Mary Ann Moon

An intensive 15-year program to control methicillin-resistant Staphylococcus aureus in 38 French hospitals has proved effective despite the unusually high endemic rates of the infection there, according to a report.

Until now, “the feasibility of controlling endemic situations with high MRSA rates” over a long period of time has been questioned.

The experience with this program now “demonstrates that this objective can be reached at the scale of a large medical institution,” said Dr. Vincent Jarlier of Université Pierre et Marie Curie, Paris, and his associates.

In the early 1990s an international comparison showed that MRSA rates among clinical S. aureus strains were “unacceptably” high in France, Spain, and Italy (approximately 35%), compared with countries in northern Europe (less than 2%), they said.

In response, an intensive, long-term program to control the organism was launched in 1993 at the largest public medical institution in France, according to Dr. Jarlier and his associates.

The Assistance Publique–Hôpitaux de Paris includes 38 teaching hospitals—23 acute care hospitals and 15 rehabilitation and long-term care hospitals—throughout Paris and its suburbs.

This institution admits about 1 million patients each year, and employs 19,000 physicians and 18,500 nurses.

The control program focused on rapidly identifying patients with MRSA infection or colonization and immediately notifying all caregivers of patients' MRSA status, isolation interventions such as using barrier precautions and having equipment dedicated to MRSA-positive patients, promoting hand hygiene, and providing feedback to the entire hospital community regarding the program results.

MRSA carriers were identified by special stickers on the doors to their rooms and in all lab reports and charts, the investigators said.

Hand hygiene efforts received a boost approximately halfway through the 15-year program with the promotion of alcohol-based hand-rub solutions instead of hand-washing.

Before this program was implemented in 1993, the proportion of MRSA among S. aureus strains had been 39.4% in this institution, Dr. Jarlier and his associates reported.

In 2007, that proportion had been cut to 21.6% in the acute care hospitals, a relative decrease of 45%, the investigators reported (Arch. Intern. Med. 2010;170:552-9).

The relative decrease was even greater—approximately 60%—in ICUs, and it was 44% in surgical wards, the investigators reported.

In the rehabilitation and long-term care facilities, the decrease in the proportion of MRSA among S. aureus strains was less pronounced (35%).

Similarly, the incidence of MRSA cases decreased by approximately half, from 1.16 per 1,000 hospital-days to 0.57 by the end of the study.

“When expressed per 100 admissions, the incidence of MRSA decreased in the acute care hospitals from 0.90 in 1996 to 0.44 in 2007,” Dr. Jarlier and his colleagues said.

Again, in the rehabilitation and long-term care facilities, the decline was less marked but still significant, they added.

Disclosures: None was reported.

An intensive 15-year program to control methicillin-resistant Staphylococcus aureus in 38 French hospitals has proved effective despite the unusually high endemic rates of the infection there, according to a report.

Until now, “the feasibility of controlling endemic situations with high MRSA rates” over a long period of time has been questioned.

The experience with this program now “demonstrates that this objective can be reached at the scale of a large medical institution,” said Dr. Vincent Jarlier of Université Pierre et Marie Curie, Paris, and his associates.

In the early 1990s an international comparison showed that MRSA rates among clinical S. aureus strains were “unacceptably” high in France, Spain, and Italy (approximately 35%), compared with countries in northern Europe (less than 2%), they said.

In response, an intensive, long-term program to control the organism was launched in 1993 at the largest public medical institution in France, according to Dr. Jarlier and his associates.

The Assistance Publique–Hôpitaux de Paris includes 38 teaching hospitals—23 acute care hospitals and 15 rehabilitation and long-term care hospitals—throughout Paris and its suburbs.

This institution admits about 1 million patients each year, and employs 19,000 physicians and 18,500 nurses.

The control program focused on rapidly identifying patients with MRSA infection or colonization and immediately notifying all caregivers of patients' MRSA status, isolation interventions such as using barrier precautions and having equipment dedicated to MRSA-positive patients, promoting hand hygiene, and providing feedback to the entire hospital community regarding the program results.

MRSA carriers were identified by special stickers on the doors to their rooms and in all lab reports and charts, the investigators said.

Hand hygiene efforts received a boost approximately halfway through the 15-year program with the promotion of alcohol-based hand-rub solutions instead of hand-washing.

Before this program was implemented in 1993, the proportion of MRSA among S. aureus strains had been 39.4% in this institution, Dr. Jarlier and his associates reported.

In 2007, that proportion had been cut to 21.6% in the acute care hospitals, a relative decrease of 45%, the investigators reported (Arch. Intern. Med. 2010;170:552-9).

The relative decrease was even greater—approximately 60%—in ICUs, and it was 44% in surgical wards, the investigators reported.

In the rehabilitation and long-term care facilities, the decrease in the proportion of MRSA among S. aureus strains was less pronounced (35%).

Similarly, the incidence of MRSA cases decreased by approximately half, from 1.16 per 1,000 hospital-days to 0.57 by the end of the study.

“When expressed per 100 admissions, the incidence of MRSA decreased in the acute care hospitals from 0.90 in 1996 to 0.44 in 2007,” Dr. Jarlier and his colleagues said.

Again, in the rehabilitation and long-term care facilities, the decline was less marked but still significant, they added.

Disclosures: None was reported.

An intensive 15-year program to control methicillin-resistant Staphylococcus aureus in 38 French hospitals has proved effective despite the unusually high endemic rates of the infection there, according to a report.

Until now, “the feasibility of controlling endemic situations with high MRSA rates” over a long period of time has been questioned.

The experience with this program now “demonstrates that this objective can be reached at the scale of a large medical institution,” said Dr. Vincent Jarlier of Université Pierre et Marie Curie, Paris, and his associates.

