure were more common than stroke in this population of patients with AF, and both increased the risk of death by a factor of 4. This finding suggests that preventing heart failure is as important as preventing strokes in this population," Dr. Yusuf and his colleagues said.

More subjects in the irbesartan group (127 patients) than in the placebo group (64 patients) discontinued their medication because of hypotension. Renal dysfunction leading to drug discontinuation also was more common with irbesartan (43 patients) than placebo (24 patients). In addition, four patients taking irbesartan required dialysis, while none of those taking placebo did.

ACTIVE-I was funded by Bristol-Myers Squibb and Sanofi-Aventis, which in partnership distribute irbesartan (Avapro). Dr. Yusuf is a consultant to those companies and to AstraZeneca and Boehringer-Ingelheim. Other investigators also reported ties to pharmaceutical companies.

The angiotensin-receptor blocker irbesartan lowered blood pressure modestly but did not reduce cardiovascular events in a study of patients with atrial fibrillation, in the randomized, controlled ACTIVE-I trial reported in the March 10 issue of the New England Journal of Medicine.

Contrary to the study hypothesis, "Among patients with atrial fibrillation, most of whom had well-controlled hypertension and 60% of whom were receiving an ACE inhibitor, the addition of irbesartan did not reduce the risk of death from cardiovascular causes, stroke, or myocardial infarction, or this composite outcome plus hospitalization for heart failure," said Dr. Salim Yusuf of McMaster University and the David Braley Cardiac, Vascular, and Stroke Research Institute at Hamilton (Ont.) Health Sciences, and his associates.

Previous research showed that lowering blood pressure cuts the risk of stroke and heart failure in patients without atrial fibrillation, but no such effect has yet been demonstrated in AF. "We hypothesized that an ARB may prevent cardiovascular events and enhance the maintenance of sinus rhythm in patients with intermittent AF by reducing BP and by special effects related to blockade of the renin-angiotensin-aldosterone system," wrote Dr. Yusuf and his associates in the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE I).

The trial, funded by Bristol-Myers Squibb and Sanofi-Aventis, involved 9,016 AF patients (mean age 70 years) who were randomly assigned to receive once-daily oral irbesartan (4,518 subjects) or a matching placebo (4,498 subjects) and were followed for a mean of 4 years.

Mean blood pressure declined by 6.8/4.5 mm Hg in subjects who received irbesartan, compared with 3.9/2.6 mm Hg, respectively, in the placebo group.

Despite this modest effect, the rate of the first coprimary outcome – a composite of stroke, MI, or death from vascular causes – was identical in both groups, at 5.4% per 100 patient-years. The rate of the second coprimary outcome – the first composite plus hospitalization for heart failure – also was not significantly different, at 7.3% and 7.7% per 100 patient-years with irbesartan and placebo, respectively.

"The only component of the coprimary outcome that showed a nominally significant reduction with irbesartan was a first hospitalization for heart failure," the investigators noted (N. Engl. J. Med. 2011;364:928-38).

There was a nonsignificant numerical trend toward fewer strokes, transient ischemic attacks, and cases of systemic emboli with active treatment.

A subgroup of 1,730 patients who had been in sinus rhythm at baseline were followed for recurrence of AF. Irbesartan had no effect on recurrence in these patients.

"An important observation in ACTIVE I was that hospitalizations for heart failure were more common than stroke in this population of patients with AF, and both increased the risk of death by a factor of 4. This finding suggests that preventing heart failure is as important as preventing strokes in this population," Dr. Yusuf and his colleagues said.

More subjects in the irbesartan group (127 patients) than in the placebo group (64 patients) discontinued their medication because of hypotension. Renal dysfunction leading to drug discontinuation also was more common with irbesartan (43 patients) than placebo (24 patients). In addition, four patients taking irbesartan required dialysis, while none of those taking placebo did.

ACTIVE-I was funded by Bristol-Myers Squibb and Sanofi-Aventis, which in partnership distribute irbesartan (Avapro). Dr. Yusuf is a consultant to those companies and to AstraZeneca and Boehringer-Ingelheim. Other investigators also reported ties to pharmaceutical companies.

Smokers with interstitial lung abnormalities on high-resolution CT show both reduced total lung capacity and a lesser amount of emphysema, compared with those who didn’t have interstitial lung abnormalities, according to a report in the March 10 issue of the New England Journal of Medicine.

In addition, the magnitude of these two reductions is greatest among smokers who also have chronic obstructive pulmonary disease (COPD), said Dr. George R. Washko of the pulmonary and critical care division at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and his associates.

"Our findings are consistent with, and add weight to, previous studies showing that cigarette smoking is associated with both spirometric restriction and areas of high attenuation on HRCT. Since emphysema and interstitial lung abnormalities have opposing effects on lung volume, our findings suggest that HRCT may provide important diagnostic information in smokers whose total lung capacity is unexpectedly ‘normal,’ " they noted.

"We speculate that this could be clinically important to physicians who may think that a patient who does not have symptoms or characteristic abnormalities on lung function tests is disease free, when in fact the patient could be affected by two of the consequences of smoking – emphysema and interstitial lung abnormalities," Dr. Washko and his colleagues said.

The investigators examined the relationship among radiographic interstitial lung abnormalities, total lung capacity, and emphysema in a cohort of 2,416 smokers who had been recruited for an ongoing study of COPD being conducted at 21 clinical centers.

The cohort included white (75%) and black (25%) subjects aged 45-80 years who reported a history of at least 10 pack-years of smoking. Slightly more than half of the subjects were men, 44% were still actively smoking, and 41% met criteria for COPD.

The overall prevalence of interstitial lung abnormalities affecting more than 5% of any lung zone on HRCT was 8%. Another 36% of the subjects showed "indeterminate" findings, and 56% showed no interstitial lung abnormalities.

The lung abnormalities included nondependent ground-glass or reticular abnormalities, diffuse centrilobular nodularity, nonemphysematous cysts, honeycombing, and traction bronchiectasis.

Interstitial lung abnormalities were associated with both a decrease in total lung capacity and a lesser amount of emphysema. In addition, there was an inverse relationship between these abnormalities and the severity of COPD, the researchers said (N. Engl. J. Med. 2011;364:897-906).

Further follow-up is needed "to determine whether these radiographic abnormalities, and the associated reductions in lung volumes, are transient or stable, or whether they will progress to clinically significant disease," Dr. Washko and his associates said.

In an editorial accompanying the report, Dr. Talmadge E. King Jr. said that the "long-term implications of this and similar studies using HRCT scans in asymptomatic subjects are unknown. There is the concern that such scans may be overinterpreted, leading to a high rate of unnecessary diagnoses and perhaps unwarranted treatment" (N. Engl. J. Med. 2011;364:968-70). In this study, more than one-third of the HRCT scans were deemed "indeterminate" for the presence of interstitial lung abnormalities, which "probably reflects the fact that the boundary between HRCT images of the lungs in health and disease is blurred," noted Dr. King of the department of medicine at the University of California, San Francisco.

However, he thought it was noteworthy that Dr. Washko and his colleagues found that interstitial lung abnormalities were associated with less radiographic emphysema. "It is interesting to speculate that the pathobiology of smoking can lead to two distinct patterns of injury – emphysema (with destruction of the lung) or interstitial lung disease (with macrophage accumulation and fibrosis).

"Conversely ... the relative lack of emphysema could be simply a reflection of the fact that interstitial lung abnormalities mask emphysema or that more severe emphysema limits the extent of interstitial lung abnormalities," Dr. King said.

This study was supported by the National Institutes of Health and the Parker B. Francis Foundation. Dr. Washko reported ties to MedImmune, and his associates reported ties to Siemens, Actelion, Gilead, InterMune, Novartis, Perceptive Imaging, GE Medical Systems, GlaxoSmithKline, AstraZeneca, Toshiba Medical, and AZE. Dr. King reported ties to Actelion, InterMune, ImmuneWorks, Philips Respironics, CV Therapeutics, and Genzyme.

Smokers with interstitial lung abnormalities on high-resolution CT show both reduced total lung capacity and a lesser amount of emphysema, compared with those who didn’t have interstitial lung abnormalities, according to a report in the March 10 issue of the New England Journal of Medicine.

In addition, the magnitude of these two reductions is greatest among smokers who also have chronic obstructive pulmonary disease (COPD), said Dr. George R. Washko of the pulmonary and critical care division at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and his associates.

"Our findings are consistent with, and add weight to, previous studies showing that cigarette smoking is associated with both spirometric restriction and areas of high attenuation on HRCT. Since emphysema and interstitial lung abnormalities have opposing effects on lung volume, our findings suggest that HRCT may provide important diagnostic information in smokers whose total lung capacity is unexpectedly ‘normal,’ " they noted.

"We speculate that this could be clinically important to physicians who may think that a patient who does not have symptoms or characteristic abnormalities on lung function tests is disease free, when in fact the patient could be affected by two of the consequences of smoking – emphysema and interstitial lung abnormalities," Dr. Washko and his colleagues said.

The investigators examined the relationship among radiographic interstitial lung abnormalities, total lung capacity, and emphysema in a cohort of 2,416 smokers who had been recruited for an ongoing study of COPD being conducted at 21 clinical centers.

The cohort included white (75%) and black (25%) subjects aged 45-80 years who reported a history of at least 10 pack-years of smoking. Slightly more than half of the subjects were men, 44% were still actively smoking, and 41% met criteria for COPD.

The overall prevalence of interstitial lung abnormalities affecting more than 5% of any lung zone on HRCT was 8%. Another 36% of the subjects showed "indeterminate" findings, and 56% showed no interstitial lung abnormalities.

The lung abnormalities included nondependent ground-glass or reticular abnormalities, diffuse centrilobular nodularity, nonemphysematous cysts, honeycombing, and traction bronchiectasis.

Interstitial lung abnormalities were associated with both a decrease in total lung capacity and a lesser amount of emphysema. In addition, there was an inverse relationship between these abnormalities and the severity of COPD, the researchers said (N. Engl. J. Med. 2011;364:897-906).

Further follow-up is needed "to determine whether these radiographic abnormalities, and the associated reductions in lung volumes, are transient or stable, or whether they will progress to clinically significant disease," Dr. Washko and his associates said.

In an editorial accompanying the report, Dr. Talmadge E. King Jr. said that the "long-term implications of this and similar studies using HRCT scans in asymptomatic subjects are unknown. There is the concern that such scans may be overinterpreted, leading to a high rate of unnecessary diagnoses and perhaps unwarranted treatment" (N. Engl. J. Med. 2011;364:968-70). In this study, more than one-third of the HRCT scans were deemed "indeterminate" for the presence of interstitial lung abnormalities, which "probably reflects the fact that the boundary between HRCT images of the lungs in health and disease is blurred," noted Dr. King of the department of medicine at the University of California, San Francisco.

However, he thought it was noteworthy that Dr. Washko and his colleagues found that interstitial lung abnormalities were associated with less radiographic emphysema. "It is interesting to speculate that the pathobiology of smoking can lead to two distinct patterns of injury – emphysema (with destruction of the lung) or interstitial lung disease (with macrophage accumulation and fibrosis).

"Conversely ... the relative lack of emphysema could be simply a reflection of the fact that interstitial lung abnormalities mask emphysema or that more severe emphysema limits the extent of interstitial lung abnormalities," Dr. King said.

This study was supported by the National Institutes of Health and the Parker B. Francis Foundation. Dr. Washko reported ties to MedImmune, and his associates reported ties to Siemens, Actelion, Gilead, InterMune, Novartis, Perceptive Imaging, GE Medical Systems, GlaxoSmithKline, AstraZeneca, Toshiba Medical, and AZE. Dr. King reported ties to Actelion, InterMune, ImmuneWorks, Philips Respironics, CV Therapeutics, and Genzyme.

Smokers with interstitial lung abnormalities on high-resolution CT show both reduced total lung capacity and a lesser amount of emphysema, compared with those who didn’t have interstitial lung abnormalities, according to a report in the March 10 issue of the New England Journal of Medicine.

In addition, the magnitude of these two reductions is greatest among smokers who also have chronic obstructive pulmonary disease (COPD), said Dr. George R. Washko of the pulmonary and critical care division at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and his associates.

"Our findings are consistent with, and add weight to, previous studies showing that cigarette smoking is associated with both spirometric restriction and areas of high attenuation on HRCT. Since emphysema and interstitial lung abnormalities have opposing effects on lung volume, our findings suggest that HRCT may provide important diagnostic information in smokers whose total lung capacity is unexpectedly ‘normal,’ " they noted.

"We speculate that this could be clinically important to physicians who may think that a patient who does not have symptoms or characteristic abnormalities on lung function tests is disease free, when in fact the patient could be affected by two of the consequences of smoking – emphysema and interstitial lung abnormalities," Dr. Washko and his colleagues said.

The investigators examined the relationship among radiographic interstitial lung abnormalities, total lung capacity, and emphysema in a cohort of 2,416 smokers who had been recruited for an ongoing study of COPD being conducted at 21 clinical centers.

The cohort included white (75%) and black (25%) subjects aged 45-80 years who reported a history of at least 10 pack-years of smoking. Slightly more than half of the subjects were men, 44% were still actively smoking, and 41% met criteria for COPD.

