Michele G. Sullivan

WASHINGTON — Take a serious look at the bone health of patients with celiac disease, Dr. Peter Green, director of the Celiac Disease Center at Columbia University, New York, advises.

Patients with this gastrointestinal disease have an increased risk of osteoporosis and fragility fractures because their intestines poorly absorb calcium and vitamin D, and the disorder induces bone-destructive inflammatory and autoimmune responses, he said.

Studies show that up to 50% of men, 40% of postmenopausal women, and 10% of premenopausal women with the disorder have osteoporosis, and up to 30% of these groups have osteopenia.

Yet only 6% of patients with celiac disease will have osteopenia or osteoporosis as their presenting symptom.

Antibodies against tissue transglutaminase (tTG), which contribute to the gluten intolerance that characterizes celiac disease, appear to have a deleterious effect on bone, said Dr. Green. “Tissue transglutaminase is a ubiquitous enzyme that is also present in bone.” Antibodies to tTG are also present in bone and emerging evidence suggests they impair active mineralization.

Studies have shown that a gluten-free diet, which decreases anti-tTG levels, directly correlates with increased bone mass in patients with celiac disease and low bone mineral density, he said at an international symposium sponsored by the National Osteoporosis Foundation.

Proinflammatory circulating cytokines also are increased in celiac disease, and may contribute to decreases in bone density, he said. Comorbidities may also play a role. Secondary hyperparathyroidism is common in patients with celiac disease and may prevent patients from attaining their maximum bone density during childhood. Premature menopause in women and reduced gonadal function in men also can contribute to poor bone health, Dr. Green said.

Bone loss associated with celiac disease results in a significantly increased risk of both peripheral and central fracture, he said. Strict adherence to a gluten-free diet seems to be the best way to boost bone health in these patients, he added.

WASHINGTON — Take a serious look at the bone health of patients with celiac disease, Dr. Peter Green, director of the Celiac Disease Center at Columbia University, New York, advises.

Patients with this gastrointestinal disease have an increased risk of osteoporosis and fragility fractures because their intestines poorly absorb calcium and vitamin D, and the disorder induces bone-destructive inflammatory and autoimmune responses, he said.

Studies show that up to 50% of men, 40% of postmenopausal women, and 10% of premenopausal women with the disorder have osteoporosis, and up to 30% of these groups have osteopenia.

Yet only 6% of patients with celiac disease will have osteopenia or osteoporosis as their presenting symptom.

Antibodies against tissue transglutaminase (tTG), which contribute to the gluten intolerance that characterizes celiac disease, appear to have a deleterious effect on bone, said Dr. Green. “Tissue transglutaminase is a ubiquitous enzyme that is also present in bone.” Antibodies to tTG are also present in bone and emerging evidence suggests they impair active mineralization.

Studies have shown that a gluten-free diet, which decreases anti-tTG levels, directly correlates with increased bone mass in patients with celiac disease and low bone mineral density, he said at an international symposium sponsored by the National Osteoporosis Foundation.

Proinflammatory circulating cytokines also are increased in celiac disease, and may contribute to decreases in bone density, he said. Comorbidities may also play a role. Secondary hyperparathyroidism is common in patients with celiac disease and may prevent patients from attaining their maximum bone density during childhood. Premature menopause in women and reduced gonadal function in men also can contribute to poor bone health, Dr. Green said.

Bone loss associated with celiac disease results in a significantly increased risk of both peripheral and central fracture, he said. Strict adherence to a gluten-free diet seems to be the best way to boost bone health in these patients, he added.

WASHINGTON — Take a serious look at the bone health of patients with celiac disease, Dr. Peter Green, director of the Celiac Disease Center at Columbia University, New York, advises.

Patients with this gastrointestinal disease have an increased risk of osteoporosis and fragility fractures because their intestines poorly absorb calcium and vitamin D, and the disorder induces bone-destructive inflammatory and autoimmune responses, he said.

Studies show that up to 50% of men, 40% of postmenopausal women, and 10% of premenopausal women with the disorder have osteoporosis, and up to 30% of these groups have osteopenia.

Yet only 6% of patients with celiac disease will have osteopenia or osteoporosis as their presenting symptom.

Antibodies against tissue transglutaminase (tTG), which contribute to the gluten intolerance that characterizes celiac disease, appear to have a deleterious effect on bone, said Dr. Green. “Tissue transglutaminase is a ubiquitous enzyme that is also present in bone.” Antibodies to tTG are also present in bone and emerging evidence suggests they impair active mineralization.

Studies have shown that a gluten-free diet, which decreases anti-tTG levels, directly correlates with increased bone mass in patients with celiac disease and low bone mineral density, he said at an international symposium sponsored by the National Osteoporosis Foundation.

Proinflammatory circulating cytokines also are increased in celiac disease, and may contribute to decreases in bone density, he said. Comorbidities may also play a role. Secondary hyperparathyroidism is common in patients with celiac disease and may prevent patients from attaining their maximum bone density during childhood. Premature menopause in women and reduced gonadal function in men also can contribute to poor bone health, Dr. Green said.

Bone loss associated with celiac disease results in a significantly increased risk of both peripheral and central fracture, he said. Strict adherence to a gluten-free diet seems to be the best way to boost bone health in these patients, he added.

The Food and Drug Administration has approved dosing the osteoporosis drug zoledronic acid (Reclast) once every 2 years for the prevention of bone loss in postmenopausal women, making it the first bisphosphonate in its class to get the nod for a 2-year indication.

The approval is based on results of the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) prevention trial in which a single infusion of the zoledronic acid agent significantly increased bone mass relative to placebo at 2 years in postmenopausal women with osteopenia, according to a statement by the drug manufacturer, Novartis Pharmaceuticals Corp.

The 2-year double-blind, placebo-controlled study was presented in April at an international symposium sponsored by the National Osteoporosis Foundation in Washington by Dr. Chris Recknor.

HORIZON comprised 581 women aged 45 years and older with low bone mineral density (T scores of −1 to −2.5) who were randomized to receive one of three regimens: 5 mg zoledronic acid at study onset and at 1 year; 5 mg zoledronic acid at study onset and placebo at 1 year; or placebo at study onset and at 1 year. The subjects' mean age was 60 years. Most (93%) were white.

The study's main outcomes were 24-month changes in bone mineral density (BMD) at the lumbar spine, trochanter, femoral neck, distal radius, and total hip. The secondary end points were changes in markers of bone turnover.

Both of the Reclast treatment groups showed significantly increased BMD, compared with placebo. At 24 months (1 year after the second infusion), both active groups showed similar BMD increases at all sites that were significantly different from BMD changes with placebo (see chart), reported Dr. Recknor, who is an internist specializing in osteoporosis in Gainesville, Ga.

Specifically, treatment with a single zoledronic acid infusion increased spine BMD by 6.3% among women in the early menopause group (within 5 years of menopause) and by 5.4% among those in the late menopause group, according Novartis's June 1 announcement of the new indication.

Both zoledronic acid regimens showed significant reductions in bone turnover markers compared with placebo. Markers in the double-infusion group were significantly lower than those in the single-infusion group.

Adverse events were most commonly observed in the first 3 days after the first infusion, when they were significantly more common in both active groups (60% vs. 25%). The most frequently reported were pain, fever, chills, myalgia, nausea, and headache. Adverse events were significantly lower after the second infusion, occurring in 18% of the double-infusion group, 11% of the single-infusion group, and 12% of the placebo group, Dr. Recknor reported.

Already approved as a once-yearly infusion for the treatment of women with postmenopausal osteoporosis and men with osteoporosis, as well as for the treatment of Paget disease of bone and the prevention and treatment of glucocorticoid-induced osteoporosis, Reclast is now the first and only approved single-dose, biyearly infusion for the prevention postmenopausal osteoporosis, according to the Novartis statement.

At the osteoporosis symposium in April, Dr. Recknor said in an interview using the drug prophylactically “allows clinicians a little more lead time in treating these patients, many of whom are at increased risk of a low-stress fracture.” Furthermore, the HORIZON results raise a tantalizing possibility. “You may be able to give this drug a couple of times to perimenopausal women and prevent the entire problem of bone loss.”

The less-frequent dosing is being touted as an advance by Dr. Mone Zaidi, director of the Mount Sinai Bone Program at Mount Sinai School of Medicine, New York, because of the convenience of biyearly treatment compared with daily, weekly, and monthly regimens.

“There were not many differences that were either statistically significant or clinically meaningful between the two treated groups in the [HORIZON] study. Once every 2 years is an excellent way to go forward, which would improve compliance in the early postmenopausal woman who rapidly loses bone,” he said in an interview after the Novartis's announcement of the new indication.

Another study presented at the osteoporosis symposium shed light on zoledronic acid's role in preventing bone loss in women who've already had a hip fracture.

A subanalysis of a second HORIZON study showed that zoledronic acid indeed benefits patients with a recent fracture—and particularly the very elderly and those with the poorest bone quality.

The HORIZON Recurrent Fracture Trial included 2,127 patients with a recent hip fracture who were randomized to an annual infusion of 5 mg zoledronic acid or placebo and followed for up to 5 years. HORIZON-RFT concluded that the drug reduced the rate of recurrent fracture by 35% (N. Engl. J. Med. 2007;357:1799–809).

The subanalysis examined response rates within specific patient groups, said Denise Orwig, Ph.D., who presented the trial data during a poster session at the meeting. The analysis showed that patients at the highest risk for a recurrent fracture—those who were at least 85 years old or who had a T score of less than −2.5 at the total hip—benefited the most from the treatment.

Although Dr. Orwig said it's unclear why the oldest, least-dense bones benefited the most, the finding does carry a strongly positive clinical implication.

“These patients who are at the highest risk are also the ones who are the least likely to be treated,” said Dr. Orwig of the department of epidemiology and preventive medicine at the University of Maryland Medical Center, Baltimore.

“The thought may be that they have already had multiple fractures and there is probably not a lot more that can be done. But this study showed us that these individuals can benefit and that we can have a big short-term impact on their bone density and possibly even reduce the risk of more fractures due to continued bone loss,” said Dr. Orwig.

Novartis Pharmaceuticals Corp. sponsored the HORIZON studies. Dr. Orwig has received research funding from the company. Dr. Recknor and Dr. Zaidi are on the Novartis speakers bureau.

Diana Mahoney contributed to this report.

ELSEVIER GLOBAL MEDICAL NEWS

The Food and Drug Administration has approved dosing the osteoporosis drug zoledronic acid (Reclast) once every 2 years for the prevention of bone loss in postmenopausal women, making it the first bisphosphonate in its class to get the nod for a 2-year indication.

The approval is based on results of the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) prevention trial in which a single infusion of the zoledronic acid agent significantly increased bone mass relative to placebo at 2 years in postmenopausal women with osteopenia, according to a statement by the drug manufacturer, Novartis Pharmaceuticals Corp.

The 2-year double-blind, placebo-controlled study was presented in April at an international symposium sponsored by the National Osteoporosis Foundation in Washington by Dr. Chris Recknor.

HORIZON comprised 581 women aged 45 years and older with low bone mineral density (T scores of −1 to −2.5) who were randomized to receive one of three regimens: 5 mg zoledronic acid at study onset and at 1 year; 5 mg zoledronic acid at study onset and placebo at 1 year; or placebo at study onset and at 1 year. The subjects' mean age was 60 years. Most (93%) were white.