In the early 1990s an international comparison showed that MRSA rates among clinical S. aureus strains were “unacceptably” high in France, Spain, and Italy (approximately 35%), compared with countries in northern Europe (less than 2%), they said.

In response, an intensive, long-term program to control the organism was launched in 1993 at the largest public medical institution in France, according to Dr. Jarlier and his associates.

The Assistance Publique–Hôpitaux de Paris includes 38 teaching hospitals—23 acute care hospitals and 15 rehabilitation and long-term care hospitals—throughout Paris and its suburbs.

This institution admits about 1 million patients each year, and employs 19,000 physicians and 18,500 nurses.

The control program focused on rapidly identifying patients with MRSA infection or colonization and immediately notifying all caregivers of patients' MRSA status, isolation interventions such as using barrier precautions and having equipment dedicated to MRSA-positive patients, promoting hand hygiene, and providing feedback to the entire hospital community regarding the program results.

MRSA carriers were identified by special stickers on the doors to their rooms and in all lab reports and charts, the investigators said.

Hand hygiene efforts received a boost approximately halfway through the 15-year program with the promotion of alcohol-based hand-rub solutions instead of hand-washing.

Before this program was implemented in 1993, the proportion of MRSA among S. aureus strains had been 39.4% in this institution, Dr. Jarlier and his associates reported.

In 2007, that proportion had been cut to 21.6% in the acute care hospitals, a relative decrease of 45%, the investigators reported (Arch. Intern. Med. 2010;170:552-9).

The relative decrease was even greater—approximately 60%—in ICUs, and it was 44% in surgical wards, the investigators reported.

In the rehabilitation and long-term care facilities, the decrease in the proportion of MRSA among S. aureus strains was less pronounced (35%).

Similarly, the incidence of MRSA cases decreased by approximately half, from 1.16 per 1,000 hospital-days to 0.57 by the end of the study.

“When expressed per 100 admissions, the incidence of MRSA decreased in the acute care hospitals from 0.90 in 1996 to 0.44 in 2007,” Dr. Jarlier and his colleagues said.

Again, in the rehabilitation and long-term care facilities, the decline was less marked but still significant, they added.

Disclosures: None was reported.

Major Finding: Proton pump inhibitor use during treatment for incident C. difficile infection was associated with a 42% higher risk of C. difficile recurrence.

Data Source: 1,136 patients in the pharmacy and administrative databases of eight Veterans Affairs medical centers in New England.

Disclosures: Support was provided by the VA Cooperative Studies Program and the VA Boston Healthcare System. No financial conflicts of interest were reported.

Use of proton pump inhibitors appears to increase the risk of recurrent Clostridium difficile infection and may even have a causal effect, according to two cohort studies.

In the first study, PPI use during treatment for an incident C. difficile infection was associated with a 42% higher risk of recurrent C. difficile infection. The second study demonstrated a dose-response effect between increasing levels of acid suppression among inpatients taking PPIs and increasing risk for nosocomial C. difficile infection.

Neither study was designed to definitively establish causality; an adequately sized randomized controlled trial would be both prohibitively expensive and possibly unethical. But both of these studies add to the growing body of evidence linking PPIs with C. difficile infection, and their findings should prompt clinicians to take several reasonable, important steps to limit patients' exposure to PPI therapy, both groups of investigators noted.

In the first study, Dr. Amy Linsky of Boston Medical Center and her associates examined pharmacy and administrative databases for eight Veterans Affairs medical centers in New England. They identified 1,166 patients who began treatment for an index case of C. difficile during a 4-year period.

This included 527 patients (45%) who used an oral PPI at some time during the 14 days following diagnosis and 639 (55%) who did not use any PPIs during that interval. Omeprazole was the PPI used by 97% of patients who were given PPI therapy.

The primary end point was recurrent C. difficile infection during the 90 days following the incident diagnosis. This occurred in 25% of the PPI-exposed group, compared with 19% of the nonexposed group, a significant difference.

After the data were adjusted to account for patient age, initial antibiotic treatment, additional antibiotic treatment, duration of hospitalization, and differences in baseline comorbidities and medications, the hazard ratio for PPI exposure remained elevated at 1.42. This represents a 42% increase in risk for recurrent C. difficile infection for patients taking PPIs, Dr. Linsky and her colleagues said (Arch. Intern. Med. 2010;170:772-8).

In the second study, Dr. Michael D. Howell of Beth Israel Deaconess Medical Center, Boston, and his associates performed a secondary analysis of data prospectively collected on 101,796 discharges from their center in 2004-2008. Nosocomial C. difficile infection had developed in 665 (0.7%) of these cases.

In unadjusted analysis, the risk of acquiring the infection rose from 0.3% with no exposure to PPIs to 0.9% with daily use of PPIs to 1.4% with more frequent than daily use of PPIs.

This dose-response effect persisted after the data were adjusted to account for patient age, comorbid conditions, and receipt of antibiotics. The odds ratios were 1 (reference) for no exposure to PPIs, 1.74 for daily exposure, and 2.36 for more frequent exposure to PPIs. This represents more than a 70% increase in the risk of developing nosocomial C. difficile if a patient is taking a daily PPI, and more than a doubling of the odds if a patient is taking the drugs more frequently, Dr. Howell and his colleagues said (Arch. Intern. Med. 2010;170:784-90).

The findings suggest that “we should expect at least 1 additional case of nosocomial C. difficile infection for every 533 patients who receive a daily PPI, after controlling for other risk factors,” Dr. Howell and associates noted.