The overall prevalence of interstitial lung abnormalities affecting more than 5% of any lung zone on HRCT was 8%. Another 36% of the subjects showed "indeterminate" findings, and 56% showed no interstitial lung abnormalities.

The lung abnormalities included nondependent ground-glass or reticular abnormalities, diffuse centrilobular nodularity, nonemphysematous cysts, honeycombing, and traction bronchiectasis.

Interstitial lung abnormalities were associated with both a decrease in total lung capacity and a lesser amount of emphysema. In addition, there was an inverse relationship between these abnormalities and the severity of COPD, the researchers said (N. Engl. J. Med. 2011;364:897-906).

Further follow-up is needed "to determine whether these radiographic abnormalities, and the associated reductions in lung volumes, are transient or stable, or whether they will progress to clinically significant disease," Dr. Washko and his associates said.

In an editorial accompanying the report, Dr. Talmadge E. King Jr. said that the "long-term implications of this and similar studies using HRCT scans in asymptomatic subjects are unknown. There is the concern that such scans may be overinterpreted, leading to a high rate of unnecessary diagnoses and perhaps unwarranted treatment" (N. Engl. J. Med. 2011;364:968-70). In this study, more than one-third of the HRCT scans were deemed "indeterminate" for the presence of interstitial lung abnormalities, which "probably reflects the fact that the boundary between HRCT images of the lungs in health and disease is blurred," noted Dr. King of the department of medicine at the University of California, San Francisco.

However, he thought it was noteworthy that Dr. Washko and his colleagues found that interstitial lung abnormalities were associated with less radiographic emphysema. "It is interesting to speculate that the pathobiology of smoking can lead to two distinct patterns of injury – emphysema (with destruction of the lung) or interstitial lung disease (with macrophage accumulation and fibrosis).

"Conversely ... the relative lack of emphysema could be simply a reflection of the fact that interstitial lung abnormalities mask emphysema or that more severe emphysema limits the extent of interstitial lung abnormalities," Dr. King said.

This study was supported by the National Institutes of Health and the Parker B. Francis Foundation. Dr. Washko reported ties to MedImmune, and his associates reported ties to Siemens, Actelion, Gilead, InterMune, Novartis, Perceptive Imaging, GE Medical Systems, GlaxoSmithKline, AstraZeneca, Toshiba Medical, and AZE. Dr. King reported ties to Actelion, InterMune, ImmuneWorks, Philips Respironics, CV Therapeutics, and Genzyme.

Smokers with interstitial lung abnormalities on high-resolution CT show both reduced total lung capacity and a lesser amount of emphysema, compared with those who didn’t have interstitial lung abnormalities, according to a report in the March 10 issue of the New England Journal of Medicine.

In addition, the magnitude of these two reductions is greatest among smokers who also have chronic obstructive pulmonary disease (COPD), said Dr. George R. Washko of the pulmonary and critical care division at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and his associates.

"Our findings are consistent with, and add weight to, previous studies showing that cigarette smoking is associated with both spirometric restriction and areas of high attenuation on HRCT. Since emphysema and interstitial lung abnormalities have opposing effects on lung volume, our findings suggest that HRCT may provide important diagnostic information in smokers whose total lung capacity is unexpectedly ‘normal,’ " they noted.

"We speculate that this could be clinically important to physicians who may think that a patient who does not have symptoms or characteristic abnormalities on lung function tests is disease free, when in fact the patient could be affected by two of the consequences of smoking – emphysema and interstitial lung abnormalities," Dr. Washko and his colleagues said.

The investigators examined the relationship among radiographic interstitial lung abnormalities, total lung capacity, and emphysema in a cohort of 2,416 smokers who had been recruited for an ongoing study of COPD being conducted at 21 clinical centers.

The cohort included white (75%) and black (25%) subjects aged 45-80 years who reported a history of at least 10 pack-years of smoking. Slightly more than half of the subjects were men, 44% were still actively smoking, and 41% met criteria for COPD.

The overall prevalence of interstitial lung abnormalities affecting more than 5% of any lung zone on HRCT was 8%. Another 36% of the subjects showed "indeterminate" findings, and 56% showed no interstitial lung abnormalities.

The lung abnormalities included nondependent ground-glass or reticular abnormalities, diffuse centrilobular nodularity, nonemphysematous cysts, honeycombing, and traction bronchiectasis.

Interstitial lung abnormalities were associated with both a decrease in total lung capacity and a lesser amount of emphysema. In addition, there was an inverse relationship between these abnormalities and the severity of COPD, the researchers said (N. Engl. J. Med. 2011;364:897-906).

Further follow-up is needed "to determine whether these radiographic abnormalities, and the associated reductions in lung volumes, are transient or stable, or whether they will progress to clinically significant disease," Dr. Washko and his associates said.

In an editorial accompanying the report, Dr. Talmadge E. King Jr. said that the "long-term implications of this and similar studies using HRCT scans in asymptomatic subjects are unknown. There is the concern that such scans may be overinterpreted, leading to a high rate of unnecessary diagnoses and perhaps unwarranted treatment" (N. Engl. J. Med. 2011;364:968-70). In this study, more than one-third of the HRCT scans were deemed "indeterminate" for the presence of interstitial lung abnormalities, which "probably reflects the fact that the boundary between HRCT images of the lungs in health and disease is blurred," noted Dr. King of the department of medicine at the University of California, San Francisco.

However, he thought it was noteworthy that Dr. Washko and his colleagues found that interstitial lung abnormalities were associated with less radiographic emphysema. "It is interesting to speculate that the pathobiology of smoking can lead to two distinct patterns of injury – emphysema (with destruction of the lung) or interstitial lung disease (with macrophage accumulation and fibrosis).

"Conversely ... the relative lack of emphysema could be simply a reflection of the fact that interstitial lung abnormalities mask emphysema or that more severe emphysema limits the extent of interstitial lung abnormalities," Dr. King said.

This study was supported by the National Institutes of Health and the Parker B. Francis Foundation. Dr. Washko reported ties to MedImmune, and his associates reported ties to Siemens, Actelion, Gilead, InterMune, Novartis, Perceptive Imaging, GE Medical Systems, GlaxoSmithKline, AstraZeneca, Toshiba Medical, and AZE. Dr. King reported ties to Actelion, InterMune, ImmuneWorks, Philips Respironics, CV Therapeutics, and Genzyme.

Smokers with interstitial lung abnormalities on high-resolution CT show both reduced total lung capacity and a lesser amount of emphysema, compared with those who didn’t have interstitial lung abnormalities, according to a report in the March 10 issue of the New England Journal of Medicine.

In addition, the magnitude of these two reductions is greatest among smokers who also have chronic obstructive pulmonary disease (COPD), said Dr. George R. Washko of the pulmonary and critical care division at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and his associates.

"Our findings are consistent with, and add weight to, previous studies showing that cigarette smoking is associated with both spirometric restriction and areas of high attenuation on HRCT. Since emphysema and interstitial lung abnormalities have opposing effects on lung volume, our findings suggest that HRCT may provide important diagnostic information in smokers whose total lung capacity is unexpectedly ‘normal,’ " they noted.

"We speculate that this could be clinically important to physicians who may think that a patient who does not have symptoms or characteristic abnormalities on lung function tests is disease free, when in fact the patient could be affected by two of the consequences of smoking – emphysema and interstitial lung abnormalities," Dr. Washko and his colleagues said.

The investigators examined the relationship among radiographic interstitial lung abnormalities, total lung capacity, and emphysema in a cohort of 2,416 smokers who had been recruited for an ongoing study of COPD being conducted at 21 clinical centers.

The cohort included white (75%) and black (25%) subjects aged 45-80 years who reported a history of at least 10 pack-years of smoking. Slightly more than half of the subjects were men, 44% were still actively smoking, and 41% met criteria for COPD.

The overall prevalence of interstitial lung abnormalities affecting more than 5% of any lung zone on HRCT was 8%. Another 36% of the subjects showed "indeterminate" findings, and 56% showed no interstitial lung abnormalities.

The lung abnormalities included nondependent ground-glass or reticular abnormalities, diffuse centrilobular nodularity, nonemphysematous cysts, honeycombing, and traction bronchiectasis.

Interstitial lung abnormalities were associated with both a decrease in total lung capacity and a lesser amount of emphysema. In addition, there was an inverse relationship between these abnormalities and the severity of COPD, the researchers said (N. Engl. J. Med. 2011;364:897-906).

Further follow-up is needed "to determine whether these radiographic abnormalities, and the associated reductions in lung volumes, are transient or stable, or whether they will progress to clinically significant disease," Dr. Washko and his associates said.

In an editorial accompanying the report, Dr. Talmadge E. King Jr. said that the "long-term implications of this and similar studies using HRCT scans in asymptomatic subjects are unknown. There is the concern that such scans may be overinterpreted, leading to a high rate of unnecessary diagnoses and perhaps unwarranted treatment" (N. Engl. J. Med. 2011;364:968-70). In this study, more than one-third of the HRCT scans were deemed "indeterminate" for the presence of interstitial lung abnormalities, which "probably reflects the fact that the boundary between HRCT images of the lungs in health and disease is blurred," noted Dr. King of the department of medicine at the University of California, San Francisco.

However, he thought it was noteworthy that Dr. Washko and his colleagues found that interstitial lung abnormalities were associated with less radiographic emphysema. "It is interesting to speculate that the pathobiology of smoking can lead to two distinct patterns of injury – emphysema (with destruction of the lung) or interstitial lung disease (with macrophage accumulation and fibrosis).

"Conversely ... the relative lack of emphysema could be simply a reflection of the fact that interstitial lung abnormalities mask emphysema or that more severe emphysema limits the extent of interstitial lung abnormalities," Dr. King said.

This study was supported by the National Institutes of Health and the Parker B. Francis Foundation. Dr. Washko reported ties to MedImmune, and his associates reported ties to Siemens, Actelion, Gilead, InterMune, Novartis, Perceptive Imaging, GE Medical Systems, GlaxoSmithKline, AstraZeneca, Toshiba Medical, and AZE. Dr. King reported ties to Actelion, InterMune, ImmuneWorks, Philips Respironics, CV Therapeutics, and Genzyme.

Smokers with interstitial lung abnormalities on high-resolution CT show both reduced total lung capacity and a lesser amount of emphysema, compared with those who didn’t have interstitial lung abnormalities, according to a report in the March 10 issue of the New England Journal of Medicine.

In addition, the magnitude of these two reductions is greatest among smokers who also have chronic obstructive pulmonary disease (COPD), said Dr. George R. Washko of the pulmonary and critical care division at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and his associates.

"Our findings are consistent with, and add weight to, previous studies showing that cigarette smoking is associated with both spirometric restriction and areas of high attenuation on HRCT. Since emphysema and interstitial lung abnormalities have opposing effects on lung volume, our findings suggest that HRCT may provide important diagnostic information in smokers whose total lung capacity is unexpectedly ‘normal,’ " they noted.

"We speculate that this could be clinically important to physicians who may think that a patient who does not have symptoms or characteristic abnormalities on lung function tests is disease free, when in fact the patient could be affected by two of the consequences of smoking – emphysema and interstitial lung abnormalities," Dr. Washko and his colleagues said.

The investigators examined the relationship among radiographic interstitial lung abnormalities, total lung capacity, and emphysema in a cohort of 2,416 smokers who had been recruited for an ongoing study of COPD being conducted at 21 clinical centers.

The cohort included white (75%) and black (25%) subjects aged 45-80 years who reported a history of at least 10 pack-years of smoking. Slightly more than half of the subjects were men, 44% were still actively smoking, and 41% met criteria for COPD.

The overall prevalence of interstitial lung abnormalities affecting more than 5% of any lung zone on HRCT was 8%. Another 36% of the subjects showed "indeterminate" findings, and 56% showed no interstitial lung abnormalities.

The lung abnormalities included nondependent ground-glass or reticular abnormalities, diffuse centrilobular nodularity, nonemphysematous cysts, honeycombing, and traction bronchiectasis.

Interstitial lung abnormalities were associated with both a decrease in total lung capacity and a lesser amount of emphysema. In addition, there was an inverse relationship between these abnormalities and the severity of COPD, the researchers said (N. Engl. J. Med. 2011;364:897-906).

Further follow-up is needed "to determine whether these radiographic abnormalities, and the associated reductions in lung volumes, are transient or stable, or whether they will progress to clinically significant disease," Dr. Washko and his associates said.

In an editorial accompanying the report, Dr. Talmadge E. King Jr. said that the "long-term implications of this and similar studies using HRCT scans in asymptomatic subjects are unknown. There is the concern that such scans may be overinterpreted, leading to a high rate of unnecessary diagnoses and perhaps unwarranted treatment" (N. Engl. J. Med. 2011;364:968-70). In this study, more than one-third of the HRCT scans were deemed "indeterminate" for the presence of interstitial lung abnormalities, which "probably reflects the fact that the boundary between HRCT images of the lungs in health and disease is blurred," noted Dr. King of the department of medicine at the University of California, San Francisco.

However, he thought it was noteworthy that Dr. Washko and his colleagues found that interstitial lung abnormalities were associated with less radiographic emphysema. "It is interesting to speculate that the pathobiology of smoking can lead to two distinct patterns of injury – emphysema (with destruction of the lung) or interstitial lung disease (with macrophage accumulation and fibrosis).

