Mary Ann Moon

Measurements of five protein biomarkers in the cerebrospinal fluid helped to differentiate Alzheimer’s disease from Parkinson’s disease with dementia and from dementia with Lewy bodies in a cross-sectional study of individuals at Swedish neurology and memory disorder clinics.

The diagnostic accuracy of this panel of tests in distinguishing Alzheimer’s disease from dementia with Lewy bodies "is at least in the same order of magnitude as that obtained with dopamine transporter imaging, and with a lower cost," Dr. Sara Hall of the department of clinical sciences, Lund (Sweden) University, Malmö, and her associates wrote in a study published Aug. 27 in Archives of Neurology.

In addition, one of the five biomarkers in this panel appears to differentiate Parkinson’s disease from atypical parkinsonism such as that seen in progressive supranuclear palsy, multiple system atrophy, or corticobasal degeneration, the researchers noted.

Their results confirmed those of previous studies postulating that CSF total tau (T-tau) and phophorylated tau (P-tau) levels are higher in Alzheimer’s than in the other two dementias, whereas amyloid-beta (Abeta) 1-42 levels are lower in Alzheimer’s than in the other two dementias.

Levels of alpha-synuclein reflect Lewy body pathology, which is typically absent in Alzheimer’s but present in the other two dementias. This study verified that there is a clear difference in these levels between patients who have Alzheimer’s disease and those who have either Parkinson’s disease with dementia or dementia with Lewy bodies.

In contrast, CSF levels of alpha-synuclein were lower in patients with certain dementias than in control subjects, but not to a degree that would assist in differential diagnosis, the investigators said.

They assessed the prognostic accuracy of the panel of five protein biomarkers in CSF samples from 107 healthy control subjects and 346 patients who were treated for parkinsonism and/or dementia at two university hospitals in Sweden. A newly developed assay allowed the simultaneous quantification of levels of alpha-synuclein, Abeta 1-42, T-tau, and P-tau in the CSF samples. Neurofilament light chain (NF-L) protein was assessed from the same samples using a conventional ELISA (enzyme-linked immunosorbent assay).

The study subjects were diagnosed as having Parkinson’s disease (90 patients), Alzheimer’s disease (48 patients), Parkinson’s disease with dementia (33 patients), dementia with Lewy bodies (70 patients), progressive supranuclear palsy (45 patients), multiple system atrophy (48 patients), or corticobasal degeneration (12 patients).

"Most important, we found that the diagnostic accuracy of a panel of 5 biomarkers representing tau-, beta-amyloid-, and alpha-synuclein pathology was high enough to be of clear value in the clinical work-up of differentiating patients with Alzheimer’s disease from those with Parkinson’s disease with dementia and dementia with Lewy bodies," Dr. Hall and her colleagues wrote (Arch. Neurol. 2012 Aug. 27 [doi:10.1001/archneurol.2012.1654]).

The five-marker panel had 90% sensitivity and 81% specificity for differentiating Alzheimer’s disease from dementia with Lewy bodies and Parkinson’s disease with dementia. It differentiated Alzheimer’s disease from dementia with Lewy bodies alone with 88% sensitivity and 81% specificity.

The investigators found that the panel could discriminate Parkinson’s disease from atypical parkinsonian disorders (progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy) with 85% sensitivity and 92% specificity.

"Our study [also] confirmed that the CSF levels of NF-L are increased in atypical parkinsonian disorders, and the observed diagnostic accuracy of NF-L is high enough to be clinically relevant," they added.

Higher levels of NF-L, but not of the other biomarkers, correlated with more severe disease in patients who had Parkinson’s disease, progressive supranuclear palsy, and Alzheimer’s disease, "which might reflect an increase in axonal pathology over time in these patients," Dr. Hall and her associates wrote.

This study was supported by the Swedish Research Council, the Swedish Alzheimer Foundation, the Torsten and Ragnar Soderberg Foundation, the Swedish Brain Power Consortium, Lund University, and Sahlgrenska Academy. No financial conflicts of interest were reported.

Measurements of five protein biomarkers in the cerebrospinal fluid helped to differentiate Alzheimer’s disease from Parkinson’s disease with dementia and from dementia with Lewy bodies in a cross-sectional study of individuals at Swedish neurology and memory disorder clinics.

The diagnostic accuracy of this panel of tests in distinguishing Alzheimer’s disease from dementia with Lewy bodies "is at least in the same order of magnitude as that obtained with dopamine transporter imaging, and with a lower cost," Dr. Sara Hall of the department of clinical sciences, Lund (Sweden) University, Malmö, and her associates wrote in a study published Aug. 27 in Archives of Neurology.

In addition, one of the five biomarkers in this panel appears to differentiate Parkinson’s disease from atypical parkinsonism such as that seen in progressive supranuclear palsy, multiple system atrophy, or corticobasal degeneration, the researchers noted.

Their results confirmed those of previous studies postulating that CSF total tau (T-tau) and phophorylated tau (P-tau) levels are higher in Alzheimer’s than in the other two dementias, whereas amyloid-beta (Abeta) 1-42 levels are lower in Alzheimer’s than in the other two dementias.

Levels of alpha-synuclein reflect Lewy body pathology, which is typically absent in Alzheimer’s but present in the other two dementias. This study verified that there is a clear difference in these levels between patients who have Alzheimer’s disease and those who have either Parkinson’s disease with dementia or dementia with Lewy bodies.

In contrast, CSF levels of alpha-synuclein were lower in patients with certain dementias than in control subjects, but not to a degree that would assist in differential diagnosis, the investigators said.

They assessed the prognostic accuracy of the panel of five protein biomarkers in CSF samples from 107 healthy control subjects and 346 patients who were treated for parkinsonism and/or dementia at two university hospitals in Sweden. A newly developed assay allowed the simultaneous quantification of levels of alpha-synuclein, Abeta 1-42, T-tau, and P-tau in the CSF samples. Neurofilament light chain (NF-L) protein was assessed from the same samples using a conventional ELISA (enzyme-linked immunosorbent assay).

The study subjects were diagnosed as having Parkinson’s disease (90 patients), Alzheimer’s disease (48 patients), Parkinson’s disease with dementia (33 patients), dementia with Lewy bodies (70 patients), progressive supranuclear palsy (45 patients), multiple system atrophy (48 patients), or corticobasal degeneration (12 patients).

"Most important, we found that the diagnostic accuracy of a panel of 5 biomarkers representing tau-, beta-amyloid-, and alpha-synuclein pathology was high enough to be of clear value in the clinical work-up of differentiating patients with Alzheimer’s disease from those with Parkinson’s disease with dementia and dementia with Lewy bodies," Dr. Hall and her colleagues wrote (Arch. Neurol. 2012 Aug. 27 [doi:10.1001/archneurol.2012.1654]).

The five-marker panel had 90% sensitivity and 81% specificity for differentiating Alzheimer’s disease from dementia with Lewy bodies and Parkinson’s disease with dementia. It differentiated Alzheimer’s disease from dementia with Lewy bodies alone with 88% sensitivity and 81% specificity.

The investigators found that the panel could discriminate Parkinson’s disease from atypical parkinsonian disorders (progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy) with 85% sensitivity and 92% specificity.

"Our study [also] confirmed that the CSF levels of NF-L are increased in atypical parkinsonian disorders, and the observed diagnostic accuracy of NF-L is high enough to be clinically relevant," they added.

Higher levels of NF-L, but not of the other biomarkers, correlated with more severe disease in patients who had Parkinson’s disease, progressive supranuclear palsy, and Alzheimer’s disease, "which might reflect an increase in axonal pathology over time in these patients," Dr. Hall and her associates wrote.

This study was supported by the Swedish Research Council, the Swedish Alzheimer Foundation, the Torsten and Ragnar Soderberg Foundation, the Swedish Brain Power Consortium, Lund University, and Sahlgrenska Academy. No financial conflicts of interest were reported.

Measurements of five protein biomarkers in the cerebrospinal fluid helped to differentiate Alzheimer’s disease from Parkinson’s disease with dementia and from dementia with Lewy bodies in a cross-sectional study of individuals at Swedish neurology and memory disorder clinics.

The diagnostic accuracy of this panel of tests in distinguishing Alzheimer’s disease from dementia with Lewy bodies "is at least in the same order of magnitude as that obtained with dopamine transporter imaging, and with a lower cost," Dr. Sara Hall of the department of clinical sciences, Lund (Sweden) University, Malmö, and her associates wrote in a study published Aug. 27 in Archives of Neurology.

In addition, one of the five biomarkers in this panel appears to differentiate Parkinson’s disease from atypical parkinsonism such as that seen in progressive supranuclear palsy, multiple system atrophy, or corticobasal degeneration, the researchers noted.

Their results confirmed those of previous studies postulating that CSF total tau (T-tau) and phophorylated tau (P-tau) levels are higher in Alzheimer’s than in the other two dementias, whereas amyloid-beta (Abeta) 1-42 levels are lower in Alzheimer’s than in the other two dementias.

Levels of alpha-synuclein reflect Lewy body pathology, which is typically absent in Alzheimer’s but present in the other two dementias. This study verified that there is a clear difference in these levels between patients who have Alzheimer’s disease and those who have either Parkinson’s disease with dementia or dementia with Lewy bodies.

In contrast, CSF levels of alpha-synuclein were lower in patients with certain dementias than in control subjects, but not to a degree that would assist in differential diagnosis, the investigators said.

They assessed the prognostic accuracy of the panel of five protein biomarkers in CSF samples from 107 healthy control subjects and 346 patients who were treated for parkinsonism and/or dementia at two university hospitals in Sweden. A newly developed assay allowed the simultaneous quantification of levels of alpha-synuclein, Abeta 1-42, T-tau, and P-tau in the CSF samples. Neurofilament light chain (NF-L) protein was assessed from the same samples using a conventional ELISA (enzyme-linked immunosorbent assay).

The study subjects were diagnosed as having Parkinson’s disease (90 patients), Alzheimer’s disease (48 patients), Parkinson’s disease with dementia (33 patients), dementia with Lewy bodies (70 patients), progressive supranuclear palsy (45 patients), multiple system atrophy (48 patients), or corticobasal degeneration (12 patients).

"Most important, we found that the diagnostic accuracy of a panel of 5 biomarkers representing tau-, beta-amyloid-, and alpha-synuclein pathology was high enough to be of clear value in the clinical work-up of differentiating patients with Alzheimer’s disease from those with Parkinson’s disease with dementia and dementia with Lewy bodies," Dr. Hall and her colleagues wrote (Arch. Neurol. 2012 Aug. 27 [doi:10.1001/archneurol.2012.1654]).

The five-marker panel had 90% sensitivity and 81% specificity for differentiating Alzheimer’s disease from dementia with Lewy bodies and Parkinson’s disease with dementia. It differentiated Alzheimer’s disease from dementia with Lewy bodies alone with 88% sensitivity and 81% specificity.

The investigators found that the panel could discriminate Parkinson’s disease from atypical parkinsonian disorders (progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy) with 85% sensitivity and 92% specificity.

"Our study [also] confirmed that the CSF levels of NF-L are increased in atypical parkinsonian disorders, and the observed diagnostic accuracy of NF-L is high enough to be clinically relevant," they added.

Higher levels of NF-L, but not of the other biomarkers, correlated with more severe disease in patients who had Parkinson’s disease, progressive supranuclear palsy, and Alzheimer’s disease, "which might reflect an increase in axonal pathology over time in these patients," Dr. Hall and her associates wrote.

This study was supported by the Swedish Research Council, the Swedish Alzheimer Foundation, the Torsten and Ragnar Soderberg Foundation, the Swedish Brain Power Consortium, Lund University, and Sahlgrenska Academy. No financial conflicts of interest were reported.

As early as fifth grade, black and Latino children show striking disparities across a broad range of health-related behaviors, experiences, and outcomes, compared with non-Latino white children, according to a study published Aug. 22 in the New England Journal of Medicine.

Data have been limited for the pediatric population concerning disparities in such health-related problems as witnessing or perpetrating violence, smoking, not using seat belts, obesity, experiencing discrimination, and drinking alcohol.

Photo credit: sjlocke/iStock

Until now researchers have not conclusively shown that these problems, which are thought to be typical of adolescence, may be rooted in earlier childhood, said Dr. Mark A. Schuster of Boston Children’s Hospital and his associates.

"In our study, the prevalence rates of many problems were high, and significant disparities already existed among preadolescents. The overall pattern of disparities in our preadolescent sample closely resembled that for older age groups, with black children having the greatest number of disparities, followed by Latino children," they noted.

Dr. Schuster and his colleagues examined the rates of a broad range of problems known to contribute heavily to morbidity and mortality, using data from a Centers for Disease Control and Prevention (CDC) study of 5,119 fifth-graders and their parents residing in the Birmingham, Ala.; Houston; and Los Angeles areas.

The 16 health-related measures they assessed were witnessing a physical assault, witnessing a threat or injury with a gun, victimization by peers, perpetrating nonphysical aggression, perpetrating physical aggression, cigarette smoking, alcohol use, seat belt use, bike-helmet use, experiencing discrimination, worrying about terrorism, obesity, vigorous exercise, health status, psychological quality of life, and physical quality of life.