The study's main outcomes were 24-month changes in bone mineral density (BMD) at the lumbar spine, trochanter, femoral neck, distal radius, and total hip. The secondary end points were changes in markers of bone turnover.

Both of the Reclast treatment groups showed significantly increased BMD, compared with placebo. At 24 months (1 year after the second infusion), both active groups showed similar BMD increases at all sites that were significantly different from BMD changes with placebo (see chart), reported Dr. Recknor, who is an internist specializing in osteoporosis in Gainesville, Ga.

Specifically, treatment with a single zoledronic acid infusion increased spine BMD by 6.3% among women in the early menopause group (within 5 years of menopause) and by 5.4% among those in the late menopause group, according Novartis's June 1 announcement of the new indication.

Both zoledronic acid regimens showed significant reductions in bone turnover markers compared with placebo. Markers in the double-infusion group were significantly lower than those in the single-infusion group.

Adverse events were most commonly observed in the first 3 days after the first infusion, when they were significantly more common in both active groups (60% vs. 25%). The most frequently reported were pain, fever, chills, myalgia, nausea, and headache. Adverse events were significantly lower after the second infusion, occurring in 18% of the double-infusion group, 11% of the single-infusion group, and 12% of the placebo group, Dr. Recknor reported.

Already approved as a once-yearly infusion for the treatment of women with postmenopausal osteoporosis and men with osteoporosis, as well as for the treatment of Paget disease of bone and the prevention and treatment of glucocorticoid-induced osteoporosis, Reclast is now the first and only approved single-dose, biyearly infusion for the prevention postmenopausal osteoporosis, according to the Novartis statement.

At the osteoporosis symposium in April, Dr. Recknor said in an interview using the drug prophylactically “allows clinicians a little more lead time in treating these patients, many of whom are at increased risk of a low-stress fracture.” Furthermore, the HORIZON results raise a tantalizing possibility. “You may be able to give this drug a couple of times to perimenopausal women and prevent the entire problem of bone loss.”

The less-frequent dosing is being touted as an advance by Dr. Mone Zaidi, director of the Mount Sinai Bone Program at Mount Sinai School of Medicine, New York, because of the convenience of biyearly treatment compared with daily, weekly, and monthly regimens.

“There were not many differences that were either statistically significant or clinically meaningful between the two treated groups in the [HORIZON] study. Once every 2 years is an excellent way to go forward, which would improve compliance in the early postmenopausal woman who rapidly loses bone,” he said in an interview after the Novartis's announcement of the new indication.

Another study presented at the osteoporosis symposium shed light on zoledronic acid's role in preventing bone loss in women who've already had a hip fracture.

A subanalysis of a second HORIZON study showed that zoledronic acid indeed benefits patients with a recent fracture—and particularly the very elderly and those with the poorest bone quality.

The HORIZON Recurrent Fracture Trial included 2,127 patients with a recent hip fracture who were randomized to an annual infusion of 5 mg zoledronic acid or placebo and followed for up to 5 years. HORIZON-RFT concluded that the drug reduced the rate of recurrent fracture by 35% (N. Engl. J. Med. 2007;357:1799–809).

The subanalysis examined response rates within specific patient groups, said Denise Orwig, Ph.D., who presented the trial data during a poster session at the meeting. The analysis showed that patients at the highest risk for a recurrent fracture—those who were at least 85 years old or who had a T score of less than −2.5 at the total hip—benefited the most from the treatment.

Although Dr. Orwig said it's unclear why the oldest, least-dense bones benefited the most, the finding does carry a strongly positive clinical implication.

“These patients who are at the highest risk are also the ones who are the least likely to be treated,” said Dr. Orwig of the department of epidemiology and preventive medicine at the University of Maryland Medical Center, Baltimore.

“The thought may be that they have already had multiple fractures and there is probably not a lot more that can be done. But this study showed us that these individuals can benefit and that we can have a big short-term impact on their bone density and possibly even reduce the risk of more fractures due to continued bone loss,” said Dr. Orwig.

Novartis Pharmaceuticals Corp. sponsored the HORIZON studies. Dr. Orwig has received research funding from the company. Dr. Recknor and Dr. Zaidi are on the Novartis speakers bureau.

Diana Mahoney contributed to this report.

ELSEVIER GLOBAL MEDICAL NEWS

The Food and Drug Administration has approved dosing the osteoporosis drug zoledronic acid (Reclast) once every 2 years for the prevention of bone loss in postmenopausal women, making it the first bisphosphonate in its class to get the nod for a 2-year indication.

The approval is based on results of the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) prevention trial in which a single infusion of the zoledronic acid agent significantly increased bone mass relative to placebo at 2 years in postmenopausal women with osteopenia, according to a statement by the drug manufacturer, Novartis Pharmaceuticals Corp.

The 2-year double-blind, placebo-controlled study was presented in April at an international symposium sponsored by the National Osteoporosis Foundation in Washington by Dr. Chris Recknor.

HORIZON comprised 581 women aged 45 years and older with low bone mineral density (T scores of −1 to −2.5) who were randomized to receive one of three regimens: 5 mg zoledronic acid at study onset and at 1 year; 5 mg zoledronic acid at study onset and placebo at 1 year; or placebo at study onset and at 1 year. The subjects' mean age was 60 years. Most (93%) were white.

The study's main outcomes were 24-month changes in bone mineral density (BMD) at the lumbar spine, trochanter, femoral neck, distal radius, and total hip. The secondary end points were changes in markers of bone turnover.

Both of the Reclast treatment groups showed significantly increased BMD, compared with placebo. At 24 months (1 year after the second infusion), both active groups showed similar BMD increases at all sites that were significantly different from BMD changes with placebo (see chart), reported Dr. Recknor, who is an internist specializing in osteoporosis in Gainesville, Ga.

Specifically, treatment with a single zoledronic acid infusion increased spine BMD by 6.3% among women in the early menopause group (within 5 years of menopause) and by 5.4% among those in the late menopause group, according Novartis's June 1 announcement of the new indication.

Both zoledronic acid regimens showed significant reductions in bone turnover markers compared with placebo. Markers in the double-infusion group were significantly lower than those in the single-infusion group.

Adverse events were most commonly observed in the first 3 days after the first infusion, when they were significantly more common in both active groups (60% vs. 25%). The most frequently reported were pain, fever, chills, myalgia, nausea, and headache. Adverse events were significantly lower after the second infusion, occurring in 18% of the double-infusion group, 11% of the single-infusion group, and 12% of the placebo group, Dr. Recknor reported.

Already approved as a once-yearly infusion for the treatment of women with postmenopausal osteoporosis and men with osteoporosis, as well as for the treatment of Paget disease of bone and the prevention and treatment of glucocorticoid-induced osteoporosis, Reclast is now the first and only approved single-dose, biyearly infusion for the prevention postmenopausal osteoporosis, according to the Novartis statement.

At the osteoporosis symposium in April, Dr. Recknor said in an interview using the drug prophylactically “allows clinicians a little more lead time in treating these patients, many of whom are at increased risk of a low-stress fracture.” Furthermore, the HORIZON results raise a tantalizing possibility. “You may be able to give this drug a couple of times to perimenopausal women and prevent the entire problem of bone loss.”

The less-frequent dosing is being touted as an advance by Dr. Mone Zaidi, director of the Mount Sinai Bone Program at Mount Sinai School of Medicine, New York, because of the convenience of biyearly treatment compared with daily, weekly, and monthly regimens.

“There were not many differences that were either statistically significant or clinically meaningful between the two treated groups in the [HORIZON] study. Once every 2 years is an excellent way to go forward, which would improve compliance in the early postmenopausal woman who rapidly loses bone,” he said in an interview after the Novartis's announcement of the new indication.

Another study presented at the osteoporosis symposium shed light on zoledronic acid's role in preventing bone loss in women who've already had a hip fracture.

A subanalysis of a second HORIZON study showed that zoledronic acid indeed benefits patients with a recent fracture—and particularly the very elderly and those with the poorest bone quality.

The HORIZON Recurrent Fracture Trial included 2,127 patients with a recent hip fracture who were randomized to an annual infusion of 5 mg zoledronic acid or placebo and followed for up to 5 years. HORIZON-RFT concluded that the drug reduced the rate of recurrent fracture by 35% (N. Engl. J. Med. 2007;357:1799–809).

The subanalysis examined response rates within specific patient groups, said Denise Orwig, Ph.D., who presented the trial data during a poster session at the meeting. The analysis showed that patients at the highest risk for a recurrent fracture—those who were at least 85 years old or who had a T score of less than −2.5 at the total hip—benefited the most from the treatment.

Although Dr. Orwig said it's unclear why the oldest, least-dense bones benefited the most, the finding does carry a strongly positive clinical implication.

“These patients who are at the highest risk are also the ones who are the least likely to be treated,” said Dr. Orwig of the department of epidemiology and preventive medicine at the University of Maryland Medical Center, Baltimore.

“The thought may be that they have already had multiple fractures and there is probably not a lot more that can be done. But this study showed us that these individuals can benefit and that we can have a big short-term impact on their bone density and possibly even reduce the risk of more fractures due to continued bone loss,” said Dr. Orwig.

Novartis Pharmaceuticals Corp. sponsored the HORIZON studies. Dr. Orwig has received research funding from the company. Dr. Recknor and Dr. Zaidi are on the Novartis speakers bureau.

Diana Mahoney contributed to this report.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — A rapid-delivery transdermal teriparatide patch is more effective at increasing total hip bone mineral density than is a daily subcutaneous teriparatide injection, based on the results of a phase II study.

Furthermore, the patch is just as effective as the injection at building lumbar spine bone mineral density (BMD), Dr. Felicia Cosman said at an international symposium sponsored by the National Osteoporosis Foundation.

The phase II trial, sponsored by Zosano Pharma Inc., found that the 40-mcg patch increased total hip BMD by 1.3% in 24 weeks, whereas the daily injected dose failed to increase total hip BMD at all.

The patches are loaded into a cylindrical delivery system. The patient places the patch by pressing the open end of the device against the skin. Once it has adhered to the skin, the quarter-sized patch rapidly delivers the drug, which reaches its peak plasma concentration within just a few minutes. Delivered this way, 40% of the drug is bioavailable.

The placebo-controlled, multidose trial included 165 postmenopausal women (mean age, 64 years). They were randomized to the daily injection (20 mcg), to a placebo patch, or to an active patch of 20, 30, or 40 mcg teriparatide.

After 24 weeks of treatment, all the active comparators resulted in significant BMD gains at the lumbar spine, relative to placebo. Patients using the 40-mcg patch gained a mean of 5% at the lumbar spine. Patients using the 30-mcg patch and taking the daily injections gained a mean of 3.5%, whereas those using the 20-mcg patch gained a mean of 2%. Patients using a placebo patch lost a mean of 0.5% BMD from baseline, reported Dr. Cosman, medical director of the clinical research center at Helen Hayes Hospital in West Haverstraw, N.Y.

Patients using the 40-mcg patch also showed a significant 1.3% increase in total hip BMD. Those using the 30-mcg patch gained 0.5% at the total hip. Patients using the 20-mcg patch, and those using the injectable drug, showed no significant gain in total hip BMD. The placebo patients experienced a BMD decrease of 0.6%.

Adverse events were localized and transient, and included mild to moderate erythema at the patch site.

Dr. Cosman is a paid consultant to Zosano.

