Mary Ann Moon

The risk for hip fracture rises steeply after patients have a major cardiovascular event, most likely because of genetic factors common to both vascular and bone disorders, a Swedish study has shown.

In a population-based study of nearly 32,000 twins in Sweden, the rate of hip fracture rose “considerably” in both men and women following any of several cardiovascular disease (CVD) diagnoses. Most of that increase appeared to be explained “by genes or by early environmental sharing” rather than individual lifestyle habits or other individual-specific environmental factors, said Dr. Ulf Sennerby of Uppsala (Sweden) University and associates.

“We advocate that individuals with a recent diagnosis of CVD should have their future fracture risk evaluated with clinical risk factors and bone scans,” such as the recently established 10-year probability using the FRAX (the World Health Organization's fracture risk assessment tool) algorithm, they noted.

The researchers used data from an extensive twin registry to examine the relation between CVD events and hip fracture. It included twin pairs who were born between 1914 and 1944 and were subsequently followed from the age of 50 years. It identified 31,936 pairs in which one twin developed CVD or hip fracture by Dec. 31, 2005.

The crude absolute rate of hip fractures in the cohort was 12.6 per 1,000 person-years after a diagnosis of heart failure, 12.6 per 1,000 person-years after a stroke, 6.6 per 1,000 person-years after a diagnosis of peripheral atherosclerosis, and 5.2 per 1,000 person-years after a diagnosis of ischemic heart disease, compared with 1.2 per 1,000 person-years for those without a CVD diagnosis.

All CVD diagnoses were associated with a higher risk of hip fracture independent of other CVD diagnoses and other comorbidities, the investigators said (JAMA 2009;302:1666-73).

The association was stronger in women than in men, but it was significant in both sexes.

Co-twins of subjects who had CVD also were at increased risk of sustaining hip fracture during follow-up, even if they had not had a cardiovascular event. For example, co-twins of subjects who had heart failure were at fourfold higher risk of fracturing a hip, compared with co-twins of subjects with no CVD.

The risk of hip fracture was higher in identical twins who had such “pseudoexposure” and lower in fraternal twins, indicating that an as-yet unidentified genetic factor predisposes people to both vascular and bone disorders, Dr. Sennerby and his associates said.

A subgroup of 24,598 subjects participated in telephone interviews to assess anthropomorphic, lifestyle, and medical factors. The inclusion of these factors into the data analysis did not materially change the results.

It is possible that “specific genes involved in cellular mechanisms shared by the vasculature and bone” may eventually explain this association between CVD and hip fracture, the authors wrote. “Matrix proteins supporting bone, vessel walls, and the myocardium [may] be of special relevance.

Dr. Sennerby reported no financial conflicts of interest.

The risk for hip fracture rises steeply after patients have a major cardiovascular event, most likely because of genetic factors common to both vascular and bone disorders, a Swedish study has shown.

In a population-based study of nearly 32,000 twins in Sweden, the rate of hip fracture rose “considerably” in both men and women following any of several cardiovascular disease (CVD) diagnoses. Most of that increase appeared to be explained “by genes or by early environmental sharing” rather than individual lifestyle habits or other individual-specific environmental factors, said Dr. Ulf Sennerby of Uppsala (Sweden) University and associates.

“We advocate that individuals with a recent diagnosis of CVD should have their future fracture risk evaluated with clinical risk factors and bone scans,” such as the recently established 10-year probability using the FRAX (the World Health Organization's fracture risk assessment tool) algorithm, they noted.

The researchers used data from an extensive twin registry to examine the relation between CVD events and hip fracture. It included twin pairs who were born between 1914 and 1944 and were subsequently followed from the age of 50 years. It identified 31,936 pairs in which one twin developed CVD or hip fracture by Dec. 31, 2005.

The crude absolute rate of hip fractures in the cohort was 12.6 per 1,000 person-years after a diagnosis of heart failure, 12.6 per 1,000 person-years after a stroke, 6.6 per 1,000 person-years after a diagnosis of peripheral atherosclerosis, and 5.2 per 1,000 person-years after a diagnosis of ischemic heart disease, compared with 1.2 per 1,000 person-years for those without a CVD diagnosis.

All CVD diagnoses were associated with a higher risk of hip fracture independent of other CVD diagnoses and other comorbidities, the investigators said (JAMA 2009;302:1666-73).

The association was stronger in women than in men, but it was significant in both sexes.

Co-twins of subjects who had CVD also were at increased risk of sustaining hip fracture during follow-up, even if they had not had a cardiovascular event. For example, co-twins of subjects who had heart failure were at fourfold higher risk of fracturing a hip, compared with co-twins of subjects with no CVD.

The risk of hip fracture was higher in identical twins who had such “pseudoexposure” and lower in fraternal twins, indicating that an as-yet unidentified genetic factor predisposes people to both vascular and bone disorders, Dr. Sennerby and his associates said.

A subgroup of 24,598 subjects participated in telephone interviews to assess anthropomorphic, lifestyle, and medical factors. The inclusion of these factors into the data analysis did not materially change the results.

It is possible that “specific genes involved in cellular mechanisms shared by the vasculature and bone” may eventually explain this association between CVD and hip fracture, the authors wrote. “Matrix proteins supporting bone, vessel walls, and the myocardium [may] be of special relevance.

Dr. Sennerby reported no financial conflicts of interest.

The risk for hip fracture rises steeply after patients have a major cardiovascular event, most likely because of genetic factors common to both vascular and bone disorders, a Swedish study has shown.

In a population-based study of nearly 32,000 twins in Sweden, the rate of hip fracture rose “considerably” in both men and women following any of several cardiovascular disease (CVD) diagnoses. Most of that increase appeared to be explained “by genes or by early environmental sharing” rather than individual lifestyle habits or other individual-specific environmental factors, said Dr. Ulf Sennerby of Uppsala (Sweden) University and associates.

“We advocate that individuals with a recent diagnosis of CVD should have their future fracture risk evaluated with clinical risk factors and bone scans,” such as the recently established 10-year probability using the FRAX (the World Health Organization's fracture risk assessment tool) algorithm, they noted.

The researchers used data from an extensive twin registry to examine the relation between CVD events and hip fracture. It included twin pairs who were born between 1914 and 1944 and were subsequently followed from the age of 50 years. It identified 31,936 pairs in which one twin developed CVD or hip fracture by Dec. 31, 2005.

The crude absolute rate of hip fractures in the cohort was 12.6 per 1,000 person-years after a diagnosis of heart failure, 12.6 per 1,000 person-years after a stroke, 6.6 per 1,000 person-years after a diagnosis of peripheral atherosclerosis, and 5.2 per 1,000 person-years after a diagnosis of ischemic heart disease, compared with 1.2 per 1,000 person-years for those without a CVD diagnosis.

All CVD diagnoses were associated with a higher risk of hip fracture independent of other CVD diagnoses and other comorbidities, the investigators said (JAMA 2009;302:1666-73).

The association was stronger in women than in men, but it was significant in both sexes.

Co-twins of subjects who had CVD also were at increased risk of sustaining hip fracture during follow-up, even if they had not had a cardiovascular event. For example, co-twins of subjects who had heart failure were at fourfold higher risk of fracturing a hip, compared with co-twins of subjects with no CVD.

The risk of hip fracture was higher in identical twins who had such “pseudoexposure” and lower in fraternal twins, indicating that an as-yet unidentified genetic factor predisposes people to both vascular and bone disorders, Dr. Sennerby and his associates said.

A subgroup of 24,598 subjects participated in telephone interviews to assess anthropomorphic, lifestyle, and medical factors. The inclusion of these factors into the data analysis did not materially change the results.

It is possible that “specific genes involved in cellular mechanisms shared by the vasculature and bone” may eventually explain this association between CVD and hip fracture, the authors wrote. “Matrix proteins supporting bone, vessel walls, and the myocardium [may] be of special relevance.

Dr. Sennerby reported no financial conflicts of interest.

A vaccine containing peptides targeting HPV-16 oncoproteins E6 and E7 was effective against high-grade, HPV-16–positive vulvar intraepithelial neoplasia, according to small phase II study results.

“This clinical efficacy is probably related to a vaccine-induced HPV-16 T-cell response,” said Dr. Gemma G. Kenter and her associates at Leiden (the Netherlands) University Medical Center.

In the blood of patients with high-grade vulvar intraepithelial neoplasia (VIN), researchers have noted low or undetectable numbers of T cells directed against the HPV-16 oncoproteins E6 and E7.

Reasoning that “vaccination might overcome this inertia of the immune system,” Dr. Kenter and her colleagues developed a vaccine containing synthetic long peptides “that represent the entire length” of these two oncoproteins.

They tested the vaccine in 20 women in a single-center observational study in 2004-2007.

The study was sponsored by the Dutch Cancer Society, the European Union, and ISA Pharmaceuticals B.V.

These subjects were slated to receive three to four vaccinations at 3-week intervals and were followed for 24 months.

After 3 months, blood samples showed that 17 subjects had an HPV-16–specific immunologic response and enhanced production of interferon, Dr. Kenter and her associates said.

Eleven patients reported symptom relief. Five patients showed a complete histologic and clinical response, and seven showed partial responses.

After 1 year, the number of women showing a complete response increased to nine, and six continued to show a partial response.

Twelve women reported symptom relief.

All nine women who showed a complete response were still free of disease at 2-year follow-up.

Tumor microinvasion was found in one woman who had shown a partial response, and carcinoma developed in two other patients 2.5 and 3.5 years after vaccination (N. Engl. J. Med. 2009;361:1838-47).

In an editorial comment accompanying this report, Olivera J. Finn, Ph.D., and Dr. Robert P. Edwards, both of the University of Pittsburgh, noted that this report was the latest in a series from the same group of investigators “who over the past several years have tested this vaccine in preclinical settings for its tumor-rejection potential and for its safety and immunogenicity in end-stage cervical cancer.”