“Although this seems like a relatively large number-needed-to-harm, the magnitude of exposure is large. We found that 60% of patients received acid-suppressive therapy, similar to others' estimates,” the researchers added.

Given the widespread use of PPIs and the millions of hospital discharges every year, “the number of potentially attributable nosocomial C. difficile cases in the United States numbers in the tens of thousands per year,” they noted.

This figure is particularly alarming because research has shown that PPIs are not strictly indicated for more than two-thirds of inpatients who receive them, added Dr. Howell and his colleagues, who reported no conflicts of interest.

To limit unnecessary exposure to PPIs, physicians should ensure that every hospitalized patient is given the least-intense acid-suppressive therapy that is appropriate for his or her condition. “In particular, unless and until there is clear evidence that low-risk, noncritically ill patients receive benefit from stress ulcer prophylaxis, we should strive to minimize exposure to acid-suppressive medications in this group,” they said.

Hospitals should reexamine standing protocols that include stress ulcer prophylaxis, and also should ensure that such medications are discontinued at discharge, they added.

Major Finding: Proton pump inhibitor use during treatment for incident C. difficile infection was associated with a 42% higher risk of C. difficile recurrence.

Data Source: 1,136 patients in the pharmacy and administrative databases of eight Veterans Affairs medical centers in New England.

Disclosures: Support was provided by the VA Cooperative Studies Program and the VA Boston Healthcare System. No financial conflicts of interest were reported.

Use of proton pump inhibitors appears to increase the risk of recurrent Clostridium difficile infection and may even have a causal effect, according to two cohort studies.

In the first study, PPI use during treatment for an incident C. difficile infection was associated with a 42% higher risk of recurrent C. difficile infection. The second study demonstrated a dose-response effect between increasing levels of acid suppression among inpatients taking PPIs and increasing risk for nosocomial C. difficile infection.

Neither study was designed to definitively establish causality; an adequately sized randomized controlled trial would be both prohibitively expensive and possibly unethical. But both of these studies add to the growing body of evidence linking PPIs with C. difficile infection, and their findings should prompt clinicians to take several reasonable, important steps to limit patients' exposure to PPI therapy, both groups of investigators noted.

In the first study, Dr. Amy Linsky of Boston Medical Center and her associates examined pharmacy and administrative databases for eight Veterans Affairs medical centers in New England. They identified 1,166 patients who began treatment for an index case of C. difficile during a 4-year period.

This included 527 patients (45%) who used an oral PPI at some time during the 14 days following diagnosis and 639 (55%) who did not use any PPIs during that interval. Omeprazole was the PPI used by 97% of patients who were given PPI therapy.

The primary end point was recurrent C. difficile infection during the 90 days following the incident diagnosis. This occurred in 25% of the PPI-exposed group, compared with 19% of the nonexposed group, a significant difference.

After the data were adjusted to account for patient age, initial antibiotic treatment, additional antibiotic treatment, duration of hospitalization, and differences in baseline comorbidities and medications, the hazard ratio for PPI exposure remained elevated at 1.42. This represents a 42% increase in risk for recurrent C. difficile infection for patients taking PPIs, Dr. Linsky and her colleagues said (Arch. Intern. Med. 2010;170:772-8).

In the second study, Dr. Michael D. Howell of Beth Israel Deaconess Medical Center, Boston, and his associates performed a secondary analysis of data prospectively collected on 101,796 discharges from their center in 2004-2008. Nosocomial C. difficile infection had developed in 665 (0.7%) of these cases.

In unadjusted analysis, the risk of acquiring the infection rose from 0.3% with no exposure to PPIs to 0.9% with daily use of PPIs to 1.4% with more frequent than daily use of PPIs.

This dose-response effect persisted after the data were adjusted to account for patient age, comorbid conditions, and receipt of antibiotics. The odds ratios were 1 (reference) for no exposure to PPIs, 1.74 for daily exposure, and 2.36 for more frequent exposure to PPIs. This represents more than a 70% increase in the risk of developing nosocomial C. difficile if a patient is taking a daily PPI, and more than a doubling of the odds if a patient is taking the drugs more frequently, Dr. Howell and his colleagues said (Arch. Intern. Med. 2010;170:784-90).

The findings suggest that “we should expect at least 1 additional case of nosocomial C. difficile infection for every 533 patients who receive a daily PPI, after controlling for other risk factors,” Dr. Howell and associates noted.

“Although this seems like a relatively large number-needed-to-harm, the magnitude of exposure is large. We found that 60% of patients received acid-suppressive therapy, similar to others' estimates,” the researchers added.

Given the widespread use of PPIs and the millions of hospital discharges every year, “the number of potentially attributable nosocomial C. difficile cases in the United States numbers in the tens of thousands per year,” they noted.

This figure is particularly alarming because research has shown that PPIs are not strictly indicated for more than two-thirds of inpatients who receive them, added Dr. Howell and his colleagues, who reported no conflicts of interest.

To limit unnecessary exposure to PPIs, physicians should ensure that every hospitalized patient is given the least-intense acid-suppressive therapy that is appropriate for his or her condition. “In particular, unless and until there is clear evidence that low-risk, noncritically ill patients receive benefit from stress ulcer prophylaxis, we should strive to minimize exposure to acid-suppressive medications in this group,” they said.

Hospitals should reexamine standing protocols that include stress ulcer prophylaxis, and also should ensure that such medications are discontinued at discharge, they added.

Major Finding: Proton pump inhibitor use during treatment for incident C. difficile infection was associated with a 42% higher risk of C. difficile recurrence.

Data Source: 1,136 patients in the pharmacy and administrative databases of eight Veterans Affairs medical centers in New England.