WASHINGTON — A rapid-delivery transdermal teriparatide patch is more effective at increasing total hip bone mineral density than is a daily subcutaneous teriparatide injection, based on the results of a phase II study.

Furthermore, the patch is just as effective as the injection at building lumbar spine bone mineral density (BMD), Dr. Felicia Cosman said at an international symposium sponsored by the National Osteoporosis Foundation.

The phase II trial, sponsored by Zosano Pharma Inc., found that the 40-mcg patch increased total hip BMD by 1.3% in 24 weeks, whereas the daily injected dose failed to increase total hip BMD at all.

The patches are loaded into a cylindrical delivery system. The patient places the patch by pressing the open end of the device against the skin. Once it has adhered to the skin, the quarter-sized patch rapidly delivers the drug, which reaches its peak plasma concentration within just a few minutes. Delivered this way, 40% of the drug is bioavailable.

The placebo-controlled, multidose trial included 165 postmenopausal women (mean age, 64 years). They were randomized to the daily injection (20 mcg), to a placebo patch, or to an active patch of 20, 30, or 40 mcg teriparatide.

After 24 weeks of treatment, all the active comparators resulted in significant BMD gains at the lumbar spine, relative to placebo. Patients using the 40-mcg patch gained a mean of 5% at the lumbar spine. Patients using the 30-mcg patch and taking the daily injections gained a mean of 3.5%, whereas those using the 20-mcg patch gained a mean of 2%. Patients using a placebo patch lost a mean of 0.5% BMD from baseline, reported Dr. Cosman, medical director of the clinical research center at Helen Hayes Hospital in West Haverstraw, N.Y.

Patients using the 40-mcg patch also showed a significant 1.3% increase in total hip BMD. Those using the 30-mcg patch gained 0.5% at the total hip. Patients using the 20-mcg patch, and those using the injectable drug, showed no significant gain in total hip BMD. The placebo patients experienced a BMD decrease of 0.6%.

Adverse events were localized and transient, and included mild to moderate erythema at the patch site.

Dr. Cosman is a paid consultant to Zosano.

WASHINGTON — A rapid-delivery transdermal teriparatide patch is more effective at increasing total hip bone mineral density than is a daily subcutaneous teriparatide injection, based on the results of a phase II study.

Furthermore, the patch is just as effective as the injection at building lumbar spine bone mineral density (BMD), Dr. Felicia Cosman said at an international symposium sponsored by the National Osteoporosis Foundation.

The phase II trial, sponsored by Zosano Pharma Inc., found that the 40-mcg patch increased total hip BMD by 1.3% in 24 weeks, whereas the daily injected dose failed to increase total hip BMD at all.

The patches are loaded into a cylindrical delivery system. The patient places the patch by pressing the open end of the device against the skin. Once it has adhered to the skin, the quarter-sized patch rapidly delivers the drug, which reaches its peak plasma concentration within just a few minutes. Delivered this way, 40% of the drug is bioavailable.

The placebo-controlled, multidose trial included 165 postmenopausal women (mean age, 64 years). They were randomized to the daily injection (20 mcg), to a placebo patch, or to an active patch of 20, 30, or 40 mcg teriparatide.

After 24 weeks of treatment, all the active comparators resulted in significant BMD gains at the lumbar spine, relative to placebo. Patients using the 40-mcg patch gained a mean of 5% at the lumbar spine. Patients using the 30-mcg patch and taking the daily injections gained a mean of 3.5%, whereas those using the 20-mcg patch gained a mean of 2%. Patients using a placebo patch lost a mean of 0.5% BMD from baseline, reported Dr. Cosman, medical director of the clinical research center at Helen Hayes Hospital in West Haverstraw, N.Y.

Patients using the 40-mcg patch also showed a significant 1.3% increase in total hip BMD. Those using the 30-mcg patch gained 0.5% at the total hip. Patients using the 20-mcg patch, and those using the injectable drug, showed no significant gain in total hip BMD. The placebo patients experienced a BMD decrease of 0.6%.

Adverse events were localized and transient, and included mild to moderate erythema at the patch site.

Dr. Cosman is a paid consultant to Zosano.

WASHINGTON — Three-fourths of patients hospitalized for a hip fracture do not receive an osteoporosis diagnosis before discharge, and the majority are not taking a bisphosphonate at discharge or 6 months after the injury, a small study has shown.

The findings are dismaying, said Dr. Pardeep Bansal, because 24% of patients older than 50 years who sustain an osteoporotic hip fracture die within a year.

“The 1-year mortality rate is higher than it is in some cancers, and even higher than it is after a heart attack,” said Dr. Bansal, chief resident at the Scranton-Temple Residency Program, Scranton, Pa. “But if you have a heart attack, no physician is going to let you leave the hospital without aspirin, a beta-blocker, and a statin. If you have a hip fracture, you're likely to be discharged without even the underlying diagnosis, much less the appropriate treatment.”

The two-part study began with a chart review of 191 patients who were admitted to a hospital with a hip fracture. Most (80%) were white females older than 70 years. At the time of discharge, 25% had been assigned a diagnosis of osteoporosis. Only 30% were taking calcium; patients who had been diagnosed with osteoporosis were significantly more likely to be taking both calcium and vitamin D than were patients without a diagnosis. Furthermore, only 15% were taking a bisphosphonate at discharge, Dr Bansal said in a poster session at an international symposium sponsored by the National Osteoporosis Foundation. Clinical contraindications did not appear to play a significant role in the lack of treatment: Only 2% of patients had a glomerular filtration rate of less than 30 mL/min per 1.73 m

Dr. Bansal then performed a telephone survey of the 105 patients who could be contacted; 33% of the original cohort had died since their fractures, and another 12% could not be found. All of the patients interviewed reported having seen their primary care physicians within 6 months of the fracture. Yet only 50% had received a diagnosis of osteoporosis, 50% were taking calcium, 40% were taking vitamin D, and only 28% were taking a bisphosphonate.

“Another painful finding was that 14% of the group had experienced a subsequent fragility fracture,” Dr. Bansal said.

To help improve the rate of osteoporosis diagnosis at his hospital, Dr. Bansal and his colleagues have instituted a standardized protocol. “It's very simple,” he said. “Any patient who comes in with a fracture suggestive of osteoporosis is started on calcium, vitamin D, and a bisphosphonate before discharge. If they have a contraindication to a bisphosphonate, such as an allergy or a low GFR, then we call the family physician and discuss an alternative treatment.”

Although a dual-energy x-ray absorptiometry scan is a helpful diagnostic tool, Dr. Bansal said treatment should not be delayed until a scan can be obtained. “You have to wait for the fracture to heal and then schedule that as an outpatient, and during that time the patient can be lost to follow-up.”

He had no conflicts of interest.

'If you have a hip fracture, you're likely to be discharged without even the underlying diagnosis.' DR. BANSAL

WASHINGTON — Three-fourths of patients hospitalized for a hip fracture do not receive an osteoporosis diagnosis before discharge, and the majority are not taking a bisphosphonate at discharge or 6 months after the injury, a small study has shown.

The findings are dismaying, said Dr. Pardeep Bansal, because 24% of patients older than 50 years who sustain an osteoporotic hip fracture die within a year.

“The 1-year mortality rate is higher than it is in some cancers, and even higher than it is after a heart attack,” said Dr. Bansal, chief resident at the Scranton-Temple Residency Program, Scranton, Pa. “But if you have a heart attack, no physician is going to let you leave the hospital without aspirin, a beta-blocker, and a statin. If you have a hip fracture, you're likely to be discharged without even the underlying diagnosis, much less the appropriate treatment.”

The two-part study began with a chart review of 191 patients who were admitted to a hospital with a hip fracture. Most (80%) were white females older than 70 years. At the time of discharge, 25% had been assigned a diagnosis of osteoporosis. Only 30% were taking calcium; patients who had been diagnosed with osteoporosis were significantly more likely to be taking both calcium and vitamin D than were patients without a diagnosis. Furthermore, only 15% were taking a bisphosphonate at discharge, Dr Bansal said in a poster session at an international symposium sponsored by the National Osteoporosis Foundation. Clinical contraindications did not appear to play a significant role in the lack of treatment: Only 2% of patients had a glomerular filtration rate of less than 30 mL/min per 1.73 m

Dr. Bansal then performed a telephone survey of the 105 patients who could be contacted; 33% of the original cohort had died since their fractures, and another 12% could not be found. All of the patients interviewed reported having seen their primary care physicians within 6 months of the fracture. Yet only 50% had received a diagnosis of osteoporosis, 50% were taking calcium, 40% were taking vitamin D, and only 28% were taking a bisphosphonate.

“Another painful finding was that 14% of the group had experienced a subsequent fragility fracture,” Dr. Bansal said.

To help improve the rate of osteoporosis diagnosis at his hospital, Dr. Bansal and his colleagues have instituted a standardized protocol. “It's very simple,” he said. “Any patient who comes in with a fracture suggestive of osteoporosis is started on calcium, vitamin D, and a bisphosphonate before discharge. If they have a contraindication to a bisphosphonate, such as an allergy or a low GFR, then we call the family physician and discuss an alternative treatment.”

Although a dual-energy x-ray absorptiometry scan is a helpful diagnostic tool, Dr. Bansal said treatment should not be delayed until a scan can be obtained. “You have to wait for the fracture to heal and then schedule that as an outpatient, and during that time the patient can be lost to follow-up.”

He had no conflicts of interest.

'If you have a hip fracture, you're likely to be discharged without even the underlying diagnosis.' DR. BANSAL

WASHINGTON — Three-fourths of patients hospitalized for a hip fracture do not receive an osteoporosis diagnosis before discharge, and the majority are not taking a bisphosphonate at discharge or 6 months after the injury, a small study has shown.

The findings are dismaying, said Dr. Pardeep Bansal, because 24% of patients older than 50 years who sustain an osteoporotic hip fracture die within a year.

“The 1-year mortality rate is higher than it is in some cancers, and even higher than it is after a heart attack,” said Dr. Bansal, chief resident at the Scranton-Temple Residency Program, Scranton, Pa. “But if you have a heart attack, no physician is going to let you leave the hospital without aspirin, a beta-blocker, and a statin. If you have a hip fracture, you're likely to be discharged without even the underlying diagnosis, much less the appropriate treatment.”

The two-part study began with a chart review of 191 patients who were admitted to a hospital with a hip fracture. Most (80%) were white females older than 70 years. At the time of discharge, 25% had been assigned a diagnosis of osteoporosis. Only 30% were taking calcium; patients who had been diagnosed with osteoporosis were significantly more likely to be taking both calcium and vitamin D than were patients without a diagnosis. Furthermore, only 15% were taking a bisphosphonate at discharge, Dr Bansal said in a poster session at an international symposium sponsored by the National Osteoporosis Foundation. Clinical contraindications did not appear to play a significant role in the lack of treatment: Only 2% of patients had a glomerular filtration rate of less than 30 mL/min per 1.73 m

Dr. Bansal then performed a telephone survey of the 105 patients who could be contacted; 33% of the original cohort had died since their fractures, and another 12% could not be found. All of the patients interviewed reported having seen their primary care physicians within 6 months of the fracture. Yet only 50% had received a diagnosis of osteoporosis, 50% were taking calcium, 40% were taking vitamin D, and only 28% were taking a bisphosphonate.

“Another painful finding was that 14% of the group had experienced a subsequent fragility fracture,” Dr. Bansal said.