"Conversely ... the relative lack of emphysema could be simply a reflection of the fact that interstitial lung abnormalities mask emphysema or that more severe emphysema limits the extent of interstitial lung abnormalities," Dr. King said.

This study was supported by the National Institutes of Health and the Parker B. Francis Foundation. Dr. Washko reported ties to MedImmune, and his associates reported ties to Siemens, Actelion, Gilead, InterMune, Novartis, Perceptive Imaging, GE Medical Systems, GlaxoSmithKline, AstraZeneca, Toshiba Medical, and AZE. Dr. King reported ties to Actelion, InterMune, ImmuneWorks, Philips Respironics, CV Therapeutics, and Genzyme.

Smokers with interstitial lung abnormalities on high-resolution CT show both reduced total lung capacity and a lesser amount of emphysema, compared with those who didn’t have interstitial lung abnormalities, according to a report in the March 10 issue of the New England Journal of Medicine.

In addition, the magnitude of these two reductions is greatest among smokers who also have chronic obstructive pulmonary disease (COPD), said Dr. George R. Washko of the pulmonary and critical care division at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and his associates.

"Our findings are consistent with, and add weight to, previous studies showing that cigarette smoking is associated with both spirometric restriction and areas of high attenuation on HRCT. Since emphysema and interstitial lung abnormalities have opposing effects on lung volume, our findings suggest that HRCT may provide important diagnostic information in smokers whose total lung capacity is unexpectedly ‘normal,’ " they noted.

"We speculate that this could be clinically important to physicians who may think that a patient who does not have symptoms or characteristic abnormalities on lung function tests is disease free, when in fact the patient could be affected by two of the consequences of smoking – emphysema and interstitial lung abnormalities," Dr. Washko and his colleagues said.

The investigators examined the relationship among radiographic interstitial lung abnormalities, total lung capacity, and emphysema in a cohort of 2,416 smokers who had been recruited for an ongoing study of COPD being conducted at 21 clinical centers.

The cohort included white (75%) and black (25%) subjects aged 45-80 years who reported a history of at least 10 pack-years of smoking. Slightly more than half of the subjects were men, 44% were still actively smoking, and 41% met criteria for COPD.

The overall prevalence of interstitial lung abnormalities affecting more than 5% of any lung zone on HRCT was 8%. Another 36% of the subjects showed "indeterminate" findings, and 56% showed no interstitial lung abnormalities.

The lung abnormalities included nondependent ground-glass or reticular abnormalities, diffuse centrilobular nodularity, nonemphysematous cysts, honeycombing, and traction bronchiectasis.

Interstitial lung abnormalities were associated with both a decrease in total lung capacity and a lesser amount of emphysema. In addition, there was an inverse relationship between these abnormalities and the severity of COPD, the researchers said (N. Engl. J. Med. 2011;364:897-906).

Further follow-up is needed "to determine whether these radiographic abnormalities, and the associated reductions in lung volumes, are transient or stable, or whether they will progress to clinically significant disease," Dr. Washko and his associates said.

In an editorial accompanying the report, Dr. Talmadge E. King Jr. said that the "long-term implications of this and similar studies using HRCT scans in asymptomatic subjects are unknown. There is the concern that such scans may be overinterpreted, leading to a high rate of unnecessary diagnoses and perhaps unwarranted treatment" (N. Engl. J. Med. 2011;364:968-70). In this study, more than one-third of the HRCT scans were deemed "indeterminate" for the presence of interstitial lung abnormalities, which "probably reflects the fact that the boundary between HRCT images of the lungs in health and disease is blurred," noted Dr. King of the department of medicine at the University of California, San Francisco.

However, he thought it was noteworthy that Dr. Washko and his colleagues found that interstitial lung abnormalities were associated with less radiographic emphysema. "It is interesting to speculate that the pathobiology of smoking can lead to two distinct patterns of injury – emphysema (with destruction of the lung) or interstitial lung disease (with macrophage accumulation and fibrosis).

"Conversely ... the relative lack of emphysema could be simply a reflection of the fact that interstitial lung abnormalities mask emphysema or that more severe emphysema limits the extent of interstitial lung abnormalities," Dr. King said.

This study was supported by the National Institutes of Health and the Parker B. Francis Foundation. Dr. Washko reported ties to MedImmune, and his associates reported ties to Siemens, Actelion, Gilead, InterMune, Novartis, Perceptive Imaging, GE Medical Systems, GlaxoSmithKline, AstraZeneca, Toshiba Medical, and AZE. Dr. King reported ties to Actelion, InterMune, ImmuneWorks, Philips Respironics, CV Therapeutics, and Genzyme.

Smokers with interstitial lung abnormalities on high-resolution CT show both reduced total lung capacity and a lesser amount of emphysema, compared with those who didn’t have interstitial lung abnormalities, according to a report in the March 10 issue of the New England Journal of Medicine.

In addition, the magnitude of these two reductions is greatest among smokers who also have chronic obstructive pulmonary disease (COPD), said Dr. George R. Washko of the pulmonary and critical care division at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and his associates.

"Our findings are consistent with, and add weight to, previous studies showing that cigarette smoking is associated with both spirometric restriction and areas of high attenuation on HRCT. Since emphysema and interstitial lung abnormalities have opposing effects on lung volume, our findings suggest that HRCT may provide important diagnostic information in smokers whose total lung capacity is unexpectedly ‘normal,’ " they noted.

"We speculate that this could be clinically important to physicians who may think that a patient who does not have symptoms or characteristic abnormalities on lung function tests is disease free, when in fact the patient could be affected by two of the consequences of smoking – emphysema and interstitial lung abnormalities," Dr. Washko and his colleagues said.

The investigators examined the relationship among radiographic interstitial lung abnormalities, total lung capacity, and emphysema in a cohort of 2,416 smokers who had been recruited for an ongoing study of COPD being conducted at 21 clinical centers.

The cohort included white (75%) and black (25%) subjects aged 45-80 years who reported a history of at least 10 pack-years of smoking. Slightly more than half of the subjects were men, 44% were still actively smoking, and 41% met criteria for COPD.

The overall prevalence of interstitial lung abnormalities affecting more than 5% of any lung zone on HRCT was 8%. Another 36% of the subjects showed "indeterminate" findings, and 56% showed no interstitial lung abnormalities.

The lung abnormalities included nondependent ground-glass or reticular abnormalities, diffuse centrilobular nodularity, nonemphysematous cysts, honeycombing, and traction bronchiectasis.

Interstitial lung abnormalities were associated with both a decrease in total lung capacity and a lesser amount of emphysema. In addition, there was an inverse relationship between these abnormalities and the severity of COPD, the researchers said (N. Engl. J. Med. 2011;364:897-906).

Further follow-up is needed "to determine whether these radiographic abnormalities, and the associated reductions in lung volumes, are transient or stable, or whether they will progress to clinically significant disease," Dr. Washko and his associates said.

In an editorial accompanying the report, Dr. Talmadge E. King Jr. said that the "long-term implications of this and similar studies using HRCT scans in asymptomatic subjects are unknown. There is the concern that such scans may be overinterpreted, leading to a high rate of unnecessary diagnoses and perhaps unwarranted treatment" (N. Engl. J. Med. 2011;364:968-70). In this study, more than one-third of the HRCT scans were deemed "indeterminate" for the presence of interstitial lung abnormalities, which "probably reflects the fact that the boundary between HRCT images of the lungs in health and disease is blurred," noted Dr. King of the department of medicine at the University of California, San Francisco.

However, he thought it was noteworthy that Dr. Washko and his colleagues found that interstitial lung abnormalities were associated with less radiographic emphysema. "It is interesting to speculate that the pathobiology of smoking can lead to two distinct patterns of injury – emphysema (with destruction of the lung) or interstitial lung disease (with macrophage accumulation and fibrosis).

"Conversely ... the relative lack of emphysema could be simply a reflection of the fact that interstitial lung abnormalities mask emphysema or that more severe emphysema limits the extent of interstitial lung abnormalities," Dr. King said.

This study was supported by the National Institutes of Health and the Parker B. Francis Foundation. Dr. Washko reported ties to MedImmune, and his associates reported ties to Siemens, Actelion, Gilead, InterMune, Novartis, Perceptive Imaging, GE Medical Systems, GlaxoSmithKline, AstraZeneca, Toshiba Medical, and AZE. Dr. King reported ties to Actelion, InterMune, ImmuneWorks, Philips Respironics, CV Therapeutics, and Genzyme.

Smokers with interstitial lung abnormalities on high-resolution CT show both reduced total lung capacity and a lesser amount of emphysema, compared with those who didn’t have interstitial lung abnormalities, according to a report in the March 10 issue of the New England Journal of Medicine.

In addition, the magnitude of these two reductions is greatest among smokers who also have chronic obstructive pulmonary disease (COPD), said Dr. George R. Washko of the pulmonary and critical care division at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and his associates.

"Our findings are consistent with, and add weight to, previous studies showing that cigarette smoking is associated with both spirometric restriction and areas of high attenuation on HRCT. Since emphysema and interstitial lung abnormalities have opposing effects on lung volume, our findings suggest that HRCT may provide important diagnostic information in smokers whose total lung capacity is unexpectedly ‘normal,’ " they noted.

"We speculate that this could be clinically important to physicians who may think that a patient who does not have symptoms or characteristic abnormalities on lung function tests is disease free, when in fact the patient could be affected by two of the consequences of smoking – emphysema and interstitial lung abnormalities," Dr. Washko and his colleagues said.

The investigators examined the relationship among radiographic interstitial lung abnormalities, total lung capacity, and emphysema in a cohort of 2,416 smokers who had been recruited for an ongoing study of COPD being conducted at 21 clinical centers.

The cohort included white (75%) and black (25%) subjects aged 45-80 years who reported a history of at least 10 pack-years of smoking. Slightly more than half of the subjects were men, 44% were still actively smoking, and 41% met criteria for COPD.

The overall prevalence of interstitial lung abnormalities affecting more than 5% of any lung zone on HRCT was 8%. Another 36% of the subjects showed "indeterminate" findings, and 56% showed no interstitial lung abnormalities.

The lung abnormalities included nondependent ground-glass or reticular abnormalities, diffuse centrilobular nodularity, nonemphysematous cysts, honeycombing, and traction bronchiectasis.

Interstitial lung abnormalities were associated with both a decrease in total lung capacity and a lesser amount of emphysema. In addition, there was an inverse relationship between these abnormalities and the severity of COPD, the researchers said (N. Engl. J. Med. 2011;364:897-906).

Further follow-up is needed "to determine whether these radiographic abnormalities, and the associated reductions in lung volumes, are transient or stable, or whether they will progress to clinically significant disease," Dr. Washko and his associates said.

In an editorial accompanying the report, Dr. Talmadge E. King Jr. said that the "long-term implications of this and similar studies using HRCT scans in asymptomatic subjects are unknown. There is the concern that such scans may be overinterpreted, leading to a high rate of unnecessary diagnoses and perhaps unwarranted treatment" (N. Engl. J. Med. 2011;364:968-70). In this study, more than one-third of the HRCT scans were deemed "indeterminate" for the presence of interstitial lung abnormalities, which "probably reflects the fact that the boundary between HRCT images of the lungs in health and disease is blurred," noted Dr. King of the department of medicine at the University of California, San Francisco.

However, he thought it was noteworthy that Dr. Washko and his colleagues found that interstitial lung abnormalities were associated with less radiographic emphysema. "It is interesting to speculate that the pathobiology of smoking can lead to two distinct patterns of injury – emphysema (with destruction of the lung) or interstitial lung disease (with macrophage accumulation and fibrosis).

"Conversely ... the relative lack of emphysema could be simply a reflection of the fact that interstitial lung abnormalities mask emphysema or that more severe emphysema limits the extent of interstitial lung abnormalities," Dr. King said.

This study was supported by the National Institutes of Health and the Parker B. Francis Foundation. Dr. Washko reported ties to MedImmune, and his associates reported ties to Siemens, Actelion, Gilead, InterMune, Novartis, Perceptive Imaging, GE Medical Systems, GlaxoSmithKline, AstraZeneca, Toshiba Medical, and AZE. Dr. King reported ties to Actelion, InterMune, ImmuneWorks, Philips Respironics, CV Therapeutics, and Genzyme.

Long-term mortality for adult trauma patients is much higher than expected, given their age and health status before being injured, according to a report March 9 in JAMA.

In a retrospective cohort study of 124,421 patients, mortality was approximately 10% during the first year after hospital discharge, and 16% during the 3 years after hospital discharge. "These results suggest that in an adult trauma patient, acute injury is not just a brief physiological setback to a healthy life, but rather signals significant long-term mortality in a large number of patients," said Dr. Giana H. Davidson of Harborview Injury Prevention and Research Center, Seattle, and her associates.

Inpatient mortality declined steadily over time, both within emergency departments and within hospitals. In dramatic contrast, postdischarge mortality increased over time and "was sharply higher than that expected for the general Washington population at 1, 2, and 3 years," Dr. Davidson and her colleagues said (JAMA 2011;305:1001-7).

The researchers performed the study because "little is known about long-term outcomes following trauma admissions," and the information could be helpful in counseling patients and their families about prognosis.