Disclosures: Support was provided by the VA Cooperative Studies Program and the VA Boston Healthcare System. No financial conflicts of interest were reported.

Use of proton pump inhibitors appears to increase the risk of recurrent Clostridium difficile infection and may even have a causal effect, according to two cohort studies.

In the first study, PPI use during treatment for an incident C. difficile infection was associated with a 42% higher risk of recurrent C. difficile infection. The second study demonstrated a dose-response effect between increasing levels of acid suppression among inpatients taking PPIs and increasing risk for nosocomial C. difficile infection.

Neither study was designed to definitively establish causality; an adequately sized randomized controlled trial would be both prohibitively expensive and possibly unethical. But both of these studies add to the growing body of evidence linking PPIs with C. difficile infection, and their findings should prompt clinicians to take several reasonable, important steps to limit patients' exposure to PPI therapy, both groups of investigators noted.

In the first study, Dr. Amy Linsky of Boston Medical Center and her associates examined pharmacy and administrative databases for eight Veterans Affairs medical centers in New England. They identified 1,166 patients who began treatment for an index case of C. difficile during a 4-year period.

This included 527 patients (45%) who used an oral PPI at some time during the 14 days following diagnosis and 639 (55%) who did not use any PPIs during that interval. Omeprazole was the PPI used by 97% of patients who were given PPI therapy.

The primary end point was recurrent C. difficile infection during the 90 days following the incident diagnosis. This occurred in 25% of the PPI-exposed group, compared with 19% of the nonexposed group, a significant difference.

After the data were adjusted to account for patient age, initial antibiotic treatment, additional antibiotic treatment, duration of hospitalization, and differences in baseline comorbidities and medications, the hazard ratio for PPI exposure remained elevated at 1.42. This represents a 42% increase in risk for recurrent C. difficile infection for patients taking PPIs, Dr. Linsky and her colleagues said (Arch. Intern. Med. 2010;170:772-8).

In the second study, Dr. Michael D. Howell of Beth Israel Deaconess Medical Center, Boston, and his associates performed a secondary analysis of data prospectively collected on 101,796 discharges from their center in 2004-2008. Nosocomial C. difficile infection had developed in 665 (0.7%) of these cases.

In unadjusted analysis, the risk of acquiring the infection rose from 0.3% with no exposure to PPIs to 0.9% with daily use of PPIs to 1.4% with more frequent than daily use of PPIs.

This dose-response effect persisted after the data were adjusted to account for patient age, comorbid conditions, and receipt of antibiotics. The odds ratios were 1 (reference) for no exposure to PPIs, 1.74 for daily exposure, and 2.36 for more frequent exposure to PPIs. This represents more than a 70% increase in the risk of developing nosocomial C. difficile if a patient is taking a daily PPI, and more than a doubling of the odds if a patient is taking the drugs more frequently, Dr. Howell and his colleagues said (Arch. Intern. Med. 2010;170:784-90).

The findings suggest that “we should expect at least 1 additional case of nosocomial C. difficile infection for every 533 patients who receive a daily PPI, after controlling for other risk factors,” Dr. Howell and associates noted.

“Although this seems like a relatively large number-needed-to-harm, the magnitude of exposure is large. We found that 60% of patients received acid-suppressive therapy, similar to others' estimates,” the researchers added.

Given the widespread use of PPIs and the millions of hospital discharges every year, “the number of potentially attributable nosocomial C. difficile cases in the United States numbers in the tens of thousands per year,” they noted.

This figure is particularly alarming because research has shown that PPIs are not strictly indicated for more than two-thirds of inpatients who receive them, added Dr. Howell and his colleagues, who reported no conflicts of interest.

To limit unnecessary exposure to PPIs, physicians should ensure that every hospitalized patient is given the least-intense acid-suppressive therapy that is appropriate for his or her condition. “In particular, unless and until there is clear evidence that low-risk, noncritically ill patients receive benefit from stress ulcer prophylaxis, we should strive to minimize exposure to acid-suppressive medications in this group,” they said.

Hospitals should reexamine standing protocols that include stress ulcer prophylaxis, and also should ensure that such medications are discontinued at discharge, they added.

The use of proton pump inhibitors doesn't appear to raise the risk of hip fracture in postmenopausal women but may raise the risk of spine, forearm, wrist, and total fractures modestly.

Several large epidemiologic studies have suggested that PPI use may be associated with an increased risk for osteoporotic fractures, but other studies have found no such link. Shelly L. Gray, Pharm.D., and her associates examined the issue using data from the Women's Health Initiative, a large study of an ethnically diverse cohort of postmenopausal women followed at 40 U.S. medical centers for a mean of 7.8 years.

For this analysis, data on 161,806 women aged 50–79 years were included. A total of 3,396 (2%) of these study subjects were taking omeprazole or lansoprazole at baseline.

Women who took PPIs were more likely than those who didn't to have osteoporosis or a history of fractures, obesity, treated diabetes, or a history of several health conditions; to take other medications chronically; and to have poorer self-reported health and physical function. “We did our best to adjust for these baseline differences, but, like all observational studies, residual or unmeasured confounding could explain increased associations for some fracture types,” said Dr. Gray of the University of Washington School of Pharmacy, Seattle, and her colleagues.

During more than a million person-years of follow-up, there were 1,500 hip fractures, 4,881 forearm or wrist fractures, 2,315 clinical spine fractures, and 21,247 total fractures.

After the data were adjusted to account for possible confounding factors, PPI use was not related to hip fracture risk. There also was no association between hip fracture risk and longer duration of PPI use, Dr. Gray and her associates reported (Arch. Intern. Med. 2010;170:765-71).