To help improve the rate of osteoporosis diagnosis at his hospital, Dr. Bansal and his colleagues have instituted a standardized protocol. “It's very simple,” he said. “Any patient who comes in with a fracture suggestive of osteoporosis is started on calcium, vitamin D, and a bisphosphonate before discharge. If they have a contraindication to a bisphosphonate, such as an allergy or a low GFR, then we call the family physician and discuss an alternative treatment.”

Although a dual-energy x-ray absorptiometry scan is a helpful diagnostic tool, Dr. Bansal said treatment should not be delayed until a scan can be obtained. “You have to wait for the fracture to heal and then schedule that as an outpatient, and during that time the patient can be lost to follow-up.”

He had no conflicts of interest.

'If you have a hip fracture, you're likely to be discharged without even the underlying diagnosis.' DR. BANSAL

Children exposed to valproate in utero have significantly lower IQs at age 3 than do children exposed to other antiepileptics during gestation, according to findings from the interim analysis of a large international study.

The drug previously had been associated with a higher rate of birth defects in children exposed prenatally. The combination of findings strengthens a recommendation to avoid valproate as a first-line antiepileptic in women who may bear children, Dr. Kimford J. Meador said in an interview.

“Valproate poses a special risk for both congenital malformations and for cognitive impairment,” said Dr. Meador, principal investigator in the Neurodevelopmental Effects of Antiepileptics Drugs (NEAD) study. “Since there are other therapeutic options, it would seem prudent to try those first. At a minimum, it is critical that physicians inform women of this risk when prescribing valproate so that they may make an informed choice.”

NEAD is an ongoing study of 309 children, including three sets of twins, born in either the United States or the United Kingdom from 1999 to 2004, whose mothers were taking a single antiepileptic drug (AED): carbamazepine, lamotrigine, phenytoin, or valproate. The children are being followed to age 6. Dr. Meador, professor of neurology at Emory University, Atlanta, and his associates reported the results of a planned 3-year interim analysis in the New England Journal of Medicine (2009;360:1597–605).

All of the 303 women in the study were taking the drugs for a seizure disorder. Their mean age at delivery was 30 years. Most women were well controlled on their AED, with about 80% having no seizures during their pregnancy.

Most of the children in the study (258) underwent cognitive assessment at either 2 or 3 years of age, or at both ages. Of these, 73 (28%) had been exposed to carbamazepine, 84 (32%) to lamotrigine, 48 (19%) to phenytoin, and 53 (21%) to valproate. Cognitive testing consisted of the Bayley Scales of Infant Development and the Differential Ability Scales.

IQ scores were adjusted for factors that could significantly affect cognitive development, some of which were maternal IQ; age at delivery; education; type of epilepsy; seizure frequency; socioeconomic status; the use of folate, alcohol, tobacco, and drugs; obstetrical complications; gestational age; birth weight; and breastfeeding.

Children exposed to valproate had the lowest mean IQs of any of the exposure groups (92)—significantly lower than those of any other treatment group. The mean IQ in those exposed to carbamazepine was 98; to lamotrigine, 101; and to phenytoin, 99. These did not vary significantly from one another.

The association of valproate with reduced IQ held after adjustment for the confounders in both a linear regression and subgroup analysis, the investigators said. They also examined whether the IQ scores were related to AED dosage. In this analysis, only valproate maintained a significant dose-response relationship.

Additionally, higher maternal IQs were associated with higher child IQs in all of the treatment groups except valproate.

The results are consistent with several European studies that have found poor cognitive outcomes in children exposed to the drug prenatally, the investigators said. The drug also has been found to increase the rate of congenital malformations, compared with other AEDs. A recent meta-analysis found the rate to be as many as 11% of births.

Unfortunately, Dr. Meador and his colleagues wrote, women whose seizures are well controlled on valproate may be placed on the horns of a dilemma when trying to balance gestational safety with seizure control.

“For some patients, valproate is the only medication that adequately controls seizures. Such women should be informed of the potential risks associated with the use of this medication in pregnancy. If a woman taking valproate is already pregnant, it's critical that she not stop valproate without consultation with her physician, since stopping an antiepileptic drug could lead to seizures and serious consequences for both the woman and her fetus.”

“One other important point is that less than half of the prescriptions for valproate are for seizures or epilepsy. The majority are for pain or psychiatric indications. I believe that the women taking valproate for other indications are at the same risk as our women with epilepsy,” he said in the interview.

The study was supported by grants from the United Kingdom Epilepsy Research Foundation and the National Institute of Neurological Disorders and Stroke. Dr. Meador reported receiving research support from GlaxoSmithKline, Myriad Pharmaceuticals, Marinus Pharmaceuticals, UCB Pharmaceuticals, and several other companies and foundations.

Children exposed to valproate in utero have significantly lower IQs at age 3 than do children exposed to other antiepileptics during gestation, according to findings from the interim analysis of a large international study.

The drug previously had been associated with a higher rate of birth defects in children exposed prenatally. The combination of findings strengthens a recommendation to avoid valproate as a first-line antiepileptic in women who may bear children, Dr. Kimford J. Meador said in an interview.

“Valproate poses a special risk for both congenital malformations and for cognitive impairment,” said Dr. Meador, principal investigator in the Neurodevelopmental Effects of Antiepileptics Drugs (NEAD) study. “Since there are other therapeutic options, it would seem prudent to try those first. At a minimum, it is critical that physicians inform women of this risk when prescribing valproate so that they may make an informed choice.”

NEAD is an ongoing study of 309 children, including three sets of twins, born in either the United States or the United Kingdom from 1999 to 2004, whose mothers were taking a single antiepileptic drug (AED): carbamazepine, lamotrigine, phenytoin, or valproate. The children are being followed to age 6. Dr. Meador, professor of neurology at Emory University, Atlanta, and his associates reported the results of a planned 3-year interim analysis in the New England Journal of Medicine (2009;360:1597–605).

All of the 303 women in the study were taking the drugs for a seizure disorder. Their mean age at delivery was 30 years. Most women were well controlled on their AED, with about 80% having no seizures during their pregnancy.

Most of the children in the study (258) underwent cognitive assessment at either 2 or 3 years of age, or at both ages. Of these, 73 (28%) had been exposed to carbamazepine, 84 (32%) to lamotrigine, 48 (19%) to phenytoin, and 53 (21%) to valproate. Cognitive testing consisted of the Bayley Scales of Infant Development and the Differential Ability Scales.

IQ scores were adjusted for factors that could significantly affect cognitive development, some of which were maternal IQ; age at delivery; education; type of epilepsy; seizure frequency; socioeconomic status; the use of folate, alcohol, tobacco, and drugs; obstetrical complications; gestational age; birth weight; and breastfeeding.

Children exposed to valproate had the lowest mean IQs of any of the exposure groups (92)—significantly lower than those of any other treatment group. The mean IQ in those exposed to carbamazepine was 98; to lamotrigine, 101; and to phenytoin, 99. These did not vary significantly from one another.

The association of valproate with reduced IQ held after adjustment for the confounders in both a linear regression and subgroup analysis, the investigators said. They also examined whether the IQ scores were related to AED dosage. In this analysis, only valproate maintained a significant dose-response relationship.

Additionally, higher maternal IQs were associated with higher child IQs in all of the treatment groups except valproate.

The results are consistent with several European studies that have found poor cognitive outcomes in children exposed to the drug prenatally, the investigators said. The drug also has been found to increase the rate of congenital malformations, compared with other AEDs. A recent meta-analysis found the rate to be as many as 11% of births.

Unfortunately, Dr. Meador and his colleagues wrote, women whose seizures are well controlled on valproate may be placed on the horns of a dilemma when trying to balance gestational safety with seizure control.

“For some patients, valproate is the only medication that adequately controls seizures. Such women should be informed of the potential risks associated with the use of this medication in pregnancy. If a woman taking valproate is already pregnant, it's critical that she not stop valproate without consultation with her physician, since stopping an antiepileptic drug could lead to seizures and serious consequences for both the woman and her fetus.”

“One other important point is that less than half of the prescriptions for valproate are for seizures or epilepsy. The majority are for pain or psychiatric indications. I believe that the women taking valproate for other indications are at the same risk as our women with epilepsy,” he said in the interview.

The study was supported by grants from the United Kingdom Epilepsy Research Foundation and the National Institute of Neurological Disorders and Stroke. Dr. Meador reported receiving research support from GlaxoSmithKline, Myriad Pharmaceuticals, Marinus Pharmaceuticals, UCB Pharmaceuticals, and several other companies and foundations.

Children exposed to valproate in utero have significantly lower IQs at age 3 than do children exposed to other antiepileptics during gestation, according to findings from the interim analysis of a large international study.

The drug previously had been associated with a higher rate of birth defects in children exposed prenatally. The combination of findings strengthens a recommendation to avoid valproate as a first-line antiepileptic in women who may bear children, Dr. Kimford J. Meador said in an interview.

“Valproate poses a special risk for both congenital malformations and for cognitive impairment,” said Dr. Meador, principal investigator in the Neurodevelopmental Effects of Antiepileptics Drugs (NEAD) study. “Since there are other therapeutic options, it would seem prudent to try those first. At a minimum, it is critical that physicians inform women of this risk when prescribing valproate so that they may make an informed choice.”

NEAD is an ongoing study of 309 children, including three sets of twins, born in either the United States or the United Kingdom from 1999 to 2004, whose mothers were taking a single antiepileptic drug (AED): carbamazepine, lamotrigine, phenytoin, or valproate. The children are being followed to age 6. Dr. Meador, professor of neurology at Emory University, Atlanta, and his associates reported the results of a planned 3-year interim analysis in the New England Journal of Medicine (2009;360:1597–605).

All of the 303 women in the study were taking the drugs for a seizure disorder. Their mean age at delivery was 30 years. Most women were well controlled on their AED, with about 80% having no seizures during their pregnancy.

Most of the children in the study (258) underwent cognitive assessment at either 2 or 3 years of age, or at both ages. Of these, 73 (28%) had been exposed to carbamazepine, 84 (32%) to lamotrigine, 48 (19%) to phenytoin, and 53 (21%) to valproate. Cognitive testing consisted of the Bayley Scales of Infant Development and the Differential Ability Scales.

IQ scores were adjusted for factors that could significantly affect cognitive development, some of which were maternal IQ; age at delivery; education; type of epilepsy; seizure frequency; socioeconomic status; the use of folate, alcohol, tobacco, and drugs; obstetrical complications; gestational age; birth weight; and breastfeeding.

Children exposed to valproate had the lowest mean IQs of any of the exposure groups (92)—significantly lower than those of any other treatment group. The mean IQ in those exposed to carbamazepine was 98; to lamotrigine, 101; and to phenytoin, 99. These did not vary significantly from one another.

The association of valproate with reduced IQ held after adjustment for the confounders in both a linear regression and subgroup analysis, the investigators said. They also examined whether the IQ scores were related to AED dosage. In this analysis, only valproate maintained a significant dose-response relationship.

Additionally, higher maternal IQs were associated with higher child IQs in all of the treatment groups except valproate.

The results are consistent with several European studies that have found poor cognitive outcomes in children exposed to the drug prenatally, the investigators said. The drug also has been found to increase the rate of congenital malformations, compared with other AEDs. A recent meta-analysis found the rate to be as many as 11% of births.

Unfortunately, Dr. Meador and his colleagues wrote, women whose seizures are well controlled on valproate may be placed on the horns of a dilemma when trying to balance gestational safety with seizure control.