The mean age of the study subjects was 53 years, and 59% were men. The study did not include burn patients, and injuries were categorized as being caused by blunt trauma (39%), penetrating trauma (11%), falls (47%), or other causes (3%). The patients were treated at 78 trauma centers throughout Washington State in 1995-2008.

"Washington State had a well-organized and mature statewide trauma system (established in 1990) during the study period," the investigators noted.

A total of 7,243 patients (6%) died during their initial hospitalization, leaving 117,178 for this analysis. The median length of stay was 4 days and the mean was 6 days.

Data were adjusted to account for patient age and sex; the presence and severity of head trauma; overall injury severity; the Glasgow Coma Scale score; the FIM (Functional Independence Measure) mobility score at discharge; mechanism of injury; hospital length of stay; ICU length of stay; need for tracheotomy; comorbidity index; and insurance status.

Several factors at admission were found to strongly predict risk of death after hospital discharge. Older patient age, a systolic blood pressure less than 90 mm Hg, a Glasgow Coma Scale score less than 9, male sex, blunt injury, and injury from falling all substantially raised the mortality risk (to 44%) for the first postdischarge year.

This information can help guide clinician and family decision making for the adult trauma patient, the researchers said.

Approximately 25% of patients were discharged to a skilled nursing facility. In the subgroup of patients older than 65 years at the time of their injury, more than half (54%) were discharged to a skilled nursing facility.

Discharge to a skilled nursing facility was associated with a higher risk of postdischarge death in every age group (34% cumulative mortality at 3 years), compared with discharge home (with or without assistance); discharge to a rehabilitation facility; discharge to jail; transfer to a psychiatric hospital; or transfer to another acute-care facility, including ventilator-weaning facilities.

"Due to the substantial difference between the expected and observed mortality rates for our trauma population, we conclude that trauma itself may be an indicator of higher long-term mortality or marker of patient decline," Dr. Davidson and her associates said.

"Interventions should be aimed at improving the care of the injured patient following discharge from the hospital and narrowing the gap in outcomes for those patients discharged to skilled nursing facilities," they said.

This study was supported by the National Institute of Child Health and Human Development. The authors reported having no financial conflicts of interest.

Long-term mortality for adult trauma patients is much higher than expected, given their age and health status before being injured, according to a report March 9 in JAMA.

In a retrospective cohort study of 124,421 patients, mortality was approximately 10% during the first year after hospital discharge, and 16% during the 3 years after hospital discharge. "These results suggest that in an adult trauma patient, acute injury is not just a brief physiological setback to a healthy life, but rather signals significant long-term mortality in a large number of patients," said Dr. Giana H. Davidson of Harborview Injury Prevention and Research Center, Seattle, and her associates.

Inpatient mortality declined steadily over time, both within emergency departments and within hospitals. In dramatic contrast, postdischarge mortality increased over time and "was sharply higher than that expected for the general Washington population at 1, 2, and 3 years," Dr. Davidson and her colleagues said (JAMA 2011;305:1001-7).

The researchers performed the study because "little is known about long-term outcomes following trauma admissions," and the information could be helpful in counseling patients and their families about prognosis.

The mean age of the study subjects was 53 years, and 59% were men. The study did not include burn patients, and injuries were categorized as being caused by blunt trauma (39%), penetrating trauma (11%), falls (47%), or other causes (3%). The patients were treated at 78 trauma centers throughout Washington State in 1995-2008.

"Washington State had a well-organized and mature statewide trauma system (established in 1990) during the study period," the investigators noted.

A total of 7,243 patients (6%) died during their initial hospitalization, leaving 117,178 for this analysis. The median length of stay was 4 days and the mean was 6 days.

Data were adjusted to account for patient age and sex; the presence and severity of head trauma; overall injury severity; the Glasgow Coma Scale score; the FIM (Functional Independence Measure) mobility score at discharge; mechanism of injury; hospital length of stay; ICU length of stay; need for tracheotomy; comorbidity index; and insurance status.

Several factors at admission were found to strongly predict risk of death after hospital discharge. Older patient age, a systolic blood pressure less than 90 mm Hg, a Glasgow Coma Scale score less than 9, male sex, blunt injury, and injury from falling all substantially raised the mortality risk (to 44%) for the first postdischarge year.

This information can help guide clinician and family decision making for the adult trauma patient, the researchers said.

Approximately 25% of patients were discharged to a skilled nursing facility. In the subgroup of patients older than 65 years at the time of their injury, more than half (54%) were discharged to a skilled nursing facility.

Discharge to a skilled nursing facility was associated with a higher risk of postdischarge death in every age group (34% cumulative mortality at 3 years), compared with discharge home (with or without assistance); discharge to a rehabilitation facility; discharge to jail; transfer to a psychiatric hospital; or transfer to another acute-care facility, including ventilator-weaning facilities.

"Due to the substantial difference between the expected and observed mortality rates for our trauma population, we conclude that trauma itself may be an indicator of higher long-term mortality or marker of patient decline," Dr. Davidson and her associates said.

"Interventions should be aimed at improving the care of the injured patient following discharge from the hospital and narrowing the gap in outcomes for those patients discharged to skilled nursing facilities," they said.

This study was supported by the National Institute of Child Health and Human Development. The authors reported having no financial conflicts of interest.

Long-term mortality for adult trauma patients is much higher than expected, given their age and health status before being injured, according to a report March 9 in JAMA.

In a retrospective cohort study of 124,421 patients, mortality was approximately 10% during the first year after hospital discharge, and 16% during the 3 years after hospital discharge. "These results suggest that in an adult trauma patient, acute injury is not just a brief physiological setback to a healthy life, but rather signals significant long-term mortality in a large number of patients," said Dr. Giana H. Davidson of Harborview Injury Prevention and Research Center, Seattle, and her associates.

Inpatient mortality declined steadily over time, both within emergency departments and within hospitals. In dramatic contrast, postdischarge mortality increased over time and "was sharply higher than that expected for the general Washington population at 1, 2, and 3 years," Dr. Davidson and her colleagues said (JAMA 2011;305:1001-7).

The researchers performed the study because "little is known about long-term outcomes following trauma admissions," and the information could be helpful in counseling patients and their families about prognosis.

The mean age of the study subjects was 53 years, and 59% were men. The study did not include burn patients, and injuries were categorized as being caused by blunt trauma (39%), penetrating trauma (11%), falls (47%), or other causes (3%). The patients were treated at 78 trauma centers throughout Washington State in 1995-2008.

"Washington State had a well-organized and mature statewide trauma system (established in 1990) during the study period," the investigators noted.

A total of 7,243 patients (6%) died during their initial hospitalization, leaving 117,178 for this analysis. The median length of stay was 4 days and the mean was 6 days.

Data were adjusted to account for patient age and sex; the presence and severity of head trauma; overall injury severity; the Glasgow Coma Scale score; the FIM (Functional Independence Measure) mobility score at discharge; mechanism of injury; hospital length of stay; ICU length of stay; need for tracheotomy; comorbidity index; and insurance status.

Several factors at admission were found to strongly predict risk of death after hospital discharge. Older patient age, a systolic blood pressure less than 90 mm Hg, a Glasgow Coma Scale score less than 9, male sex, blunt injury, and injury from falling all substantially raised the mortality risk (to 44%) for the first postdischarge year.

This information can help guide clinician and family decision making for the adult trauma patient, the researchers said.

Approximately 25% of patients were discharged to a skilled nursing facility. In the subgroup of patients older than 65 years at the time of their injury, more than half (54%) were discharged to a skilled nursing facility.

Discharge to a skilled nursing facility was associated with a higher risk of postdischarge death in every age group (34% cumulative mortality at 3 years), compared with discharge home (with or without assistance); discharge to a rehabilitation facility; discharge to jail; transfer to a psychiatric hospital; or transfer to another acute-care facility, including ventilator-weaning facilities.

"Due to the substantial difference between the expected and observed mortality rates for our trauma population, we conclude that trauma itself may be an indicator of higher long-term mortality or marker of patient decline," Dr. Davidson and her associates said.

"Interventions should be aimed at improving the care of the injured patient following discharge from the hospital and narrowing the gap in outcomes for those patients discharged to skilled nursing facilities," they said.

This study was supported by the National Institute of Child Health and Human Development. The authors reported having no financial conflicts of interest.

Worldwide, the prevalence of bipolar disorder type I is estimated to be 0.6%, that of type II is 0.4%, and that of subthreshold bipolar disorder is 1.4%, yielding a total bipolar disorder spectrum prevalence of 2.4%, according to a new report in the March issue of the Archives of General Psychiatry.

These estimates were derived from what the investigators described as the first international data ever collected using Diagnostic and Statistical Manual–IV definitions for the full spectrum of bipolar disorders and standardized measures to survey nationally representative samples in 11 low-income, middle-income, and high-income countries.

Even though prevalence varied from one country to the next, disease severity, impact on daily life, and patterns of comorbidity remained strikingly similar, said Kathleen R. Merikangas, Ph.D., of the Intramural Research Program of the National Institute of Mental Health (NIMH), and her associates in the World Mental Health Survey Initiative.

This World Health Organization (WHO) project "aims to obtain accurate cross-national information on the prevalence, correlates, and service patterns of mental disorders." The investigators conducted in-person, population-based surveys of 61,392 adults in Brazil, Colombia, Mexico, the United States, Bulgaria, Romania, China, India, Japan, Lebanon, and New Zealand.

In addition to the overall prevalences, they found that the 1-year prevalence of bipolar disorder type I was 0.4%, that of bipolar disorder type II was 0.3%, and that of subthreshold bipolar disorder was 0.8%, for a total bipolar spectrum disorder annual prevalence of 1.5%.

In general, high-income countries had the highest prevalences of bipolar disease and low-income countries had the lowest. The United States had the highest prevalence of overall (4.4%) and annual (2.8%) disease, while India had the lowest (0.1% for both). Two exceptions to this rule were Japan, a high-income country with very low overall (0.7%) and annual (0.2%) prevalences, and Colombia, a low-income country with a high overall prevalence (2.6%).

The mean ages at onset were 18 years for bipolar disorder type I, 20 years for bipolar disorder type II, and 22 years for subthreshold bipolar disorder.

Patterns of comorbidity were remarkably consistent among the different countries. Three-fourths of patients with bipolar spectrum disorders also met criteria for other psychiatric disorders, and the majority had three or more of them. "Anxiety disorders, particularly panic attacks, were the most common comorbid conditions (63%), followed by behavior disorders (45%) and substance use disorders (37%)," Dr. Merikangas and her colleagues said (Arch. Gen. Psychiatry 2011;68:241-51).

The association between bipolar disorders and substance use disorders across the globe was particularly striking in light of the large differences between countries in rates of substance use and abuse. "This suggests that [bipolar disorder] can be considered a risk factor for the development of substance use disorders ... [and supports] the need for careful probing of a history of bipolarity among those with substance use disorders," they said.

The proportion of patients with suicidal behaviors rose with increasing severity of bipolar disease. Approximately 10% of those with subthreshold bipolar disorder, 20% of those with bipolar disorder type II, and 25% of those with bipolar disorder type I said that they had attempted suicide over the last 12 months.

This "striking" finding of suicidality, together with the early age at onset and the strong association with other mental health disorders, provides "further documentation of the individual and societal disability associated with this disorder," they noted.

A substantially higher proportion of patients in high-income countries, compared with middle- or low-income countries, reported having used mental health services. Lifetime use of such services was 50% in high-income countries, 34% in middle-income countries, and 25% in low-income countries.

"Because [bipolar disorder] has an average age at onset at one of the most critical periods of educational, occupational, and social development, its consequences often lead to lifelong disability," the investigators said, and this lack of mental health treatment, especially in low-income countries, is therefore "alarming."

"These data also provide the first aggregate international evidence, to our knowledge, that supports the validity of the spectrum concept of bipolarity," they added. The proportion of mood episodes rated as clinically severe, as well as the proportion in which patients reported severe impairment of work, home management, social life, and close relationships, were directly associated with increasingly severe forms of bipolar disease.

This study was supported by the NIMH’s Intramural Research Program, the U.S. Public Health Service, numerous organizations in the participating countries, and numerous drug companies. Dr. Merikangas reported her affiliation with the Intramural Research Program, and one of her associates, Ronald Kessler, Ph.D., reported ties to numerous pharmaceutical companies.

Worldwide, the prevalence of bipolar disorder type I is estimated to be 0.6%, that of type II is 0.4%, and that of subthreshold bipolar disorder is 1.4%, yielding a total bipolar disorder spectrum prevalence of 2.4%, according to a new report in the March issue of the Archives of General Psychiatry.

These estimates were derived from what the investigators described as the first international data ever collected using Diagnostic and Statistical Manual–IV definitions for the full spectrum of bipolar disorders and standardized measures to survey nationally representative samples in 11 low-income, middle-income, and high-income countries.

Even though prevalence varied from one country to the next, disease severity, impact on daily life, and patterns of comorbidity remained strikingly similar, said Kathleen R. Merikangas, Ph.D., of the Intramural Research Program of the National Institute of Mental Health (NIMH), and her associates in the World Mental Health Survey Initiative.

This World Health Organization (WHO) project "aims to obtain accurate cross-national information on the prevalence, correlates, and service patterns of mental disorders." The investigators conducted in-person, population-based surveys of 61,392 adults in Brazil, Colombia, Mexico, the United States, Bulgaria, Romania, China, India, Japan, Lebanon, and New Zealand.