In addition, there were no differences between women who used PPIs and women who didn't in the change in bone mineral density over time. Similarly, there was no consistent relationship between duration of PPI use and risk of any fracture. However, the drugs raised the relative risk of clinical spine fracture by 47% (hazard ratio, 1.47); the relative risk of forearm or wrist fracture by 26% (HR, 1.26); and the relative risk of total fractures by 25% (HR, 1.25).

For older patients who do require the treatment, “it is reasonable to focus on using the lowest effective dose, ensuring adequate dietary calcium intake, and adding calcium supplements when necessary,” the investigators said.

In an editorial comment accompanying this report, Dr. Mitchell H. Katz of the San Francisco Department of Public Health characterized the increases in nonhip fractures as “modest” but said that PPIs are so widely used that those modest increases “add up to a lot of morbidity on a population level” (Arch. Intern. Med. 2010;170:747-8).

“Once our patients fully appreciate the adverse effects of PPIs, they themselves may prefer other treatments, including tincture of time”; behavioral changes such as smaller meals, losing weight, quitting smoking, and reducing stress; and nonmedical interventions such as raising the head of the bed, he said.

Disclosures: The WHI Program was funded by the National Heart, Lung, and Blood Institute. Dr. Gray reported no financial conflicts. Her associate, Andrea Z. LaCroix, Ph.D., reported ties to Pfizer Inc., Procter & Gamble Co., and Sanofi-Aventis. Dr. Katz is an independent consultant for Health Management Associates.

The use of proton pump inhibitors doesn't appear to raise the risk of hip fracture in postmenopausal women but may raise the risk of spine, forearm, wrist, and total fractures modestly.

Several large epidemiologic studies have suggested that PPI use may be associated with an increased risk for osteoporotic fractures, but other studies have found no such link. Shelly L. Gray, Pharm.D., and her associates examined the issue using data from the Women's Health Initiative, a large study of an ethnically diverse cohort of postmenopausal women followed at 40 U.S. medical centers for a mean of 7.8 years.

For this analysis, data on 161,806 women aged 50–79 years were included. A total of 3,396 (2%) of these study subjects were taking omeprazole or lansoprazole at baseline.

Women who took PPIs were more likely than those who didn't to have osteoporosis or a history of fractures, obesity, treated diabetes, or a history of several health conditions; to take other medications chronically; and to have poorer self-reported health and physical function. “We did our best to adjust for these baseline differences, but, like all observational studies, residual or unmeasured confounding could explain increased associations for some fracture types,” said Dr. Gray of the University of Washington School of Pharmacy, Seattle, and her colleagues.

During more than a million person-years of follow-up, there were 1,500 hip fractures, 4,881 forearm or wrist fractures, 2,315 clinical spine fractures, and 21,247 total fractures.

After the data were adjusted to account for possible confounding factors, PPI use was not related to hip fracture risk. There also was no association between hip fracture risk and longer duration of PPI use, Dr. Gray and her associates reported (Arch. Intern. Med. 2010;170:765-71).

In addition, there were no differences between women who used PPIs and women who didn't in the change in bone mineral density over time. Similarly, there was no consistent relationship between duration of PPI use and risk of any fracture. However, the drugs raised the relative risk of clinical spine fracture by 47% (hazard ratio, 1.47); the relative risk of forearm or wrist fracture by 26% (HR, 1.26); and the relative risk of total fractures by 25% (HR, 1.25).

For older patients who do require the treatment, “it is reasonable to focus on using the lowest effective dose, ensuring adequate dietary calcium intake, and adding calcium supplements when necessary,” the investigators said.

In an editorial comment accompanying this report, Dr. Mitchell H. Katz of the San Francisco Department of Public Health characterized the increases in nonhip fractures as “modest” but said that PPIs are so widely used that those modest increases “add up to a lot of morbidity on a population level” (Arch. Intern. Med. 2010;170:747-8).

“Once our patients fully appreciate the adverse effects of PPIs, they themselves may prefer other treatments, including tincture of time”; behavioral changes such as smaller meals, losing weight, quitting smoking, and reducing stress; and nonmedical interventions such as raising the head of the bed, he said.

Disclosures: The WHI Program was funded by the National Heart, Lung, and Blood Institute. Dr. Gray reported no financial conflicts. Her associate, Andrea Z. LaCroix, Ph.D., reported ties to Pfizer Inc., Procter & Gamble Co., and Sanofi-Aventis. Dr. Katz is an independent consultant for Health Management Associates.

The use of proton pump inhibitors doesn't appear to raise the risk of hip fracture in postmenopausal women but may raise the risk of spine, forearm, wrist, and total fractures modestly.

Several large epidemiologic studies have suggested that PPI use may be associated with an increased risk for osteoporotic fractures, but other studies have found no such link. Shelly L. Gray, Pharm.D., and her associates examined the issue using data from the Women's Health Initiative, a large study of an ethnically diverse cohort of postmenopausal women followed at 40 U.S. medical centers for a mean of 7.8 years.

For this analysis, data on 161,806 women aged 50–79 years were included. A total of 3,396 (2%) of these study subjects were taking omeprazole or lansoprazole at baseline.

Women who took PPIs were more likely than those who didn't to have osteoporosis or a history of fractures, obesity, treated diabetes, or a history of several health conditions; to take other medications chronically; and to have poorer self-reported health and physical function. “We did our best to adjust for these baseline differences, but, like all observational studies, residual or unmeasured confounding could explain increased associations for some fracture types,” said Dr. Gray of the University of Washington School of Pharmacy, Seattle, and her colleagues.

During more than a million person-years of follow-up, there were 1,500 hip fractures, 4,881 forearm or wrist fractures, 2,315 clinical spine fractures, and 21,247 total fractures.