“For some patients, valproate is the only medication that adequately controls seizures. Such women should be informed of the potential risks associated with the use of this medication in pregnancy. If a woman taking valproate is already pregnant, it's critical that she not stop valproate without consultation with her physician, since stopping an antiepileptic drug could lead to seizures and serious consequences for both the woman and her fetus.”

“One other important point is that less than half of the prescriptions for valproate are for seizures or epilepsy. The majority are for pain or psychiatric indications. I believe that the women taking valproate for other indications are at the same risk as our women with epilepsy,” he said in the interview.

The study was supported by grants from the United Kingdom Epilepsy Research Foundation and the National Institute of Neurological Disorders and Stroke. Dr. Meador reported receiving research support from GlaxoSmithKline, Myriad Pharmaceuticals, Marinus Pharmaceuticals, UCB Pharmaceuticals, and several other companies and foundations.

Children whose parents refused the pertussis vaccine were 23 times more likely to contract the disease than were children whose parents allowed them to receive the vaccine, a case-control study found.

Of 156 pediatric pertussis cases identified in a large health care database, 18 (12%) had not received the pertussis vaccine because of parental refusal. Of the 595 matched controls, only 3 (0.5%) had parents who refused to have them vaccinated, Jason M. Glanz, Ph.D., and his colleagues reported (Pediatrics 2009;123:1446–51).

The study was conducted in Colorado, a state with generally high rates of childhood immunization, wrote Dr. Glanz of the Kaiser Permanente Colorado Institute for Health Research, Denver. “Despite high pertussis immunization rates in Colorado, herd immunity did not prevent a high relative risk for pertussis in vaccine refusers,” he and his colleagues observed. “This is likely because of a combination of waning immunity to pertussis in adolescents and adults, ongoing endemic circulation, the highly contagious nature of the bacterium, and frequent asymptomatic infections.”

The study offers a sobering look at the results of the growing trend of vaccine refusal, Dr. Randy Bergen said in an interview. Dr. Bergen, chair of the pediatric infectious disease section at Kaiser Permanente of Northern California, Walnut Creek, said the antivaccine campaigns of several outspoken celebrities continue to influence parental decisions about their children's health care. “And not only are these unvaccinated children being put at risk of contracting an infectious disease, they are putting vaccinated children at risk as well.”

The study examined pertussis vaccination rates and disease prevalence in children aged 2 months to 18 years enrolled in the Kaiser Permanente of Colorado health plan between 1996 and 2007. Each case of pertussis was matched to four randomly selected controls.

Children were considered “vaccine refusers” if their medical charts documented a parental refusal of one or more pertussis immunizations for nonmedical reasons. The review identified 156 children who had a confirmed diagnosis of pertussis during the study period. Of these, 17 (11%) had parents who refused all the recommended pertussis immunizations; 1 additional child received only one of the five recommended doses. Six percent had to be hospitalized for the illness. The mean duration of cough at diagnosis was 12 days.

The cases (mean age, 9 years) were matched with 595 controls, none of whom contracted the disease. Only three of the control children (0.5%) had parents who refused one or more pertussis immunizations. Children who were not vaccinated were 23 times more likely to contract pertussis than were vaccinated children.

Because some of the children in the primary analysis were not Kaiser members during the entire first 20 months of their life, when they would have received all four primary vaccine doses, the investigators conducted a secondary analysis of 27,748 children who were continuously enrolled in the program from 2 to 20 months of age. This cohort included 31 children with confirmed pertussis infections, who were matched with 308 controls. Among the cases, 13% had parents who refused the vaccine; only 0.7% of controls had parents who refused.

“The study highlights the need for effective risk communication between parents and physicians about vaccines and the diseases they prevent,” Dr. Glanz and his colleagues wrote.

Dr. Bergen, who is also a practicing pediatrician, agreed, saying that many parents who express concerns about vaccine safety feel more confident after hearing the scientific evidence of their safety. A second group, however, is tougher to convince. “These parents are adamant in their mistaken impression that vaccines are dangerous, and they will not be dissuaded by any information about the severity of the infections vaccines prevent, or the lack of any evidence that vaccines cause autism or any other harm.”

“This study suggests that parents who don't vaccinate are putting the community at risk, as well as their own children,” Dr. Bergen suggested. “It's similar to the secondhand smoke argument. I understand that those parents are entitled to their choice, but why is that choice more important than another parent's choice to vaccinate? I may not have the right to make the decision for a parent, but as a parent, I do have the right to have some input about the environment my child is in.”

Dr. Glanz and his associates indicated that they had no conflicts to disclose. Dr. Bergen likewise had no conflicts of interest.

Children whose parents refused the pertussis vaccine were 23 times more likely to contract the disease than were children whose parents allowed them to receive the vaccine, a case-control study found.

Of 156 pediatric pertussis cases identified in a large health care database, 18 (12%) had not received the pertussis vaccine because of parental refusal. Of the 595 matched controls, only 3 (0.5%) had parents who refused to have them vaccinated, Jason M. Glanz, Ph.D., and his colleagues reported (Pediatrics 2009;123:1446–51).

The study was conducted in Colorado, a state with generally high rates of childhood immunization, wrote Dr. Glanz of the Kaiser Permanente Colorado Institute for Health Research, Denver. “Despite high pertussis immunization rates in Colorado, herd immunity did not prevent a high relative risk for pertussis in vaccine refusers,” he and his colleagues observed. “This is likely because of a combination of waning immunity to pertussis in adolescents and adults, ongoing endemic circulation, the highly contagious nature of the bacterium, and frequent asymptomatic infections.”

The study offers a sobering look at the results of the growing trend of vaccine refusal, Dr. Randy Bergen said in an interview. Dr. Bergen, chair of the pediatric infectious disease section at Kaiser Permanente of Northern California, Walnut Creek, said the antivaccine campaigns of several outspoken celebrities continue to influence parental decisions about their children's health care. “And not only are these unvaccinated children being put at risk of contracting an infectious disease, they are putting vaccinated children at risk as well.”

The study examined pertussis vaccination rates and disease prevalence in children aged 2 months to 18 years enrolled in the Kaiser Permanente of Colorado health plan between 1996 and 2007. Each case of pertussis was matched to four randomly selected controls.

Children were considered “vaccine refusers” if their medical charts documented a parental refusal of one or more pertussis immunizations for nonmedical reasons. The review identified 156 children who had a confirmed diagnosis of pertussis during the study period. Of these, 17 (11%) had parents who refused all the recommended pertussis immunizations; 1 additional child received only one of the five recommended doses. Six percent had to be hospitalized for the illness. The mean duration of cough at diagnosis was 12 days.

The cases (mean age, 9 years) were matched with 595 controls, none of whom contracted the disease. Only three of the control children (0.5%) had parents who refused one or more pertussis immunizations. Children who were not vaccinated were 23 times more likely to contract pertussis than were vaccinated children.

Because some of the children in the primary analysis were not Kaiser members during the entire first 20 months of their life, when they would have received all four primary vaccine doses, the investigators conducted a secondary analysis of 27,748 children who were continuously enrolled in the program from 2 to 20 months of age. This cohort included 31 children with confirmed pertussis infections, who were matched with 308 controls. Among the cases, 13% had parents who refused the vaccine; only 0.7% of controls had parents who refused.

“The study highlights the need for effective risk communication between parents and physicians about vaccines and the diseases they prevent,” Dr. Glanz and his colleagues wrote.

Dr. Bergen, who is also a practicing pediatrician, agreed, saying that many parents who express concerns about vaccine safety feel more confident after hearing the scientific evidence of their safety. A second group, however, is tougher to convince. “These parents are adamant in their mistaken impression that vaccines are dangerous, and they will not be dissuaded by any information about the severity of the infections vaccines prevent, or the lack of any evidence that vaccines cause autism or any other harm.”

“This study suggests that parents who don't vaccinate are putting the community at risk, as well as their own children,” Dr. Bergen suggested. “It's similar to the secondhand smoke argument. I understand that those parents are entitled to their choice, but why is that choice more important than another parent's choice to vaccinate? I may not have the right to make the decision for a parent, but as a parent, I do have the right to have some input about the environment my child is in.”

Dr. Glanz and his associates indicated that they had no conflicts to disclose. Dr. Bergen likewise had no conflicts of interest.

Children whose parents refused the pertussis vaccine were 23 times more likely to contract the disease than were children whose parents allowed them to receive the vaccine, a case-control study found.

Of 156 pediatric pertussis cases identified in a large health care database, 18 (12%) had not received the pertussis vaccine because of parental refusal. Of the 595 matched controls, only 3 (0.5%) had parents who refused to have them vaccinated, Jason M. Glanz, Ph.D., and his colleagues reported (Pediatrics 2009;123:1446–51).

The study was conducted in Colorado, a state with generally high rates of childhood immunization, wrote Dr. Glanz of the Kaiser Permanente Colorado Institute for Health Research, Denver. “Despite high pertussis immunization rates in Colorado, herd immunity did not prevent a high relative risk for pertussis in vaccine refusers,” he and his colleagues observed. “This is likely because of a combination of waning immunity to pertussis in adolescents and adults, ongoing endemic circulation, the highly contagious nature of the bacterium, and frequent asymptomatic infections.”

The study offers a sobering look at the results of the growing trend of vaccine refusal, Dr. Randy Bergen said in an interview. Dr. Bergen, chair of the pediatric infectious disease section at Kaiser Permanente of Northern California, Walnut Creek, said the antivaccine campaigns of several outspoken celebrities continue to influence parental decisions about their children's health care. “And not only are these unvaccinated children being put at risk of contracting an infectious disease, they are putting vaccinated children at risk as well.”

The study examined pertussis vaccination rates and disease prevalence in children aged 2 months to 18 years enrolled in the Kaiser Permanente of Colorado health plan between 1996 and 2007. Each case of pertussis was matched to four randomly selected controls.

Children were considered “vaccine refusers” if their medical charts documented a parental refusal of one or more pertussis immunizations for nonmedical reasons. The review identified 156 children who had a confirmed diagnosis of pertussis during the study period. Of these, 17 (11%) had parents who refused all the recommended pertussis immunizations; 1 additional child received only one of the five recommended doses. Six percent had to be hospitalized for the illness. The mean duration of cough at diagnosis was 12 days.

The cases (mean age, 9 years) were matched with 595 controls, none of whom contracted the disease. Only three of the control children (0.5%) had parents who refused one or more pertussis immunizations. Children who were not vaccinated were 23 times more likely to contract pertussis than were vaccinated children.

Because some of the children in the primary analysis were not Kaiser members during the entire first 20 months of their life, when they would have received all four primary vaccine doses, the investigators conducted a secondary analysis of 27,748 children who were continuously enrolled in the program from 2 to 20 months of age. This cohort included 31 children with confirmed pertussis infections, who were matched with 308 controls. Among the cases, 13% had parents who refused the vaccine; only 0.7% of controls had parents who refused.

“The study highlights the need for effective risk communication between parents and physicians about vaccines and the diseases they prevent,” Dr. Glanz and his colleagues wrote.

Dr. Bergen, who is also a practicing pediatrician, agreed, saying that many parents who express concerns about vaccine safety feel more confident after hearing the scientific evidence of their safety. A second group, however, is tougher to convince. “These parents are adamant in their mistaken impression that vaccines are dangerous, and they will not be dissuaded by any information about the severity of the infections vaccines prevent, or the lack of any evidence that vaccines cause autism or any other harm.”