The findings from this small study suggest that “more effective immune responses can be generated against precursor lesions than against late-stage disease.

“Many cancer vaccines based on nonviral tumor–associated antigens have been judged to be suboptimal because of their lack of efficacy in advanced disease, yet they might perform very differently if used in patients with premalignant disease,” the investigators wrote (N. Engl. J. Med. 2009;361:1899-901).

If the vaccine approach is developed further, it may offer a less invasive and more durable treatment than is currently available for VIN, Dr. Finn and Dr. Edwards said.

Leiden University Medical Center holds a patent on the use of synthetic long peptides as vaccine.

Dr. Kenter reported serving as an unpaid member of the strategy team of ISA Pharmaceuticals. Dr. Edwards reported receiving consulting fees from Fresenius SE and grant support from Sanofi-Aventis.

A vaccine containing peptides targeting HPV-16 oncoproteins E6 and E7 was effective against high-grade, HPV-16–positive vulvar intraepithelial neoplasia, according to small phase II study results.

“This clinical efficacy is probably related to a vaccine-induced HPV-16 T-cell response,” said Dr. Gemma G. Kenter and her associates at Leiden (the Netherlands) University Medical Center.

In the blood of patients with high-grade vulvar intraepithelial neoplasia (VIN), researchers have noted low or undetectable numbers of T cells directed against the HPV-16 oncoproteins E6 and E7.

Reasoning that “vaccination might overcome this inertia of the immune system,” Dr. Kenter and her colleagues developed a vaccine containing synthetic long peptides “that represent the entire length” of these two oncoproteins.

They tested the vaccine in 20 women in a single-center observational study in 2004-2007.

The study was sponsored by the Dutch Cancer Society, the European Union, and ISA Pharmaceuticals B.V.

These subjects were slated to receive three to four vaccinations at 3-week intervals and were followed for 24 months.

After 3 months, blood samples showed that 17 subjects had an HPV-16–specific immunologic response and enhanced production of interferon, Dr. Kenter and her associates said.

Eleven patients reported symptom relief. Five patients showed a complete histologic and clinical response, and seven showed partial responses.

After 1 year, the number of women showing a complete response increased to nine, and six continued to show a partial response.

Twelve women reported symptom relief.

All nine women who showed a complete response were still free of disease at 2-year follow-up.

Tumor microinvasion was found in one woman who had shown a partial response, and carcinoma developed in two other patients 2.5 and 3.5 years after vaccination (N. Engl. J. Med. 2009;361:1838-47).

In an editorial comment accompanying this report, Olivera J. Finn, Ph.D., and Dr. Robert P. Edwards, both of the University of Pittsburgh, noted that this report was the latest in a series from the same group of investigators “who over the past several years have tested this vaccine in preclinical settings for its tumor-rejection potential and for its safety and immunogenicity in end-stage cervical cancer.”

The findings from this small study suggest that “more effective immune responses can be generated against precursor lesions than against late-stage disease.

“Many cancer vaccines based on nonviral tumor–associated antigens have been judged to be suboptimal because of their lack of efficacy in advanced disease, yet they might perform very differently if used in patients with premalignant disease,” the investigators wrote (N. Engl. J. Med. 2009;361:1899-901).

If the vaccine approach is developed further, it may offer a less invasive and more durable treatment than is currently available for VIN, Dr. Finn and Dr. Edwards said.

Leiden University Medical Center holds a patent on the use of synthetic long peptides as vaccine.

Dr. Kenter reported serving as an unpaid member of the strategy team of ISA Pharmaceuticals. Dr. Edwards reported receiving consulting fees from Fresenius SE and grant support from Sanofi-Aventis.

A vaccine containing peptides targeting HPV-16 oncoproteins E6 and E7 was effective against high-grade, HPV-16–positive vulvar intraepithelial neoplasia, according to small phase II study results.

“This clinical efficacy is probably related to a vaccine-induced HPV-16 T-cell response,” said Dr. Gemma G. Kenter and her associates at Leiden (the Netherlands) University Medical Center.

In the blood of patients with high-grade vulvar intraepithelial neoplasia (VIN), researchers have noted low or undetectable numbers of T cells directed against the HPV-16 oncoproteins E6 and E7.

Reasoning that “vaccination might overcome this inertia of the immune system,” Dr. Kenter and her colleagues developed a vaccine containing synthetic long peptides “that represent the entire length” of these two oncoproteins.

They tested the vaccine in 20 women in a single-center observational study in 2004-2007.

The study was sponsored by the Dutch Cancer Society, the European Union, and ISA Pharmaceuticals B.V.

These subjects were slated to receive three to four vaccinations at 3-week intervals and were followed for 24 months.

After 3 months, blood samples showed that 17 subjects had an HPV-16–specific immunologic response and enhanced production of interferon, Dr. Kenter and her associates said.

Eleven patients reported symptom relief. Five patients showed a complete histologic and clinical response, and seven showed partial responses.

After 1 year, the number of women showing a complete response increased to nine, and six continued to show a partial response.

Twelve women reported symptom relief.

All nine women who showed a complete response were still free of disease at 2-year follow-up.

Tumor microinvasion was found in one woman who had shown a partial response, and carcinoma developed in two other patients 2.5 and 3.5 years after vaccination (N. Engl. J. Med. 2009;361:1838-47).

In an editorial comment accompanying this report, Olivera J. Finn, Ph.D., and Dr. Robert P. Edwards, both of the University of Pittsburgh, noted that this report was the latest in a series from the same group of investigators “who over the past several years have tested this vaccine in preclinical settings for its tumor-rejection potential and for its safety and immunogenicity in end-stage cervical cancer.”

The findings from this small study suggest that “more effective immune responses can be generated against precursor lesions than against late-stage disease.

“Many cancer vaccines based on nonviral tumor–associated antigens have been judged to be suboptimal because of their lack of efficacy in advanced disease, yet they might perform very differently if used in patients with premalignant disease,” the investigators wrote (N. Engl. J. Med. 2009;361:1899-901).

If the vaccine approach is developed further, it may offer a less invasive and more durable treatment than is currently available for VIN, Dr. Finn and Dr. Edwards said.

Leiden University Medical Center holds a patent on the use of synthetic long peptides as vaccine.

Dr. Kenter reported serving as an unpaid member of the strategy team of ISA Pharmaceuticals. Dr. Edwards reported receiving consulting fees from Fresenius SE and grant support from Sanofi-Aventis.

Most commonly used antibacterial drugs were not associated with birth defects in a large surveillance study.

The study was performed because even though some antibiotics have been used relatively safely during pregnancy for decades, until now “there have been no large-scale studies addressing safety or risk [of birth defects] for many classes of antibacterial drugs,” said Krista S. Crider, Ph.D., and her associates in the National Birth Defects Prevention Study. She reported no financial conflicts.

Their findings lend “support to the established safety profiles for certain classes of antibacterial [drugs] such as penicillins, erythromycins, and cephalosporins.” The investigators also found it “encouraging” that the use of antibacterial drugs suspected of being teratogenic—such as aminoglycosides, chloramphenicol, and tetracyclines—was “extremely low to none at all” among women just before conception and in early pregnancy (Arch. Ped. Adolesc. Med. 2009;163:978-85). However, the use of other classes of antibacterial drugs, notably sulfonamides and nitrofurantoins, appeared to be associated with a higher risk for several birth defects, said Dr. Crider of the Centers for Disease Control and Prevention and her colleagues.

The researchers assessed prenatal exposure to antimicrobial drugs in 13,155 mothers of infants with birth defects (cases) born in 1997-2003 and 4,941 mothers of infants without major birth defects (controls) born in the same geographical locations during the same interval.

The case infants had at least 1 of more than 30 categories of major birth defects identified by surveillance systems in 10 states across the country. The cases included live births, stillbirths, and induced abortions. Infants with either isolated or multiple defects were included, although those with suspected chromosomal abnormalities or single-gene conditions were excluded. The mothers reported their use of antimicrobial drugs from the month prior to the estimated date of conception through the end of the first trimester via telephone interviews conducted 6 weeks to 2 years following delivery. Exposure to antibacterial drugs was common among both case (29.4%) and control (29.7%) mothers.

Penicillins, the most frequently used agents, were associated with an increased odds ratio for only one defect (intercalary limb deficiency). Erythromycins, the next most frequently used antibacterial drugs, were associated only with anencephaly and transverse limb deficiency. Similarly, cephalosporins showed only one significantly increased odds ratio, and that was for atrial septal defects.

Nitrofurantoins were associated with anophthalmia or microphthalmos, hypoplastic left heart syndrome, atrial septal defects, and cleft lip with cleft palate. Tetracyclines were associated with a variety of heart defects plus left ventricular outflow obstruction defects, septal heart defects, and oral clefts. Exposure to sulfonamides was associated with the most defects, including anencephaly, hypoplastic left heart syndrome, coarctation of the aorta, choanal atresia, and transverse limb deficiency.

Most commonly used antibacterial drugs were not associated with birth defects in a large surveillance study.

The study was performed because even though some antibiotics have been used relatively safely during pregnancy for decades, until now “there have been no large-scale studies addressing safety or risk [of birth defects] for many classes of antibacterial drugs,” said Krista S. Crider, Ph.D., and her associates in the National Birth Defects Prevention Study. She reported no financial conflicts.

Their findings lend “support to the established safety profiles for certain classes of antibacterial [drugs] such as penicillins, erythromycins, and cephalosporins.” The investigators also found it “encouraging” that the use of antibacterial drugs suspected of being teratogenic—such as aminoglycosides, chloramphenicol, and tetracyclines—was “extremely low to none at all” among women just before conception and in early pregnancy (Arch. Ped. Adolesc. Med. 2009;163:978-85). However, the use of other classes of antibacterial drugs, notably sulfonamides and nitrofurantoins, appeared to be associated with a higher risk for several birth defects, said Dr. Crider of the Centers for Disease Control and Prevention and her colleagues.