After the data were adjusted to account for possible confounding factors, PPI use was not related to hip fracture risk. There also was no association between hip fracture risk and longer duration of PPI use, Dr. Gray and her associates reported (Arch. Intern. Med. 2010;170:765-71).

In addition, there were no differences between women who used PPIs and women who didn't in the change in bone mineral density over time. Similarly, there was no consistent relationship between duration of PPI use and risk of any fracture. However, the drugs raised the relative risk of clinical spine fracture by 47% (hazard ratio, 1.47); the relative risk of forearm or wrist fracture by 26% (HR, 1.26); and the relative risk of total fractures by 25% (HR, 1.25).

For older patients who do require the treatment, “it is reasonable to focus on using the lowest effective dose, ensuring adequate dietary calcium intake, and adding calcium supplements when necessary,” the investigators said.

In an editorial comment accompanying this report, Dr. Mitchell H. Katz of the San Francisco Department of Public Health characterized the increases in nonhip fractures as “modest” but said that PPIs are so widely used that those modest increases “add up to a lot of morbidity on a population level” (Arch. Intern. Med. 2010;170:747-8).

“Once our patients fully appreciate the adverse effects of PPIs, they themselves may prefer other treatments, including tincture of time”; behavioral changes such as smaller meals, losing weight, quitting smoking, and reducing stress; and nonmedical interventions such as raising the head of the bed, he said.

Disclosures: The WHI Program was funded by the National Heart, Lung, and Blood Institute. Dr. Gray reported no financial conflicts. Her associate, Andrea Z. LaCroix, Ph.D., reported ties to Pfizer Inc., Procter & Gamble Co., and Sanofi-Aventis. Dr. Katz is an independent consultant for Health Management Associates.

Far from protecting older women from falls and fractures, once-yearly high-dose oral vitamin D raised the risk of falls by 15% and that of fractures by 26%, according to a study by researchers in Australia.

As this study used the “largest total annual dose of vitamin D (500,000 IU) reported in any large randomized controlled trial,” it is possible that these adverse outcomes are related to the dosage, or perhaps to the once-a-year regimen. But the levels of 25-hydroxycholecalciferol achieved in these subjects can also occur with other dosing regimens, so it appears that the safety of all high-dose vitamin D supplementation warrants further examination, said Kerrie M. Sanders, Ph.D., of the University of Melbourne and her associates.

Dr. Sanders and her colleagues performed their single-center study in 2,256 white women aged 70 and older who resided in southern Victoria. They were considered at risk for hip fracture because of their family or personal histories or because they reported recent falls.

The subjects were randomly assigned to receive a single oral dose of vitamin D (cholecalciferol) or a matching placebo at the same time every year for 3–5 years. Lab studies in a subgroup of the subjects showed that the active treatment raised levels of 25-hydroxycholecalciferol an average of 41%, as expected.

There were 5,404 falls during follow-up, involving 74% of the women taking vitamin D and 68% of those taking placebo. The rate of falls was 83 per 100 person-years with vitamin D, compared with 73 per 100 person-years with placebo, a statistically significant difference.

The increase in falls with active treatment was noted in falls that produced fractures, falls that did not produce fractures, and falls that produced soft-tissue injury. The percentage of falls requiring a physician's visit was similar between the two groups of subjects, at approximately 27% in both.

A total of 155 women taking vitamin D sustained 171 fractures during follow-up, compared with 125 women taking placebo who sustained 135 fractures. This translates to a rate of 4.9 fractures per 100 person-years with active treatment and 3.9 fractures per 100 person-years with placebo. These risks did not change after the data were adjusted to account for subjects' calcium intake.

“Contrary to our hypothesis, participants receiving annual high-dose oral cholecalciferol experienced 15% more falls and 26% more fractures than [did] the placebo group. Women not only experienced excess fractures after more frequent falls but also experienced more fractures that were not associated with a fall,” the investigators noted (JAMA 2010;303:1815-22).

“A post hoc analysis found that the increased likelihood of falls in the vitamin D group was exacerbated in the 3-month period immediately following the annual dose, and a similar temporal trend was observed for fractures,” they added.

In an accompanying editorial, Dr. Bess Dawson-Hughes and Susan S. Harris, D.Sc., of the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, said that these study findings should not detract from the importance of “correcting widespread vitamin D deficiency and insufficiency. “There is no evidence for adverse effects of more frequent, lower-dose regimens, so daily, weekly, or monthly dosing with vitamin D₃ appears to be the best option for clinicians at this time,” hey noted (JAMA 2010;303:1861-2).

Dr. Dawson-Hughes and Dr. Harris also explored possible explanations for the study's surprising results. It may be that the single large dose of vitamin D triggered a short-term “protective” reaction in which the enzyme that catabolizes it was upregulated, “resulting in decreased blood and tissue levels of 1,25-dihydroxyvitamin D.” This dropoff may have, in turn, raised the risk of falls and fractures. Alternatively, some as-yet unknown benefit of vitamin D therapy may have had the unintended effect of raising fall and fracture risks. For example, the treatment may have improved physical performance, reduced chronic pain, or improved mood, any of which could lead to increased activity and thereby increased chances for falling.

Disclosures: This study was supported by the National Health and Medical Research Council and the Australian Government Department of Health and Ageing. No conflicts of interest were reported by Dr. Sanders and her associates, Dr. Dawson-Hughes, or Dr. Harris.

Far from protecting older women from falls and fractures, once-yearly high-dose oral vitamin D raised the risk of falls by 15% and that of fractures by 26%, according to a study by researchers in Australia.