In addition to the overall prevalences, they found that the 1-year prevalence of bipolar disorder type I was 0.4%, that of bipolar disorder type II was 0.3%, and that of subthreshold bipolar disorder was 0.8%, for a total bipolar spectrum disorder annual prevalence of 1.5%.

In general, high-income countries had the highest prevalences of bipolar disease and low-income countries had the lowest. The United States had the highest prevalence of overall (4.4%) and annual (2.8%) disease, while India had the lowest (0.1% for both). Two exceptions to this rule were Japan, a high-income country with very low overall (0.7%) and annual (0.2%) prevalences, and Colombia, a low-income country with a high overall prevalence (2.6%).

The mean ages at onset were 18 years for bipolar disorder type I, 20 years for bipolar disorder type II, and 22 years for subthreshold bipolar disorder.

Patterns of comorbidity were remarkably consistent among the different countries. Three-fourths of patients with bipolar spectrum disorders also met criteria for other psychiatric disorders, and the majority had three or more of them. "Anxiety disorders, particularly panic attacks, were the most common comorbid conditions (63%), followed by behavior disorders (45%) and substance use disorders (37%)," Dr. Merikangas and her colleagues said (Arch. Gen. Psychiatry 2011;68:241-51).

The association between bipolar disorders and substance use disorders across the globe was particularly striking in light of the large differences between countries in rates of substance use and abuse. "This suggests that [bipolar disorder] can be considered a risk factor for the development of substance use disorders ... [and supports] the need for careful probing of a history of bipolarity among those with substance use disorders," they said.

The proportion of patients with suicidal behaviors rose with increasing severity of bipolar disease. Approximately 10% of those with subthreshold bipolar disorder, 20% of those with bipolar disorder type II, and 25% of those with bipolar disorder type I said that they had attempted suicide over the last 12 months.

This "striking" finding of suicidality, together with the early age at onset and the strong association with other mental health disorders, provides "further documentation of the individual and societal disability associated with this disorder," they noted.

A substantially higher proportion of patients in high-income countries, compared with middle- or low-income countries, reported having used mental health services. Lifetime use of such services was 50% in high-income countries, 34% in middle-income countries, and 25% in low-income countries.

"Because [bipolar disorder] has an average age at onset at one of the most critical periods of educational, occupational, and social development, its consequences often lead to lifelong disability," the investigators said, and this lack of mental health treatment, especially in low-income countries, is therefore "alarming."

"These data also provide the first aggregate international evidence, to our knowledge, that supports the validity of the spectrum concept of bipolarity," they added. The proportion of mood episodes rated as clinically severe, as well as the proportion in which patients reported severe impairment of work, home management, social life, and close relationships, were directly associated with increasingly severe forms of bipolar disease.

This study was supported by the NIMH’s Intramural Research Program, the U.S. Public Health Service, numerous organizations in the participating countries, and numerous drug companies. Dr. Merikangas reported her affiliation with the Intramural Research Program, and one of her associates, Ronald Kessler, Ph.D., reported ties to numerous pharmaceutical companies.

Worldwide, the prevalence of bipolar disorder type I is estimated to be 0.6%, that of type II is 0.4%, and that of subthreshold bipolar disorder is 1.4%, yielding a total bipolar disorder spectrum prevalence of 2.4%, according to a new report in the March issue of the Archives of General Psychiatry.

These estimates were derived from what the investigators described as the first international data ever collected using Diagnostic and Statistical Manual–IV definitions for the full spectrum of bipolar disorders and standardized measures to survey nationally representative samples in 11 low-income, middle-income, and high-income countries.

Even though prevalence varied from one country to the next, disease severity, impact on daily life, and patterns of comorbidity remained strikingly similar, said Kathleen R. Merikangas, Ph.D., of the Intramural Research Program of the National Institute of Mental Health (NIMH), and her associates in the World Mental Health Survey Initiative.

This World Health Organization (WHO) project "aims to obtain accurate cross-national information on the prevalence, correlates, and service patterns of mental disorders." The investigators conducted in-person, population-based surveys of 61,392 adults in Brazil, Colombia, Mexico, the United States, Bulgaria, Romania, China, India, Japan, Lebanon, and New Zealand.

In addition to the overall prevalences, they found that the 1-year prevalence of bipolar disorder type I was 0.4%, that of bipolar disorder type II was 0.3%, and that of subthreshold bipolar disorder was 0.8%, for a total bipolar spectrum disorder annual prevalence of 1.5%.

In general, high-income countries had the highest prevalences of bipolar disease and low-income countries had the lowest. The United States had the highest prevalence of overall (4.4%) and annual (2.8%) disease, while India had the lowest (0.1% for both). Two exceptions to this rule were Japan, a high-income country with very low overall (0.7%) and annual (0.2%) prevalences, and Colombia, a low-income country with a high overall prevalence (2.6%).

The mean ages at onset were 18 years for bipolar disorder type I, 20 years for bipolar disorder type II, and 22 years for subthreshold bipolar disorder.

Patterns of comorbidity were remarkably consistent among the different countries. Three-fourths of patients with bipolar spectrum disorders also met criteria for other psychiatric disorders, and the majority had three or more of them. "Anxiety disorders, particularly panic attacks, were the most common comorbid conditions (63%), followed by behavior disorders (45%) and substance use disorders (37%)," Dr. Merikangas and her colleagues said (Arch. Gen. Psychiatry 2011;68:241-51).

The association between bipolar disorders and substance use disorders across the globe was particularly striking in light of the large differences between countries in rates of substance use and abuse. "This suggests that [bipolar disorder] can be considered a risk factor for the development of substance use disorders ... [and supports] the need for careful probing of a history of bipolarity among those with substance use disorders," they said.

The proportion of patients with suicidal behaviors rose with increasing severity of bipolar disease. Approximately 10% of those with subthreshold bipolar disorder, 20% of those with bipolar disorder type II, and 25% of those with bipolar disorder type I said that they had attempted suicide over the last 12 months.

This "striking" finding of suicidality, together with the early age at onset and the strong association with other mental health disorders, provides "further documentation of the individual and societal disability associated with this disorder," they noted.

A substantially higher proportion of patients in high-income countries, compared with middle- or low-income countries, reported having used mental health services. Lifetime use of such services was 50% in high-income countries, 34% in middle-income countries, and 25% in low-income countries.

"Because [bipolar disorder] has an average age at onset at one of the most critical periods of educational, occupational, and social development, its consequences often lead to lifelong disability," the investigators said, and this lack of mental health treatment, especially in low-income countries, is therefore "alarming."

"These data also provide the first aggregate international evidence, to our knowledge, that supports the validity of the spectrum concept of bipolarity," they added. The proportion of mood episodes rated as clinically severe, as well as the proportion in which patients reported severe impairment of work, home management, social life, and close relationships, were directly associated with increasingly severe forms of bipolar disease.

This study was supported by the NIMH’s Intramural Research Program, the U.S. Public Health Service, numerous organizations in the participating countries, and numerous drug companies. Dr. Merikangas reported her affiliation with the Intramural Research Program, and one of her associates, Ronald Kessler, Ph.D., reported ties to numerous pharmaceutical companies.

Worldwide, the prevalence of bipolar disorder type I is estimated to be 0.6%, that of type II is 0.4%, and that of subthreshold bipolar disorder is 1.4%, yielding a total bipolar disorder spectrum prevalence of 2.4%, according to a new report in the March issue of the Archives of General Psychiatry.

These estimates were derived from what the investigators described as the first international data ever collected using Diagnostic and Statistical Manual–IV definitions for the full spectrum of bipolar disorders and standardized measures to survey nationally representative samples in 11 low-income, middle-income, and high-income countries.

Even though prevalence varied from one country to the next, disease severity, impact on daily life, and patterns of comorbidity remained strikingly similar, said Kathleen R. Merikangas, Ph.D., of the Intramural Research Program of the National Institute of Mental Health (NIMH), and her associates in the World Mental Health Survey Initiative.

This World Health Organization (WHO) project "aims to obtain accurate cross-national information on the prevalence, correlates, and service patterns of mental disorders." The investigators conducted in-person, population-based surveys of 61,392 adults in Brazil, Colombia, Mexico, the United States, Bulgaria, Romania, China, India, Japan, Lebanon, and New Zealand.

In addition to the overall prevalences, they found that the 1-year prevalence of bipolar disorder type I was 0.4%, that of bipolar disorder type II was 0.3%, and that of subthreshold bipolar disorder was 0.8%, for a total bipolar spectrum disorder annual prevalence of 1.5%.

In general, high-income countries had the highest prevalences of bipolar disease and low-income countries had the lowest. The United States had the highest prevalence of overall (4.4%) and annual (2.8%) disease, while India had the lowest (0.1% for both). Two exceptions to this rule were Japan, a high-income country with very low overall (0.7%) and annual (0.2%) prevalences, and Colombia, a low-income country with a high overall prevalence (2.6%).

The mean ages at onset were 18 years for bipolar disorder type I, 20 years for bipolar disorder type II, and 22 years for subthreshold bipolar disorder.

Patterns of comorbidity were remarkably consistent among the different countries. Three-fourths of patients with bipolar spectrum disorders also met criteria for other psychiatric disorders, and the majority had three or more of them. "Anxiety disorders, particularly panic attacks, were the most common comorbid conditions (63%), followed by behavior disorders (45%) and substance use disorders (37%)," Dr. Merikangas and her colleagues said (Arch. Gen. Psychiatry 2011;68:241-51).

The association between bipolar disorders and substance use disorders across the globe was particularly striking in light of the large differences between countries in rates of substance use and abuse. "This suggests that [bipolar disorder] can be considered a risk factor for the development of substance use disorders ... [and supports] the need for careful probing of a history of bipolarity among those with substance use disorders," they said.

The proportion of patients with suicidal behaviors rose with increasing severity of bipolar disease. Approximately 10% of those with subthreshold bipolar disorder, 20% of those with bipolar disorder type II, and 25% of those with bipolar disorder type I said that they had attempted suicide over the last 12 months.

This "striking" finding of suicidality, together with the early age at onset and the strong association with other mental health disorders, provides "further documentation of the individual and societal disability associated with this disorder," they noted.

A substantially higher proportion of patients in high-income countries, compared with middle- or low-income countries, reported having used mental health services. Lifetime use of such services was 50% in high-income countries, 34% in middle-income countries, and 25% in low-income countries.

"Because [bipolar disorder] has an average age at onset at one of the most critical periods of educational, occupational, and social development, its consequences often lead to lifelong disability," the investigators said, and this lack of mental health treatment, especially in low-income countries, is therefore "alarming."

"These data also provide the first aggregate international evidence, to our knowledge, that supports the validity of the spectrum concept of bipolarity," they added. The proportion of mood episodes rated as clinically severe, as well as the proportion in which patients reported severe impairment of work, home management, social life, and close relationships, were directly associated with increasingly severe forms of bipolar disease.

This study was supported by the NIMH’s Intramural Research Program, the U.S. Public Health Service, numerous organizations in the participating countries, and numerous drug companies. Dr. Merikangas reported her affiliation with the Intramural Research Program, and one of her associates, Ronald Kessler, Ph.D., reported ties to numerous pharmaceutical companies.

Worldwide, the prevalence of bipolar disorder type I is estimated to be 0.6%, that of type II is 0.4%, and that of subthreshold bipolar disorder is 1.4%, yielding a total bipolar disorder spectrum prevalence of 2.4%, according to a new report in the March issue of the Archives of General Psychiatry.

These estimates were derived from what the investigators described as the first international data ever collected using Diagnostic and Statistical Manual–IV definitions for the full spectrum of bipolar disorders and standardized measures to survey nationally representative samples in 11 low-income, middle-income, and high-income countries.

Even though prevalence varied from one country to the next, disease severity, impact on daily life, and patterns of comorbidity remained strikingly similar, said Kathleen R. Merikangas, Ph.D., of the Intramural Research Program of the National Institute of Mental Health (NIMH), and her associates in the World Mental Health Survey Initiative.

This World Health Organization (WHO) project "aims to obtain accurate cross-national information on the prevalence, correlates, and service patterns of mental disorders." The investigators conducted in-person, population-based surveys of 61,392 adults in Brazil, Colombia, Mexico, the United States, Bulgaria, Romania, China, India, Japan, Lebanon, and New Zealand.

In addition to the overall prevalences, they found that the 1-year prevalence of bipolar disorder type I was 0.4%, that of bipolar disorder type II was 0.3%, and that of subthreshold bipolar disorder was 0.8%, for a total bipolar spectrum disorder annual prevalence of 1.5%.

In general, high-income countries had the highest prevalences of bipolar disease and low-income countries had the lowest. The United States had the highest prevalence of overall (4.4%) and annual (2.8%) disease, while India had the lowest (0.1% for both). Two exceptions to this rule were Japan, a high-income country with very low overall (0.7%) and annual (0.2%) prevalences, and Colombia, a low-income country with a high overall prevalence (2.6%).

The mean ages at onset were 18 years for bipolar disorder type I, 20 years for bipolar disorder type II, and 22 years for subthreshold bipolar disorder.