Many of these are major contributors to unintentional injuries, which are the leading cause of death among both children and adolescents, and to violence, which is the second largest cause of death in adolescents. Many also cause dysregulation of physiologic stress responses and are associated with substantial mental and physical health problems among youths, the investigators said (N. Engl. J. Med. 2012;367:735-45 [doi: 10.1056/NEJMsa1114353]).

There were significant differences in all 16 health-related measures between black children and white children, and significant differences in 12 of the measures between Latino children and white children.

For example, 20% of black fifth-graders had witnessed a threat or an injury with a gun, compared with 11% of Latino and 5% of white fifth-graders, in unadjusted analyses. And the number of days during the preceding week in which the study subject had engaged in vigorous exercise was markedly lower for black children (3.56 days) and Latino children (3.77 days) than for white children (4.33 days).

Also in unadjusted analyses, compared with white fifth-graders, black fifth-graders were 5% more likely to smoke cigarettes, 15% less likely to use seat belts, 36% less likely to use a bike helmet, and 12% more likely to be obese. Compared with white fifth-graders, Latino fifth-graders were 11% less likely to use seat belts, 32% less likely to use a bike helmet, and 15% more likely to be obese.

However, for almost all of the 16 health measures, adjusting the data to account for variables such as the child’s sex and the parent’s income, education, and marital status eliminated or dramatically reduced most of these disparities.

For example, in adjusted analyses the disparities between black children and white children disappeared for 6 of the 16 health measures, were reduced by half for another 5 measures, and were reduced by approximately a third in the remaining 5 measures. Similarly, in adjusted analyses, 7 of the 12 disparities between Latino children and white children disappeared, 2 were reduced by half, and the remaining 3 were reduced by approximately a third.

The two variables that contributed the most to the disparities among racial/ethnic groups were the child’s school and socioeconomic status.

The study findings demonstrate to physicians that "some consequential health-related behaviors and experiences that are associated with adolescence have already begun in elementary school. Even when they have not, counseling and screening can reasonably begin in anticipation of what may soon emerge," Dr. Schuster and his associates said.

The results also suggest that efforts to change school environments – for example, school-based antibullying programs – may "merit particular consideration." Parent and child health education that subsidizes safety equipment might also reduce some of the disparity for children in lower socioeconomic groups, they added.

Among the study’s limitations, investigators said, is that the data are from just three metropolitan areas. “The results might differ elsewhere, especially where differences in socioeconomic status are smaller,” they wrote. Further, they added, other than body-mass index, all measures in the study were self-reported by the children or their parents.

This study was supported by the CDC. Susan Davies, Ph.D., reported ties to Mao Pharmaceuticals, and Susan Tortolero, Ph.D., reported ties to several organizations including RAND, Texas Education Agency Region VI, the Baylor College of Medicine, and the Women’s Fund of Mississippi.

As early as fifth grade, black and Latino children show striking disparities across a broad range of health-related behaviors, experiences, and outcomes, compared with non-Latino white children, according to a study published Aug. 22 in the New England Journal of Medicine.

Data have been limited for the pediatric population concerning disparities in such health-related problems as witnessing or perpetrating violence, smoking, not using seat belts, obesity, experiencing discrimination, and drinking alcohol.

Photo credit: sjlocke/iStock

Until now researchers have not conclusively shown that these problems, which are thought to be typical of adolescence, may be rooted in earlier childhood, said Dr. Mark A. Schuster of Boston Children’s Hospital and his associates.

"In our study, the prevalence rates of many problems were high, and significant disparities already existed among preadolescents. The overall pattern of disparities in our preadolescent sample closely resembled that for older age groups, with black children having the greatest number of disparities, followed by Latino children," they noted.

Dr. Schuster and his colleagues examined the rates of a broad range of problems known to contribute heavily to morbidity and mortality, using data from a Centers for Disease Control and Prevention (CDC) study of 5,119 fifth-graders and their parents residing in the Birmingham, Ala.; Houston; and Los Angeles areas.

The 16 health-related measures they assessed were witnessing a physical assault, witnessing a threat or injury with a gun, victimization by peers, perpetrating nonphysical aggression, perpetrating physical aggression, cigarette smoking, alcohol use, seat belt use, bike-helmet use, experiencing discrimination, worrying about terrorism, obesity, vigorous exercise, health status, psychological quality of life, and physical quality of life.

Many of these are major contributors to unintentional injuries, which are the leading cause of death among both children and adolescents, and to violence, which is the second largest cause of death in adolescents. Many also cause dysregulation of physiologic stress responses and are associated with substantial mental and physical health problems among youths, the investigators said (N. Engl. J. Med. 2012;367:735-45 [doi: 10.1056/NEJMsa1114353]).

There were significant differences in all 16 health-related measures between black children and white children, and significant differences in 12 of the measures between Latino children and white children.

For example, 20% of black fifth-graders had witnessed a threat or an injury with a gun, compared with 11% of Latino and 5% of white fifth-graders, in unadjusted analyses. And the number of days during the preceding week in which the study subject had engaged in vigorous exercise was markedly lower for black children (3.56 days) and Latino children (3.77 days) than for white children (4.33 days).

Also in unadjusted analyses, compared with white fifth-graders, black fifth-graders were 5% more likely to smoke cigarettes, 15% less likely to use seat belts, 36% less likely to use a bike helmet, and 12% more likely to be obese. Compared with white fifth-graders, Latino fifth-graders were 11% less likely to use seat belts, 32% less likely to use a bike helmet, and 15% more likely to be obese.

However, for almost all of the 16 health measures, adjusting the data to account for variables such as the child’s sex and the parent’s income, education, and marital status eliminated or dramatically reduced most of these disparities.

For example, in adjusted analyses the disparities between black children and white children disappeared for 6 of the 16 health measures, were reduced by half for another 5 measures, and were reduced by approximately a third in the remaining 5 measures. Similarly, in adjusted analyses, 7 of the 12 disparities between Latino children and white children disappeared, 2 were reduced by half, and the remaining 3 were reduced by approximately a third.

The two variables that contributed the most to the disparities among racial/ethnic groups were the child’s school and socioeconomic status.

The study findings demonstrate to physicians that "some consequential health-related behaviors and experiences that are associated with adolescence have already begun in elementary school. Even when they have not, counseling and screening can reasonably begin in anticipation of what may soon emerge," Dr. Schuster and his associates said.

The results also suggest that efforts to change school environments – for example, school-based antibullying programs – may "merit particular consideration." Parent and child health education that subsidizes safety equipment might also reduce some of the disparity for children in lower socioeconomic groups, they added.

Among the study’s limitations, investigators said, is that the data are from just three metropolitan areas. “The results might differ elsewhere, especially where differences in socioeconomic status are smaller,” they wrote. Further, they added, other than body-mass index, all measures in the study were self-reported by the children or their parents.

This study was supported by the CDC. Susan Davies, Ph.D., reported ties to Mao Pharmaceuticals, and Susan Tortolero, Ph.D., reported ties to several organizations including RAND, Texas Education Agency Region VI, the Baylor College of Medicine, and the Women’s Fund of Mississippi.

As early as fifth grade, black and Latino children show striking disparities across a broad range of health-related behaviors, experiences, and outcomes, compared with non-Latino white children, according to a study published Aug. 22 in the New England Journal of Medicine.

Data have been limited for the pediatric population concerning disparities in such health-related problems as witnessing or perpetrating violence, smoking, not using seat belts, obesity, experiencing discrimination, and drinking alcohol.

Photo credit: sjlocke/iStock

Until now researchers have not conclusively shown that these problems, which are thought to be typical of adolescence, may be rooted in earlier childhood, said Dr. Mark A. Schuster of Boston Children’s Hospital and his associates.

"In our study, the prevalence rates of many problems were high, and significant disparities already existed among preadolescents. The overall pattern of disparities in our preadolescent sample closely resembled that for older age groups, with black children having the greatest number of disparities, followed by Latino children," they noted.

Dr. Schuster and his colleagues examined the rates of a broad range of problems known to contribute heavily to morbidity and mortality, using data from a Centers for Disease Control and Prevention (CDC) study of 5,119 fifth-graders and their parents residing in the Birmingham, Ala.; Houston; and Los Angeles areas.

The 16 health-related measures they assessed were witnessing a physical assault, witnessing a threat or injury with a gun, victimization by peers, perpetrating nonphysical aggression, perpetrating physical aggression, cigarette smoking, alcohol use, seat belt use, bike-helmet use, experiencing discrimination, worrying about terrorism, obesity, vigorous exercise, health status, psychological quality of life, and physical quality of life.

Many of these are major contributors to unintentional injuries, which are the leading cause of death among both children and adolescents, and to violence, which is the second largest cause of death in adolescents. Many also cause dysregulation of physiologic stress responses and are associated with substantial mental and physical health problems among youths, the investigators said (N. Engl. J. Med. 2012;367:735-45 [doi: 10.1056/NEJMsa1114353]).

There were significant differences in all 16 health-related measures between black children and white children, and significant differences in 12 of the measures between Latino children and white children.

For example, 20% of black fifth-graders had witnessed a threat or an injury with a gun, compared with 11% of Latino and 5% of white fifth-graders, in unadjusted analyses. And the number of days during the preceding week in which the study subject had engaged in vigorous exercise was markedly lower for black children (3.56 days) and Latino children (3.77 days) than for white children (4.33 days).

Also in unadjusted analyses, compared with white fifth-graders, black fifth-graders were 5% more likely to smoke cigarettes, 15% less likely to use seat belts, 36% less likely to use a bike helmet, and 12% more likely to be obese. Compared with white fifth-graders, Latino fifth-graders were 11% less likely to use seat belts, 32% less likely to use a bike helmet, and 15% more likely to be obese.

However, for almost all of the 16 health measures, adjusting the data to account for variables such as the child’s sex and the parent’s income, education, and marital status eliminated or dramatically reduced most of these disparities.

For example, in adjusted analyses the disparities between black children and white children disappeared for 6 of the 16 health measures, were reduced by half for another 5 measures, and were reduced by approximately a third in the remaining 5 measures. Similarly, in adjusted analyses, 7 of the 12 disparities between Latino children and white children disappeared, 2 were reduced by half, and the remaining 3 were reduced by approximately a third.

The two variables that contributed the most to the disparities among racial/ethnic groups were the child’s school and socioeconomic status.

The study findings demonstrate to physicians that "some consequential health-related behaviors and experiences that are associated with adolescence have already begun in elementary school. Even when they have not, counseling and screening can reasonably begin in anticipation of what may soon emerge," Dr. Schuster and his associates said.

The results also suggest that efforts to change school environments – for example, school-based antibullying programs – may "merit particular consideration." Parent and child health education that subsidizes safety equipment might also reduce some of the disparity for children in lower socioeconomic groups, they added.

Among the study’s limitations, investigators said, is that the data are from just three metropolitan areas. “The results might differ elsewhere, especially where differences in socioeconomic status are smaller,” they wrote. Further, they added, other than body-mass index, all measures in the study were self-reported by the children or their parents.

This study was supported by the CDC. Susan Davies, Ph.D., reported ties to Mao Pharmaceuticals, and Susan Tortolero, Ph.D., reported ties to several organizations including RAND, Texas Education Agency Region VI, the Baylor College of Medicine, and the Women’s Fund of Mississippi.

Systemic treatments for psoriasis – including tumor necrosis factor inhibitors, oral drugs, and phototherapy – reduce the risk of myocardial infarction by approximately half, according to a study published online Aug. 20 in the Archives of Dermatology.

Psoriasis is a systemic inflammatory disease known to raise the risk of cardiovascular disorders, which also have a major inflammatory component. "It seems that controlling psoriasis with aggressive therapy and, thus, lowering inflammation, leads to a reduction in MI risk," said Dr. Jashin J. Wu of Kaiser Permanente Los Angeles Medical Center, and his associates.

The effect of systemic psoriasis therapy on cardiovascular disease "has been largely unexplored" until now. Dr. Wu and his colleagues performed a retrospective cohort study to examine the issue, using their HMO’s large database to examine the medical and prescription data on 8,845 adults who were diagnosed as having psoriasis between 2004 and 2009, and were followed for a median of 4 years for incident MI. The mean age of these study subjects was 53 years at baseline; half were men and half were women.

In all, 1,673 subjects (19%) were treated with TNF inhibitors, 2,097 (24%) were treated with oral systemic agents or phototherapy, and the remaining 5,075 received only topical treatment.

There were 221 incident MIs during follow-up.

For patients who took TNF inhibitors, the rate of MI was 3.05 per 1,000 patient-years, and for those who received systemic drugs or phototherapy, the rate of MI was 3.85 per 1,000 patient-years. These rates were not significantly different from each other, but were significantly lower than the rate of 6.73 MIs per 1,000 patient-years seen in the topical therapy–only group.

Compared with patients who used only topical treatment, those who took TNF inhibitors showed a 55% reduction in MI incidence and those who used other systemic treatments showed a 43% reduction in MI incidence, the investigators said (Arch. Dermatol. 2012 Aug. 20 [doi:10.1001/archdermatol.2012.2502]).

This is the first large-scale study to show that TNF inhibitors in particular, when they are taken for the treatment of psoriasis, reduce the incidence of MI. A previous study using a large database of patients with rheumatoid arthritis, another inflammatory disease associated with cardiovascular disease, found that therapy with TNF agonists also reduced the rate of cardiovascular events in that patient population, Dr. Wu and his associates noted.