“This study suggests that parents who don't vaccinate are putting the community at risk, as well as their own children,” Dr. Bergen suggested. “It's similar to the secondhand smoke argument. I understand that those parents are entitled to their choice, but why is that choice more important than another parent's choice to vaccinate? I may not have the right to make the decision for a parent, but as a parent, I do have the right to have some input about the environment my child is in.”

Dr. Glanz and his associates indicated that they had no conflicts to disclose. Dr. Bergen likewise had no conflicts of interest.

Patients with diabetes who receive drug-eluting stents are significantly more likely to experience restenosis than are nondiabetic patients, particularly if they get the Endeavor zotarolimus-eluting stent, a large Swedish registry study has found.

Cautioning that the finding should be prospectively evaluated, Dr. Ole Frobert and his colleagues wrote, “This study represents the first large-scale evaluation of the zotarolimus-eluting Endeavor stent in patients with diabetes and underlines the importance of continuous registry monitoring of new coronary stents.”

Dr. Frobert of Orebro University Hospital, Sweden, and his coauthors analyzed data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). The registry includes information on all patients who have undergone percutaneous coronary intervention at any of 26 Swedish centers.

The study included those patients who underwent the procedure from 2004 to 2008 and who received any of four different drug-eluting stents: Endeavor, the Cypher sirolimus-eluting stent, or the paclitaxel-eluting Taxus Express or Taxus Liberte stents (J. Am. Coll. Cardiol. 2009;53:1660–7).

During the study period, 19,004 patients received 35,478 stents. The patients' mean age was 66 years. Those with diabetes (8,231) were significantly more likely to be women, and to have hypertension, hyperlipidemia, and previous coronary artery disease.

The mean follow-up duration was 29 months. Restenosis occurred in 3.5% of stents within 1 year, and in 5% within 2 years. Patients with diabetes were 23% more likely to experience restenosis than were those without diabetes, a significant difference. Compared with patients without diabetes, those with diabetes who received the Endeavor stent were 77% more likely to experience restenosis.

Among patients who received the Cypher stent, those with diabetes were 25% more likely to have restenosis than were those without diabetes.

In patients receiving the Taxus Express stent, the restenosis rate was similar irrespective of diabetes status, while diabetic patients who received the Taxus Liberte stent were slightly, but not significantly, more likely to have restenosis than were their nondiabetic peers.

Among patients with diabetes, restenosis rates were not significantly different between the Taxus stents and the Cypher stent. However, patients receiving the Endeavor stent were twice as likely to have restenosis as were patients receiving the other types.

There were similar, but smaller, differences in restenosis rates among nondiabetic patients; restenosis was 20% more likely with the Endeavor stent and 30% more likely with the Taxus stents compared with the Cypher stent.

“It was also noteworthy that in patients without diabetes, the adjusted risk of restenosis was significantly higher with the Taxus Express than with the Taxus Liberte stent,” the authors noted.

Beginning in 2005, the SCAAR database included diabetes treatment information. Neither insulin nor noninsulin treatment had any significant impact on restenosis rates among patients with diabetes. The doubled rate of restenosis among diabetic patients receiving the Endeavor stent remained regardless of treatment type.

However, the increased restenosis rates among patients with diabetes did not affect the rates of mortality or myocardial infarction, the authors said.

Patients with diabetes who receive drug-eluting stents are significantly more likely to experience restenosis than are nondiabetic patients, particularly if they get the Endeavor zotarolimus-eluting stent, a large Swedish registry study has found.

Cautioning that the finding should be prospectively evaluated, Dr. Ole Frobert and his colleagues wrote, “This study represents the first large-scale evaluation of the zotarolimus-eluting Endeavor stent in patients with diabetes and underlines the importance of continuous registry monitoring of new coronary stents.”

Dr. Frobert of Orebro University Hospital, Sweden, and his coauthors analyzed data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). The registry includes information on all patients who have undergone percutaneous coronary intervention at any of 26 Swedish centers.

The study included those patients who underwent the procedure from 2004 to 2008 and who received any of four different drug-eluting stents: Endeavor, the Cypher sirolimus-eluting stent, or the paclitaxel-eluting Taxus Express or Taxus Liberte stents (J. Am. Coll. Cardiol. 2009;53:1660–7).

During the study period, 19,004 patients received 35,478 stents. The patients' mean age was 66 years. Those with diabetes (8,231) were significantly more likely to be women, and to have hypertension, hyperlipidemia, and previous coronary artery disease.

The mean follow-up duration was 29 months. Restenosis occurred in 3.5% of stents within 1 year, and in 5% within 2 years. Patients with diabetes were 23% more likely to experience restenosis than were those without diabetes, a significant difference. Compared with patients without diabetes, those with diabetes who received the Endeavor stent were 77% more likely to experience restenosis.

Among patients who received the Cypher stent, those with diabetes were 25% more likely to have restenosis than were those without diabetes.

In patients receiving the Taxus Express stent, the restenosis rate was similar irrespective of diabetes status, while diabetic patients who received the Taxus Liberte stent were slightly, but not significantly, more likely to have restenosis than were their nondiabetic peers.

Among patients with diabetes, restenosis rates were not significantly different between the Taxus stents and the Cypher stent. However, patients receiving the Endeavor stent were twice as likely to have restenosis as were patients receiving the other types.

There were similar, but smaller, differences in restenosis rates among nondiabetic patients; restenosis was 20% more likely with the Endeavor stent and 30% more likely with the Taxus stents compared with the Cypher stent.

“It was also noteworthy that in patients without diabetes, the adjusted risk of restenosis was significantly higher with the Taxus Express than with the Taxus Liberte stent,” the authors noted.

Beginning in 2005, the SCAAR database included diabetes treatment information. Neither insulin nor noninsulin treatment had any significant impact on restenosis rates among patients with diabetes. The doubled rate of restenosis among diabetic patients receiving the Endeavor stent remained regardless of treatment type.

However, the increased restenosis rates among patients with diabetes did not affect the rates of mortality or myocardial infarction, the authors said.

Patients with diabetes who receive drug-eluting stents are significantly more likely to experience restenosis than are nondiabetic patients, particularly if they get the Endeavor zotarolimus-eluting stent, a large Swedish registry study has found.

Cautioning that the finding should be prospectively evaluated, Dr. Ole Frobert and his colleagues wrote, “This study represents the first large-scale evaluation of the zotarolimus-eluting Endeavor stent in patients with diabetes and underlines the importance of continuous registry monitoring of new coronary stents.”

Dr. Frobert of Orebro University Hospital, Sweden, and his coauthors analyzed data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). The registry includes information on all patients who have undergone percutaneous coronary intervention at any of 26 Swedish centers.

The study included those patients who underwent the procedure from 2004 to 2008 and who received any of four different drug-eluting stents: Endeavor, the Cypher sirolimus-eluting stent, or the paclitaxel-eluting Taxus Express or Taxus Liberte stents (J. Am. Coll. Cardiol. 2009;53:1660–7).

During the study period, 19,004 patients received 35,478 stents. The patients' mean age was 66 years. Those with diabetes (8,231) were significantly more likely to be women, and to have hypertension, hyperlipidemia, and previous coronary artery disease.

The mean follow-up duration was 29 months. Restenosis occurred in 3.5% of stents within 1 year, and in 5% within 2 years. Patients with diabetes were 23% more likely to experience restenosis than were those without diabetes, a significant difference. Compared with patients without diabetes, those with diabetes who received the Endeavor stent were 77% more likely to experience restenosis.

Among patients who received the Cypher stent, those with diabetes were 25% more likely to have restenosis than were those without diabetes.

In patients receiving the Taxus Express stent, the restenosis rate was similar irrespective of diabetes status, while diabetic patients who received the Taxus Liberte stent were slightly, but not significantly, more likely to have restenosis than were their nondiabetic peers.

Among patients with diabetes, restenosis rates were not significantly different between the Taxus stents and the Cypher stent. However, patients receiving the Endeavor stent were twice as likely to have restenosis as were patients receiving the other types.

There were similar, but smaller, differences in restenosis rates among nondiabetic patients; restenosis was 20% more likely with the Endeavor stent and 30% more likely with the Taxus stents compared with the Cypher stent.

“It was also noteworthy that in patients without diabetes, the adjusted risk of restenosis was significantly higher with the Taxus Express than with the Taxus Liberte stent,” the authors noted.

Beginning in 2005, the SCAAR database included diabetes treatment information. Neither insulin nor noninsulin treatment had any significant impact on restenosis rates among patients with diabetes. The doubled rate of restenosis among diabetic patients receiving the Endeavor stent remained regardless of treatment type.

However, the increased restenosis rates among patients with diabetes did not affect the rates of mortality or myocardial infarction, the authors said.

A recent government report finding that arthritis and rheumatism account for much of the disability in Americans may be an underestimate.

The estimated percentage of Americans reporting a disability increased by 7.7% from 1999 to 2005, from 44.1 million to 47.5 million, with arthritis and rheumatism the most common causes of physical problems that interfere with daily life, according to a report issued by the Centers for Disease Control and Prevention.

Almost 22% of the adult population reported a physical disability in 2005, Dr. Chad Helmick and his coauthors wrote. Although the percentage hasn't changed since the last disability survey in 1999, the number represents an absolute increase of 7.7%—probably because of an increase in the number of older people as Baby Boomers age, wrote Dr. Helmick, an epidemiologist for the Centers for Disease Control and Prevention, and a coauthor of the study.

The most commonly reported causes of disability were arthritis and rheumatism (8.6 million people), followed by back or spine problems (7.6 million) and cardiac problems (3 million), the report said.

Dr. John Klippel, president and chief executive officer of the Arthritis Foundation, said the survey might underestimate the true impact of arthritis and rheumatic disease.

“I believe that many people who report disability due to back pain have arthritis as the underlying cause of that pain,” Dr. Klippel said in an interview. “If you add those two together, then the overwhelming reason for disability in American would be arthritis and musculoskeletal diseases.”

The data were extracted from the 2005 Survey of Income and Program Participation, conducted by the U.S. Census Bureau. The survey included interviews with 70,300 noninstitutionalized people aged 18 years or older from 37,400 households (representing 83% of eligible households).

Disability was defined as a “yes” answer to one of three categories: required use of an assistive device (cane, crutches, walker, or wheelchair); difficulty performing activities of daily living or specified functional activities; and a limitation in the ability to work around the house or at a job or business. Respondents then chose the cause of their disability from a list of 30 disorders. National estimates were extrapolated from the completed survey.

The survey concluded that most of those reporting a disability were 65 years or older (52%) and that disability was significantly higher in women than in men (24% vs. 19%, respectively). The most commonly reported functional disabilities were difficulty walking three or more blocks (10%; 22 million people) and climbing a flight of stairs (10%).

Of those with a disability, 19%—an estimated 9 million people—identified arthritis or a rheumatic disease as the cause. These disorders were also the most common cause of disability for women, affecting 24%.

Back and spine problems affected 17% of the population, and were the leading cause of disability for men (17%). Cardiac disorders affected 7% overall (8% of men and 5% of women).

The report suggests that disability numbers will continue to rise as the American population ages.

“To accommodate the expected increase in demand for disability-related medical and public health services, expanding the reach of effective strategies and interventions aimed at preventing progression to disability and improving disability management in the population is necessary,” according to the report (MMWR 2009;58:421–6).