The researchers assessed prenatal exposure to antimicrobial drugs in 13,155 mothers of infants with birth defects (cases) born in 1997-2003 and 4,941 mothers of infants without major birth defects (controls) born in the same geographical locations during the same interval.

The case infants had at least 1 of more than 30 categories of major birth defects identified by surveillance systems in 10 states across the country. The cases included live births, stillbirths, and induced abortions. Infants with either isolated or multiple defects were included, although those with suspected chromosomal abnormalities or single-gene conditions were excluded. The mothers reported their use of antimicrobial drugs from the month prior to the estimated date of conception through the end of the first trimester via telephone interviews conducted 6 weeks to 2 years following delivery. Exposure to antibacterial drugs was common among both case (29.4%) and control (29.7%) mothers.

Penicillins, the most frequently used agents, were associated with an increased odds ratio for only one defect (intercalary limb deficiency). Erythromycins, the next most frequently used antibacterial drugs, were associated only with anencephaly and transverse limb deficiency. Similarly, cephalosporins showed only one significantly increased odds ratio, and that was for atrial septal defects.

Nitrofurantoins were associated with anophthalmia or microphthalmos, hypoplastic left heart syndrome, atrial septal defects, and cleft lip with cleft palate. Tetracyclines were associated with a variety of heart defects plus left ventricular outflow obstruction defects, septal heart defects, and oral clefts. Exposure to sulfonamides was associated with the most defects, including anencephaly, hypoplastic left heart syndrome, coarctation of the aorta, choanal atresia, and transverse limb deficiency.

Most commonly used antibacterial drugs were not associated with birth defects in a large surveillance study.

The study was performed because even though some antibiotics have been used relatively safely during pregnancy for decades, until now “there have been no large-scale studies addressing safety or risk [of birth defects] for many classes of antibacterial drugs,” said Krista S. Crider, Ph.D., and her associates in the National Birth Defects Prevention Study. She reported no financial conflicts.

Their findings lend “support to the established safety profiles for certain classes of antibacterial [drugs] such as penicillins, erythromycins, and cephalosporins.” The investigators also found it “encouraging” that the use of antibacterial drugs suspected of being teratogenic—such as aminoglycosides, chloramphenicol, and tetracyclines—was “extremely low to none at all” among women just before conception and in early pregnancy (Arch. Ped. Adolesc. Med. 2009;163:978-85). However, the use of other classes of antibacterial drugs, notably sulfonamides and nitrofurantoins, appeared to be associated with a higher risk for several birth defects, said Dr. Crider of the Centers for Disease Control and Prevention and her colleagues.

The researchers assessed prenatal exposure to antimicrobial drugs in 13,155 mothers of infants with birth defects (cases) born in 1997-2003 and 4,941 mothers of infants without major birth defects (controls) born in the same geographical locations during the same interval.

The case infants had at least 1 of more than 30 categories of major birth defects identified by surveillance systems in 10 states across the country. The cases included live births, stillbirths, and induced abortions. Infants with either isolated or multiple defects were included, although those with suspected chromosomal abnormalities or single-gene conditions were excluded. The mothers reported their use of antimicrobial drugs from the month prior to the estimated date of conception through the end of the first trimester via telephone interviews conducted 6 weeks to 2 years following delivery. Exposure to antibacterial drugs was common among both case (29.4%) and control (29.7%) mothers.

Penicillins, the most frequently used agents, were associated with an increased odds ratio for only one defect (intercalary limb deficiency). Erythromycins, the next most frequently used antibacterial drugs, were associated only with anencephaly and transverse limb deficiency. Similarly, cephalosporins showed only one significantly increased odds ratio, and that was for atrial septal defects.

Nitrofurantoins were associated with anophthalmia or microphthalmos, hypoplastic left heart syndrome, atrial septal defects, and cleft lip with cleft palate. Tetracyclines were associated with a variety of heart defects plus left ventricular outflow obstruction defects, septal heart defects, and oral clefts. Exposure to sulfonamides was associated with the most defects, including anencephaly, hypoplastic left heart syndrome, coarctation of the aorta, choanal atresia, and transverse limb deficiency.

The cardiovascular risks associated with rofecoxib (Vioxx) would have been apparent in 2001, more than 3 years before the drug was withdrawn from the market, had data from unpublished trials been disclosed, according to a report.

The data “have only now become available through litigation” against Merck & Co., the manufacturer of Vioxx, said Dr. Joseph S. Ross of Mount Sinai School of Medicine, New York, and his associates.

“These findings are particularly compelling because as early as the late 1990s there were concerns about cardiovascular risk that emerged in the drug development process,” the investigators noted (Arch. Intern. Med. 2009;169:1976-85).

Merck & Co. disavowed the research. “We believe the analysis published in Archives used flawed methods and reached incorrect conclusions,” Merck spokesman Ron Rogers said in an interview. The study notes that all of the study authors are or were consultants for plaintiffs in litigation against Merck regarding rofecoxib.

The researchers analyzed data from 30 randomized clinical trials that had already been completed by September 2004, when the APPROVe (Adenomatous Polyp Prevention on Vioxx) trial was terminated and rofecoxib was voluntarily withdrawn from the market, in response to reports of adverse cardiovascular effects.

Dr. Ross and his colleagues assessed only studies that compared a daily dose of 12.5 mg or more of rofecoxib with placebo in adults who were treated for at least 4 weeks. A total of 17,256 subjects were included.

Six of these trials were unpublished and came to light only as a result of litigation. “Therefore, data representing 36% of patients studied in placebo-controlled trials prior to APPROVe” had never been disclosed or included in safety analyses, the investigators said.

If all these data had been analyzed, the use of rofecoxib would have been seen to be associated with a 43% increase in risk of a cardiovascular thromboembolic event or death, according to the investigators.

The cardiovascular risks associated with rofecoxib (Vioxx) would have been apparent in 2001, more than 3 years before the drug was withdrawn from the market, had data from unpublished trials been disclosed, according to a report.

The data “have only now become available through litigation” against Merck & Co., the manufacturer of Vioxx, said Dr. Joseph S. Ross of Mount Sinai School of Medicine, New York, and his associates.

“These findings are particularly compelling because as early as the late 1990s there were concerns about cardiovascular risk that emerged in the drug development process,” the investigators noted (Arch. Intern. Med. 2009;169:1976-85).

Merck & Co. disavowed the research. “We believe the analysis published in Archives used flawed methods and reached incorrect conclusions,” Merck spokesman Ron Rogers said in an interview. The study notes that all of the study authors are or were consultants for plaintiffs in litigation against Merck regarding rofecoxib.

The researchers analyzed data from 30 randomized clinical trials that had already been completed by September 2004, when the APPROVe (Adenomatous Polyp Prevention on Vioxx) trial was terminated and rofecoxib was voluntarily withdrawn from the market, in response to reports of adverse cardiovascular effects.

Dr. Ross and his colleagues assessed only studies that compared a daily dose of 12.5 mg or more of rofecoxib with placebo in adults who were treated for at least 4 weeks. A total of 17,256 subjects were included.

Six of these trials were unpublished and came to light only as a result of litigation. “Therefore, data representing 36% of patients studied in placebo-controlled trials prior to APPROVe” had never been disclosed or included in safety analyses, the investigators said.

If all these data had been analyzed, the use of rofecoxib would have been seen to be associated with a 43% increase in risk of a cardiovascular thromboembolic event or death, according to the investigators.

The cardiovascular risks associated with rofecoxib (Vioxx) would have been apparent in 2001, more than 3 years before the drug was withdrawn from the market, had data from unpublished trials been disclosed, according to a report.

The data “have only now become available through litigation” against Merck & Co., the manufacturer of Vioxx, said Dr. Joseph S. Ross of Mount Sinai School of Medicine, New York, and his associates.

“These findings are particularly compelling because as early as the late 1990s there were concerns about cardiovascular risk that emerged in the drug development process,” the investigators noted (Arch. Intern. Med. 2009;169:1976-85).

Merck & Co. disavowed the research. “We believe the analysis published in Archives used flawed methods and reached incorrect conclusions,” Merck spokesman Ron Rogers said in an interview. The study notes that all of the study authors are or were consultants for plaintiffs in litigation against Merck regarding rofecoxib.

The researchers analyzed data from 30 randomized clinical trials that had already been completed by September 2004, when the APPROVe (Adenomatous Polyp Prevention on Vioxx) trial was terminated and rofecoxib was voluntarily withdrawn from the market, in response to reports of adverse cardiovascular effects.

Dr. Ross and his colleagues assessed only studies that compared a daily dose of 12.5 mg or more of rofecoxib with placebo in adults who were treated for at least 4 weeks. A total of 17,256 subjects were included.

Six of these trials were unpublished and came to light only as a result of litigation. “Therefore, data representing 36% of patients studied in placebo-controlled trials prior to APPROVe” had never been disclosed or included in safety analyses, the investigators said.

If all these data had been analyzed, the use of rofecoxib would have been seen to be associated with a 43% increase in risk of a cardiovascular thromboembolic event or death, according to the investigators.

A collaborative-care intervention delivered by telephone improved mental and physical functioning in patients who developed depression after undergoing coronary artery bypass grafting, according to a study published online in JAMA simultaneously with its presentation at the annual scientific sessions of the American Heart Association.

The treatment's benefits became evident within 2 months of surgery and persisted through 8 months of follow-up. Overall, half of the 150 patients who received the intervention reported a 50% or more reduction in mood symptoms, compared with 30% of patients who received usual post-CABG care, said Dr. Bruce L. Rollman of the University of Pittsburgh and his associates.