Patterns of comorbidity were remarkably consistent among the different countries. Three-fourths of patients with bipolar spectrum disorders also met criteria for other psychiatric disorders, and the majority had three or more of them. "Anxiety disorders, particularly panic attacks, were the most common comorbid conditions (63%), followed by behavior disorders (45%) and substance use disorders (37%)," Dr. Merikangas and her colleagues said (Arch. Gen. Psychiatry 2011;68:241-51).

The association between bipolar disorders and substance use disorders across the globe was particularly striking in light of the large differences between countries in rates of substance use and abuse. "This suggests that [bipolar disorder] can be considered a risk factor for the development of substance use disorders ... [and supports] the need for careful probing of a history of bipolarity among those with substance use disorders," they said.

The proportion of patients with suicidal behaviors rose with increasing severity of bipolar disease. Approximately 10% of those with subthreshold bipolar disorder, 20% of those with bipolar disorder type II, and 25% of those with bipolar disorder type I said that they had attempted suicide over the last 12 months.

This "striking" finding of suicidality, together with the early age at onset and the strong association with other mental health disorders, provides "further documentation of the individual and societal disability associated with this disorder," they noted.

A substantially higher proportion of patients in high-income countries, compared with middle- or low-income countries, reported having used mental health services. Lifetime use of such services was 50% in high-income countries, 34% in middle-income countries, and 25% in low-income countries.

"Because [bipolar disorder] has an average age at onset at one of the most critical periods of educational, occupational, and social development, its consequences often lead to lifelong disability," the investigators said, and this lack of mental health treatment, especially in low-income countries, is therefore "alarming."

"These data also provide the first aggregate international evidence, to our knowledge, that supports the validity of the spectrum concept of bipolarity," they added. The proportion of mood episodes rated as clinically severe, as well as the proportion in which patients reported severe impairment of work, home management, social life, and close relationships, were directly associated with increasingly severe forms of bipolar disease.

This study was supported by the NIMH’s Intramural Research Program, the U.S. Public Health Service, numerous organizations in the participating countries, and numerous drug companies. Dr. Merikangas reported her affiliation with the Intramural Research Program, and one of her associates, Ronald Kessler, Ph.D., reported ties to numerous pharmaceutical companies.

Worldwide, the prevalence of bipolar disorder type I is estimated to be 0.6%, that of type II is 0.4%, and that of subthreshold bipolar disorder is 1.4%, yielding a total bipolar disorder spectrum prevalence of 2.4%, according to a new report in the March issue of the Archives of General Psychiatry.

These estimates were derived from what the investigators described as the first international data ever collected using Diagnostic and Statistical Manual–IV definitions for the full spectrum of bipolar disorders and standardized measures to survey nationally representative samples in 11 low-income, middle-income, and high-income countries.

Even though prevalence varied from one country to the next, disease severity, impact on daily life, and patterns of comorbidity remained strikingly similar, said Kathleen R. Merikangas, Ph.D., of the Intramural Research Program of the National Institute of Mental Health (NIMH), and her associates in the World Mental Health Survey Initiative.

This World Health Organization (WHO) project "aims to obtain accurate cross-national information on the prevalence, correlates, and service patterns of mental disorders." The investigators conducted in-person, population-based surveys of 61,392 adults in Brazil, Colombia, Mexico, the United States, Bulgaria, Romania, China, India, Japan, Lebanon, and New Zealand.

In addition to the overall prevalences, they found that the 1-year prevalence of bipolar disorder type I was 0.4%, that of bipolar disorder type II was 0.3%, and that of subthreshold bipolar disorder was 0.8%, for a total bipolar spectrum disorder annual prevalence of 1.5%.

In general, high-income countries had the highest prevalences of bipolar disease and low-income countries had the lowest. The United States had the highest prevalence of overall (4.4%) and annual (2.8%) disease, while India had the lowest (0.1% for both). Two exceptions to this rule were Japan, a high-income country with very low overall (0.7%) and annual (0.2%) prevalences, and Colombia, a low-income country with a high overall prevalence (2.6%).

The mean ages at onset were 18 years for bipolar disorder type I, 20 years for bipolar disorder type II, and 22 years for subthreshold bipolar disorder.

Patterns of comorbidity were remarkably consistent among the different countries. Three-fourths of patients with bipolar spectrum disorders also met criteria for other psychiatric disorders, and the majority had three or more of them. "Anxiety disorders, particularly panic attacks, were the most common comorbid conditions (63%), followed by behavior disorders (45%) and substance use disorders (37%)," Dr. Merikangas and her colleagues said (Arch. Gen. Psychiatry 2011;68:241-51).

The association between bipolar disorders and substance use disorders across the globe was particularly striking in light of the large differences between countries in rates of substance use and abuse. "This suggests that [bipolar disorder] can be considered a risk factor for the development of substance use disorders ... [and supports] the need for careful probing of a history of bipolarity among those with substance use disorders," they said.

The proportion of patients with suicidal behaviors rose with increasing severity of bipolar disease. Approximately 10% of those with subthreshold bipolar disorder, 20% of those with bipolar disorder type II, and 25% of those with bipolar disorder type I said that they had attempted suicide over the last 12 months.

This "striking" finding of suicidality, together with the early age at onset and the strong association with other mental health disorders, provides "further documentation of the individual and societal disability associated with this disorder," they noted.

A substantially higher proportion of patients in high-income countries, compared with middle- or low-income countries, reported having used mental health services. Lifetime use of such services was 50% in high-income countries, 34% in middle-income countries, and 25% in low-income countries.

"Because [bipolar disorder] has an average age at onset at one of the most critical periods of educational, occupational, and social development, its consequences often lead to lifelong disability," the investigators said, and this lack of mental health treatment, especially in low-income countries, is therefore "alarming."

"These data also provide the first aggregate international evidence, to our knowledge, that supports the validity of the spectrum concept of bipolarity," they added. The proportion of mood episodes rated as clinically severe, as well as the proportion in which patients reported severe impairment of work, home management, social life, and close relationships, were directly associated with increasingly severe forms of bipolar disease.

This study was supported by the NIMH’s Intramural Research Program, the U.S. Public Health Service, numerous organizations in the participating countries, and numerous drug companies. Dr. Merikangas reported her affiliation with the Intramural Research Program, and one of her associates, Ronald Kessler, Ph.D., reported ties to numerous pharmaceutical companies.

Worldwide, the prevalence of bipolar disorder type I is estimated to be 0.6%, that of type II is 0.4%, and that of subthreshold bipolar disorder is 1.4%, yielding a total bipolar disorder spectrum prevalence of 2.4%, according to a new report in the March issue of the Archives of General Psychiatry.

These estimates were derived from what the investigators described as the first international data ever collected using Diagnostic and Statistical Manual–IV definitions for the full spectrum of bipolar disorders and standardized measures to survey nationally representative samples in 11 low-income, middle-income, and high-income countries.

Even though prevalence varied from one country to the next, disease severity, impact on daily life, and patterns of comorbidity remained strikingly similar, said Kathleen R. Merikangas, Ph.D., of the Intramural Research Program of the National Institute of Mental Health (NIMH), and her associates in the World Mental Health Survey Initiative.

This World Health Organization (WHO) project "aims to obtain accurate cross-national information on the prevalence, correlates, and service patterns of mental disorders." The investigators conducted in-person, population-based surveys of 61,392 adults in Brazil, Colombia, Mexico, the United States, Bulgaria, Romania, China, India, Japan, Lebanon, and New Zealand.

In addition to the overall prevalences, they found that the 1-year prevalence of bipolar disorder type I was 0.4%, that of bipolar disorder type II was 0.3%, and that of subthreshold bipolar disorder was 0.8%, for a total bipolar spectrum disorder annual prevalence of 1.5%.

In general, high-income countries had the highest prevalences of bipolar disease and low-income countries had the lowest. The United States had the highest prevalence of overall (4.4%) and annual (2.8%) disease, while India had the lowest (0.1% for both). Two exceptions to this rule were Japan, a high-income country with very low overall (0.7%) and annual (0.2%) prevalences, and Colombia, a low-income country with a high overall prevalence (2.6%).

The mean ages at onset were 18 years for bipolar disorder type I, 20 years for bipolar disorder type II, and 22 years for subthreshold bipolar disorder.

Patterns of comorbidity were remarkably consistent among the different countries. Three-fourths of patients with bipolar spectrum disorders also met criteria for other psychiatric disorders, and the majority had three or more of them. "Anxiety disorders, particularly panic attacks, were the most common comorbid conditions (63%), followed by behavior disorders (45%) and substance use disorders (37%)," Dr. Merikangas and her colleagues said (Arch. Gen. Psychiatry 2011;68:241-51).

The association between bipolar disorders and substance use disorders across the globe was particularly striking in light of the large differences between countries in rates of substance use and abuse. "This suggests that [bipolar disorder] can be considered a risk factor for the development of substance use disorders ... [and supports] the need for careful probing of a history of bipolarity among those with substance use disorders," they said.

The proportion of patients with suicidal behaviors rose with increasing severity of bipolar disease. Approximately 10% of those with subthreshold bipolar disorder, 20% of those with bipolar disorder type II, and 25% of those with bipolar disorder type I said that they had attempted suicide over the last 12 months.

This "striking" finding of suicidality, together with the early age at onset and the strong association with other mental health disorders, provides "further documentation of the individual and societal disability associated with this disorder," they noted.

A substantially higher proportion of patients in high-income countries, compared with middle- or low-income countries, reported having used mental health services. Lifetime use of such services was 50% in high-income countries, 34% in middle-income countries, and 25% in low-income countries.

"Because [bipolar disorder] has an average age at onset at one of the most critical periods of educational, occupational, and social development, its consequences often lead to lifelong disability," the investigators said, and this lack of mental health treatment, especially in low-income countries, is therefore "alarming."

"These data also provide the first aggregate international evidence, to our knowledge, that supports the validity of the spectrum concept of bipolarity," they added. The proportion of mood episodes rated as clinically severe, as well as the proportion in which patients reported severe impairment of work, home management, social life, and close relationships, were directly associated with increasingly severe forms of bipolar disease.

This study was supported by the NIMH’s Intramural Research Program, the U.S. Public Health Service, numerous organizations in the participating countries, and numerous drug companies. Dr. Merikangas reported her affiliation with the Intramural Research Program, and one of her associates, Ronald Kessler, Ph.D., reported ties to numerous pharmaceutical companies.

Worldwide, the prevalence of bipolar disorder type I is estimated to be 0.6%, that of type II is 0.4%, and that of subthreshold bipolar disorder is 1.4%, yielding a total bipolar disorder spectrum prevalence of 2.4%, according to a new report in the March issue of the Archives of General Psychiatry.

These estimates were derived from what the investigators described as the first international data ever collected using Diagnostic and Statistical Manual–IV definitions for the full spectrum of bipolar disorders and standardized measures to survey nationally representative samples in 11 low-income, middle-income, and high-income countries.

Even though prevalence varied from one country to the next, disease severity, impact on daily life, and patterns of comorbidity remained strikingly similar, said Kathleen R. Merikangas, Ph.D., of the Intramural Research Program of the National Institute of Mental Health (NIMH), and her associates in the World Mental Health Survey Initiative.

This World Health Organization (WHO) project "aims to obtain accurate cross-national information on the prevalence, correlates, and service patterns of mental disorders." The investigators conducted in-person, population-based surveys of 61,392 adults in Brazil, Colombia, Mexico, the United States, Bulgaria, Romania, China, India, Japan, Lebanon, and New Zealand.

In addition to the overall prevalences, they found that the 1-year prevalence of bipolar disorder type I was 0.4%, that of bipolar disorder type II was 0.3%, and that of subthreshold bipolar disorder was 0.8%, for a total bipolar spectrum disorder annual prevalence of 1.5%.

In general, high-income countries had the highest prevalences of bipolar disease and low-income countries had the lowest. The United States had the highest prevalence of overall (4.4%) and annual (2.8%) disease, while India had the lowest (0.1% for both). Two exceptions to this rule were Japan, a high-income country with very low overall (0.7%) and annual (0.2%) prevalences, and Colombia, a low-income country with a high overall prevalence (2.6%).

The mean ages at onset were 18 years for bipolar disorder type I, 20 years for bipolar disorder type II, and 22 years for subthreshold bipolar disorder.

Patterns of comorbidity were remarkably consistent among the different countries. Three-fourths of patients with bipolar spectrum disorders also met criteria for other psychiatric disorders, and the majority had three or more of them. "Anxiety disorders, particularly panic attacks, were the most common comorbid conditions (63%), followed by behavior disorders (45%) and substance use disorders (37%)," Dr. Merikangas and her colleagues said (Arch. Gen. Psychiatry 2011;68:241-51).

The association between bipolar disorders and substance use disorders across the globe was particularly striking in light of the large differences between countries in rates of substance use and abuse. "This suggests that [bipolar disorder] can be considered a risk factor for the development of substance use disorders ... [and supports] the need for careful probing of a history of bipolarity among those with substance use disorders," they said.

The proportion of patients with suicidal behaviors rose with increasing severity of bipolar disease. Approximately 10% of those with subthreshold bipolar disorder, 20% of those with bipolar disorder type II, and 25% of those with bipolar disorder type I said that they had attempted suicide over the last 12 months.