Over the next 20 years as they age, the number of people reporting arthritis-related disability and the economic costs associated with it will skyrocket.” Arthritis and other rheumatic disease cost the U.S. $128 billion annually. “These will go up logarithmically,” Dr. Klippel said. “Given all the concerns for our economy, we have even more reasons to start focusing on health care reform, and arthritis and musculoskeletal diseases need to be at the top of the list.”

Only 12 states have CDC-funded arthritis health programs, Dr. Klippel said. “We at the Arthritis Foundation would like to see the CDC invest more in chronic disease prevention programs, including those for osteoarthritis. Without a greater investment in research, we will not have more effective therapies.”

A recent government report finding that arthritis and rheumatism account for much of the disability in Americans may be an underestimate.

The estimated percentage of Americans reporting a disability increased by 7.7% from 1999 to 2005, from 44.1 million to 47.5 million, with arthritis and rheumatism the most common causes of physical problems that interfere with daily life, according to a report issued by the Centers for Disease Control and Prevention.

Almost 22% of the adult population reported a physical disability in 2005, Dr. Chad Helmick and his coauthors wrote. Although the percentage hasn't changed since the last disability survey in 1999, the number represents an absolute increase of 7.7%—probably because of an increase in the number of older people as Baby Boomers age, wrote Dr. Helmick, an epidemiologist for the Centers for Disease Control and Prevention, and a coauthor of the study.

The most commonly reported causes of disability were arthritis and rheumatism (8.6 million people), followed by back or spine problems (7.6 million) and cardiac problems (3 million), the report said.

Dr. John Klippel, president and chief executive officer of the Arthritis Foundation, said the survey might underestimate the true impact of arthritis and rheumatic disease.

“I believe that many people who report disability due to back pain have arthritis as the underlying cause of that pain,” Dr. Klippel said in an interview. “If you add those two together, then the overwhelming reason for disability in American would be arthritis and musculoskeletal diseases.”

The data were extracted from the 2005 Survey of Income and Program Participation, conducted by the U.S. Census Bureau. The survey included interviews with 70,300 noninstitutionalized people aged 18 years or older from 37,400 households (representing 83% of eligible households).

Disability was defined as a “yes” answer to one of three categories: required use of an assistive device (cane, crutches, walker, or wheelchair); difficulty performing activities of daily living or specified functional activities; and a limitation in the ability to work around the house or at a job or business. Respondents then chose the cause of their disability from a list of 30 disorders. National estimates were extrapolated from the completed survey.

The survey concluded that most of those reporting a disability were 65 years or older (52%) and that disability was significantly higher in women than in men (24% vs. 19%, respectively). The most commonly reported functional disabilities were difficulty walking three or more blocks (10%; 22 million people) and climbing a flight of stairs (10%).

Of those with a disability, 19%—an estimated 9 million people—identified arthritis or a rheumatic disease as the cause. These disorders were also the most common cause of disability for women, affecting 24%.

Back and spine problems affected 17% of the population, and were the leading cause of disability for men (17%). Cardiac disorders affected 7% overall (8% of men and 5% of women).

The report suggests that disability numbers will continue to rise as the American population ages.

“To accommodate the expected increase in demand for disability-related medical and public health services, expanding the reach of effective strategies and interventions aimed at preventing progression to disability and improving disability management in the population is necessary,” according to the report (MMWR 2009;58:421–6).

Over the next 20 years as they age, the number of people reporting arthritis-related disability and the economic costs associated with it will skyrocket.” Arthritis and other rheumatic disease cost the U.S. $128 billion annually. “These will go up logarithmically,” Dr. Klippel said. “Given all the concerns for our economy, we have even more reasons to start focusing on health care reform, and arthritis and musculoskeletal diseases need to be at the top of the list.”

Only 12 states have CDC-funded arthritis health programs, Dr. Klippel said. “We at the Arthritis Foundation would like to see the CDC invest more in chronic disease prevention programs, including those for osteoarthritis. Without a greater investment in research, we will not have more effective therapies.”

A recent government report finding that arthritis and rheumatism account for much of the disability in Americans may be an underestimate.

The estimated percentage of Americans reporting a disability increased by 7.7% from 1999 to 2005, from 44.1 million to 47.5 million, with arthritis and rheumatism the most common causes of physical problems that interfere with daily life, according to a report issued by the Centers for Disease Control and Prevention.

Almost 22% of the adult population reported a physical disability in 2005, Dr. Chad Helmick and his coauthors wrote. Although the percentage hasn't changed since the last disability survey in 1999, the number represents an absolute increase of 7.7%—probably because of an increase in the number of older people as Baby Boomers age, wrote Dr. Helmick, an epidemiologist for the Centers for Disease Control and Prevention, and a coauthor of the study.

The most commonly reported causes of disability were arthritis and rheumatism (8.6 million people), followed by back or spine problems (7.6 million) and cardiac problems (3 million), the report said.

Dr. John Klippel, president and chief executive officer of the Arthritis Foundation, said the survey might underestimate the true impact of arthritis and rheumatic disease.

“I believe that many people who report disability due to back pain have arthritis as the underlying cause of that pain,” Dr. Klippel said in an interview. “If you add those two together, then the overwhelming reason for disability in American would be arthritis and musculoskeletal diseases.”

The data were extracted from the 2005 Survey of Income and Program Participation, conducted by the U.S. Census Bureau. The survey included interviews with 70,300 noninstitutionalized people aged 18 years or older from 37,400 households (representing 83% of eligible households).

Disability was defined as a “yes” answer to one of three categories: required use of an assistive device (cane, crutches, walker, or wheelchair); difficulty performing activities of daily living or specified functional activities; and a limitation in the ability to work around the house or at a job or business. Respondents then chose the cause of their disability from a list of 30 disorders. National estimates were extrapolated from the completed survey.

The survey concluded that most of those reporting a disability were 65 years or older (52%) and that disability was significantly higher in women than in men (24% vs. 19%, respectively). The most commonly reported functional disabilities were difficulty walking three or more blocks (10%; 22 million people) and climbing a flight of stairs (10%).

Of those with a disability, 19%—an estimated 9 million people—identified arthritis or a rheumatic disease as the cause. These disorders were also the most common cause of disability for women, affecting 24%.

Back and spine problems affected 17% of the population, and were the leading cause of disability for men (17%). Cardiac disorders affected 7% overall (8% of men and 5% of women).

The report suggests that disability numbers will continue to rise as the American population ages.

“To accommodate the expected increase in demand for disability-related medical and public health services, expanding the reach of effective strategies and interventions aimed at preventing progression to disability and improving disability management in the population is necessary,” according to the report (MMWR 2009;58:421–6).

Over the next 20 years as they age, the number of people reporting arthritis-related disability and the economic costs associated with it will skyrocket.” Arthritis and other rheumatic disease cost the U.S. $128 billion annually. “These will go up logarithmically,” Dr. Klippel said. “Given all the concerns for our economy, we have even more reasons to start focusing on health care reform, and arthritis and musculoskeletal diseases need to be at the top of the list.”

Only 12 states have CDC-funded arthritis health programs, Dr. Klippel said. “We at the Arthritis Foundation would like to see the CDC invest more in chronic disease prevention programs, including those for osteoarthritis. Without a greater investment in research, we will not have more effective therapies.”

NASHVILLE, TENN. — Candida infections are associated with a significant increase in hospital length of stay and a twofold increase in mortality in patients who require mechanical ventilation during a stay in the intensive care unit.

“Whether Candida species colonization of the respiratory tract secretions is a marker of disease severity or actually contributes to prolonged mechanical ventilation, ICU and hospital stay, and mortality requires further evaluation,” Dr. Marc M. Perrault said in a poster presented at the annual congress of the Society of Critical Care Medicine.

“The role of antifungal therapy in these patients also remains to be determined,” said Dr. Perrault, a pharmacist at the McGill University Health Center in Montreal.

He and his colleagues retrospectively analyzed data collected during a large clinical trial that randomized 740 critically ill, mechanically ventilated patients to bronchoscopy or endotracheal aspiration, followed by randomization to treatment with meropenem alone or in combination with ciprofloxacin.

Of the 274 patients who had negative bacterial cultures on enrollment, 64 subsequently tested positive for a Candida species. The mean age was 60 years; the mean APACHE II score was 20. At baseline, three characteristics were significantly different between the groups: antibiotic use in the past 3 days, respiratory rate, and white blood cell count. The final analysis controlled for these risk factors.

In the univariate analysis, 14-day mortality was not significantly different between the groups. But at 28 days, patients with Candida infections were more than twice as likely to have died—31% vs. 15%, a significant difference. ICU mortality was also significantly higher in the Candida group (29% vs. 14%; odds ratio, 2.65). Cumulative in-hospital mortality was more than twice as common in Candida-infected patients (43% vs. 20%).

When the researchers controlled for the risk factors, patients with Candida infections were still more than twice as likely to die in the hospital as those without the infections.

Intravenous antifungal treatment was given to 15 patients with Candida (22%) and 26 without (13%). No treated patient developed candidemia, but the report did not state how many untreated patients developed that complication.

NASHVILLE, TENN. — Candida infections are associated with a significant increase in hospital length of stay and a twofold increase in mortality in patients who require mechanical ventilation during a stay in the intensive care unit.

“Whether Candida species colonization of the respiratory tract secretions is a marker of disease severity or actually contributes to prolonged mechanical ventilation, ICU and hospital stay, and mortality requires further evaluation,” Dr. Marc M. Perrault said in a poster presented at the annual congress of the Society of Critical Care Medicine.

“The role of antifungal therapy in these patients also remains to be determined,” said Dr. Perrault, a pharmacist at the McGill University Health Center in Montreal.

He and his colleagues retrospectively analyzed data collected during a large clinical trial that randomized 740 critically ill, mechanically ventilated patients to bronchoscopy or endotracheal aspiration, followed by randomization to treatment with meropenem alone or in combination with ciprofloxacin.

Of the 274 patients who had negative bacterial cultures on enrollment, 64 subsequently tested positive for a Candida species. The mean age was 60 years; the mean APACHE II score was 20. At baseline, three characteristics were significantly different between the groups: antibiotic use in the past 3 days, respiratory rate, and white blood cell count. The final analysis controlled for these risk factors.

In the univariate analysis, 14-day mortality was not significantly different between the groups. But at 28 days, patients with Candida infections were more than twice as likely to have died—31% vs. 15%, a significant difference. ICU mortality was also significantly higher in the Candida group (29% vs. 14%; odds ratio, 2.65). Cumulative in-hospital mortality was more than twice as common in Candida-infected patients (43% vs. 20%).

When the researchers controlled for the risk factors, patients with Candida infections were still more than twice as likely to die in the hospital as those without the infections.

Intravenous antifungal treatment was given to 15 patients with Candida (22%) and 26 without (13%). No treated patient developed candidemia, but the report did not state how many untreated patients developed that complication.

NASHVILLE, TENN. — Candida infections are associated with a significant increase in hospital length of stay and a twofold increase in mortality in patients who require mechanical ventilation during a stay in the intensive care unit.

“Whether Candida species colonization of the respiratory tract secretions is a marker of disease severity or actually contributes to prolonged mechanical ventilation, ICU and hospital stay, and mortality requires further evaluation,” Dr. Marc M. Perrault said in a poster presented at the annual congress of the Society of Critical Care Medicine.