The investigators described their study as the first clinical trial to assess a collaborative-care strategy for treating depression following an acute cardiac event.

“Collaborative care emphasizes a flexible real-world treatment package that involves active follow-up by a nonphysician care manager who adheres to evidence-based treatment protocols, supports patients with timely education about their illness, considers patients' prior treatment experiences and current preferences, teaches self-management techniques, actively involves primary care physicians in their patients' care through regular exchanges of real-time information, proactively monitors treatment responses and suggests adjustments when indicated, and facilitates comanagement or transfer of care to local mental health specialists when patients do not respond to treatment or have clinically complicated cases, or upon request by the patient or primary care physician,” they explained.

For this intervention, 2,485 post-CABG patients were first screened for depression before hospital discharge, then screened again 2 weeks later to determine whether depression symptoms persisted. A total of 302 were found to have moderate depression and agreed to participate in the study.

The patients had been treated at two university-affiliated and five community hospitals in the Pittsburgh area between 2004 and 2007. They were randomly assigned to the intervention group (150 subjects) or to usual care (152 subjects). A comparison group of 151 post-CABG patients who did not have depression was included in the study.

The intervention was run by a nurse care manager who reported weekly to a study psychiatrist and internist. The care manager contacted patients by phone in 15- to 45-minute sessions, providing “basic psychoeducation” about depression and its effect on cardiac disease, initiating and adjusting antidepressant pharmacotherapy through the patients' primary care physicians, closely monitoring mood symptoms, and coordinating care with a local psychiatrist or psychologist as necessary.

The care manager also performed serial assessments with the 36-item Short Form health survey (SF-36) to measure general mental and physical health, the Duke Activity Status Index to measure disease-specific physical functioning, and the Hamilton Rating Scale for Depression to measure mood symptoms.

After 8 months, the intervention group showed significant clinical improvement on the SF-36 of 3.2 points, with an effect size of 0.30. Improvements of at least 3 points or an effect size of 0.25 on these measures are considered “minimally clinically important,” Dr. Rollman and his colleagues said (JAMA 2009;302:2095-103).

Men showed a better treatment response then did women.

For men in the intervention group, there was a nearly 6-point rise on the SF-36. Moreover, 61% of the men who received the intervention reported a 50% or more reduction in depression scores, compared with only 33% of men who received usual care.

In contrast, 38% of women who received the intervention reported that degree of reduction in depression scores, compared with 23% of women who received usual care.

The study subjects who responded well to the intervention showed better outcomes than did those who received usual care, but both groups of patients with post-CABG depression had poorer outcomes than did the comparison group of patients without depression. Overall, 33% of intervention patients and 32% of usual care patients required rehospitalization, compared with only 25% of the control group.

Noting that “a substantial minority of patients,” particularly women, did not benefit from the collaborative-care intervention, “it is vital to identify post-CABG patients most likely to become treatment resistant so as to develop more effective treatments for them,” the researchers added.

This study was supported by the National Institutes of Health and the University of Pittsburgh.

Dr. Rollman reported no financial conflicts of interest.

A collaborative-care intervention delivered by telephone improved mental and physical functioning in patients who developed depression after undergoing coronary artery bypass grafting, according to a study published online in JAMA simultaneously with its presentation at the annual scientific sessions of the American Heart Association.

The treatment's benefits became evident within 2 months of surgery and persisted through 8 months of follow-up. Overall, half of the 150 patients who received the intervention reported a 50% or more reduction in mood symptoms, compared with 30% of patients who received usual post-CABG care, said Dr. Bruce L. Rollman of the University of Pittsburgh and his associates.

The investigators described their study as the first clinical trial to assess a collaborative-care strategy for treating depression following an acute cardiac event.

“Collaborative care emphasizes a flexible real-world treatment package that involves active follow-up by a nonphysician care manager who adheres to evidence-based treatment protocols, supports patients with timely education about their illness, considers patients' prior treatment experiences and current preferences, teaches self-management techniques, actively involves primary care physicians in their patients' care through regular exchanges of real-time information, proactively monitors treatment responses and suggests adjustments when indicated, and facilitates comanagement or transfer of care to local mental health specialists when patients do not respond to treatment or have clinically complicated cases, or upon request by the patient or primary care physician,” they explained.

For this intervention, 2,485 post-CABG patients were first screened for depression before hospital discharge, then screened again 2 weeks later to determine whether depression symptoms persisted. A total of 302 were found to have moderate depression and agreed to participate in the study.

The patients had been treated at two university-affiliated and five community hospitals in the Pittsburgh area between 2004 and 2007. They were randomly assigned to the intervention group (150 subjects) or to usual care (152 subjects). A comparison group of 151 post-CABG patients who did not have depression was included in the study.

The intervention was run by a nurse care manager who reported weekly to a study psychiatrist and internist. The care manager contacted patients by phone in 15- to 45-minute sessions, providing “basic psychoeducation” about depression and its effect on cardiac disease, initiating and adjusting antidepressant pharmacotherapy through the patients' primary care physicians, closely monitoring mood symptoms, and coordinating care with a local psychiatrist or psychologist as necessary.

The care manager also performed serial assessments with the 36-item Short Form health survey (SF-36) to measure general mental and physical health, the Duke Activity Status Index to measure disease-specific physical functioning, and the Hamilton Rating Scale for Depression to measure mood symptoms.

After 8 months, the intervention group showed significant clinical improvement on the SF-36 of 3.2 points, with an effect size of 0.30. Improvements of at least 3 points or an effect size of 0.25 on these measures are considered “minimally clinically important,” Dr. Rollman and his colleagues said (JAMA 2009;302:2095-103).

Men showed a better treatment response then did women.

For men in the intervention group, there was a nearly 6-point rise on the SF-36. Moreover, 61% of the men who received the intervention reported a 50% or more reduction in depression scores, compared with only 33% of men who received usual care.

In contrast, 38% of women who received the intervention reported that degree of reduction in depression scores, compared with 23% of women who received usual care.

The study subjects who responded well to the intervention showed better outcomes than did those who received usual care, but both groups of patients with post-CABG depression had poorer outcomes than did the comparison group of patients without depression. Overall, 33% of intervention patients and 32% of usual care patients required rehospitalization, compared with only 25% of the control group.

Noting that “a substantial minority of patients,” particularly women, did not benefit from the collaborative-care intervention, “it is vital to identify post-CABG patients most likely to become treatment resistant so as to develop more effective treatments for them,” the researchers added.

This study was supported by the National Institutes of Health and the University of Pittsburgh.

Dr. Rollman reported no financial conflicts of interest.

A collaborative-care intervention delivered by telephone improved mental and physical functioning in patients who developed depression after undergoing coronary artery bypass grafting, according to a study published online in JAMA simultaneously with its presentation at the annual scientific sessions of the American Heart Association.

The treatment's benefits became evident within 2 months of surgery and persisted through 8 months of follow-up. Overall, half of the 150 patients who received the intervention reported a 50% or more reduction in mood symptoms, compared with 30% of patients who received usual post-CABG care, said Dr. Bruce L. Rollman of the University of Pittsburgh and his associates.

The investigators described their study as the first clinical trial to assess a collaborative-care strategy for treating depression following an acute cardiac event.

“Collaborative care emphasizes a flexible real-world treatment package that involves active follow-up by a nonphysician care manager who adheres to evidence-based treatment protocols, supports patients with timely education about their illness, considers patients' prior treatment experiences and current preferences, teaches self-management techniques, actively involves primary care physicians in their patients' care through regular exchanges of real-time information, proactively monitors treatment responses and suggests adjustments when indicated, and facilitates comanagement or transfer of care to local mental health specialists when patients do not respond to treatment or have clinically complicated cases, or upon request by the patient or primary care physician,” they explained.

For this intervention, 2,485 post-CABG patients were first screened for depression before hospital discharge, then screened again 2 weeks later to determine whether depression symptoms persisted. A total of 302 were found to have moderate depression and agreed to participate in the study.

The patients had been treated at two university-affiliated and five community hospitals in the Pittsburgh area between 2004 and 2007. They were randomly assigned to the intervention group (150 subjects) or to usual care (152 subjects). A comparison group of 151 post-CABG patients who did not have depression was included in the study.

The intervention was run by a nurse care manager who reported weekly to a study psychiatrist and internist. The care manager contacted patients by phone in 15- to 45-minute sessions, providing “basic psychoeducation” about depression and its effect on cardiac disease, initiating and adjusting antidepressant pharmacotherapy through the patients' primary care physicians, closely monitoring mood symptoms, and coordinating care with a local psychiatrist or psychologist as necessary.

The care manager also performed serial assessments with the 36-item Short Form health survey (SF-36) to measure general mental and physical health, the Duke Activity Status Index to measure disease-specific physical functioning, and the Hamilton Rating Scale for Depression to measure mood symptoms.

After 8 months, the intervention group showed significant clinical improvement on the SF-36 of 3.2 points, with an effect size of 0.30. Improvements of at least 3 points or an effect size of 0.25 on these measures are considered “minimally clinically important,” Dr. Rollman and his colleagues said (JAMA 2009;302:2095-103).

Men showed a better treatment response then did women.

For men in the intervention group, there was a nearly 6-point rise on the SF-36. Moreover, 61% of the men who received the intervention reported a 50% or more reduction in depression scores, compared with only 33% of men who received usual care.

In contrast, 38% of women who received the intervention reported that degree of reduction in depression scores, compared with 23% of women who received usual care.

The study subjects who responded well to the intervention showed better outcomes than did those who received usual care, but both groups of patients with post-CABG depression had poorer outcomes than did the comparison group of patients without depression. Overall, 33% of intervention patients and 32% of usual care patients required rehospitalization, compared with only 25% of the control group.