In their study, an analysis of the data that stratified study subjects by age suggested that TNF inhibitors, oral agents, and phototherapy all exerted stronger protective effects in those older than 60 years, compared with younger patients. One explanation may be that older patients are more likely to develop type 2 diabetes, and these systemic therapies may cut the risk of that disease as well, they said.

This study was limited in that it could not account for study subjects’ use of nonprescription drugs, such as NSAIDs.

This study was supported by Kaiser Permanente’s Garfield Memorial Fund. Dr. Wu reported ties to Abbott Laboratories, Amgen, and Pfizer.

Systemic treatments for psoriasis – including tumor necrosis factor inhibitors, oral drugs, and phototherapy – reduce the risk of myocardial infarction by approximately half, according to a study published online Aug. 20 in the Archives of Dermatology.

Psoriasis is a systemic inflammatory disease known to raise the risk of cardiovascular disorders, which also have a major inflammatory component. "It seems that controlling psoriasis with aggressive therapy and, thus, lowering inflammation, leads to a reduction in MI risk," said Dr. Jashin J. Wu of Kaiser Permanente Los Angeles Medical Center, and his associates.

The effect of systemic psoriasis therapy on cardiovascular disease "has been largely unexplored" until now. Dr. Wu and his colleagues performed a retrospective cohort study to examine the issue, using their HMO’s large database to examine the medical and prescription data on 8,845 adults who were diagnosed as having psoriasis between 2004 and 2009, and were followed for a median of 4 years for incident MI. The mean age of these study subjects was 53 years at baseline; half were men and half were women.

In all, 1,673 subjects (19%) were treated with TNF inhibitors, 2,097 (24%) were treated with oral systemic agents or phototherapy, and the remaining 5,075 received only topical treatment.

There were 221 incident MIs during follow-up.

For patients who took TNF inhibitors, the rate of MI was 3.05 per 1,000 patient-years, and for those who received systemic drugs or phototherapy, the rate of MI was 3.85 per 1,000 patient-years. These rates were not significantly different from each other, but were significantly lower than the rate of 6.73 MIs per 1,000 patient-years seen in the topical therapy–only group.

Compared with patients who used only topical treatment, those who took TNF inhibitors showed a 55% reduction in MI incidence and those who used other systemic treatments showed a 43% reduction in MI incidence, the investigators said (Arch. Dermatol. 2012 Aug. 20 [doi:10.1001/archdermatol.2012.2502]).

This is the first large-scale study to show that TNF inhibitors in particular, when they are taken for the treatment of psoriasis, reduce the incidence of MI. A previous study using a large database of patients with rheumatoid arthritis, another inflammatory disease associated with cardiovascular disease, found that therapy with TNF agonists also reduced the rate of cardiovascular events in that patient population, Dr. Wu and his associates noted.

In their study, an analysis of the data that stratified study subjects by age suggested that TNF inhibitors, oral agents, and phototherapy all exerted stronger protective effects in those older than 60 years, compared with younger patients. One explanation may be that older patients are more likely to develop type 2 diabetes, and these systemic therapies may cut the risk of that disease as well, they said.

This study was limited in that it could not account for study subjects’ use of nonprescription drugs, such as NSAIDs.

This study was supported by Kaiser Permanente’s Garfield Memorial Fund. Dr. Wu reported ties to Abbott Laboratories, Amgen, and Pfizer.

Systemic treatments for psoriasis – including tumor necrosis factor inhibitors, oral drugs, and phototherapy – reduce the risk of myocardial infarction by approximately half, according to a study published online Aug. 20 in the Archives of Dermatology.

Psoriasis is a systemic inflammatory disease known to raise the risk of cardiovascular disorders, which also have a major inflammatory component. "It seems that controlling psoriasis with aggressive therapy and, thus, lowering inflammation, leads to a reduction in MI risk," said Dr. Jashin J. Wu of Kaiser Permanente Los Angeles Medical Center, and his associates.

The effect of systemic psoriasis therapy on cardiovascular disease "has been largely unexplored" until now. Dr. Wu and his colleagues performed a retrospective cohort study to examine the issue, using their HMO’s large database to examine the medical and prescription data on 8,845 adults who were diagnosed as having psoriasis between 2004 and 2009, and were followed for a median of 4 years for incident MI. The mean age of these study subjects was 53 years at baseline; half were men and half were women.

In all, 1,673 subjects (19%) were treated with TNF inhibitors, 2,097 (24%) were treated with oral systemic agents or phototherapy, and the remaining 5,075 received only topical treatment.

There were 221 incident MIs during follow-up.

For patients who took TNF inhibitors, the rate of MI was 3.05 per 1,000 patient-years, and for those who received systemic drugs or phototherapy, the rate of MI was 3.85 per 1,000 patient-years. These rates were not significantly different from each other, but were significantly lower than the rate of 6.73 MIs per 1,000 patient-years seen in the topical therapy–only group.

Compared with patients who used only topical treatment, those who took TNF inhibitors showed a 55% reduction in MI incidence and those who used other systemic treatments showed a 43% reduction in MI incidence, the investigators said (Arch. Dermatol. 2012 Aug. 20 [doi:10.1001/archdermatol.2012.2502]).

This is the first large-scale study to show that TNF inhibitors in particular, when they are taken for the treatment of psoriasis, reduce the incidence of MI. A previous study using a large database of patients with rheumatoid arthritis, another inflammatory disease associated with cardiovascular disease, found that therapy with TNF agonists also reduced the rate of cardiovascular events in that patient population, Dr. Wu and his associates noted.

In their study, an analysis of the data that stratified study subjects by age suggested that TNF inhibitors, oral agents, and phototherapy all exerted stronger protective effects in those older than 60 years, compared with younger patients. One explanation may be that older patients are more likely to develop type 2 diabetes, and these systemic therapies may cut the risk of that disease as well, they said.

This study was limited in that it could not account for study subjects’ use of nonprescription drugs, such as NSAIDs.

This study was supported by Kaiser Permanente’s Garfield Memorial Fund. Dr. Wu reported ties to Abbott Laboratories, Amgen, and Pfizer.

It appears that breast cancer diagnosed during pregnancy can be treated much the same as breast cancer diagnosed in nonpregnant women without substantially raising the risks to mother or child, according to a study published online August 16 in the Lancet Oncology .

This conclusion, from an observational study involving 447 European women included in registries of cancers diagnosed during pregnancy, must still be validated in other studies. But until then, the current evidence indicates that pregnancy outcomes are not significantly different between women who receive breast cancer chemotherapy during the second or third trimesters and those who wait until after delivery to start treatment, said Dr. Sibylle Loibl of the German Breast Group, Neu-Isenburg, Germany, and her associates.

In this study, infants exposed to their mothers’ breast cancer chemotherapy while in utero had slightly lower birth weights and slightly more complications than those not exposed to chemotherapy, but these differences were not clinically significant.

Breast cancer diagnosed during pregnancy is rare, estimated to occur in less than 1% of breast cancers in Europe. But its incidence is increasing in high-income countries due to the trend of women delaying childbirth until they are older, when breast cancer is more prevalent.

The German Breast Group established its Breast Cancer During Pregnancy registry in 2003 and expanded it to include cases in the Netherlands, the United Kingdom, Poland, Italy, and the Czech Republic in 2009. In the same time period, Belgium also established a registry of all cancers diagnosed during pregnancy. Dr. Loibl and her colleagues assessed outcomes in 447 cases from these registries in which women were diagnosed as having early (413 patients) or metastatic (34 patients) breast cancer while pregnant (Lancet Oncol. 2012 Aug. 15 [doi:10.1016/S1470-2045(12)70261-9]).

The median gestational age at diagnosis was 24 weeks (range, 5-40 weeks), and the median age of the women was 33 years (range, 22-51 years).

Data on chemotherapy were available for 368 women. Of these, 197 received chemotherapy while pregnant and 171 received it after delivery.

Overall, 1,187 cycles of chemotherapy were given, and 63% of these were given during pregnancy. The women received a median of four cycles (range, one to eight cycles) during pregnancy.

A total of 90% of those treated during pregnancy received an anthracyline; 8% received a combination of cyclophosphamide, methotrexate, and fluorouracil; and 7% received a taxane. None of the women received trastuzumab, endocrine therapy, or radiotherapy during pregnancy.

Women with early breast cancer who opted for chemotherapy during pregnancy tended to have more advanced disease, with more unfavorable tumor stage and nodal status, than did those who chose to begin chemotherapy after delivery. After the data were adjusted to account for this difference, the researchers found no significant difference between the two groups in disease-free or overall survival.

The estimated 3-year disease-free survival was 70.2% in women with early disease who underwent chemotherapy while pregnant and 74.3% in those who waited until after delivery. Similarly, the estimated overall 3-year survival was 84.9% in women with early breast cancer who underwent chemotherapy while pregnant and 87.4% in those who delayed chemotherapy until after delivery.

The estimated 5-year disease-free survival was 61.1% in women who had chemotherapy while pregnant and 64.4% in those who waited, and the estimated 5-year overall survival was 77% and 82.4%, respectively.

Data were available for 373 newborns, of whom 203 had been exposed to chemotherapy in utero and 170 had not.

Birth weight was slightly lower in the exposed than in the nonexposed infants, but this difference was judged to be "clinically irrelevant" because it didn’t affect the health of the babies, Dr. Loibl and her associates said.

Moreover, there were no significant differences between the two groups in major birth defects, infant height, Apgar scores, hemoglobin concentration, leukocyte counts, thrombocyte counts, or alopecia. And there was no significant difference in the proportion of infants discharged with their mothers (34% vs. 41%).

Adverse events occurred more often when chemotherapy was received during pregnancy (15%) than when it was delayed (4%). However, this difference was attributed to the higher rates of preterm labor and premature rupture of the membrane among exposed pregnancies. "Most complications were reported in babies who were delivered prematurely, regardless of exposure to chemotherapy," the investigators said.

The data were not adequate to determine why women who received chemotherapy had a higher rate of preterm delivery. Both physical stress and psychological stress may have played a role, and it is possible that women who received chemotherapy were more prone to infections that may have triggered labor.

In addition, the cytotoxic agents themselves may have hastened labor through some as yet unknown mechanism. However, the rate of preeclampsia was similar between the two groups, so oxidative stress, which is known to be induced by cytoxic agents, was not responsible.

Further study of the data being collected in the registries of cancers diagnosed during pregnancy will likely shed light on these issues. Dr. Loibl and her colleagues are now performing a matched-pair analysis to assess whether the prognosis of breast cancer in nonpregnant women differs from that in pregnant women when the latter are treated according to current guidelines.

This study was supported by BANSS Foundation, University Hospital Frankfurt, the German Breast Group, Research Foundation-Flanders, Clinical Research Fund-UZ Gasthuisberg, and the Belgian Cancer Plan. No financial conflicts of interest were reported.

It appears that breast cancer diagnosed during pregnancy can be treated much the same as breast cancer diagnosed in nonpregnant women without substantially raising the risks to mother or child, according to a study published online August 16 in the Lancet Oncology .

This conclusion, from an observational study involving 447 European women included in registries of cancers diagnosed during pregnancy, must still be validated in other studies. But until then, the current evidence indicates that pregnancy outcomes are not significantly different between women who receive breast cancer chemotherapy during the second or third trimesters and those who wait until after delivery to start treatment, said Dr. Sibylle Loibl of the German Breast Group, Neu-Isenburg, Germany, and her associates.

In this study, infants exposed to their mothers’ breast cancer chemotherapy while in utero had slightly lower birth weights and slightly more complications than those not exposed to chemotherapy, but these differences were not clinically significant.

Breast cancer diagnosed during pregnancy is rare, estimated to occur in less than 1% of breast cancers in Europe. But its incidence is increasing in high-income countries due to the trend of women delaying childbirth until they are older, when breast cancer is more prevalent.

The German Breast Group established its Breast Cancer During Pregnancy registry in 2003 and expanded it to include cases in the Netherlands, the United Kingdom, Poland, Italy, and the Czech Republic in 2009. In the same time period, Belgium also established a registry of all cancers diagnosed during pregnancy. Dr. Loibl and her colleagues assessed outcomes in 447 cases from these registries in which women were diagnosed as having early (413 patients) or metastatic (34 patients) breast cancer while pregnant (Lancet Oncol. 2012 Aug. 15 [doi:10.1016/S1470-2045(12)70261-9]).

The median gestational age at diagnosis was 24 weeks (range, 5-40 weeks), and the median age of the women was 33 years (range, 22-51 years).

Data on chemotherapy were available for 368 women. Of these, 197 received chemotherapy while pregnant and 171 received it after delivery.

Overall, 1,187 cycles of chemotherapy were given, and 63% of these were given during pregnancy. The women received a median of four cycles (range, one to eight cycles) during pregnancy.

A total of 90% of those treated during pregnancy received an anthracyline; 8% received a combination of cyclophosphamide, methotrexate, and fluorouracil; and 7% received a taxane. None of the women received trastuzumab, endocrine therapy, or radiotherapy during pregnancy.

Women with early breast cancer who opted for chemotherapy during pregnancy tended to have more advanced disease, with more unfavorable tumor stage and nodal status, than did those who chose to begin chemotherapy after delivery. After the data were adjusted to account for this difference, the researchers found no significant difference between the two groups in disease-free or overall survival.