As this study used the “largest total annual dose of vitamin D (500,000 IU) reported in any large randomized controlled trial,” it is possible that these adverse outcomes are related to the dosage, or perhaps to the once-a-year regimen. But the levels of 25-hydroxycholecalciferol achieved in these subjects can also occur with other dosing regimens, so it appears that the safety of all high-dose vitamin D supplementation warrants further examination, said Kerrie M. Sanders, Ph.D., of the University of Melbourne and her associates.

Dr. Sanders and her colleagues performed their single-center study in 2,256 white women aged 70 and older who resided in southern Victoria. They were considered at risk for hip fracture because of their family or personal histories or because they reported recent falls.

The subjects were randomly assigned to receive a single oral dose of vitamin D (cholecalciferol) or a matching placebo at the same time every year for 3–5 years. Lab studies in a subgroup of the subjects showed that the active treatment raised levels of 25-hydroxycholecalciferol an average of 41%, as expected.

There were 5,404 falls during follow-up, involving 74% of the women taking vitamin D and 68% of those taking placebo. The rate of falls was 83 per 100 person-years with vitamin D, compared with 73 per 100 person-years with placebo, a statistically significant difference.

The increase in falls with active treatment was noted in falls that produced fractures, falls that did not produce fractures, and falls that produced soft-tissue injury. The percentage of falls requiring a physician's visit was similar between the two groups of subjects, at approximately 27% in both.

A total of 155 women taking vitamin D sustained 171 fractures during follow-up, compared with 125 women taking placebo who sustained 135 fractures. This translates to a rate of 4.9 fractures per 100 person-years with active treatment and 3.9 fractures per 100 person-years with placebo. These risks did not change after the data were adjusted to account for subjects' calcium intake.

“Contrary to our hypothesis, participants receiving annual high-dose oral cholecalciferol experienced 15% more falls and 26% more fractures than [did] the placebo group. Women not only experienced excess fractures after more frequent falls but also experienced more fractures that were not associated with a fall,” the investigators noted (JAMA 2010;303:1815-22).

“A post hoc analysis found that the increased likelihood of falls in the vitamin D group was exacerbated in the 3-month period immediately following the annual dose, and a similar temporal trend was observed for fractures,” they added.

In an accompanying editorial, Dr. Bess Dawson-Hughes and Susan S. Harris, D.Sc., of the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, said that these study findings should not detract from the importance of “correcting widespread vitamin D deficiency and insufficiency. “There is no evidence for adverse effects of more frequent, lower-dose regimens, so daily, weekly, or monthly dosing with vitamin D₃ appears to be the best option for clinicians at this time,” hey noted (JAMA 2010;303:1861-2).

Dr. Dawson-Hughes and Dr. Harris also explored possible explanations for the study's surprising results. It may be that the single large dose of vitamin D triggered a short-term “protective” reaction in which the enzyme that catabolizes it was upregulated, “resulting in decreased blood and tissue levels of 1,25-dihydroxyvitamin D.” This dropoff may have, in turn, raised the risk of falls and fractures. Alternatively, some as-yet unknown benefit of vitamin D therapy may have had the unintended effect of raising fall and fracture risks. For example, the treatment may have improved physical performance, reduced chronic pain, or improved mood, any of which could lead to increased activity and thereby increased chances for falling.

Disclosures: This study was supported by the National Health and Medical Research Council and the Australian Government Department of Health and Ageing. No conflicts of interest were reported by Dr. Sanders and her associates, Dr. Dawson-Hughes, or Dr. Harris.

Far from protecting older women from falls and fractures, once-yearly high-dose oral vitamin D raised the risk of falls by 15% and that of fractures by 26%, according to a study by researchers in Australia.

As this study used the “largest total annual dose of vitamin D (500,000 IU) reported in any large randomized controlled trial,” it is possible that these adverse outcomes are related to the dosage, or perhaps to the once-a-year regimen. But the levels of 25-hydroxycholecalciferol achieved in these subjects can also occur with other dosing regimens, so it appears that the safety of all high-dose vitamin D supplementation warrants further examination, said Kerrie M. Sanders, Ph.D., of the University of Melbourne and her associates.

Dr. Sanders and her colleagues performed their single-center study in 2,256 white women aged 70 and older who resided in southern Victoria. They were considered at risk for hip fracture because of their family or personal histories or because they reported recent falls.

The subjects were randomly assigned to receive a single oral dose of vitamin D (cholecalciferol) or a matching placebo at the same time every year for 3–5 years. Lab studies in a subgroup of the subjects showed that the active treatment raised levels of 25-hydroxycholecalciferol an average of 41%, as expected.

There were 5,404 falls during follow-up, involving 74% of the women taking vitamin D and 68% of those taking placebo. The rate of falls was 83 per 100 person-years with vitamin D, compared with 73 per 100 person-years with placebo, a statistically significant difference.

The increase in falls with active treatment was noted in falls that produced fractures, falls that did not produce fractures, and falls that produced soft-tissue injury. The percentage of falls requiring a physician's visit was similar between the two groups of subjects, at approximately 27% in both.

A total of 155 women taking vitamin D sustained 171 fractures during follow-up, compared with 125 women taking placebo who sustained 135 fractures. This translates to a rate of 4.9 fractures per 100 person-years with active treatment and 3.9 fractures per 100 person-years with placebo. These risks did not change after the data were adjusted to account for subjects' calcium intake.

“Contrary to our hypothesis, participants receiving annual high-dose oral cholecalciferol experienced 15% more falls and 26% more fractures than [did] the placebo group. Women not only experienced excess fractures after more frequent falls but also experienced more fractures that were not associated with a fall,” the investigators noted (JAMA 2010;303:1815-22).