Noting that “a substantial minority of patients,” particularly women, did not benefit from the collaborative-care intervention, “it is vital to identify post-CABG patients most likely to become treatment resistant so as to develop more effective treatments for them,” the researchers added.

This study was supported by the National Institutes of Health and the University of Pittsburgh.

Dr. Rollman reported no financial conflicts of interest.

Public release of hospital “report cards” did not measurably improve indicators of care for acute MI or chronic heart failure, according to a Canadian study.

Even though most of the hospitals involved in the study undertook at least one quality improvement initiative in response to the report cards, only 1 of 12 indicators of care for acute MI and only 1 of 6 indicators of care for chronic heart failure improved, said Dr. Jack V. Tu, a professor in the department of health policy, management, and evaluation at the University of Toronto, and his associates.

Proponents of such report cards maintain that publicly releasing hospital performance data will increase “the accountability and transparency of the health care system,” thereby stimulating hospitals and clinicians to improve their performance.

However, “no large randomized clinical trials have been conducted to evaluate the effectiveness of public report cards as a method for improving quality of care,” the investigators said.

They performed such a trial at 81 Ontario hospitals, focusing on cardiac care because of the well-known gap between ideal practice and actual practice in patients hospitalized with acute MI or chronic heart failure.

At each hospital, a sample of 125 charts from 1999-2001 was reviewed. Participating hospitals were randomly assigned to receive early feedback (in October 2003, before the results were released to the public and received extensive media coverage in January 2004) or delayed feedback (in September 2005, at the same time as their results were released to the public but without any media coverage) on a publicly released report card of their performance in the reviewed cases.

Follow-up performance data was obtained on 15,997 patients treated for the same conditions at the same hospitals in 2004-2005.

Despite the fact that many hospitals (73%) that received early feedback changed order sets and/or clinical pathways or care maps for these patient groups during that interval, there was no significant change over time in performance for either the early-feedback or the late-feedback groups.

Only 1 of 12 factors measured in patients with acute MI—the percentage of patients receiving fibrinolytic therapy before transfer to a coronary care or intensive care unit—improved significantly more with early feedback. Similarly, only 1 of 6 factors measured in patients with chronic heart failure—the rate of ACE inhibitor or angiotensin II receptor blocker use in those with left ventricular dysfunction—improved significantly more with early feedback.

These findings “suggest that public release of hospital-specific performance data may not be a particularly effective system-wide intervention for measurably improving processes of care” for either of these conditions, Dr. Tu and his associates said (JAMA 2009 Nov. 18; doi:10.1001/jama.2009.1731). The study was released online simultaneously with Dr. Tu's presentation of the data at the annual scientific sessions of the American Heart Association.

An unexpected finding was that several hospitals (47%) in the delayed-feedback group started quality improvement initiatives after learning about the public release of report cards for other hospitals but before receiving their own results, the investigators said.

A limitation of this study was that it involved one-time-only report cards. “It is possible that more frequent and timely feedback of publicly released report cards on a regular basis might have been more effective,” they added.

Dr. Tu reported no financial conflicts of interest.

Public release of hospital “report cards” did not measurably improve indicators of care for acute MI or chronic heart failure, according to a Canadian study.

Even though most of the hospitals involved in the study undertook at least one quality improvement initiative in response to the report cards, only 1 of 12 indicators of care for acute MI and only 1 of 6 indicators of care for chronic heart failure improved, said Dr. Jack V. Tu, a professor in the department of health policy, management, and evaluation at the University of Toronto, and his associates.

Proponents of such report cards maintain that publicly releasing hospital performance data will increase “the accountability and transparency of the health care system,” thereby stimulating hospitals and clinicians to improve their performance.

However, “no large randomized clinical trials have been conducted to evaluate the effectiveness of public report cards as a method for improving quality of care,” the investigators said.

They performed such a trial at 81 Ontario hospitals, focusing on cardiac care because of the well-known gap between ideal practice and actual practice in patients hospitalized with acute MI or chronic heart failure.

At each hospital, a sample of 125 charts from 1999-2001 was reviewed. Participating hospitals were randomly assigned to receive early feedback (in October 2003, before the results were released to the public and received extensive media coverage in January 2004) or delayed feedback (in September 2005, at the same time as their results were released to the public but without any media coverage) on a publicly released report card of their performance in the reviewed cases.

Follow-up performance data was obtained on 15,997 patients treated for the same conditions at the same hospitals in 2004-2005.

Despite the fact that many hospitals (73%) that received early feedback changed order sets and/or clinical pathways or care maps for these patient groups during that interval, there was no significant change over time in performance for either the early-feedback or the late-feedback groups.

Only 1 of 12 factors measured in patients with acute MI—the percentage of patients receiving fibrinolytic therapy before transfer to a coronary care or intensive care unit—improved significantly more with early feedback. Similarly, only 1 of 6 factors measured in patients with chronic heart failure—the rate of ACE inhibitor or angiotensin II receptor blocker use in those with left ventricular dysfunction—improved significantly more with early feedback.

These findings “suggest that public release of hospital-specific performance data may not be a particularly effective system-wide intervention for measurably improving processes of care” for either of these conditions, Dr. Tu and his associates said (JAMA 2009 Nov. 18; doi:10.1001/jama.2009.1731). The study was released online simultaneously with Dr. Tu's presentation of the data at the annual scientific sessions of the American Heart Association.

An unexpected finding was that several hospitals (47%) in the delayed-feedback group started quality improvement initiatives after learning about the public release of report cards for other hospitals but before receiving their own results, the investigators said.

A limitation of this study was that it involved one-time-only report cards. “It is possible that more frequent and timely feedback of publicly released report cards on a regular basis might have been more effective,” they added.

Dr. Tu reported no financial conflicts of interest.

Public release of hospital “report cards” did not measurably improve indicators of care for acute MI or chronic heart failure, according to a Canadian study.

Even though most of the hospitals involved in the study undertook at least one quality improvement initiative in response to the report cards, only 1 of 12 indicators of care for acute MI and only 1 of 6 indicators of care for chronic heart failure improved, said Dr. Jack V. Tu, a professor in the department of health policy, management, and evaluation at the University of Toronto, and his associates.

Proponents of such report cards maintain that publicly releasing hospital performance data will increase “the accountability and transparency of the health care system,” thereby stimulating hospitals and clinicians to improve their performance.

However, “no large randomized clinical trials have been conducted to evaluate the effectiveness of public report cards as a method for improving quality of care,” the investigators said.

They performed such a trial at 81 Ontario hospitals, focusing on cardiac care because of the well-known gap between ideal practice and actual practice in patients hospitalized with acute MI or chronic heart failure.

At each hospital, a sample of 125 charts from 1999-2001 was reviewed. Participating hospitals were randomly assigned to receive early feedback (in October 2003, before the results were released to the public and received extensive media coverage in January 2004) or delayed feedback (in September 2005, at the same time as their results were released to the public but without any media coverage) on a publicly released report card of their performance in the reviewed cases.

Follow-up performance data was obtained on 15,997 patients treated for the same conditions at the same hospitals in 2004-2005.

Despite the fact that many hospitals (73%) that received early feedback changed order sets and/or clinical pathways or care maps for these patient groups during that interval, there was no significant change over time in performance for either the early-feedback or the late-feedback groups.

Only 1 of 12 factors measured in patients with acute MI—the percentage of patients receiving fibrinolytic therapy before transfer to a coronary care or intensive care unit—improved significantly more with early feedback. Similarly, only 1 of 6 factors measured in patients with chronic heart failure—the rate of ACE inhibitor or angiotensin II receptor blocker use in those with left ventricular dysfunction—improved significantly more with early feedback.

These findings “suggest that public release of hospital-specific performance data may not be a particularly effective system-wide intervention for measurably improving processes of care” for either of these conditions, Dr. Tu and his associates said (JAMA 2009 Nov. 18; doi:10.1001/jama.2009.1731). The study was released online simultaneously with Dr. Tu's presentation of the data at the annual scientific sessions of the American Heart Association.

An unexpected finding was that several hospitals (47%) in the delayed-feedback group started quality improvement initiatives after learning about the public release of report cards for other hospitals but before receiving their own results, the investigators said.

A limitation of this study was that it involved one-time-only report cards. “It is possible that more frequent and timely feedback of publicly released report cards on a regular basis might have been more effective,” they added.

Dr. Tu reported no financial conflicts of interest.

Chronic musculoskeletal pain raises elderly people's risk of falling, independent of their underlying pathologies or the medications they may be taking for the pain, according to a study of more than 700 elders living independently.

The finding that pain is “an overlooked and potentially important risk factor for falls” suggests that “the common complaint of aches and pains of old age is related to a greater hazard than previously thought,” Suzanne G. Leveille, Ph.D., R.N., of the University of Massachusetts, Boston, and her associates wrote.

“Daily discomfort may accompany not only difficulties in performing daily activities but equally as important may be a risk for falls and possibly fall-related injuries in the older population,” the authors wrote.

Dr. Leveille and her colleagues used data from the MOBILIZE Boston study to identify new strategies for preventing falls. (The study's title stands for Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly.) The researchers assessed data on 749 men and women aged 70 and older who were living in a variety of urban and suburban settings.

The study participants were evaluated during home and clinic visits at the beginning of the study. The researchers noted the severity and location of musculoskeletal pain, as well as its interference with daily activities. Monthly for up to 18 months thereafter, the participants reported pain symptoms and all falls on postcards.

This study design enabled the researchers to track the risk of falls over time in relation to baseline chronic pain and pain reported periodically.

Overall, 40% of the study subjects reported chronic polyarticular pain, and another 24% reported chronic pain in just one joint area. A total of 1,029 falls occurred during follow-up, with 405 subjects (54%) falling at least once during the study.