The estimated 3-year disease-free survival was 70.2% in women with early disease who underwent chemotherapy while pregnant and 74.3% in those who waited until after delivery. Similarly, the estimated overall 3-year survival was 84.9% in women with early breast cancer who underwent chemotherapy while pregnant and 87.4% in those who delayed chemotherapy until after delivery.

The estimated 5-year disease-free survival was 61.1% in women who had chemotherapy while pregnant and 64.4% in those who waited, and the estimated 5-year overall survival was 77% and 82.4%, respectively.

Data were available for 373 newborns, of whom 203 had been exposed to chemotherapy in utero and 170 had not.

Birth weight was slightly lower in the exposed than in the nonexposed infants, but this difference was judged to be "clinically irrelevant" because it didn’t affect the health of the babies, Dr. Loibl and her associates said.

Moreover, there were no significant differences between the two groups in major birth defects, infant height, Apgar scores, hemoglobin concentration, leukocyte counts, thrombocyte counts, or alopecia. And there was no significant difference in the proportion of infants discharged with their mothers (34% vs. 41%).

Adverse events occurred more often when chemotherapy was received during pregnancy (15%) than when it was delayed (4%). However, this difference was attributed to the higher rates of preterm labor and premature rupture of the membrane among exposed pregnancies. "Most complications were reported in babies who were delivered prematurely, regardless of exposure to chemotherapy," the investigators said.

The data were not adequate to determine why women who received chemotherapy had a higher rate of preterm delivery. Both physical stress and psychological stress may have played a role, and it is possible that women who received chemotherapy were more prone to infections that may have triggered labor.

In addition, the cytotoxic agents themselves may have hastened labor through some as yet unknown mechanism. However, the rate of preeclampsia was similar between the two groups, so oxidative stress, which is known to be induced by cytoxic agents, was not responsible.

Further study of the data being collected in the registries of cancers diagnosed during pregnancy will likely shed light on these issues. Dr. Loibl and her colleagues are now performing a matched-pair analysis to assess whether the prognosis of breast cancer in nonpregnant women differs from that in pregnant women when the latter are treated according to current guidelines.

This study was supported by BANSS Foundation, University Hospital Frankfurt, the German Breast Group, Research Foundation-Flanders, Clinical Research Fund-UZ Gasthuisberg, and the Belgian Cancer Plan. No financial conflicts of interest were reported.

It appears that breast cancer diagnosed during pregnancy can be treated much the same as breast cancer diagnosed in nonpregnant women without substantially raising the risks to mother or child, according to a study published online August 16 in the Lancet Oncology .

This conclusion, from an observational study involving 447 European women included in registries of cancers diagnosed during pregnancy, must still be validated in other studies. But until then, the current evidence indicates that pregnancy outcomes are not significantly different between women who receive breast cancer chemotherapy during the second or third trimesters and those who wait until after delivery to start treatment, said Dr. Sibylle Loibl of the German Breast Group, Neu-Isenburg, Germany, and her associates.

In this study, infants exposed to their mothers’ breast cancer chemotherapy while in utero had slightly lower birth weights and slightly more complications than those not exposed to chemotherapy, but these differences were not clinically significant.

Breast cancer diagnosed during pregnancy is rare, estimated to occur in less than 1% of breast cancers in Europe. But its incidence is increasing in high-income countries due to the trend of women delaying childbirth until they are older, when breast cancer is more prevalent.

The German Breast Group established its Breast Cancer During Pregnancy registry in 2003 and expanded it to include cases in the Netherlands, the United Kingdom, Poland, Italy, and the Czech Republic in 2009. In the same time period, Belgium also established a registry of all cancers diagnosed during pregnancy. Dr. Loibl and her colleagues assessed outcomes in 447 cases from these registries in which women were diagnosed as having early (413 patients) or metastatic (34 patients) breast cancer while pregnant (Lancet Oncol. 2012 Aug. 15 [doi:10.1016/S1470-2045(12)70261-9]).

The median gestational age at diagnosis was 24 weeks (range, 5-40 weeks), and the median age of the women was 33 years (range, 22-51 years).

Data on chemotherapy were available for 368 women. Of these, 197 received chemotherapy while pregnant and 171 received it after delivery.

Overall, 1,187 cycles of chemotherapy were given, and 63% of these were given during pregnancy. The women received a median of four cycles (range, one to eight cycles) during pregnancy.

A total of 90% of those treated during pregnancy received an anthracyline; 8% received a combination of cyclophosphamide, methotrexate, and fluorouracil; and 7% received a taxane. None of the women received trastuzumab, endocrine therapy, or radiotherapy during pregnancy.

Women with early breast cancer who opted for chemotherapy during pregnancy tended to have more advanced disease, with more unfavorable tumor stage and nodal status, than did those who chose to begin chemotherapy after delivery. After the data were adjusted to account for this difference, the researchers found no significant difference between the two groups in disease-free or overall survival.

The estimated 3-year disease-free survival was 70.2% in women with early disease who underwent chemotherapy while pregnant and 74.3% in those who waited until after delivery. Similarly, the estimated overall 3-year survival was 84.9% in women with early breast cancer who underwent chemotherapy while pregnant and 87.4% in those who delayed chemotherapy until after delivery.

The estimated 5-year disease-free survival was 61.1% in women who had chemotherapy while pregnant and 64.4% in those who waited, and the estimated 5-year overall survival was 77% and 82.4%, respectively.

Data were available for 373 newborns, of whom 203 had been exposed to chemotherapy in utero and 170 had not.

Birth weight was slightly lower in the exposed than in the nonexposed infants, but this difference was judged to be "clinically irrelevant" because it didn’t affect the health of the babies, Dr. Loibl and her associates said.

Moreover, there were no significant differences between the two groups in major birth defects, infant height, Apgar scores, hemoglobin concentration, leukocyte counts, thrombocyte counts, or alopecia. And there was no significant difference in the proportion of infants discharged with their mothers (34% vs. 41%).

Adverse events occurred more often when chemotherapy was received during pregnancy (15%) than when it was delayed (4%). However, this difference was attributed to the higher rates of preterm labor and premature rupture of the membrane among exposed pregnancies. "Most complications were reported in babies who were delivered prematurely, regardless of exposure to chemotherapy," the investigators said.

The data were not adequate to determine why women who received chemotherapy had a higher rate of preterm delivery. Both physical stress and psychological stress may have played a role, and it is possible that women who received chemotherapy were more prone to infections that may have triggered labor.

In addition, the cytotoxic agents themselves may have hastened labor through some as yet unknown mechanism. However, the rate of preeclampsia was similar between the two groups, so oxidative stress, which is known to be induced by cytoxic agents, was not responsible.

Further study of the data being collected in the registries of cancers diagnosed during pregnancy will likely shed light on these issues. Dr. Loibl and her colleagues are now performing a matched-pair analysis to assess whether the prognosis of breast cancer in nonpregnant women differs from that in pregnant women when the latter are treated according to current guidelines.

This study was supported by BANSS Foundation, University Hospital Frankfurt, the German Breast Group, Research Foundation-Flanders, Clinical Research Fund-UZ Gasthuisberg, and the Belgian Cancer Plan. No financial conflicts of interest were reported.

Tofacitinib, an oral Janus kinase inhibitor that blocks signaling for several cytokines that are integral to lymphocyte function, was found to be effective as either a monotherapy or an adjunctive therapy in two industry-sponsored phase III studies of adults with refractory rheumatoid arthritis, which were reported separately online Aug. 9 in the New England Journal of Medicine.

Compared with placebo, two doses of tofacitinib induced clinically meaningful and statistically significant reductions in the signs and symptoms of RA, and improved physical function. However, the drug was no better than placebo at inducing remission.

In the first study, 611 patients who previously had an inadequate response or excess toxicity to at least one nonbiologic or biologic disease-modifying agent were treated for 6 months at 94 medical centers worldwide, said Dr. Roy Fleischmann of the Metroplex Clinical Research Center, Dallas, and his associates in the Oral Rheumatoid Arthritis–Solo (ORAL-Solo) trial.

The study subjects were randomly assigned to receive 5-mg tofacitinib twice daily for 6 months, 10-mg tofacitinib twice daily for 6 months, or placebo twice daily for 3 months followed by 5-mg or 10-mg tofacitinib for 3 months. They were permitted to continue on stable doses of antimalarials and to use NSAIDs and glucocorticoids if needed.

The mean patient age was approximately 50 years, and the mean duration of RA was approximately 8 years. In all, 67% of the subjects were white and 87% were women.

The first efficacy end point was the percentage of patients who met the criteria for an ACR 20 (American College of Rheumatology 20) response, defined as at least a 20% reduction in the number of tender and swollen joints and at least a 20% improvement in three of the following measures: pain, disability, C-reactive protein level, patient’s global assessment of disease, and physician’s global assessment of disease.

At 3 months, 59.8% of patients receiving 5-mg tofacitinib and 65.7% of those receiving 10-mg tofacitinib achieved this end point, a significantly higher percentage than the 26.7% receiving placebo, the investigators said (N. Engl. J. Med. 2012 Aug. 9 [doi:10.1056/NEJMoa1109071]).

The second efficacy end point was the percentage of patients who showed improvement in physical function as measured by the HAQ-DI (Health Assessment Questionnaire–Disability Index). Again, significantly more patients in both tofacitinib groups showed significant improvement by week 2 and continued to improve throughout the study, compared with patients in the placebo group. At 3 months, the proportions were 52.9% with 5-mg tofacitinib and 55.7% with 10-mg tofacitinib, compared with 31.7% with placebo.

The third efficacy end point was the percentage of patients who showed significant improvement on the DAS28-4(ESR), a measure of disease activity that includes a 28-joint count and the erythrocyte sedimentation rate. Tofacitinib was not superior to placebo in this outcome measure. At 3 months, the percentage of patients with a DAS28-4(ESR) score less than 2.6, which indicates remission, was 5.6% with 5-mg tofacitinib, 8.7% with 10-mg tofacitinb, and 4.4% with placebo.

Serious adverse events were more common with both doses of tofacitinib than with placebo. Six patients developed seven serious infections, including cellulitis, liver abscess, bronchitis, pyelonephritis, one case of tuberculous pleural effusion in a patient from India, and one case of nondisseminated herpes zoster. Other serious adverse events included heart failure in two patients.

Nonserious adverse events occurred in approximately half of the study subjects, with similar frequencies across the treatment subgroups. In all, 12 patients (2%) discontinued the study drug because of adverse events during the first 3 months, and another 6 (1%) discontinued during the final 3 months of the study.

Neutropenia developed more frequently with the active treatment than with placebo. In addition, tofacitinib raised LDL cholesterol levels, liver aminotransferase levels, and serum creatinine levels.

In the second phase-III study, oral tofacitinib was compared against subcutaneous injections of adalimumab and placebo in 717 patients who were also taking stable doses of methotrexate. These subjects were treated at 115 medical centers worldwide for 1 year, said Dr. Ronald F. van Vollenhoven of the Karolinska Institute, Stockholm, and his associates in the Oral Rheumatoid Arthritis–Standard (ORAL-Standard) trial.

In this study, the patient population also was predominantly female (approximately 80%) and white (approximately 70%), and the mean duration of RA was approximately 8 years.

The study subjects were randomly assigned to receive 5-mg oral tofacitinib twice daily, 10-mg oral tofacitinib twice daily, subcutaneous adalimumab every 2 weeks, or placebo for either 3 months or 6 months. At 3 months, patients in the placebo group who showed an inadequate response were blindly switched to either 5-mg or 10-mg tofacitinib. At 6 months, all patients in the placebo group were blindly switched to 5-mg or 10-mg tofacitinib.

The three efficacy end points were the same as those in the ORAL-Solo study.

At 6 months, the percentages of patients who met criteria for an ACR 20 response were significantly higher with both doses of tofacitinib and with adalimumab than with placebo, and the magnitudes of the treatment effect were similar between tofacitinib and adalimumab (5-mg tofacitinib, 51.5%; 10-mg tofacitinib, 52.6%; adalimumab, 47.2%; placebo, 28.3%).

Similarly, the percentages of patients who showed significant improvement on both the HAQ-DI score and the DAS28-4(ESR) score were significantly higher with both tofacitinib and adalimumab than with placebo, Dr. van Vollenhoven and his colleagues said (N. Engl. J. Med. 2012 Aug. 9 [doi:10.1056/NEJMoa1112072]).

As in the ORAL-Solo study, the treatment responses in the ORAL-Standard study were rapid and were sustained throughout the 1-year study period.

Also as in the ORAL-Solo study, serious adverse events – including serious infections such as tuberculosis – were significantly higher with tofacitinib than with either adalimumab or placebo. Notable adverse events included cytopenia, respiratory and urinary tract infections, and gastrointestinal side effects.

Tofacitinib also raised cholesterol and serum creatinine levels. "Given the duration and size of the study, the implications ... for the risk of cardiac events ... could not be assessed. Longer-term monitoring of patients receiving tofacitinib is ongoing," Dr. van Vollenhoven and his associates said.

Both studies were funded by Pfizer. The investigators reported numerous ties to industry sources.