This "striking" finding of suicidality, together with the early age at onset and the strong association with other mental health disorders, provides "further documentation of the individual and societal disability associated with this disorder," they noted.

A substantially higher proportion of patients in high-income countries, compared with middle- or low-income countries, reported having used mental health services. Lifetime use of such services was 50% in high-income countries, 34% in middle-income countries, and 25% in low-income countries.

"Because [bipolar disorder] has an average age at onset at one of the most critical periods of educational, occupational, and social development, its consequences often lead to lifelong disability," the investigators said, and this lack of mental health treatment, especially in low-income countries, is therefore "alarming."

"These data also provide the first aggregate international evidence, to our knowledge, that supports the validity of the spectrum concept of bipolarity," they added. The proportion of mood episodes rated as clinically severe, as well as the proportion in which patients reported severe impairment of work, home management, social life, and close relationships, were directly associated with increasingly severe forms of bipolar disease.

This study was supported by the NIMH’s Intramural Research Program, the U.S. Public Health Service, numerous organizations in the participating countries, and numerous drug companies. Dr. Merikangas reported her affiliation with the Intramural Research Program, and one of her associates, Ronald Kessler, Ph.D., reported ties to numerous pharmaceutical companies.

Worldwide, the prevalence of bipolar disorder type I is estimated to be 0.6%, that of type II is 0.4%, and that of subthreshold bipolar disorder is 1.4%, yielding a total bipolar disorder spectrum prevalence of 2.4%, according to a new report in the March issue of the Archives of General Psychiatry.

These estimates were derived from what the investigators described as the first international data ever collected using Diagnostic and Statistical Manual–IV definitions for the full spectrum of bipolar disorders and standardized measures to survey nationally representative samples in 11 low-income, middle-income, and high-income countries.

Even though prevalence varied from one country to the next, disease severity, impact on daily life, and patterns of comorbidity remained strikingly similar, said Kathleen R. Merikangas, Ph.D., of the Intramural Research Program of the National Institute of Mental Health (NIMH), and her associates in the World Mental Health Survey Initiative.

This World Health Organization (WHO) project "aims to obtain accurate cross-national information on the prevalence, correlates, and service patterns of mental disorders." The investigators conducted in-person, population-based surveys of 61,392 adults in Brazil, Colombia, Mexico, the United States, Bulgaria, Romania, China, India, Japan, Lebanon, and New Zealand.

In addition to the overall prevalences, they found that the 1-year prevalence of bipolar disorder type I was 0.4%, that of bipolar disorder type II was 0.3%, and that of subthreshold bipolar disorder was 0.8%, for a total bipolar spectrum disorder annual prevalence of 1.5%.

In general, high-income countries had the highest prevalences of bipolar disease and low-income countries had the lowest. The United States had the highest prevalence of overall (4.4%) and annual (2.8%) disease, while India had the lowest (0.1% for both). Two exceptions to this rule were Japan, a high-income country with very low overall (0.7%) and annual (0.2%) prevalences, and Colombia, a low-income country with a high overall prevalence (2.6%).

The mean ages at onset were 18 years for bipolar disorder type I, 20 years for bipolar disorder type II, and 22 years for subthreshold bipolar disorder.

Patterns of comorbidity were remarkably consistent among the different countries. Three-fourths of patients with bipolar spectrum disorders also met criteria for other psychiatric disorders, and the majority had three or more of them. "Anxiety disorders, particularly panic attacks, were the most common comorbid conditions (63%), followed by behavior disorders (45%) and substance use disorders (37%)," Dr. Merikangas and her colleagues said (Arch. Gen. Psychiatry 2011;68:241-51).

The association between bipolar disorders and substance use disorders across the globe was particularly striking in light of the large differences between countries in rates of substance use and abuse. "This suggests that [bipolar disorder] can be considered a risk factor for the development of substance use disorders ... [and supports] the need for careful probing of a history of bipolarity among those with substance use disorders," they said.

The proportion of patients with suicidal behaviors rose with increasing severity of bipolar disease. Approximately 10% of those with subthreshold bipolar disorder, 20% of those with bipolar disorder type II, and 25% of those with bipolar disorder type I said that they had attempted suicide over the last 12 months.

This "striking" finding of suicidality, together with the early age at onset and the strong association with other mental health disorders, provides "further documentation of the individual and societal disability associated with this disorder," they noted.

A substantially higher proportion of patients in high-income countries, compared with middle- or low-income countries, reported having used mental health services. Lifetime use of such services was 50% in high-income countries, 34% in middle-income countries, and 25% in low-income countries.

"Because [bipolar disorder] has an average age at onset at one of the most critical periods of educational, occupational, and social development, its consequences often lead to lifelong disability," the investigators said, and this lack of mental health treatment, especially in low-income countries, is therefore "alarming."

"These data also provide the first aggregate international evidence, to our knowledge, that supports the validity of the spectrum concept of bipolarity," they added. The proportion of mood episodes rated as clinically severe, as well as the proportion in which patients reported severe impairment of work, home management, social life, and close relationships, were directly associated with increasingly severe forms of bipolar disease.

This study was supported by the NIMH’s Intramural Research Program, the U.S. Public Health Service, numerous organizations in the participating countries, and numerous drug companies. Dr. Merikangas reported her affiliation with the Intramural Research Program, and one of her associates, Ronald Kessler, Ph.D., reported ties to numerous pharmaceutical companies.

A variety of "exergames" raised children’s energy expenditure to a moderate to vigorous level of intensity, comparing favorably with treadmill walking at 3 mph, according to a report published online in the Archives of Pediatrics and Adolescent Medicine.

Middle school–aged children showed a four- to eightfold increase in energy expenditure when they played any of six interactive video or electronic games that featured player movement similar to what would occur with real-life participation in the games, said Bruce W. Bailey, Ph.D., of the department of exercise sciences at Brigham Young University, Provo, Utah, and Kyle McInnis, Sc.D., of the department of exercise and health sciences at the University of Massachusetts, Boston.

Photo (c)Christophe Schmid/ Fotolia.com

The investigators assessed energy expenditure with three commercial and three consumer exergaming systems with multiple games as well as multiple levels of intensity within each game. These had been selected to include the most aerobically challenging games available and included running, dancing, and simulated boxing.

This is the first published study to examine "commercial exergaming equipment that is currently being marketed to schools and fitness facilities as an alternative form of exercise," the investigators noted.

The 19 boys and 20 girls, aged 9-13 years, were healthy and of diverse ethnic backgrounds (57% African American, 11% white, 12% Hispanic, and 20% other). A total of 21 subjects (54%) were either overweight or at risk for overweight, while 18 (46%) were of normal weight.

Energy expenditure was measured using indirect calorimetry and a portable metabolic cart. The subjects were evaluated at rest, during 10 minutes of activity as they rotated through all of the games, and while walking on a treadmill.

Every game significantly raised energy expenditure to a moderate to vigorous level, and four of the six games raised it above the level expended during treadmill walking. "This level of intensity is consistent with current physical activity recommendations for children and can be used to alter energy balance," Dr. Bailey and Dr. McInnis said (Arch. Pediatr. Adolesc. Med. 2011 [doi:10.1001/archpediatrics.2011.15]).

Surprisingly, energy expenditure was the same between subjects in the top 15% of body mass index (BMI) and subjects with lower BMI. In fact, higher-weight children enjoyed one particular system, Sportwall, more than did normal-weight children.

"Sportwall was unique in that it was played in teams [of four to five children], and the activity was intermittent and of a high intensity. Thus, the social interaction and intermittent high-intensity nature of the activity may be why the children with higher BMIs enjoyed it more," the researchers said.

Boys and girls reported equally high levels of enjoyment with all the games. Boys tended to like the boxing game more than girls did, and girls preferred the dancing game more than boys did.

"Although exergaming is most likely not the solution to the epidemic of reduced physical activity in children, it appears to be a potentially innovative strategy that can be used to reduce sedentary time, increase adherence to exercise programs, and promote enjoyment of physical activity. This may be especially important for at-risk populations, specifically children who carry excess body weight," the investigators said.

Future studies should assess how prolonged participation in exergaming alters energy balance and adiposity, Dr. Bailey and Dr. McInnis added.

James F. Sallis, Ph.D., of the department of psychology at San Diego State University, said that the findings of this study "show how much physical activity exergames have the potential to yield. The next question is how much activity they actually yield."

Clinicians must keep in mind that the effect on health outcomes depends on the frequency, intensity, duration, and types of exergames played in everyday life, and that such use typically declines within a few weeks or months.

Nevertheless, "the use of such games is an approach that should be encouraged, improved, and expanded," he said in an editorial comment accompanying the study (Arch. Pediatr. Adolesc. Med. 2011 [doi:10.1001/archpediatrics.2011.16]). "We need to pursue every avenue for getting adolescents active and not place our hopes on any single option."

Dr. Sallis reported financial ties to Santech Inc. and is the cofounder of the Sports, Play, and Active Recreation for Kids (SPARK) program of School Specialty Inc. His preparation of the editorial comment from which these remarks were taken was supported by the Robert Wood Johnson Foundation.

This study was funded by the University of Massachusetts. Dr. Bailey and Dr. McInnis reported no financial disclosures.

A variety of "exergames" raised children’s energy expenditure to a moderate to vigorous level of intensity, comparing favorably with treadmill walking at 3 mph, according to a report published online in the Archives of Pediatrics and Adolescent Medicine.

Middle school–aged children showed a four- to eightfold increase in energy expenditure when they played any of six interactive video or electronic games that featured player movement similar to what would occur with real-life participation in the games, said Bruce W. Bailey, Ph.D., of the department of exercise sciences at Brigham Young University, Provo, Utah, and Kyle McInnis, Sc.D., of the department of exercise and health sciences at the University of Massachusetts, Boston.

Photo (c)Christophe Schmid/ Fotolia.com

The investigators assessed energy expenditure with three commercial and three consumer exergaming systems with multiple games as well as multiple levels of intensity within each game. These had been selected to include the most aerobically challenging games available and included running, dancing, and simulated boxing.

This is the first published study to examine "commercial exergaming equipment that is currently being marketed to schools and fitness facilities as an alternative form of exercise," the investigators noted.

The 19 boys and 20 girls, aged 9-13 years, were healthy and of diverse ethnic backgrounds (57% African American, 11% white, 12% Hispanic, and 20% other). A total of 21 subjects (54%) were either overweight or at risk for overweight, while 18 (46%) were of normal weight.

Energy expenditure was measured using indirect calorimetry and a portable metabolic cart. The subjects were evaluated at rest, during 10 minutes of activity as they rotated through all of the games, and while walking on a treadmill.

Every game significantly raised energy expenditure to a moderate to vigorous level, and four of the six games raised it above the level expended during treadmill walking. "This level of intensity is consistent with current physical activity recommendations for children and can be used to alter energy balance," Dr. Bailey and Dr. McInnis said (Arch. Pediatr. Adolesc. Med. 2011 [doi:10.1001/archpediatrics.2011.15]).

Surprisingly, energy expenditure was the same between subjects in the top 15% of body mass index (BMI) and subjects with lower BMI. In fact, higher-weight children enjoyed one particular system, Sportwall, more than did normal-weight children.

"Sportwall was unique in that it was played in teams [of four to five children], and the activity was intermittent and of a high intensity. Thus, the social interaction and intermittent high-intensity nature of the activity may be why the children with higher BMIs enjoyed it more," the researchers said.

Boys and girls reported equally high levels of enjoyment with all the games. Boys tended to like the boxing game more than girls did, and girls preferred the dancing game more than boys did.

"Although exergaming is most likely not the solution to the epidemic of reduced physical activity in children, it appears to be a potentially innovative strategy that can be used to reduce sedentary time, increase adherence to exercise programs, and promote enjoyment of physical activity. This may be especially important for at-risk populations, specifically children who carry excess body weight," the investigators said.

Future studies should assess how prolonged participation in exergaming alters energy balance and adiposity, Dr. Bailey and Dr. McInnis added.

James F. Sallis, Ph.D., of the department of psychology at San Diego State University, said that the findings of this study "show how much physical activity exergames have the potential to yield. The next question is how much activity they actually yield."

Clinicians must keep in mind that the effect on health outcomes depends on the frequency, intensity, duration, and types of exergames played in everyday life, and that such use typically declines within a few weeks or months.

Nevertheless, "the use of such games is an approach that should be encouraged, improved, and expanded," he said in an editorial comment accompanying the study (Arch. Pediatr. Adolesc. Med. 2011 [doi:10.1001/archpediatrics.2011.16]). "We need to pursue every avenue for getting adolescents active and not place our hopes on any single option."

Dr. Sallis reported financial ties to Santech Inc. and is the cofounder of the Sports, Play, and Active Recreation for Kids (SPARK) program of School Specialty Inc. His preparation of the editorial comment from which these remarks were taken was supported by the Robert Wood Johnson Foundation.

This study was funded by the University of Massachusetts. Dr. Bailey and Dr. McInnis reported no financial disclosures.

A variety of "exergames" raised children’s energy expenditure to a moderate to vigorous level of intensity, comparing favorably with treadmill walking at 3 mph, according to a report published online in the Archives of Pediatrics and Adolescent Medicine.