Compared with participants who did not report chronic pain, those who did had a significantly higher rate of falls, regardless of whether their pain was measured by location, severity, or degree of interference with daily life, Dr. Leveille and colleagues said (JAMA 2009;302:2214-21).

Chronic pain was persistently associated with fall risk after the data were adjusted to account for coexisting chronic conditions, other risk factors for falling, baseline balance and mobility, the use of psychotherapeutic medications, and the use of analgesics.

There also was a strong, graded relationship between monthly pain-severity ratings and the risk for falling during the subsequent month. “For example, among persons who reported severe or very severe pain for any given month on their calendar postcard, there was a 77% increased likelihood for a fall in the subsequent month, compared with those who reported no pain,” the investigators said. “Persons reporting even very mild pain also had an elevated risk of falling in any given month,” they added.

There are three possible mechanisms underlying the link between pain and falling, according to the researchers. First, joint pathology may cause both pain and the instability that can lead to falling. However, Dr. Leveille and her colleagues deemed that explanation unlikely because the association in this study was independent of hand and knee osteoarthritis and of mobility.

Second, the neuromuscular effects of pain could cause muscle weakness, slowed responses to an impending fall, or gait alterations, all of which can lead to falling. Third, chronic pain may distract patients or otherwise interfere with the cognitive activity needed to prevent falling.

Other studies have shown that patients with chronic pain show decreased executive function and attention. Moreover, avoiding or interrupting a fall “typically requires a cognitively mediated physical maneuver,” they noted.

Dr. Leveille reported no financial conflict of interest. The MOBILIZE Boston study was supported in part by a grant from Pfizer Inc.

Chronic musculoskeletal pain raises elderly people's risk of falling, independent of their underlying pathologies or the medications they may be taking for the pain, according to a study of more than 700 elders living independently.

The finding that pain is “an overlooked and potentially important risk factor for falls” suggests that “the common complaint of aches and pains of old age is related to a greater hazard than previously thought,” Suzanne G. Leveille, Ph.D., R.N., of the University of Massachusetts, Boston, and her associates wrote.

“Daily discomfort may accompany not only difficulties in performing daily activities but equally as important may be a risk for falls and possibly fall-related injuries in the older population,” the authors wrote.

Dr. Leveille and her colleagues used data from the MOBILIZE Boston study to identify new strategies for preventing falls. (The study's title stands for Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly.) The researchers assessed data on 749 men and women aged 70 and older who were living in a variety of urban and suburban settings.

The study participants were evaluated during home and clinic visits at the beginning of the study. The researchers noted the severity and location of musculoskeletal pain, as well as its interference with daily activities. Monthly for up to 18 months thereafter, the participants reported pain symptoms and all falls on postcards.

This study design enabled the researchers to track the risk of falls over time in relation to baseline chronic pain and pain reported periodically.

Overall, 40% of the study subjects reported chronic polyarticular pain, and another 24% reported chronic pain in just one joint area. A total of 1,029 falls occurred during follow-up, with 405 subjects (54%) falling at least once during the study.

Compared with participants who did not report chronic pain, those who did had a significantly higher rate of falls, regardless of whether their pain was measured by location, severity, or degree of interference with daily life, Dr. Leveille and colleagues said (JAMA 2009;302:2214-21).

Chronic pain was persistently associated with fall risk after the data were adjusted to account for coexisting chronic conditions, other risk factors for falling, baseline balance and mobility, the use of psychotherapeutic medications, and the use of analgesics.

There also was a strong, graded relationship between monthly pain-severity ratings and the risk for falling during the subsequent month. “For example, among persons who reported severe or very severe pain for any given month on their calendar postcard, there was a 77% increased likelihood for a fall in the subsequent month, compared with those who reported no pain,” the investigators said. “Persons reporting even very mild pain also had an elevated risk of falling in any given month,” they added.

There are three possible mechanisms underlying the link between pain and falling, according to the researchers. First, joint pathology may cause both pain and the instability that can lead to falling. However, Dr. Leveille and her colleagues deemed that explanation unlikely because the association in this study was independent of hand and knee osteoarthritis and of mobility.

Second, the neuromuscular effects of pain could cause muscle weakness, slowed responses to an impending fall, or gait alterations, all of which can lead to falling. Third, chronic pain may distract patients or otherwise interfere with the cognitive activity needed to prevent falling.

Other studies have shown that patients with chronic pain show decreased executive function and attention. Moreover, avoiding or interrupting a fall “typically requires a cognitively mediated physical maneuver,” they noted.

Dr. Leveille reported no financial conflict of interest. The MOBILIZE Boston study was supported in part by a grant from Pfizer Inc.

Chronic musculoskeletal pain raises elderly people's risk of falling, independent of their underlying pathologies or the medications they may be taking for the pain, according to a study of more than 700 elders living independently.

The finding that pain is “an overlooked and potentially important risk factor for falls” suggests that “the common complaint of aches and pains of old age is related to a greater hazard than previously thought,” Suzanne G. Leveille, Ph.D., R.N., of the University of Massachusetts, Boston, and her associates wrote.

“Daily discomfort may accompany not only difficulties in performing daily activities but equally as important may be a risk for falls and possibly fall-related injuries in the older population,” the authors wrote.

Dr. Leveille and her colleagues used data from the MOBILIZE Boston study to identify new strategies for preventing falls. (The study's title stands for Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly.) The researchers assessed data on 749 men and women aged 70 and older who were living in a variety of urban and suburban settings.

The study participants were evaluated during home and clinic visits at the beginning of the study. The researchers noted the severity and location of musculoskeletal pain, as well as its interference with daily activities. Monthly for up to 18 months thereafter, the participants reported pain symptoms and all falls on postcards.

This study design enabled the researchers to track the risk of falls over time in relation to baseline chronic pain and pain reported periodically.

Overall, 40% of the study subjects reported chronic polyarticular pain, and another 24% reported chronic pain in just one joint area. A total of 1,029 falls occurred during follow-up, with 405 subjects (54%) falling at least once during the study.

Compared with participants who did not report chronic pain, those who did had a significantly higher rate of falls, regardless of whether their pain was measured by location, severity, or degree of interference with daily life, Dr. Leveille and colleagues said (JAMA 2009;302:2214-21).

Chronic pain was persistently associated with fall risk after the data were adjusted to account for coexisting chronic conditions, other risk factors for falling, baseline balance and mobility, the use of psychotherapeutic medications, and the use of analgesics.

There also was a strong, graded relationship between monthly pain-severity ratings and the risk for falling during the subsequent month. “For example, among persons who reported severe or very severe pain for any given month on their calendar postcard, there was a 77% increased likelihood for a fall in the subsequent month, compared with those who reported no pain,” the investigators said. “Persons reporting even very mild pain also had an elevated risk of falling in any given month,” they added.

There are three possible mechanisms underlying the link between pain and falling, according to the researchers. First, joint pathology may cause both pain and the instability that can lead to falling. However, Dr. Leveille and her colleagues deemed that explanation unlikely because the association in this study was independent of hand and knee osteoarthritis and of mobility.

Second, the neuromuscular effects of pain could cause muscle weakness, slowed responses to an impending fall, or gait alterations, all of which can lead to falling. Third, chronic pain may distract patients or otherwise interfere with the cognitive activity needed to prevent falling.

Other studies have shown that patients with chronic pain show decreased executive function and attention. Moreover, avoiding or interrupting a fall “typically requires a cognitively mediated physical maneuver,” they noted.

Dr. Leveille reported no financial conflict of interest. The MOBILIZE Boston study was supported in part by a grant from Pfizer Inc.

Nearly half of women with breast cancer report persistent pain, and 58% report sensory disturbances up to 3 years after surgery, according to Dr. Rune Gärtner of the University of Copenhagen and her associates.

In more than half of these cases, the women describe their pain as moderate to severe, Dr. Gärtner and her associates said (JAMA 2009;302:1985-92).

The researchers assessed persistent breast cancer pain in a nationwide study of 3,253 Danish women who underwent surgery for unilateral primary breast cancer in 2005-2006. They categorized the patients into 12 treatment groups according to the type of surgery, adjuvant radiotherapy, and adjuvant chemotherapy they received.

Surgeries included breast-conserving surgery with either sentinel node dissection or axillary node dissection and mastectomy.

The mean interval between the surgery and this pain assessment was 26 months (range, 13-41 months). Very few of these patients were receiving aromatase inhibitors when they were assessed, which are known to cause muscular and joint pain.

A total of 1,543 women (47%) reported pain in the area of the affected breast, the axilla, the arm, or the side of the body. Eighteen percent reported pain in one of these areas, 28% in two areas, 28% in three areas, and 26% in all four areas.

Thirteen percent of the women reported severe pain and 39% reported moderate pain, while 48% reported light pain. Among the women who reported severe pain, 77% had pain every day, Dr. Gärtner and her colleagues said.

One-fifth of the study subjects had consulted a physician about the pain during the preceding 3 months. A total of 28% had taken analgesics, and 26% had received other therapies, such as physiotherapy or massage.

Fifty-eight percent of women reported persistent sensory disturbances. The rate was lowest (31%) among women who had breast-conserving surgery with sentinel node dissection, and it was highest (85%) among women who had breast-conserving therapy with axillary node dissection and radiotherapy.

“The most important determinant of persistent pain and sensory disturbance was young age (less than 40 years),” they noted. Radiotherapy also was an independent and significant risk factor for persistent pain.

Taken together with the results of previous research, these findings indicate that “chronic pain after breast cancer surgery and adjuvant therapy may predominantly be characterized as a neuropathic pain state and [is] probably related to intraoperative injury of the intercostal-brachial nerve,” Dr. Gärtner and her colleagues said.