“The role of antifungal therapy in these patients also remains to be determined,” said Dr. Perrault, a pharmacist at the McGill University Health Center in Montreal.

He and his colleagues retrospectively analyzed data collected during a large clinical trial that randomized 740 critically ill, mechanically ventilated patients to bronchoscopy or endotracheal aspiration, followed by randomization to treatment with meropenem alone or in combination with ciprofloxacin.

Of the 274 patients who had negative bacterial cultures on enrollment, 64 subsequently tested positive for a Candida species. The mean age was 60 years; the mean APACHE II score was 20. At baseline, three characteristics were significantly different between the groups: antibiotic use in the past 3 days, respiratory rate, and white blood cell count. The final analysis controlled for these risk factors.

In the univariate analysis, 14-day mortality was not significantly different between the groups. But at 28 days, patients with Candida infections were more than twice as likely to have died—31% vs. 15%, a significant difference. ICU mortality was also significantly higher in the Candida group (29% vs. 14%; odds ratio, 2.65). Cumulative in-hospital mortality was more than twice as common in Candida-infected patients (43% vs. 20%).

When the researchers controlled for the risk factors, patients with Candida infections were still more than twice as likely to die in the hospital as those without the infections.

Intravenous antifungal treatment was given to 15 patients with Candida (22%) and 26 without (13%). No treated patient developed candidemia, but the report did not state how many untreated patients developed that complication.

While rosuvastatin significantly improved the lipid profile of patients with end-stage renal disease, those improvements did not translate into a decrease in the combined rate of heart attack, stroke, or cardiovascular death, a large randomized, controlled trial has confirmed.

“Although the patients tolerated the treatment very well, and it did lower their low-density lipoprotein by the expected amount, rosuvastatin had absolutely no treatment effect on either the composite cardiovascular end point or any of our secondary end points,” Dr. Bengt Fellstrom said at a teleconference held at the annual meeting of the American College of Cardiology.

“We suspect very strongly that the vascular disease they have is quite different from that in patients without end-stage renal disease. It has more to do with endothelial dysfunction and calcification, while cholesterol is not a significant risk factor,” Dr. Fellstrom said.

The 4-year AURORA study randomized 2,776 patients, all of whom had been on regular hemodialysis for at least 3 months, to either rosuvastatin 10 mg per day or placebo. The study's primary end points were time to nonfatal heart attack or stroke, or cardiovascular death. Secondary end points included all-cause mortality, event-free survival, and coronary or peripheral revascularization.

The patients' mean age was 64 years. At baseline, their average total cholesterol level was 175 mg/dL, with an LDL level of 99 mg/dL and HDL level of 45 mg/dL.

By 3 months, patients on rosuvastatin experienced a significantly larger decrease in LDL cholesterol than those taking placebo (43% vs. 2%, respectively). Rosuvastatin also significantly reduced total cholesterol (27% vs. 0.5%, respectively) and triglycerides (16% vs. an increase of 0.9% in placebo group). HDL increased in the active treatment group, but not significantly so.

The primary end point of stroke, heart attack, or death from those causes occurred in 396 patients taking the study drug and 408 taking placebo—not a significant difference. Neither were there any significant differences when the investigators examined the primary end points individually.

Death for any reason occurred in 636 patients taking rosuvastatin and 660 taking placebo, again not a significant difference. None of the prespecified secondary outcomes were significantly affected by the study drug.

The findings echo those of the German Diabetes and Dialysis study, which found that atorvastatin conferred no cardiovascular benefits on dialyzed patients with type 2 diabetes.

“Since that didn't work either, I suspect this is a class effect for all statins,” said Dr. Fellstrom of the University Hospital, Uppsala, Sweden.

AURORA enrolled only statin-naive patients. Dr. Fellstrom noted that the drugs do have an important place in the care of many other patients with end-stage renal disease. “Up to 40% of these patients have been put on statins before going on dialysis, after having a coronary event. Those patients should stay on the treatment.”

The study was published simultaneously online in the New England Journal of Medicine (doi:10.1056/NEJMoa0810177). An accompanying editorial discussed the disappointing finding that yet another possible intervention for improving cardiovascular survival in dialyzed patients had failed (doi:10.1056/NEJMe0901067).

“AURORA has shown that the hope of effective interventions to lower cardiovascular risk among patients undergoing hemodialysis remains unrealized,” wrote Jonathan C. Craig, Ph.D., of the University of Sydney, Australia. “The search is on for more promising interventions for a desperately needy group of people with very poor outcomes. Such interventions need to be based on a more complete understanding of the causal pathway of cardiac disease in patients undergoing dialysis.”

Dr. Fellstrom reported receiving consulting fees from Astra-Zeneca, the maker of rosuvastatin (Crestor), and other large pharmaceutical companies. Dr. Craig reported no conflict of interest.

While rosuvastatin significantly improved the lipid profile of patients with end-stage renal disease, those improvements did not translate into a decrease in the combined rate of heart attack, stroke, or cardiovascular death, a large randomized, controlled trial has confirmed.

“Although the patients tolerated the treatment very well, and it did lower their low-density lipoprotein by the expected amount, rosuvastatin had absolutely no treatment effect on either the composite cardiovascular end point or any of our secondary end points,” Dr. Bengt Fellstrom said at a teleconference held at the annual meeting of the American College of Cardiology.

“We suspect very strongly that the vascular disease they have is quite different from that in patients without end-stage renal disease. It has more to do with endothelial dysfunction and calcification, while cholesterol is not a significant risk factor,” Dr. Fellstrom said.

The 4-year AURORA study randomized 2,776 patients, all of whom had been on regular hemodialysis for at least 3 months, to either rosuvastatin 10 mg per day or placebo. The study's primary end points were time to nonfatal heart attack or stroke, or cardiovascular death. Secondary end points included all-cause mortality, event-free survival, and coronary or peripheral revascularization.

The patients' mean age was 64 years. At baseline, their average total cholesterol level was 175 mg/dL, with an LDL level of 99 mg/dL and HDL level of 45 mg/dL.

By 3 months, patients on rosuvastatin experienced a significantly larger decrease in LDL cholesterol than those taking placebo (43% vs. 2%, respectively). Rosuvastatin also significantly reduced total cholesterol (27% vs. 0.5%, respectively) and triglycerides (16% vs. an increase of 0.9% in placebo group). HDL increased in the active treatment group, but not significantly so.

The primary end point of stroke, heart attack, or death from those causes occurred in 396 patients taking the study drug and 408 taking placebo—not a significant difference. Neither were there any significant differences when the investigators examined the primary end points individually.

Death for any reason occurred in 636 patients taking rosuvastatin and 660 taking placebo, again not a significant difference. None of the prespecified secondary outcomes were significantly affected by the study drug.

The findings echo those of the German Diabetes and Dialysis study, which found that atorvastatin conferred no cardiovascular benefits on dialyzed patients with type 2 diabetes.

“Since that didn't work either, I suspect this is a class effect for all statins,” said Dr. Fellstrom of the University Hospital, Uppsala, Sweden.

AURORA enrolled only statin-naive patients. Dr. Fellstrom noted that the drugs do have an important place in the care of many other patients with end-stage renal disease. “Up to 40% of these patients have been put on statins before going on dialysis, after having a coronary event. Those patients should stay on the treatment.”

The study was published simultaneously online in the New England Journal of Medicine (doi:10.1056/NEJMoa0810177). An accompanying editorial discussed the disappointing finding that yet another possible intervention for improving cardiovascular survival in dialyzed patients had failed (doi:10.1056/NEJMe0901067).

“AURORA has shown that the hope of effective interventions to lower cardiovascular risk among patients undergoing hemodialysis remains unrealized,” wrote Jonathan C. Craig, Ph.D., of the University of Sydney, Australia. “The search is on for more promising interventions for a desperately needy group of people with very poor outcomes. Such interventions need to be based on a more complete understanding of the causal pathway of cardiac disease in patients undergoing dialysis.”

Dr. Fellstrom reported receiving consulting fees from Astra-Zeneca, the maker of rosuvastatin (Crestor), and other large pharmaceutical companies. Dr. Craig reported no conflict of interest.

While rosuvastatin significantly improved the lipid profile of patients with end-stage renal disease, those improvements did not translate into a decrease in the combined rate of heart attack, stroke, or cardiovascular death, a large randomized, controlled trial has confirmed.

“Although the patients tolerated the treatment very well, and it did lower their low-density lipoprotein by the expected amount, rosuvastatin had absolutely no treatment effect on either the composite cardiovascular end point or any of our secondary end points,” Dr. Bengt Fellstrom said at a teleconference held at the annual meeting of the American College of Cardiology.

“We suspect very strongly that the vascular disease they have is quite different from that in patients without end-stage renal disease. It has more to do with endothelial dysfunction and calcification, while cholesterol is not a significant risk factor,” Dr. Fellstrom said.

The 4-year AURORA study randomized 2,776 patients, all of whom had been on regular hemodialysis for at least 3 months, to either rosuvastatin 10 mg per day or placebo. The study's primary end points were time to nonfatal heart attack or stroke, or cardiovascular death. Secondary end points included all-cause mortality, event-free survival, and coronary or peripheral revascularization.

The patients' mean age was 64 years. At baseline, their average total cholesterol level was 175 mg/dL, with an LDL level of 99 mg/dL and HDL level of 45 mg/dL.

By 3 months, patients on rosuvastatin experienced a significantly larger decrease in LDL cholesterol than those taking placebo (43% vs. 2%, respectively). Rosuvastatin also significantly reduced total cholesterol (27% vs. 0.5%, respectively) and triglycerides (16% vs. an increase of 0.9% in placebo group). HDL increased in the active treatment group, but not significantly so.

The primary end point of stroke, heart attack, or death from those causes occurred in 396 patients taking the study drug and 408 taking placebo—not a significant difference. Neither were there any significant differences when the investigators examined the primary end points individually.

Death for any reason occurred in 636 patients taking rosuvastatin and 660 taking placebo, again not a significant difference. None of the prespecified secondary outcomes were significantly affected by the study drug.

The findings echo those of the German Diabetes and Dialysis study, which found that atorvastatin conferred no cardiovascular benefits on dialyzed patients with type 2 diabetes.

“Since that didn't work either, I suspect this is a class effect for all statins,” said Dr. Fellstrom of the University Hospital, Uppsala, Sweden.

AURORA enrolled only statin-naive patients. Dr. Fellstrom noted that the drugs do have an important place in the care of many other patients with end-stage renal disease. “Up to 40% of these patients have been put on statins before going on dialysis, after having a coronary event. Those patients should stay on the treatment.”

The study was published simultaneously online in the New England Journal of Medicine (doi:10.1056/NEJMoa0810177). An accompanying editorial discussed the disappointing finding that yet another possible intervention for improving cardiovascular survival in dialyzed patients had failed (doi:10.1056/NEJMe0901067).

“AURORA has shown that the hope of effective interventions to lower cardiovascular risk among patients undergoing hemodialysis remains unrealized,” wrote Jonathan C. Craig, Ph.D., of the University of Sydney, Australia. “The search is on for more promising interventions for a desperately needy group of people with very poor outcomes. Such interventions need to be based on a more complete understanding of the causal pathway of cardiac disease in patients undergoing dialysis.”

Dr. Fellstrom reported receiving consulting fees from Astra-Zeneca, the maker of rosuvastatin (Crestor), and other large pharmaceutical companies. Dr. Craig reported no conflict of interest.