Middle school–aged children showed a four- to eightfold increase in energy expenditure when they played any of six interactive video or electronic games that featured player movement similar to what would occur with real-life participation in the games, said Bruce W. Bailey, Ph.D., of the department of exercise sciences at Brigham Young University, Provo, Utah, and Kyle McInnis, Sc.D., of the department of exercise and health sciences at the University of Massachusetts, Boston.

Photo (c)Christophe Schmid/ Fotolia.com

The investigators assessed energy expenditure with three commercial and three consumer exergaming systems with multiple games as well as multiple levels of intensity within each game. These had been selected to include the most aerobically challenging games available and included running, dancing, and simulated boxing.

This is the first published study to examine "commercial exergaming equipment that is currently being marketed to schools and fitness facilities as an alternative form of exercise," the investigators noted.

The 19 boys and 20 girls, aged 9-13 years, were healthy and of diverse ethnic backgrounds (57% African American, 11% white, 12% Hispanic, and 20% other). A total of 21 subjects (54%) were either overweight or at risk for overweight, while 18 (46%) were of normal weight.

Energy expenditure was measured using indirect calorimetry and a portable metabolic cart. The subjects were evaluated at rest, during 10 minutes of activity as they rotated through all of the games, and while walking on a treadmill.

Every game significantly raised energy expenditure to a moderate to vigorous level, and four of the six games raised it above the level expended during treadmill walking. "This level of intensity is consistent with current physical activity recommendations for children and can be used to alter energy balance," Dr. Bailey and Dr. McInnis said (Arch. Pediatr. Adolesc. Med. 2011 [doi:10.1001/archpediatrics.2011.15]).

Surprisingly, energy expenditure was the same between subjects in the top 15% of body mass index (BMI) and subjects with lower BMI. In fact, higher-weight children enjoyed one particular system, Sportwall, more than did normal-weight children.

"Sportwall was unique in that it was played in teams [of four to five children], and the activity was intermittent and of a high intensity. Thus, the social interaction and intermittent high-intensity nature of the activity may be why the children with higher BMIs enjoyed it more," the researchers said.

Boys and girls reported equally high levels of enjoyment with all the games. Boys tended to like the boxing game more than girls did, and girls preferred the dancing game more than boys did.

"Although exergaming is most likely not the solution to the epidemic of reduced physical activity in children, it appears to be a potentially innovative strategy that can be used to reduce sedentary time, increase adherence to exercise programs, and promote enjoyment of physical activity. This may be especially important for at-risk populations, specifically children who carry excess body weight," the investigators said.

Future studies should assess how prolonged participation in exergaming alters energy balance and adiposity, Dr. Bailey and Dr. McInnis added.

James F. Sallis, Ph.D., of the department of psychology at San Diego State University, said that the findings of this study "show how much physical activity exergames have the potential to yield. The next question is how much activity they actually yield."

Clinicians must keep in mind that the effect on health outcomes depends on the frequency, intensity, duration, and types of exergames played in everyday life, and that such use typically declines within a few weeks or months.

Nevertheless, "the use of such games is an approach that should be encouraged, improved, and expanded," he said in an editorial comment accompanying the study (Arch. Pediatr. Adolesc. Med. 2011 [doi:10.1001/archpediatrics.2011.16]). "We need to pursue every avenue for getting adolescents active and not place our hopes on any single option."

Dr. Sallis reported financial ties to Santech Inc. and is the cofounder of the Sports, Play, and Active Recreation for Kids (SPARK) program of School Specialty Inc. His preparation of the editorial comment from which these remarks were taken was supported by the Robert Wood Johnson Foundation.

This study was funded by the University of Massachusetts. Dr. Bailey and Dr. McInnis reported no financial disclosures.

Patients with treatment-naive chronic hepatitis C virus infection who carry the rs12979860 C/C or rs8099917 T/T polymorphisms in the region of the IL28B gene are more likely than are noncarriers to show an early virologic response, as well as a sustained virologic response, to interferon-based therapy, Dr. Albert Stättermayer and his colleagues reported in the April issue of Clinical Gastroenterology and Hepatology.

Currently, the IL28B status of patients is obtained routinely and is used to predict the likelihood of their response to combined peginterferon/ribavirin therapy. If further prospective, controlled research confirms the findings of this study, determining patients’ status regarding these polymorphisms will also become useful in treatment planning, the researchers said (Clin. Gastroenterol. Hepatol. 2011 April [doi:10.1016/j.cgh.2010.07.019]).

Previous genome-wide association studies in patients with chronic HCV infection found strong associations between treatment response and the single-nucleotide polymorphisms (SNPs) rs12979860 and rs8099917. Dr. Stättermayer of the Medical University of Vienna and his associates examined these associations in 682 treatment-naive patients with chronic HCV.

The study subjects were patients who completed a full course of peginterferon-alpha plus ribavirin treatment in 2001-2009 at several medical centers across Austria. All had tested positive for HCV RNA for at least 6 months before beginning the therapy.

HCV RNA levels were assessed at baseline, after 4 weeks of treatment, and after 12 weeks of treatment. Treatment duration ranged from 24 to 72 weeks. Patients’ SNP status was determined from whole blood samples using real-time PCR.

A total of 36% of patients showed a rapid virologic response to peginterferon-based therapy. These patients also had a high rate of sustained virologic response (92%), compared with patients who had not shown a rapid response (46%). A rapid virologic response was the single strongest predictor of achieving a sustained virologic response, with an odds ratio of 17.

Overall, 63% of patients showed a sustained virologic response to peginterferon-based therapy. Patients with either the rs12979860 SNP or the 8099917 SNP were the most likely to achieve a sustained virologic response, with rates of over 80%. Baseline viral load, patient age, and fibrosis stage all were independent predictors of a sustained virologic response, but SNP status remained the most strongly predictive factor.

"Our study confirms the previously reported findings in various populations around the world," Dr. Stättermayer and his colleagues said. "The precise role of this polymorphism remains unknown. Based on our data, the SNP in the IL28B region appears to be associated with the early phases of viral clearance.

"Differences in viral load reduction between genotypes were detectable as early as week 2, which was the earliest time point evaluated." In addition, the divergence in treatment response peaked at week 4.

"The main focus of our study was the clinical applicability of genetic testing. The positive predictive value of rs12979860 C/C (the favorable genotype) for a sustained virologic response was high, but specificity and sensitivity were low," the researchers noted.

Their results indicate that "a patient with a low baseline viral load and 2 C alleles may benefit from standard of care, with a possible reduction of treatment duration to 24 weeks. On the other hand, T-allele carriers with advanced fibrosis and a high baseline viral load could possibly benefit from novel therapeutic strategies such as polymerase or protease inhibitors added to peginterferon and ribavirin, to maximize viral response," the investigators said.

Dr. Stättermayer had no disclosures, but several coauthors, including Dr. Peter Ferenci, the principal investigator, reported financial relationships with Roche. Dr. Ferenci receives an unrestricted research grant from Roche Austria.

Patients with treatment-naive chronic hepatitis C virus infection who carry the rs12979860 C/C or rs8099917 T/T polymorphisms in the region of the IL28B gene are more likely than are noncarriers to show an early virologic response, as well as a sustained virologic response, to interferon-based therapy, Dr. Albert Stättermayer and his colleagues reported in the April issue of Clinical Gastroenterology and Hepatology.

Currently, the IL28B status of patients is obtained routinely and is used to predict the likelihood of their response to combined peginterferon/ribavirin therapy. If further prospective, controlled research confirms the findings of this study, determining patients’ status regarding these polymorphisms will also become useful in treatment planning, the researchers said (Clin. Gastroenterol. Hepatol. 2011 April [doi:10.1016/j.cgh.2010.07.019]).

Previous genome-wide association studies in patients with chronic HCV infection found strong associations between treatment response and the single-nucleotide polymorphisms (SNPs) rs12979860 and rs8099917. Dr. Stättermayer of the Medical University of Vienna and his associates examined these associations in 682 treatment-naive patients with chronic HCV.

The study subjects were patients who completed a full course of peginterferon-alpha plus ribavirin treatment in 2001-2009 at several medical centers across Austria. All had tested positive for HCV RNA for at least 6 months before beginning the therapy.

HCV RNA levels were assessed at baseline, after 4 weeks of treatment, and after 12 weeks of treatment. Treatment duration ranged from 24 to 72 weeks. Patients’ SNP status was determined from whole blood samples using real-time PCR.

A total of 36% of patients showed a rapid virologic response to peginterferon-based therapy. These patients also had a high rate of sustained virologic response (92%), compared with patients who had not shown a rapid response (46%). A rapid virologic response was the single strongest predictor of achieving a sustained virologic response, with an odds ratio of 17.

Overall, 63% of patients showed a sustained virologic response to peginterferon-based therapy. Patients with either the rs12979860 SNP or the 8099917 SNP were the most likely to achieve a sustained virologic response, with rates of over 80%. Baseline viral load, patient age, and fibrosis stage all were independent predictors of a sustained virologic response, but SNP status remained the most strongly predictive factor.

"Our study confirms the previously reported findings in various populations around the world," Dr. Stättermayer and his colleagues said. "The precise role of this polymorphism remains unknown. Based on our data, the SNP in the IL28B region appears to be associated with the early phases of viral clearance.

"Differences in viral load reduction between genotypes were detectable as early as week 2, which was the earliest time point evaluated." In addition, the divergence in treatment response peaked at week 4.

"The main focus of our study was the clinical applicability of genetic testing. The positive predictive value of rs12979860 C/C (the favorable genotype) for a sustained virologic response was high, but specificity and sensitivity were low," the researchers noted.

Their results indicate that "a patient with a low baseline viral load and 2 C alleles may benefit from standard of care, with a possible reduction of treatment duration to 24 weeks. On the other hand, T-allele carriers with advanced fibrosis and a high baseline viral load could possibly benefit from novel therapeutic strategies such as polymerase or protease inhibitors added to peginterferon and ribavirin, to maximize viral response," the investigators said.

Dr. Stättermayer had no disclosures, but several coauthors, including Dr. Peter Ferenci, the principal investigator, reported financial relationships with Roche. Dr. Ferenci receives an unrestricted research grant from Roche Austria.

Patients with treatment-naive chronic hepatitis C virus infection who carry the rs12979860 C/C or rs8099917 T/T polymorphisms in the region of the IL28B gene are more likely than are noncarriers to show an early virologic response, as well as a sustained virologic response, to interferon-based therapy, Dr. Albert Stättermayer and his colleagues reported in the April issue of Clinical Gastroenterology and Hepatology.

Currently, the IL28B status of patients is obtained routinely and is used to predict the likelihood of their response to combined peginterferon/ribavirin therapy. If further prospective, controlled research confirms the findings of this study, determining patients’ status regarding these polymorphisms will also become useful in treatment planning, the researchers said (Clin. Gastroenterol. Hepatol. 2011 April [doi:10.1016/j.cgh.2010.07.019]).

Previous genome-wide association studies in patients with chronic HCV infection found strong associations between treatment response and the single-nucleotide polymorphisms (SNPs) rs12979860 and rs8099917. Dr. Stättermayer of the Medical University of Vienna and his associates examined these associations in 682 treatment-naive patients with chronic HCV.

The study subjects were patients who completed a full course of peginterferon-alpha plus ribavirin treatment in 2001-2009 at several medical centers across Austria. All had tested positive for HCV RNA for at least 6 months before beginning the therapy.

HCV RNA levels were assessed at baseline, after 4 weeks of treatment, and after 12 weeks of treatment. Treatment duration ranged from 24 to 72 weeks. Patients’ SNP status was determined from whole blood samples using real-time PCR.

A total of 36% of patients showed a rapid virologic response to peginterferon-based therapy. These patients also had a high rate of sustained virologic response (92%), compared with patients who had not shown a rapid response (46%). A rapid virologic response was the single strongest predictor of achieving a sustained virologic response, with an odds ratio of 17.

Overall, 63% of patients showed a sustained virologic response to peginterferon-based therapy. Patients with either the rs12979860 SNP or the 8099917 SNP were the most likely to achieve a sustained virologic response, with rates of over 80%. Baseline viral load, patient age, and fibrosis stage all were independent predictors of a sustained virologic response, but SNP status remained the most strongly predictive factor.

"Our study confirms the previously reported findings in various populations around the world," Dr. Stättermayer and his colleagues said. "The precise role of this polymorphism remains unknown. Based on our data, the SNP in the IL28B region appears to be associated with the early phases of viral clearance.

"Differences in viral load reduction between genotypes were detectable as early as week 2, which was the earliest time point evaluated." In addition, the divergence in treatment response peaked at week 4.

"The main focus of our study was the clinical applicability of genetic testing. The positive predictive value of rs12979860 C/C (the favorable genotype) for a sustained virologic response was high, but specificity and sensitivity were low," the researchers noted.

Their results indicate that "a patient with a low baseline viral load and 2 C alleles may benefit from standard of care, with a possible reduction of treatment duration to 24 weeks. On the other hand, T-allele carriers with advanced fibrosis and a high baseline viral load could possibly benefit from novel therapeutic strategies such as polymerase or protease inhibitors added to peginterferon and ribavirin, to maximize viral response," the investigators said.

Dr. Stättermayer had no disclosures, but several coauthors, including Dr. Peter Ferenci, the principal investigator, reported financial relationships with Roche. Dr. Ferenci receives an unrestricted research grant from Roche Austria.