In the future, using nerve-sparing surgical and radiotherapy techniques may reduce the risk of persistent breast cancer pain, they added, but larger, more detailed studies are needed.

No conflicts of interest were reported. The work was supported by grants from the Danish Cancer Society, Breast Friends, and the Lundbeck Foundation.

Nearly half of women with breast cancer report persistent pain, and 58% report sensory disturbances up to 3 years after surgery, according to Dr. Rune Gärtner of the University of Copenhagen and her associates.

In more than half of these cases, the women describe their pain as moderate to severe, Dr. Gärtner and her associates said (JAMA 2009;302:1985-92).

The researchers assessed persistent breast cancer pain in a nationwide study of 3,253 Danish women who underwent surgery for unilateral primary breast cancer in 2005-2006. They categorized the patients into 12 treatment groups according to the type of surgery, adjuvant radiotherapy, and adjuvant chemotherapy they received.

Surgeries included breast-conserving surgery with either sentinel node dissection or axillary node dissection and mastectomy.

The mean interval between the surgery and this pain assessment was 26 months (range, 13-41 months). Very few of these patients were receiving aromatase inhibitors when they were assessed, which are known to cause muscular and joint pain.

A total of 1,543 women (47%) reported pain in the area of the affected breast, the axilla, the arm, or the side of the body. Eighteen percent reported pain in one of these areas, 28% in two areas, 28% in three areas, and 26% in all four areas.

Thirteen percent of the women reported severe pain and 39% reported moderate pain, while 48% reported light pain. Among the women who reported severe pain, 77% had pain every day, Dr. Gärtner and her colleagues said.

One-fifth of the study subjects had consulted a physician about the pain during the preceding 3 months. A total of 28% had taken analgesics, and 26% had received other therapies, such as physiotherapy or massage.

Fifty-eight percent of women reported persistent sensory disturbances. The rate was lowest (31%) among women who had breast-conserving surgery with sentinel node dissection, and it was highest (85%) among women who had breast-conserving therapy with axillary node dissection and radiotherapy.

“The most important determinant of persistent pain and sensory disturbance was young age (less than 40 years),” they noted. Radiotherapy also was an independent and significant risk factor for persistent pain.

Taken together with the results of previous research, these findings indicate that “chronic pain after breast cancer surgery and adjuvant therapy may predominantly be characterized as a neuropathic pain state and [is] probably related to intraoperative injury of the intercostal-brachial nerve,” Dr. Gärtner and her colleagues said.

In the future, using nerve-sparing surgical and radiotherapy techniques may reduce the risk of persistent breast cancer pain, they added, but larger, more detailed studies are needed.

No conflicts of interest were reported. The work was supported by grants from the Danish Cancer Society, Breast Friends, and the Lundbeck Foundation.

Nearly half of women with breast cancer report persistent pain, and 58% report sensory disturbances up to 3 years after surgery, according to Dr. Rune Gärtner of the University of Copenhagen and her associates.

In more than half of these cases, the women describe their pain as moderate to severe, Dr. Gärtner and her associates said (JAMA 2009;302:1985-92).

The researchers assessed persistent breast cancer pain in a nationwide study of 3,253 Danish women who underwent surgery for unilateral primary breast cancer in 2005-2006. They categorized the patients into 12 treatment groups according to the type of surgery, adjuvant radiotherapy, and adjuvant chemotherapy they received.

Surgeries included breast-conserving surgery with either sentinel node dissection or axillary node dissection and mastectomy.

The mean interval between the surgery and this pain assessment was 26 months (range, 13-41 months). Very few of these patients were receiving aromatase inhibitors when they were assessed, which are known to cause muscular and joint pain.

A total of 1,543 women (47%) reported pain in the area of the affected breast, the axilla, the arm, or the side of the body. Eighteen percent reported pain in one of these areas, 28% in two areas, 28% in three areas, and 26% in all four areas.

Thirteen percent of the women reported severe pain and 39% reported moderate pain, while 48% reported light pain. Among the women who reported severe pain, 77% had pain every day, Dr. Gärtner and her colleagues said.

One-fifth of the study subjects had consulted a physician about the pain during the preceding 3 months. A total of 28% had taken analgesics, and 26% had received other therapies, such as physiotherapy or massage.

Fifty-eight percent of women reported persistent sensory disturbances. The rate was lowest (31%) among women who had breast-conserving surgery with sentinel node dissection, and it was highest (85%) among women who had breast-conserving therapy with axillary node dissection and radiotherapy.

“The most important determinant of persistent pain and sensory disturbance was young age (less than 40 years),” they noted. Radiotherapy also was an independent and significant risk factor for persistent pain.

Taken together with the results of previous research, these findings indicate that “chronic pain after breast cancer surgery and adjuvant therapy may predominantly be characterized as a neuropathic pain state and [is] probably related to intraoperative injury of the intercostal-brachial nerve,” Dr. Gärtner and her colleagues said.

In the future, using nerve-sparing surgical and radiotherapy techniques may reduce the risk of persistent breast cancer pain, they added, but larger, more detailed studies are needed.

No conflicts of interest were reported. The work was supported by grants from the Danish Cancer Society, Breast Friends, and the Lundbeck Foundation.

A group of nine easily obtained measures reliably differentiates eosinophilic esophagitis from gastroesophageal reflux disease in adults, and a slightly different set of factors reliably distinguishes between these two disorders in the pediatric population, Dr. Evan S. Dellon and his colleagues reported.

It is often difficult to distinguish eosinophilic esophagitis from GERD because many symptoms, clinical features, endoscopic findings, and histologic features of the two conditions overlap or are nonspecific, Dr. Dellon of the University of North Carolina, Chapel Hill, and his associates wrote (Clin. Gastroenterol. Hepatol. 2009 [doi: 10.1016/j.cgh.2009.08.030]).

To find a way to reliably establish a differential diagnosis, the investigators performed what they described as the largest study of the issue to date, reviewing extensive data on 151 cases that met strict criteria for eosinophilic esophagitis, as well as 226 cases of GERD. All the patients were treated at a single medical center from 2000 to 2007.

In the eosinophilic esophagitis (EoE) cases, all other potential causes of eosinophilia had been excluded, and biopsies had been performed while patients were taking acid suppressors or after they had failed to respond to acid suppression.

Nine factors were found to reliably predict EoE and distinguish it from GERD. Clinically, adults with EoE were younger (mean age 25 years) than those with GERD (mean age 33 years), more likely to report dysphagia and food impaction while GERD patients reported heartburn and abdominal pain, and much more likely to have concomitant food allergies, allergic rhinitis or dermatitis, and asthma. Therefore patient age, the presence of dysphagia, and the presence of documented food allergy made up the first three of the nine factors.

Endoscopically, adults with EoE were “substantially” more likely to have esophageal rings, strictures, stenoses, linear furrows, crepe-paper mucosa, and white plaques or exudates, while patients with GERD were more likely to have hiatal hernias. Thus, esophageal rings, furrows, and plaques on esophagogastroduodenoscopy, plus the absence of hiatal hernia, comprised the next four of the nine predictive factors.

Histologically, the mean maximum eosinophil count was much higher in the EoE group (121) than in the GERD group (34), as was the mean eosinophil count per five high-powered fields (76 for EoE vs. 16 for GERD). The distribution of eosinophils also was different, with mucosal distribution being diffuse in almost every case of EoE, compared with only 77% of GERD patients.

Eosinophilic degranulation also was much more frequent with EoE (94% of cases) than with GERD (52%). Spongiosis was more common, affecting 89% of EoE cases but only 59% of GERD cases.

Therefore, the maximum eosinophil count and the presence of eosinophilic degranulation on biopsy specimens were the final two in the set of nine factors that distinguished the two disorders.

A model that included these nine factors showed “excellent predictive ability” and correctly classified approximately 90% of the study subjects as having either EoE or GERD.

In children, a similar model that included eight factors was constructed to differentiate EoE from GERD. These factors were male gender, the finding of linear furrows on endoscopy, a high eosinophil count, the presence of eosinophil degranulation, and the presence of heartburn, food allergy, atopic disease, or asthma.

The study was funded by the American College of Gastroenterology. No conflicts of interest were reported.

A group of nine easily obtained measures reliably differentiates eosinophilic esophagitis from gastroesophageal reflux disease in adults, and a slightly different set of factors reliably distinguishes between these two disorders in the pediatric population, Dr. Evan S. Dellon and his colleagues reported.

It is often difficult to distinguish eosinophilic esophagitis from GERD because many symptoms, clinical features, endoscopic findings, and histologic features of the two conditions overlap or are nonspecific, Dr. Dellon of the University of North Carolina, Chapel Hill, and his associates wrote (Clin. Gastroenterol. Hepatol. 2009 [doi: 10.1016/j.cgh.2009.08.030]).

To find a way to reliably establish a differential diagnosis, the investigators performed what they described as the largest study of the issue to date, reviewing extensive data on 151 cases that met strict criteria for eosinophilic esophagitis, as well as 226 cases of GERD. All the patients were treated at a single medical center from 2000 to 2007.

In the eosinophilic esophagitis (EoE) cases, all other potential causes of eosinophilia had been excluded, and biopsies had been performed while patients were taking acid suppressors or after they had failed to respond to acid suppression.

Nine factors were found to reliably predict EoE and distinguish it from GERD. Clinically, adults with EoE were younger (mean age 25 years) than those with GERD (mean age 33 years), more likely to report dysphagia and food impaction while GERD patients reported heartburn and abdominal pain, and much more likely to have concomitant food allergies, allergic rhinitis or dermatitis, and asthma. Therefore patient age, the presence of dysphagia, and the presence of documented food allergy made up the first three of the nine factors.