Tofacitinib, an oral Janus kinase inhibitor that blocks signaling for several cytokines that are integral to lymphocyte function, was found to be effective as either a monotherapy or an adjunctive therapy in two industry-sponsored phase III studies of adults with refractory rheumatoid arthritis, which were reported separately online Aug. 9 in the New England Journal of Medicine.

Compared with placebo, two doses of tofacitinib induced clinically meaningful and statistically significant reductions in the signs and symptoms of RA, and improved physical function. However, the drug was no better than placebo at inducing remission.

In the first study, 611 patients who previously had an inadequate response or excess toxicity to at least one nonbiologic or biologic disease-modifying agent were treated for 6 months at 94 medical centers worldwide, said Dr. Roy Fleischmann of the Metroplex Clinical Research Center, Dallas, and his associates in the Oral Rheumatoid Arthritis–Solo (ORAL-Solo) trial.

The study subjects were randomly assigned to receive 5-mg tofacitinib twice daily for 6 months, 10-mg tofacitinib twice daily for 6 months, or placebo twice daily for 3 months followed by 5-mg or 10-mg tofacitinib for 3 months. They were permitted to continue on stable doses of antimalarials and to use NSAIDs and glucocorticoids if needed.

The mean patient age was approximately 50 years, and the mean duration of RA was approximately 8 years. In all, 67% of the subjects were white and 87% were women.

The first efficacy end point was the percentage of patients who met the criteria for an ACR 20 (American College of Rheumatology 20) response, defined as at least a 20% reduction in the number of tender and swollen joints and at least a 20% improvement in three of the following measures: pain, disability, C-reactive protein level, patient’s global assessment of disease, and physician’s global assessment of disease.

At 3 months, 59.8% of patients receiving 5-mg tofacitinib and 65.7% of those receiving 10-mg tofacitinib achieved this end point, a significantly higher percentage than the 26.7% receiving placebo, the investigators said (N. Engl. J. Med. 2012 Aug. 9 [doi:10.1056/NEJMoa1109071]).

The second efficacy end point was the percentage of patients who showed improvement in physical function as measured by the HAQ-DI (Health Assessment Questionnaire–Disability Index). Again, significantly more patients in both tofacitinib groups showed significant improvement by week 2 and continued to improve throughout the study, compared with patients in the placebo group. At 3 months, the proportions were 52.9% with 5-mg tofacitinib and 55.7% with 10-mg tofacitinib, compared with 31.7% with placebo.

The third efficacy end point was the percentage of patients who showed significant improvement on the DAS28-4(ESR), a measure of disease activity that includes a 28-joint count and the erythrocyte sedimentation rate. Tofacitinib was not superior to placebo in this outcome measure. At 3 months, the percentage of patients with a DAS28-4(ESR) score less than 2.6, which indicates remission, was 5.6% with 5-mg tofacitinib, 8.7% with 10-mg tofacitinb, and 4.4% with placebo.

Serious adverse events were more common with both doses of tofacitinib than with placebo. Six patients developed seven serious infections, including cellulitis, liver abscess, bronchitis, pyelonephritis, one case of tuberculous pleural effusion in a patient from India, and one case of nondisseminated herpes zoster. Other serious adverse events included heart failure in two patients.

Nonserious adverse events occurred in approximately half of the study subjects, with similar frequencies across the treatment subgroups. In all, 12 patients (2%) discontinued the study drug because of adverse events during the first 3 months, and another 6 (1%) discontinued during the final 3 months of the study.

Neutropenia developed more frequently with the active treatment than with placebo. In addition, tofacitinib raised LDL cholesterol levels, liver aminotransferase levels, and serum creatinine levels.

In the second phase-III study, oral tofacitinib was compared against subcutaneous injections of adalimumab and placebo in 717 patients who were also taking stable doses of methotrexate. These subjects were treated at 115 medical centers worldwide for 1 year, said Dr. Ronald F. van Vollenhoven of the Karolinska Institute, Stockholm, and his associates in the Oral Rheumatoid Arthritis–Standard (ORAL-Standard) trial.

In this study, the patient population also was predominantly female (approximately 80%) and white (approximately 70%), and the mean duration of RA was approximately 8 years.

The study subjects were randomly assigned to receive 5-mg oral tofacitinib twice daily, 10-mg oral tofacitinib twice daily, subcutaneous adalimumab every 2 weeks, or placebo for either 3 months or 6 months. At 3 months, patients in the placebo group who showed an inadequate response were blindly switched to either 5-mg or 10-mg tofacitinib. At 6 months, all patients in the placebo group were blindly switched to 5-mg or 10-mg tofacitinib.

The three efficacy end points were the same as those in the ORAL-Solo study.

At 6 months, the percentages of patients who met criteria for an ACR 20 response were significantly higher with both doses of tofacitinib and with adalimumab than with placebo, and the magnitudes of the treatment effect were similar between tofacitinib and adalimumab (5-mg tofacitinib, 51.5%; 10-mg tofacitinib, 52.6%; adalimumab, 47.2%; placebo, 28.3%).

Similarly, the percentages of patients who showed significant improvement on both the HAQ-DI score and the DAS28-4(ESR) score were significantly higher with both tofacitinib and adalimumab than with placebo, Dr. van Vollenhoven and his colleagues said (N. Engl. J. Med. 2012 Aug. 9 [doi:10.1056/NEJMoa1112072]).

As in the ORAL-Solo study, the treatment responses in the ORAL-Standard study were rapid and were sustained throughout the 1-year study period.

Also as in the ORAL-Solo study, serious adverse events – including serious infections such as tuberculosis – were significantly higher with tofacitinib than with either adalimumab or placebo. Notable adverse events included cytopenia, respiratory and urinary tract infections, and gastrointestinal side effects.

Tofacitinib also raised cholesterol and serum creatinine levels. "Given the duration and size of the study, the implications ... for the risk of cardiac events ... could not be assessed. Longer-term monitoring of patients receiving tofacitinib is ongoing," Dr. van Vollenhoven and his associates said.

Both studies were funded by Pfizer. The investigators reported numerous ties to industry sources.

Tofacitinib, an oral Janus kinase inhibitor that blocks signaling for several cytokines that are integral to lymphocyte function, was found to be effective as either a monotherapy or an adjunctive therapy in two industry-sponsored phase III studies of adults with refractory rheumatoid arthritis, which were reported separately online Aug. 9 in the New England Journal of Medicine.

Compared with placebo, two doses of tofacitinib induced clinically meaningful and statistically significant reductions in the signs and symptoms of RA, and improved physical function. However, the drug was no better than placebo at inducing remission.

In the first study, 611 patients who previously had an inadequate response or excess toxicity to at least one nonbiologic or biologic disease-modifying agent were treated for 6 months at 94 medical centers worldwide, said Dr. Roy Fleischmann of the Metroplex Clinical Research Center, Dallas, and his associates in the Oral Rheumatoid Arthritis–Solo (ORAL-Solo) trial.

The study subjects were randomly assigned to receive 5-mg tofacitinib twice daily for 6 months, 10-mg tofacitinib twice daily for 6 months, or placebo twice daily for 3 months followed by 5-mg or 10-mg tofacitinib for 3 months. They were permitted to continue on stable doses of antimalarials and to use NSAIDs and glucocorticoids if needed.

The mean patient age was approximately 50 years, and the mean duration of RA was approximately 8 years. In all, 67% of the subjects were white and 87% were women.

The first efficacy end point was the percentage of patients who met the criteria for an ACR 20 (American College of Rheumatology 20) response, defined as at least a 20% reduction in the number of tender and swollen joints and at least a 20% improvement in three of the following measures: pain, disability, C-reactive protein level, patient’s global assessment of disease, and physician’s global assessment of disease.

At 3 months, 59.8% of patients receiving 5-mg tofacitinib and 65.7% of those receiving 10-mg tofacitinib achieved this end point, a significantly higher percentage than the 26.7% receiving placebo, the investigators said (N. Engl. J. Med. 2012 Aug. 9 [doi:10.1056/NEJMoa1109071]).

The second efficacy end point was the percentage of patients who showed improvement in physical function as measured by the HAQ-DI (Health Assessment Questionnaire–Disability Index). Again, significantly more patients in both tofacitinib groups showed significant improvement by week 2 and continued to improve throughout the study, compared with patients in the placebo group. At 3 months, the proportions were 52.9% with 5-mg tofacitinib and 55.7% with 10-mg tofacitinib, compared with 31.7% with placebo.

The third efficacy end point was the percentage of patients who showed significant improvement on the DAS28-4(ESR), a measure of disease activity that includes a 28-joint count and the erythrocyte sedimentation rate. Tofacitinib was not superior to placebo in this outcome measure. At 3 months, the percentage of patients with a DAS28-4(ESR) score less than 2.6, which indicates remission, was 5.6% with 5-mg tofacitinib, 8.7% with 10-mg tofacitinb, and 4.4% with placebo.

Serious adverse events were more common with both doses of tofacitinib than with placebo. Six patients developed seven serious infections, including cellulitis, liver abscess, bronchitis, pyelonephritis, one case of tuberculous pleural effusion in a patient from India, and one case of nondisseminated herpes zoster. Other serious adverse events included heart failure in two patients.

Nonserious adverse events occurred in approximately half of the study subjects, with similar frequencies across the treatment subgroups. In all, 12 patients (2%) discontinued the study drug because of adverse events during the first 3 months, and another 6 (1%) discontinued during the final 3 months of the study.

Neutropenia developed more frequently with the active treatment than with placebo. In addition, tofacitinib raised LDL cholesterol levels, liver aminotransferase levels, and serum creatinine levels.

In the second phase-III study, oral tofacitinib was compared against subcutaneous injections of adalimumab and placebo in 717 patients who were also taking stable doses of methotrexate. These subjects were treated at 115 medical centers worldwide for 1 year, said Dr. Ronald F. van Vollenhoven of the Karolinska Institute, Stockholm, and his associates in the Oral Rheumatoid Arthritis–Standard (ORAL-Standard) trial.

In this study, the patient population also was predominantly female (approximately 80%) and white (approximately 70%), and the mean duration of RA was approximately 8 years.

The study subjects were randomly assigned to receive 5-mg oral tofacitinib twice daily, 10-mg oral tofacitinib twice daily, subcutaneous adalimumab every 2 weeks, or placebo for either 3 months or 6 months. At 3 months, patients in the placebo group who showed an inadequate response were blindly switched to either 5-mg or 10-mg tofacitinib. At 6 months, all patients in the placebo group were blindly switched to 5-mg or 10-mg tofacitinib.

The three efficacy end points were the same as those in the ORAL-Solo study.

At 6 months, the percentages of patients who met criteria for an ACR 20 response were significantly higher with both doses of tofacitinib and with adalimumab than with placebo, and the magnitudes of the treatment effect were similar between tofacitinib and adalimumab (5-mg tofacitinib, 51.5%; 10-mg tofacitinib, 52.6%; adalimumab, 47.2%; placebo, 28.3%).

Similarly, the percentages of patients who showed significant improvement on both the HAQ-DI score and the DAS28-4(ESR) score were significantly higher with both tofacitinib and adalimumab than with placebo, Dr. van Vollenhoven and his colleagues said (N. Engl. J. Med. 2012 Aug. 9 [doi:10.1056/NEJMoa1112072]).

As in the ORAL-Solo study, the treatment responses in the ORAL-Standard study were rapid and were sustained throughout the 1-year study period.

Also as in the ORAL-Solo study, serious adverse events – including serious infections such as tuberculosis – were significantly higher with tofacitinib than with either adalimumab or placebo. Notable adverse events included cytopenia, respiratory and urinary tract infections, and gastrointestinal side effects.

Tofacitinib also raised cholesterol and serum creatinine levels. "Given the duration and size of the study, the implications ... for the risk of cardiac events ... could not be assessed. Longer-term monitoring of patients receiving tofacitinib is ongoing," Dr. van Vollenhoven and his associates said.

Both studies were funded by Pfizer. The investigators reported numerous ties to industry sources.

Overall lipid profiles have improved among children and adolescents in the United States since the late 1980s, although they still fall well short of public health goals, according to a report in the Aug. 8 issue of JAMA.

In what researchers described as the first study to track serum lipid concentrations in a nationally representative sample over more than 2 decades, youths aged 6-19 years showed significant declines in total cholesterol and non-HDL cholesterol accompanied by rises in HDL cholesterol; adolescents also showed decreases in triglycerides, said Dr. Brian K. Kit of the National Center for Health Statistics, Hyattsville, Md., and his associates.

These changes "are comparable to those reported among U.S. adults during a similar time frame," they noted.

Dr. Kit and his colleagues assessed time trends in serum lipid concentrations, comparing data from the National Health and Nutrition Examination Surveys (NHANES) for 1988-1994 with data from the 2007-2010 NHANES of 16,116 youths. For these surveys, cholesterol levels were measured in subjects aged 6-19 years and triglycerides were measured in those aged 12-19 years.

The overall study population showed a 5-mg/dL decrease in mean serum total cholesterol over time, from 165 mg/dL to 160 mg/dL, and a concomitant rise in mean serum HDL cholesterol from 50.5 mg/dL to 52.2 mg/dL. Mean serum non-HDL cholesterol dropped 8 mg/dL, from 115 mg/dL to 107 mg/dL.

"Generally, the sex-, age-, and race/ethnicity-specific trends ... were similar in direction to the overall trends and consistent with a favorable trend, although for each group the magnitude was not the same and the trend was not always significant," the investigators said (JAMA 2012;308:591-600).

For example, Mexican-American children of both sexes and black girls and adolescents did not show significant increases in HDL cholesterol.

Adolescents as a whole also showed a 9-mg/dL decline in mean serum triglycerides over time, from 82 mg/dL to 73 mg/dL. But again, there were some exceptions in specific age, gender, and race/ethnicity subgroups. For example, Mexican-American boys and adolescents showed no increase or decrease in triglyceride concentration between the late 1980s and 2010.

The subgroup of obese children and adolescents showed similar significant declines in total cholesterol and non-HDL cholesterol, compared with the overall study population, but their increases in HDL cholesterol did not reach significance. Their overall improvement was encouraging, given the marked increase in childhood obesity that occurred in the United States during the study period, Dr. Kit and his associates said.

In accordance with the main finding of this study, the prevalence of elevated total cholesterol decreased from 11.3% to 8.1% and that of non-HDL cholesterol dropped from 13.6% to 10% during the study period.

This study was funded by the Heart, Lung, and Blood Institute. No financial conflicts of interest were reported.

Overall lipid profiles have improved among children and adolescents in the United States since the late 1980s, although they still fall well short of public health goals, according to a report in the Aug. 8 issue of JAMA.

In what researchers described as the first study to track serum lipid concentrations in a nationally representative sample over more than 2 decades, youths aged 6-19 years showed significant declines in total cholesterol and non-HDL cholesterol accompanied by rises in HDL cholesterol; adolescents also showed decreases in triglycerides, said Dr. Brian K. Kit of the National Center for Health Statistics, Hyattsville, Md., and his associates.

These changes "are comparable to those reported among U.S. adults during a similar time frame," they noted.

Dr. Kit and his colleagues assessed time trends in serum lipid concentrations, comparing data from the National Health and Nutrition Examination Surveys (NHANES) for 1988-1994 with data from the 2007-2010 NHANES of 16,116 youths. For these surveys, cholesterol levels were measured in subjects aged 6-19 years and triglycerides were measured in those aged 12-19 years.

The overall study population showed a 5-mg/dL decrease in mean serum total cholesterol over time, from 165 mg/dL to 160 mg/dL, and a concomitant rise in mean serum HDL cholesterol from 50.5 mg/dL to 52.2 mg/dL. Mean serum non-HDL cholesterol dropped 8 mg/dL, from 115 mg/dL to 107 mg/dL.

"Generally, the sex-, age-, and race/ethnicity-specific trends ... were similar in direction to the overall trends and consistent with a favorable trend, although for each group the magnitude was not the same and the trend was not always significant," the investigators said (JAMA 2012;308:591-600).

For example, Mexican-American children of both sexes and black girls and adolescents did not show significant increases in HDL cholesterol.

Adolescents as a whole also showed a 9-mg/dL decline in mean serum triglycerides over time, from 82 mg/dL to 73 mg/dL. But again, there were some exceptions in specific age, gender, and race/ethnicity subgroups. For example, Mexican-American boys and adolescents showed no increase or decrease in triglyceride concentration between the late 1980s and 2010.

The subgroup of obese children and adolescents showed similar significant declines in total cholesterol and non-HDL cholesterol, compared with the overall study population, but their increases in HDL cholesterol did not reach significance. Their overall improvement was encouraging, given the marked increase in childhood obesity that occurred in the United States during the study period, Dr. Kit and his associates said.

In accordance with the main finding of this study, the prevalence of elevated total cholesterol decreased from 11.3% to 8.1% and that of non-HDL cholesterol dropped from 13.6% to 10% during the study period.

This study was funded by the Heart, Lung, and Blood Institute. No financial conflicts of interest were reported.

Overall lipid profiles have improved among children and adolescents in the United States since the late 1980s, although they still fall well short of public health goals, according to a report in the Aug. 8 issue of JAMA.

In what researchers described as the first study to track serum lipid concentrations in a nationally representative sample over more than 2 decades, youths aged 6-19 years showed significant declines in total cholesterol and non-HDL cholesterol accompanied by rises in HDL cholesterol; adolescents also showed decreases in triglycerides, said Dr. Brian K. Kit of the National Center for Health Statistics, Hyattsville, Md., and his associates.

These changes "are comparable to those reported among U.S. adults during a similar time frame," they noted.

Dr. Kit and his colleagues assessed time trends in serum lipid concentrations, comparing data from the National Health and Nutrition Examination Surveys (NHANES) for 1988-1994 with data from the 2007-2010 NHANES of 16,116 youths. For these surveys, cholesterol levels were measured in subjects aged 6-19 years and triglycerides were measured in those aged 12-19 years.

The overall study population showed a 5-mg/dL decrease in mean serum total cholesterol over time, from 165 mg/dL to 160 mg/dL, and a concomitant rise in mean serum HDL cholesterol from 50.5 mg/dL to 52.2 mg/dL. Mean serum non-HDL cholesterol dropped 8 mg/dL, from 115 mg/dL to 107 mg/dL.

"Generally, the sex-, age-, and race/ethnicity-specific trends ... were similar in direction to the overall trends and consistent with a favorable trend, although for each group the magnitude was not the same and the trend was not always significant," the investigators said (JAMA 2012;308:591-600).

For example, Mexican-American children of both sexes and black girls and adolescents did not show significant increases in HDL cholesterol.

Adolescents as a whole also showed a 9-mg/dL decline in mean serum triglycerides over time, from 82 mg/dL to 73 mg/dL. But again, there were some exceptions in specific age, gender, and race/ethnicity subgroups. For example, Mexican-American boys and adolescents showed no increase or decrease in triglyceride concentration between the late 1980s and 2010.

The subgroup of obese children and adolescents showed similar significant declines in total cholesterol and non-HDL cholesterol, compared with the overall study population, but their increases in HDL cholesterol did not reach significance. Their overall improvement was encouraging, given the marked increase in childhood obesity that occurred in the United States during the study period, Dr. Kit and his associates said.

In accordance with the main finding of this study, the prevalence of elevated total cholesterol decreased from 11.3% to 8.1% and that of non-HDL cholesterol dropped from 13.6% to 10% during the study period.

This study was funded by the Heart, Lung, and Blood Institute. No financial conflicts of interest were reported.

Commonly used photosensitizing antihypertensive drugs increase the risk for lip cancer by two- to fourfold, according to a study published online Aug. 6 in Archives of Internal Medicine.

"Lip cancer is rare, and an increased risk of its development is generally outweighed by the benefits of drugs that are effective for other conditions. However, physicians prescribing photosensitizing drugs should ascertain whether patients are at high risk of lip cancer because of their fair skin and long-term sun exposure, and discuss lip protection with them," wrote Dr. Gary D. Friedman of the division of research, Kaiser Permanente Medical Care Program, Oakland Calif., and his colleagues. "Likely preventive measures are simple: a hat with a sufficiently wide brim to shade the lips, and lip sunscreens," they added.

The diuretics hydrochlorothiazide and hydrochlorothiazide-triamterene, as well as the calcium channel blocker nifedipine, were associated with at least a doubling in the risk for lip cancer in a study involving 23,616 hypertensive non-Hispanic white adults. The association between lip cancer and the ACE inhibitor lisinopril, which also is photosensitizing, was characterized as "equivocal." And atenolol, a beta-adrenergic blocker that is not photosensitizing, was not linked to a higher risk.

Dr. Friedman and his colleagues used prescription data from the Kaiser Permanente pharmacy database and information from its cancer registry to perform a case-control study examining the relationship between the four classes of antihypertensive medications and lip cancer. They assessed the period from 1994 through 2008. The database includes an ethnically and socioeconomically diverse population of residents in the San Francisco and central valley regions of California.

There were few cases of lip cancer among nonwhite patients, so the analysis was restricted to white patients. Those with human immunodeficiency virus infection and those taking immunosuppressants after receiving organ transplants also were excluded because these factors were likely to be confounders.

The study population comprised 712 patients with lip cancer and 22,904 age-matched control patients. Nearly all malignancies were squamous cell. As expected, cigarette smokers in both study groups were more likely than nonsmokers to develop lip cancer.

The risk of developing lip cancer showed a dose-response relationship with the use of certain antihypertensive drugs, with the risk increasing as the duration of drug use increased. For patients treated with hydrochlorothiazide for 5 years or more, the odds ratio of developing lip cancer was 4.22. The OR for the combination drug hydrochlorothiazide-triamterene was 2.82, and the OR for nifedipine was 2.50. The OR was of borderline significance for lisinopril (1.42).

In contrast, for patients treated with atenolol for 5 years or more, the risk of developing lip cancer was reduced, with an odds ratio of 0.54, the investigators reported (Arch. Intern. Med. 2012 Aug. 6 [doi:10.1001/archinternmed.2012.2754]).

It should not be surprising that previous large clinical trials of these drugs’ efficacy failed to find an association with lip cancer, because of the rarity of the malignancy, they added.

For example, one study of antihypertensive medications involved more than 33,000 patients followed for a mean of 5 years. And after the investigators excluded the nonwhite patients, adjusted for the much lower incidence of lip cancer in women (who comprised half of the study population) than in men, and considered the low background incidence of the malignancy, they found that only seven lip cancers would have been expected to be detected in all the treatment groups combined, reported Dr. Friedman, also of the department of health research and policy, Stanford (Calif.) University, and his associates.

"Although the relatively high odds ratios, the evidence for specificity, and the biological mechanism are consistent with a causal relationship, causality cannot usually be established by a single observational study such as ours. Further investigations are needed to confirm and characterize relationships between photosensitizing antihypertensive agents and lip cancer," the researchers noted.

The study was limited because the researchers were unable to account for patients’ sun exposure, which is the most important factor contributing to lip cancer risk. "However, it does not seem likely that users of the antihypertensive drugs associated with lip cancer experience a great deal more sun exposure than nonusers or than users of atenolol," they wrote.

This study was supported by the National Cancer Institute. Dr. Friedman reported ties to Allergan, and his associates reported ties to Genentech, Merck, Sanofi-Aventis, and Takeda.

Commonly used photosensitizing antihypertensive drugs increase the risk for lip cancer by two- to fourfold, according to a study published online Aug. 6 in Archives of Internal Medicine.

"Lip cancer is rare, and an increased risk of its development is generally outweighed by the benefits of drugs that are effective for other conditions. However, physicians prescribing photosensitizing drugs should ascertain whether patients are at high risk of lip cancer because of their fair skin and long-term sun exposure, and discuss lip protection with them," wrote Dr. Gary D. Friedman of the division of research, Kaiser Permanente Medical Care Program, Oakland Calif., and his colleagues. "Likely preventive measures are simple: a hat with a sufficiently wide brim to shade the lips, and lip sunscreens," they added.

The diuretics hydrochlorothiazide and hydrochlorothiazide-triamterene, as well as the calcium channel blocker nifedipine, were associated with at least a doubling in the risk for lip cancer in a study involving 23,616 hypertensive non-Hispanic white adults. The association between lip cancer and the ACE inhibitor lisinopril, which also is photosensitizing, was characterized as "equivocal." And atenolol, a beta-adrenergic blocker that is not photosensitizing, was not linked to a higher risk.

Dr. Friedman and his colleagues used prescription data from the Kaiser Permanente pharmacy database and information from its cancer registry to perform a case-control study examining the relationship between the four classes of antihypertensive medications and lip cancer. They assessed the period from 1994 through 2008. The database includes an ethnically and socioeconomically diverse population of residents in the San Francisco and central valley regions of California.

There were few cases of lip cancer among nonwhite patients, so the analysis was restricted to white patients. Those with human immunodeficiency virus infection and those taking immunosuppressants after receiving organ transplants also were excluded because these factors were likely to be confounders.

The study population comprised 712 patients with lip cancer and 22,904 age-matched control patients. Nearly all malignancies were squamous cell. As expected, cigarette smokers in both study groups were more likely than nonsmokers to develop lip cancer.

The risk of developing lip cancer showed a dose-response relationship with the use of certain antihypertensive drugs, with the risk increasing as the duration of drug use increased. For patients treated with hydrochlorothiazide for 5 years or more, the odds ratio of developing lip cancer was 4.22. The OR for the combination drug hydrochlorothiazide-triamterene was 2.82, and the OR for nifedipine was 2.50. The OR was of borderline significance for lisinopril (1.42).

In contrast, for patients treated with atenolol for 5 years or more, the risk of developing lip cancer was reduced, with an odds ratio of 0.54, the investigators reported (Arch. Intern. Med. 2012 Aug. 6 [doi:10.1001/archinternmed.2012.2754]).

It should not be surprising that previous large clinical trials of these drugs’ efficacy failed to find an association with lip cancer, because of the rarity of the malignancy, they added.

For example, one study of antihypertensive medications involved more than 33,000 patients followed for a mean of 5 years. And after the investigators excluded the nonwhite patients, adjusted for the much lower incidence of lip cancer in women (who comprised half of the study population) than in men, and considered the low background incidence of the malignancy, they found that only seven lip cancers would have been expected to be detected in all the treatment groups combined, reported Dr. Friedman, also of the department of health research and policy, Stanford (Calif.) University, and his associates.