Endoscopically, adults with EoE were “substantially” more likely to have esophageal rings, strictures, stenoses, linear furrows, crepe-paper mucosa, and white plaques or exudates, while patients with GERD were more likely to have hiatal hernias. Thus, esophageal rings, furrows, and plaques on esophagogastroduodenoscopy, plus the absence of hiatal hernia, comprised the next four of the nine predictive factors.

Histologically, the mean maximum eosinophil count was much higher in the EoE group (121) than in the GERD group (34), as was the mean eosinophil count per five high-powered fields (76 for EoE vs. 16 for GERD). The distribution of eosinophils also was different, with mucosal distribution being diffuse in almost every case of EoE, compared with only 77% of GERD patients.

Eosinophilic degranulation also was much more frequent with EoE (94% of cases) than with GERD (52%). Spongiosis was more common, affecting 89% of EoE cases but only 59% of GERD cases.

Therefore, the maximum eosinophil count and the presence of eosinophilic degranulation on biopsy specimens were the final two in the set of nine factors that distinguished the two disorders.

A model that included these nine factors showed “excellent predictive ability” and correctly classified approximately 90% of the study subjects as having either EoE or GERD.

In children, a similar model that included eight factors was constructed to differentiate EoE from GERD. These factors were male gender, the finding of linear furrows on endoscopy, a high eosinophil count, the presence of eosinophil degranulation, and the presence of heartburn, food allergy, atopic disease, or asthma.

The study was funded by the American College of Gastroenterology. No conflicts of interest were reported.

A group of nine easily obtained measures reliably differentiates eosinophilic esophagitis from gastroesophageal reflux disease in adults, and a slightly different set of factors reliably distinguishes between these two disorders in the pediatric population, Dr. Evan S. Dellon and his colleagues reported.

It is often difficult to distinguish eosinophilic esophagitis from GERD because many symptoms, clinical features, endoscopic findings, and histologic features of the two conditions overlap or are nonspecific, Dr. Dellon of the University of North Carolina, Chapel Hill, and his associates wrote (Clin. Gastroenterol. Hepatol. 2009 [doi: 10.1016/j.cgh.2009.08.030]).

To find a way to reliably establish a differential diagnosis, the investigators performed what they described as the largest study of the issue to date, reviewing extensive data on 151 cases that met strict criteria for eosinophilic esophagitis, as well as 226 cases of GERD. All the patients were treated at a single medical center from 2000 to 2007.

In the eosinophilic esophagitis (EoE) cases, all other potential causes of eosinophilia had been excluded, and biopsies had been performed while patients were taking acid suppressors or after they had failed to respond to acid suppression.

Nine factors were found to reliably predict EoE and distinguish it from GERD. Clinically, adults with EoE were younger (mean age 25 years) than those with GERD (mean age 33 years), more likely to report dysphagia and food impaction while GERD patients reported heartburn and abdominal pain, and much more likely to have concomitant food allergies, allergic rhinitis or dermatitis, and asthma. Therefore patient age, the presence of dysphagia, and the presence of documented food allergy made up the first three of the nine factors.

Endoscopically, adults with EoE were “substantially” more likely to have esophageal rings, strictures, stenoses, linear furrows, crepe-paper mucosa, and white plaques or exudates, while patients with GERD were more likely to have hiatal hernias. Thus, esophageal rings, furrows, and plaques on esophagogastroduodenoscopy, plus the absence of hiatal hernia, comprised the next four of the nine predictive factors.

Histologically, the mean maximum eosinophil count was much higher in the EoE group (121) than in the GERD group (34), as was the mean eosinophil count per five high-powered fields (76 for EoE vs. 16 for GERD). The distribution of eosinophils also was different, with mucosal distribution being diffuse in almost every case of EoE, compared with only 77% of GERD patients.

Eosinophilic degranulation also was much more frequent with EoE (94% of cases) than with GERD (52%). Spongiosis was more common, affecting 89% of EoE cases but only 59% of GERD cases.

Therefore, the maximum eosinophil count and the presence of eosinophilic degranulation on biopsy specimens were the final two in the set of nine factors that distinguished the two disorders.

A model that included these nine factors showed “excellent predictive ability” and correctly classified approximately 90% of the study subjects as having either EoE or GERD.

In children, a similar model that included eight factors was constructed to differentiate EoE from GERD. These factors were male gender, the finding of linear furrows on endoscopy, a high eosinophil count, the presence of eosinophil degranulation, and the presence of heartburn, food allergy, atopic disease, or asthma.

The study was funded by the American College of Gastroenterology. No conflicts of interest were reported.

In evaluating patients' vascular risk, lipid assessment can be simplified without sacrificing accuracy, according to researchers in the Emerging Risk Factors Collaboration.

“Expert opinion is divided” about whether measurement of apolipoproteins should replace that of cholesterol, the importance of triglyceride measurements, and the necessity of patients' fasting before physicians obtain these measurements. Now, analysis of data amassed in the Emerging Risk Factors Collaboration [ERFC] shows that these issues are not critically important, said Dr. John Danesh of the University of Cambridge (England) and his associates in the ERFC.

The ERFC pooled data from 112 prospective studies of cardiovascular risk factors involving 1.2 million subjects in 21 countries in western Europe and North America. Subjects' mean age was 59 years at baseline; median follow-up was 6 years.

Cholesterol levels and apolipoprotein levels were found to be equally useful in predicting vascular risk, with nearly identical hazard ratios for the two approaches. “This finding suggests that current discussions about whether to measure cholesterol levels or apolipoproteins … should hinge more on practical considerations … than on major differences in strength of epidemiological associations,” the investigators said.

Moreover, hazard ratios for vascular disease were at least as strong among subjects who did not fast before testing as among those who did. In addition, triglyceride concentration showed no relation with vascular risk independently of cholesterol levels, Dr. Danesh and his colleagues said (JAMA 2009;302:1993-2000).

The ERFC is funded by the British Heart Foundation, the UK Medical Research Council, the BUPA Foundation, and GlaxoSmithKline. Dr. Danesh received funding from the British Heart Foundation; BUPA Foundation; diaDexus; European Union; Evelyn Trust; Fogarty International Center; GlaxoSmithKline; Medical Research Council; Merck Sharp and Dohme; National Heart, Lung, and Blood Institute; National Institute of Neurological Disorders and Stroke; Novartis; Roche; and Wellcome Trust.

In evaluating patients' vascular risk, lipid assessment can be simplified without sacrificing accuracy, according to researchers in the Emerging Risk Factors Collaboration.

“Expert opinion is divided” about whether measurement of apolipoproteins should replace that of cholesterol, the importance of triglyceride measurements, and the necessity of patients' fasting before physicians obtain these measurements. Now, analysis of data amassed in the Emerging Risk Factors Collaboration [ERFC] shows that these issues are not critically important, said Dr. John Danesh of the University of Cambridge (England) and his associates in the ERFC.

The ERFC pooled data from 112 prospective studies of cardiovascular risk factors involving 1.2 million subjects in 21 countries in western Europe and North America. Subjects' mean age was 59 years at baseline; median follow-up was 6 years.

Cholesterol levels and apolipoprotein levels were found to be equally useful in predicting vascular risk, with nearly identical hazard ratios for the two approaches. “This finding suggests that current discussions about whether to measure cholesterol levels or apolipoproteins … should hinge more on practical considerations … than on major differences in strength of epidemiological associations,” the investigators said.

Moreover, hazard ratios for vascular disease were at least as strong among subjects who did not fast before testing as among those who did. In addition, triglyceride concentration showed no relation with vascular risk independently of cholesterol levels, Dr. Danesh and his colleagues said (JAMA 2009;302:1993-2000).

The ERFC is funded by the British Heart Foundation, the UK Medical Research Council, the BUPA Foundation, and GlaxoSmithKline. Dr. Danesh received funding from the British Heart Foundation; BUPA Foundation; diaDexus; European Union; Evelyn Trust; Fogarty International Center; GlaxoSmithKline; Medical Research Council; Merck Sharp and Dohme; National Heart, Lung, and Blood Institute; National Institute of Neurological Disorders and Stroke; Novartis; Roche; and Wellcome Trust.

In evaluating patients' vascular risk, lipid assessment can be simplified without sacrificing accuracy, according to researchers in the Emerging Risk Factors Collaboration.

“Expert opinion is divided” about whether measurement of apolipoproteins should replace that of cholesterol, the importance of triglyceride measurements, and the necessity of patients' fasting before physicians obtain these measurements. Now, analysis of data amassed in the Emerging Risk Factors Collaboration [ERFC] shows that these issues are not critically important, said Dr. John Danesh of the University of Cambridge (England) and his associates in the ERFC.

The ERFC pooled data from 112 prospective studies of cardiovascular risk factors involving 1.2 million subjects in 21 countries in western Europe and North America. Subjects' mean age was 59 years at baseline; median follow-up was 6 years.

Cholesterol levels and apolipoprotein levels were found to be equally useful in predicting vascular risk, with nearly identical hazard ratios for the two approaches. “This finding suggests that current discussions about whether to measure cholesterol levels or apolipoproteins … should hinge more on practical considerations … than on major differences in strength of epidemiological associations,” the investigators said.

Moreover, hazard ratios for vascular disease were at least as strong among subjects who did not fast before testing as among those who did. In addition, triglyceride concentration showed no relation with vascular risk independently of cholesterol levels, Dr. Danesh and his colleagues said (JAMA 2009;302:1993-2000).

The ERFC is funded by the British Heart Foundation, the UK Medical Research Council, the BUPA Foundation, and GlaxoSmithKline. Dr. Danesh received funding from the British Heart Foundation; BUPA Foundation; diaDexus; European Union; Evelyn Trust; Fogarty International Center; GlaxoSmithKline; Medical Research Council; Merck Sharp and Dohme; National Heart, Lung, and Blood Institute; National Institute of Neurological Disorders and Stroke; Novartis; Roche; and Wellcome Trust.