"Although the relatively high odds ratios, the evidence for specificity, and the biological mechanism are consistent with a causal relationship, causality cannot usually be established by a single observational study such as ours. Further investigations are needed to confirm and characterize relationships between photosensitizing antihypertensive agents and lip cancer," the researchers noted.

The study was limited because the researchers were unable to account for patients’ sun exposure, which is the most important factor contributing to lip cancer risk. "However, it does not seem likely that users of the antihypertensive drugs associated with lip cancer experience a great deal more sun exposure than nonusers or than users of atenolol," they wrote.

This study was supported by the National Cancer Institute. Dr. Friedman reported ties to Allergan, and his associates reported ties to Genentech, Merck, Sanofi-Aventis, and Takeda.

Commonly used photosensitizing antihypertensive drugs increase the risk for lip cancer by two- to fourfold, according to a study published online Aug. 6 in Archives of Internal Medicine.

"Lip cancer is rare, and an increased risk of its development is generally outweighed by the benefits of drugs that are effective for other conditions. However, physicians prescribing photosensitizing drugs should ascertain whether patients are at high risk of lip cancer because of their fair skin and long-term sun exposure, and discuss lip protection with them," wrote Dr. Gary D. Friedman of the division of research, Kaiser Permanente Medical Care Program, Oakland Calif., and his colleagues. "Likely preventive measures are simple: a hat with a sufficiently wide brim to shade the lips, and lip sunscreens," they added.

The diuretics hydrochlorothiazide and hydrochlorothiazide-triamterene, as well as the calcium channel blocker nifedipine, were associated with at least a doubling in the risk for lip cancer in a study involving 23,616 hypertensive non-Hispanic white adults. The association between lip cancer and the ACE inhibitor lisinopril, which also is photosensitizing, was characterized as "equivocal." And atenolol, a beta-adrenergic blocker that is not photosensitizing, was not linked to a higher risk.

Dr. Friedman and his colleagues used prescription data from the Kaiser Permanente pharmacy database and information from its cancer registry to perform a case-control study examining the relationship between the four classes of antihypertensive medications and lip cancer. They assessed the period from 1994 through 2008. The database includes an ethnically and socioeconomically diverse population of residents in the San Francisco and central valley regions of California.

There were few cases of lip cancer among nonwhite patients, so the analysis was restricted to white patients. Those with human immunodeficiency virus infection and those taking immunosuppressants after receiving organ transplants also were excluded because these factors were likely to be confounders.

The study population comprised 712 patients with lip cancer and 22,904 age-matched control patients. Nearly all malignancies were squamous cell. As expected, cigarette smokers in both study groups were more likely than nonsmokers to develop lip cancer.

The risk of developing lip cancer showed a dose-response relationship with the use of certain antihypertensive drugs, with the risk increasing as the duration of drug use increased. For patients treated with hydrochlorothiazide for 5 years or more, the odds ratio of developing lip cancer was 4.22. The OR for the combination drug hydrochlorothiazide-triamterene was 2.82, and the OR for nifedipine was 2.50. The OR was of borderline significance for lisinopril (1.42).

In contrast, for patients treated with atenolol for 5 years or more, the risk of developing lip cancer was reduced, with an odds ratio of 0.54, the investigators reported (Arch. Intern. Med. 2012 Aug. 6 [doi:10.1001/archinternmed.2012.2754]).

It should not be surprising that previous large clinical trials of these drugs’ efficacy failed to find an association with lip cancer, because of the rarity of the malignancy, they added.

For example, one study of antihypertensive medications involved more than 33,000 patients followed for a mean of 5 years. And after the investigators excluded the nonwhite patients, adjusted for the much lower incidence of lip cancer in women (who comprised half of the study population) than in men, and considered the low background incidence of the malignancy, they found that only seven lip cancers would have been expected to be detected in all the treatment groups combined, reported Dr. Friedman, also of the department of health research and policy, Stanford (Calif.) University, and his associates.

"Although the relatively high odds ratios, the evidence for specificity, and the biological mechanism are consistent with a causal relationship, causality cannot usually be established by a single observational study such as ours. Further investigations are needed to confirm and characterize relationships between photosensitizing antihypertensive agents and lip cancer," the researchers noted.

The study was limited because the researchers were unable to account for patients’ sun exposure, which is the most important factor contributing to lip cancer risk. "However, it does not seem likely that users of the antihypertensive drugs associated with lip cancer experience a great deal more sun exposure than nonusers or than users of atenolol," they wrote.

This study was supported by the National Cancer Institute. Dr. Friedman reported ties to Allergan, and his associates reported ties to Genentech, Merck, Sanofi-Aventis, and Takeda.

Rankings of hospital performance in treating acute ischemic stroke must take into consideration the severity of each case, or the rankings will be extremely inaccurate, researchers say in the July 18 issue of JAMA.

Unfortunately, the rankings that are currently used by accreditation organizations, the Centers for Medicare and Medicaid Services (CMS), and other payers do not incorporate stroke severity. A study that corrected for this oversight found that close to half of the U.S. hospitals ranked in the top or bottom 5%, according to stroke patients’ 30-day mortality, should be reclassified into the middle range of the rankings.

For the 782 hospitals included in this study, the median change in rank position was 79 places when stroke severity was incorporated into the statistical model, said Dr. Gregg C. Fonarow of the Ahmanson-UCLA Cardiomyopathy Center, Los Angeles, and his associates.

When stroke severity is not considered, the rankings systematically favor hospitals that care for patients with less severe illness, regardless of whether the patient care at these hospitals produces better or worse patient outcomes.

If reliance on inaccurate rankings persists, hospitals that want to improve their ranking may consider turning away patients with more severe strokes or transferring them to other hospitals after emergency department assessment, to avoid being classified as low performance, Dr. Fonarow and his associates said.

The researchers used data from the Get With the Guidelines–Stroke Registry and from CMS inpatient claims files to create a risk-adjustment model that incorporated stroke severity, as measured by the NIHSS (National Institutes of Health Stroke Scale), into hospitals’ 30-day mortality profiling. The NIHSS is a 15-item scale that assesses the effect of acute stroke on level of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss.

All types of hospitals in all regions of the United States were represented. The study population included 127,950 patients aged 65 years and older who had acute ischemic stroke and were treated at 782 hospitals participating in the Get With the Guidelines program from April 2003 to December 2009.

The median patient age was 80 years; 57% were women and 86% were white. Patients frequently had serious comorbidities, including hypertension (83%), diabetes (29%), coronary artery disease or prior myocardial infarction (34%), and a history of atrial fibrillation or flutter (27%).

There were 18,186 deaths within 30 days of admission.

The statistical model that incorporated stroke severity into its assessment of hospital performance "demonstrated substantially more accurate classification of hospital 30-day mortality" than did the model currently in use. When hospitals were ranked according to this more accurate profile, their rank position changed by a median of 79 places.

Overall, 206 of the 782 hospitals (26%) ended up in a different performance category once the NIHSS score was incorporated into the model.

Of the 39 hospitals that had been categorized as top performers using the standard model, only 23 remained top performers using the more accurate model. And another 16 hospitals that hadn’t made the grade with the standard model were reclassified as top performers with the more accurate model.

"There was even greater disagreement about the bottom-performing hospitals," Dr. Fonarow and his colleagues said (JAMA 2012;308:257-64).

Of the 40 worst-performing hospitals according to the standard model, nearly half (19) were reclassified as having a middling performance with the more accurate model.

"These findings highlight the importance of including a valid specific measure of stroke severity in hospital risk models for mortality after acute ischemic stroke. ... Furthermore, this study suggests that inclusion of admission stroke severity may be essential for optimal ranking of hospitals with respect to 30-day mortality," they said.

This study was supported by the American Heart Association, American Stroke Association, and Janssen Pharmaceutical Companies of Johnson & Johnson. Dr. Fonarow is an employee of the University of California, which holds a patent on retriever devices for stroke. His associates reported ties to numerous industry sources.

Stroke Severity Is a Key Consideration

In an editorial accompanying Dr. Fonarow’s report, Dr. Tobias Kurth and Dr. Mitchell S.V. Elkind said that the study "clearly highlights the importance of incorporating information on stroke severity when conducting health outcomes research in stroke. Excluding this information will lead to incorrect ranking of hospital performance by failing to consider that hospitals care for different patient populations" (JAMA 2012;308:292-4).

In this study, when considering only the hospitals ranked in the best 20% and worst 20% of the total, close to one-third would have been reclassified if the more accurate statistical model incorporating stroke severity had been used, they noted.

Dr. Kurth is in neuroepidemiology at the University of Bordeaux (France). Dr. Elkind is in the department of neurology in the school of medicine and the department of epidemiology in the school of public health at Columbia University, New York. Dr. Kurth reported ties to Allergan, Merck, and MAP Pharmaceuticals, and Dr. Elkind reported ties to diaDexus, Britol-Myers Squibb/Sanofi Pharmaceuticals Partnership, Novartis, Organon, and GlaxoSmithKline.

Rankings of hospital performance in treating acute ischemic stroke must take into consideration the severity of each case, or the rankings will be extremely inaccurate, researchers say in the July 18 issue of JAMA.

Unfortunately, the rankings that are currently used by accreditation organizations, the Centers for Medicare and Medicaid Services (CMS), and other payers do not incorporate stroke severity. A study that corrected for this oversight found that close to half of the U.S. hospitals ranked in the top or bottom 5%, according to stroke patients’ 30-day mortality, should be reclassified into the middle range of the rankings.

For the 782 hospitals included in this study, the median change in rank position was 79 places when stroke severity was incorporated into the statistical model, said Dr. Gregg C. Fonarow of the Ahmanson-UCLA Cardiomyopathy Center, Los Angeles, and his associates.

When stroke severity is not considered, the rankings systematically favor hospitals that care for patients with less severe illness, regardless of whether the patient care at these hospitals produces better or worse patient outcomes.

If reliance on inaccurate rankings persists, hospitals that want to improve their ranking may consider turning away patients with more severe strokes or transferring them to other hospitals after emergency department assessment, to avoid being classified as low performance, Dr. Fonarow and his associates said.

The researchers used data from the Get With the Guidelines–Stroke Registry and from CMS inpatient claims files to create a risk-adjustment model that incorporated stroke severity, as measured by the NIHSS (National Institutes of Health Stroke Scale), into hospitals’ 30-day mortality profiling. The NIHSS is a 15-item scale that assesses the effect of acute stroke on level of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss.

All types of hospitals in all regions of the United States were represented. The study population included 127,950 patients aged 65 years and older who had acute ischemic stroke and were treated at 782 hospitals participating in the Get With the Guidelines program from April 2003 to December 2009.

The median patient age was 80 years; 57% were women and 86% were white. Patients frequently had serious comorbidities, including hypertension (83%), diabetes (29%), coronary artery disease or prior myocardial infarction (34%), and a history of atrial fibrillation or flutter (27%).

There were 18,186 deaths within 30 days of admission.

The statistical model that incorporated stroke severity into its assessment of hospital performance "demonstrated substantially more accurate classification of hospital 30-day mortality" than did the model currently in use. When hospitals were ranked according to this more accurate profile, their rank position changed by a median of 79 places.

Overall, 206 of the 782 hospitals (26%) ended up in a different performance category once the NIHSS score was incorporated into the model.

Of the 39 hospitals that had been categorized as top performers using the standard model, only 23 remained top performers using the more accurate model. And another 16 hospitals that hadn’t made the grade with the standard model were reclassified as top performers with the more accurate model.

"There was even greater disagreement about the bottom-performing hospitals," Dr. Fonarow and his colleagues said (JAMA 2012;308:257-64).

Of the 40 worst-performing hospitals according to the standard model, nearly half (19) were reclassified as having a middling performance with the more accurate model.

"These findings highlight the importance of including a valid specific measure of stroke severity in hospital risk models for mortality after acute ischemic stroke. ... Furthermore, this study suggests that inclusion of admission stroke severity may be essential for optimal ranking of hospitals with respect to 30-day mortality," they said.

This study was supported by the American Heart Association, American Stroke Association, and Janssen Pharmaceutical Companies of Johnson & Johnson. Dr. Fonarow is an employee of the University of California, which holds a patent on retriever devices for stroke. His associates reported ties to numerous industry sources.

Stroke Severity Is a Key Consideration

In an editorial accompanying Dr. Fonarow’s report, Dr. Tobias Kurth and Dr. Mitchell S.V. Elkind said that the study "clearly highlights the importance of incorporating information on stroke severity when conducting health outcomes research in stroke. Excluding this information will lead to incorrect ranking of hospital performance by failing to consider that hospitals care for different patient populations" (JAMA 2012;308:292-4).

In this study, when considering only the hospitals ranked in the best 20% and worst 20% of the total, close to one-third would have been reclassified if the more accurate statistical model incorporating stroke severity had been used, they noted.

Dr. Kurth is in neuroepidemiology at the University of Bordeaux (France). Dr. Elkind is in the department of neurology in the school of medicine and the department of epidemiology in the school of public health at Columbia University, New York. Dr. Kurth reported ties to Allergan, Merck, and MAP Pharmaceuticals, and Dr. Elkind reported ties to diaDexus, Britol-Myers Squibb/Sanofi Pharmaceuticals Partnership, Novartis, Organon, and GlaxoSmithKline.

Rankings of hospital performance in treating acute ischemic stroke must take into consideration the severity of each case, or the rankings will be extremely inaccurate, researchers say in the July 18 issue of JAMA.

Unfortunately, the rankings that are currently used by accreditation organizations, the Centers for Medicare and Medicaid Services (CMS), and other payers do not incorporate stroke severity. A study that corrected for this oversight found that close to half of the U.S. hospitals ranked in the top or bottom 5%, according to stroke patients’ 30-day mortality, should be reclassified into the middle range of the rankings.

For the 782 hospitals included in this study, the median change in rank position was 79 places when stroke severity was incorporated into the statistical model, said Dr. Gregg C. Fonarow of the Ahmanson-UCLA Cardiomyopathy Center, Los Angeles, and his associates.

When stroke severity is not considered, the rankings systematically favor hospitals that care for patients with less severe illness, regardless of whether the patient care at these hospitals produces better or worse patient outcomes.

If reliance on inaccurate rankings persists, hospitals that want to improve their ranking may consider turning away patients with more severe strokes or transferring them to other hospitals after emergency department assessment, to avoid being classified as low performance, Dr. Fonarow and his associates said.

The researchers used data from the Get With the Guidelines–Stroke Registry and from CMS inpatient claims files to create a risk-adjustment model that incorporated stroke severity, as measured by the NIHSS (National Institutes of Health Stroke Scale), into hospitals’ 30-day mortality profiling. The NIHSS is a 15-item scale that assesses the effect of acute stroke on level of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss.

All types of hospitals in all regions of the United States were represented. The study population included 127,950 patients aged 65 years and older who had acute ischemic stroke and were treated at 782 hospitals participating in the Get With the Guidelines program from April 2003 to December 2009.

The median patient age was 80 years; 57% were women and 86% were white. Patients frequently had serious comorbidities, including hypertension (83%), diabetes (29%), coronary artery disease or prior myocardial infarction (34%), and a history of atrial fibrillation or flutter (27%).

There were 18,186 deaths within 30 days of admission.

The statistical model that incorporated stroke severity into its assessment of hospital performance "demonstrated substantially more accurate classification of hospital 30-day mortality" than did the model currently in use. When hospitals were ranked according to this more accurate profile, their rank position changed by a median of 79 places.

Overall, 206 of the 782 hospitals (26%) ended up in a different performance category once the NIHSS score was incorporated into the model.

Of the 39 hospitals that had been categorized as top performers using the standard model, only 23 remained top performers using the more accurate model. And another 16 hospitals that hadn’t made the grade with the standard model were reclassified as top performers with the more accurate model.

"There was even greater disagreement about the bottom-performing hospitals," Dr. Fonarow and his colleagues said (JAMA 2012;308:257-64).

Of the 40 worst-performing hospitals according to the standard model, nearly half (19) were reclassified as having a middling performance with the more accurate model.

"These findings highlight the importance of including a valid specific measure of stroke severity in hospital risk models for mortality after acute ischemic stroke. ... Furthermore, this study suggests that inclusion of admission stroke severity may be essential for optimal ranking of hospitals with respect to 30-day mortality," they said.

This study was supported by the American Heart Association, American Stroke Association, and Janssen Pharmaceutical Companies of Johnson & Johnson. Dr. Fonarow is an employee of the University of California, which holds a patent on retriever devices for stroke. His associates reported ties to numerous industry sources.

Stroke Severity Is a Key Consideration

In an editorial accompanying Dr. Fonarow’s report, Dr. Tobias Kurth and Dr. Mitchell S.V. Elkind said that the study "clearly highlights the importance of incorporating information on stroke severity when conducting health outcomes research in stroke. Excluding this information will lead to incorrect ranking of hospital performance by failing to consider that hospitals care for different patient populations" (JAMA 2012;308:292-4).

In this study, when considering only the hospitals ranked in the best 20% and worst 20% of the total, close to one-third would have been reclassified if the more accurate statistical model incorporating stroke severity had been used, they noted.

Dr. Kurth is in neuroepidemiology at the University of Bordeaux (France). Dr. Elkind is in the department of neurology in the school of medicine and the department of epidemiology in the school of public health at Columbia University, New York. Dr. Kurth reported ties to Allergan, Merck, and MAP Pharmaceuticals, and Dr. Elkind reported ties to diaDexus, Britol-Myers Squibb/Sanofi Pharmaceuticals Partnership, Novartis, Organon, and GlaxoSmithKline.

Ninety minutes of aerobic exercise per week reduced depressive symptoms in patients with stable coronary heart disease to the same extent as did sertraline therapy, in a study of 101 patients published online Aug. 1 in the Journal of the American College of Cardiology.

In addition, the subgroup of 44 CHD patients who met the criteria for major depressive disorder were more likely to show remittance of their depressive symptoms after participating in an exercise program than were those who received either sertraline or placebo, said James A. Blumenthal, Ph.D., of the department of psychiatry and behavioral sciences at Duke University, Durham, N.C., and his associates.

Photo ©Pavel Losevsky/iStockphoto.com

At baseline, the study subjects underwent treadmill exercise testing to determine their aerobic capacity, as well as further psychological evaluation using the SCID (Structured Clinical Interview for Depression) and the HAM-D (Hamilton Rating Scale–Depression). They were stratified by age, CHD status, and depression severity, then randomly assigned to receive one of three interventions for 16 weeks: three 30-minute group exercise sessions per week (37 subjects), once-daily oral therapy with the SSRI sertraline (40 subjects), or once-daily use of a matching oral placebo (24 subjects).

In general, the study population was middle-aged (mean age, 64 years), white (73% of subjects), male (68% of subjects), married, relatively affluent, and well educated. In all, 44 subjects met the criteria for major depressive disorder, and the remainder had elevated depressive symptoms.

The primary end point was the HAM-D score at the end of the 4-month intervention.

All three study groups showed some improvements on this measure, but the two active interventions produced significantly greater reductions in HAM-D scores than did placebo. There was no significant difference in this improvement between exercise (a decline of 7.5 points) and sertraline therapy (a decline of 6.1 points), compared with placebo (a decline of 4.5 points).

In an intention-to-treat analysis, HAM-D scores were 3.3 points lower in the exercise group than in the placebo group, and 1.7 points lower in the sertraline group than in the placebo group, the investigators said (J. Am. Coll. Cardiol. 2012 Aug. 1 [doi:10.1016/j.jacc.2012.04.040]).

In the subgroup of patients with major depressive disorder, 6 of 15 (40%) in the exercise group remitted, compared with 2 of 20 (10%) in the sertraline group and 0 of 9 (0%) in the placebo group.

Sertraline was associated with more adverse effects than was exercise. Overall, 20% of the sertraline group reported worsening fatigue, compared with 2.4% of the exercise group and 8.8% of the placebo group. And 26% of the sertraline group reported increased sexual problems, compared with 2.4% of the exercise group and 11.8% of the placebo group.

These results are the first from a randomized clinical trial to show that exercise reduces depressive symptoms in stable CHD, which is particularly important "in light of the growing evidence that depression is associated with increased risk for fatal and nonfatal events in a wide range of CHD populations," Dr. Blumenthal and his colleagues said.

This study was supported by the National Heart, Lung, and Blood Institute and the National Center for Research Resources. Pfizer Pharmaceuticals provided the sertraline and matching placebo. Dr. Blumenthal did not report any financial conflicts of interest, but an associate reported ties to numerous industry sources.

Ninety minutes of aerobic exercise per week reduced depressive symptoms in patients with stable coronary heart disease to the same extent as did sertraline therapy, in a study of 101 patients published online Aug. 1 in the Journal of the American College of Cardiology.

In addition, the subgroup of 44 CHD patients who met the criteria for major depressive disorder were more likely to show remittance of their depressive symptoms after participating in an exercise program than were those who received either sertraline or placebo, said James A. Blumenthal, Ph.D., of the department of psychiatry and behavioral sciences at Duke University, Durham, N.C., and his associates.

Photo ©Pavel Losevsky/iStockphoto.com

At baseline, the study subjects underwent treadmill exercise testing to determine their aerobic capacity, as well as further psychological evaluation using the SCID (Structured Clinical Interview for Depression) and the HAM-D (Hamilton Rating Scale–Depression). They were stratified by age, CHD status, and depression severity, then randomly assigned to receive one of three interventions for 16 weeks: three 30-minute group exercise sessions per week (37 subjects), once-daily oral therapy with the SSRI sertraline (40 subjects), or once-daily use of a matching oral placebo (24 subjects).

In general, the study population was middle-aged (mean age, 64 years), white (73% of subjects), male (68% of subjects), married, relatively affluent, and well educated. In all, 44 subjects met the criteria for major depressive disorder, and the remainder had elevated depressive symptoms.

The primary end point was the HAM-D score at the end of the 4-month intervention.

All three study groups showed some improvements on this measure, but the two active interventions produced significantly greater reductions in HAM-D scores than did placebo. There was no significant difference in this improvement between exercise (a decline of 7.5 points) and sertraline therapy (a decline of 6.1 points), compared with placebo (a decline of 4.5 points).

In an intention-to-treat analysis, HAM-D scores were 3.3 points lower in the exercise group than in the placebo group, and 1.7 points lower in the sertraline group than in the placebo group, the investigators said (J. Am. Coll. Cardiol. 2012 Aug. 1 [doi:10.1016/j.jacc.2012.04.040]).

In the subgroup of patients with major depressive disorder, 6 of 15 (40%) in the exercise group remitted, compared with 2 of 20 (10%) in the sertraline group and 0 of 9 (0%) in the placebo group.

Sertraline was associated with more adverse effects than was exercise. Overall, 20% of the sertraline group reported worsening fatigue, compared with 2.4% of the exercise group and 8.8% of the placebo group. And 26% of the sertraline group reported increased sexual problems, compared with 2.4% of the exercise group and 11.8% of the placebo group.

These results are the first from a randomized clinical trial to show that exercise reduces depressive symptoms in stable CHD, which is particularly important "in light of the growing evidence that depression is associated with increased risk for fatal and nonfatal events in a wide range of CHD populations," Dr. Blumenthal and his colleagues said.

This study was supported by the National Heart, Lung, and Blood Institute and the National Center for Research Resources. Pfizer Pharmaceuticals provided the sertraline and matching placebo. Dr. Blumenthal did not report any financial conflicts of interest, but an associate reported ties to numerous industry sources.

Ninety minutes of aerobic exercise per week reduced depressive symptoms in patients with stable coronary heart disease to the same extent as did sertraline therapy, in a study of 101 patients published online Aug. 1 in the Journal of the American College of Cardiology.

In addition, the subgroup of 44 CHD patients who met the criteria for major depressive disorder were more likely to show remittance of their depressive symptoms after participating in an exercise program than were those who received either sertraline or placebo, said James A. Blumenthal, Ph.D., of the department of psychiatry and behavioral sciences at Duke University, Durham, N.C., and his associates.

Photo ©Pavel Losevsky/iStockphoto.com

At baseline, the study subjects underwent treadmill exercise testing to determine their aerobic capacity, as well as further psychological evaluation using the SCID (Structured Clinical Interview for Depression) and the HAM-D (Hamilton Rating Scale–Depression). They were stratified by age, CHD status, and depression severity, then randomly assigned to receive one of three interventions for 16 weeks: three 30-minute group exercise sessions per week (37 subjects), once-daily oral therapy with the SSRI sertraline (40 subjects), or once-daily use of a matching oral placebo (24 subjects).

In general, the study population was middle-aged (mean age, 64 years), white (73% of subjects), male (68% of subjects), married, relatively affluent, and well educated. In all, 44 subjects met the criteria for major depressive disorder, and the remainder had elevated depressive symptoms.

The primary end point was the HAM-D score at the end of the 4-month intervention.

All three study groups showed some improvements on this measure, but the two active interventions produced significantly greater reductions in HAM-D scores than did placebo. There was no significant difference in this improvement between exercise (a decline of 7.5 points) and sertraline therapy (a decline of 6.1 points), compared with placebo (a decline of 4.5 points).

In an intention-to-treat analysis, HAM-D scores were 3.3 points lower in the exercise group than in the placebo group, and 1.7 points lower in the sertraline group than in the placebo group, the investigators said (J. Am. Coll. Cardiol. 2012 Aug. 1 [doi:10.1016/j.jacc.2012.04.040]).

In the subgroup of patients with major depressive disorder, 6 of 15 (40%) in the exercise group remitted, compared with 2 of 20 (10%) in the sertraline group and 0 of 9 (0%) in the placebo group.

Sertraline was associated with more adverse effects than was exercise. Overall, 20% of the sertraline group reported worsening fatigue, compared with 2.4% of the exercise group and 8.8% of the placebo group. And 26% of the sertraline group reported increased sexual problems, compared with 2.4% of the exercise group and 11.8% of the placebo group.

These results are the first from a randomized clinical trial to show that exercise reduces depressive symptoms in stable CHD, which is particularly important "in light of the growing evidence that depression is associated with increased risk for fatal and nonfatal events in a wide range of CHD populations," Dr. Blumenthal and his colleagues said.

This study was supported by the National Heart, Lung, and Blood Institute and the National Center for Research Resources. Pfizer Pharmaceuticals provided the sertraline and matching placebo. Dr. Blumenthal did not report any financial conflicts of interest, but an associate reported ties to numerous industry sources.