“A post hoc analysis found that the increased likelihood of falls in the vitamin D group was exacerbated in the 3-month period immediately following the annual dose, and a similar temporal trend was observed for fractures,” they added.

In an accompanying editorial, Dr. Bess Dawson-Hughes and Susan S. Harris, D.Sc., of the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, said that these study findings should not detract from the importance of “correcting widespread vitamin D deficiency and insufficiency. “There is no evidence for adverse effects of more frequent, lower-dose regimens, so daily, weekly, or monthly dosing with vitamin D₃ appears to be the best option for clinicians at this time,” hey noted (JAMA 2010;303:1861-2).

Dr. Dawson-Hughes and Dr. Harris also explored possible explanations for the study's surprising results. It may be that the single large dose of vitamin D triggered a short-term “protective” reaction in which the enzyme that catabolizes it was upregulated, “resulting in decreased blood and tissue levels of 1,25-dihydroxyvitamin D.” This dropoff may have, in turn, raised the risk of falls and fractures. Alternatively, some as-yet unknown benefit of vitamin D therapy may have had the unintended effect of raising fall and fracture risks. For example, the treatment may have improved physical performance, reduced chronic pain, or improved mood, any of which could lead to increased activity and thereby increased chances for falling.

Disclosures: This study was supported by the National Health and Medical Research Council and the Australian Government Department of Health and Ageing. No conflicts of interest were reported by Dr. Sanders and her associates, Dr. Dawson-Hughes, or Dr. Harris.

Among older men in an ethnically and socioeconomically diverse California population, those who received pneumococcal vaccine did not have a lower risk of acute MI or stroke than did those who were unvaccinated.

Influenza vaccination has been shown to reduce the risk of MI, stroke, sudden cardiac death, cardiac hospitalization, and the need for revascularization, and similar results recently have been reported for vaccination against pneumococcus, said Hung Fu Tseng, Ph.D., of Kaiser Permanente Southern California, Pasadena, and his associates.

It is thought that respiratory infections can trigger an exaggerated inflammatory response that causes destabilization of atherosclerotic plaques and activation of the coagulation cascade.

To explore the possible protective effect of pneumococcal vaccine against MI and stroke, Dr. Tseng and his colleagues reviewed data from 84,170 men enrolled in the Kaiser health plan who were 45–69 years of age at baseline in 2000 and were followed through 2007.

There were 2,705 incident acute MIs and 1,134 incident strokes.

The rate of MI was 10.7 per 1,000 person-years in men who received at least one pneumococcal vaccination, compared with 6.1 per 1,000 person-years in men who had not received any pneumococcal vaccinations. The rate of stroke was 5.3 per 1,000 person-years in vaccinated men and 1.9 per 1,000 person-year in unvaccinated men.

“We found no evidence for an association between pneumococcal vaccine and reduced risk of acute MI or stroke” in the general study population. Moreover, there also was no protective effect in important subgroups such as smokers, men with diabetes, men with hypertension, and men with low cardiovascular risk (JAMA 2010;303:1699-706).

These results contrast with a well-publicized recent case-control study. Dr. Tseng's study was different in that it controlled for subjects' dietary habits, disease history, and lifestyle factors such as smoking and level of physical activity.

This study was funded by California Cancer Research Program and Kaiser Permanente. Dr. Tseng and his associates reported ties to Merck, the developer of a pneumococcal vaccine, and GlaxoSmithKline.

The MI rate was 10.7/1,000 person-years with vaccination and 6.1 without.

Source ©Pamela Moore/iStockphoto.com

Among older men in an ethnically and socioeconomically diverse California population, those who received pneumococcal vaccine did not have a lower risk of acute MI or stroke than did those who were unvaccinated.

Influenza vaccination has been shown to reduce the risk of MI, stroke, sudden cardiac death, cardiac hospitalization, and the need for revascularization, and similar results recently have been reported for vaccination against pneumococcus, said Hung Fu Tseng, Ph.D., of Kaiser Permanente Southern California, Pasadena, and his associates.

It is thought that respiratory infections can trigger an exaggerated inflammatory response that causes destabilization of atherosclerotic plaques and activation of the coagulation cascade.

To explore the possible protective effect of pneumococcal vaccine against MI and stroke, Dr. Tseng and his colleagues reviewed data from 84,170 men enrolled in the Kaiser health plan who were 45–69 years of age at baseline in 2000 and were followed through 2007.

There were 2,705 incident acute MIs and 1,134 incident strokes.

The rate of MI was 10.7 per 1,000 person-years in men who received at least one pneumococcal vaccination, compared with 6.1 per 1,000 person-years in men who had not received any pneumococcal vaccinations. The rate of stroke was 5.3 per 1,000 person-years in vaccinated men and 1.9 per 1,000 person-year in unvaccinated men.

“We found no evidence for an association between pneumococcal vaccine and reduced risk of acute MI or stroke” in the general study population. Moreover, there also was no protective effect in important subgroups such as smokers, men with diabetes, men with hypertension, and men with low cardiovascular risk (JAMA 2010;303:1699-706).

These results contrast with a well-publicized recent case-control study. Dr. Tseng's study was different in that it controlled for subjects' dietary habits, disease history, and lifestyle factors such as smoking and level of physical activity.

This study was funded by California Cancer Research Program and Kaiser Permanente. Dr. Tseng and his associates reported ties to Merck, the developer of a pneumococcal vaccine, and GlaxoSmithKline.

The MI rate was 10.7/1,000 person-years with vaccination and 6.1 without.

Source ©Pamela Moore/iStockphoto.com

Among older men in an ethnically and socioeconomically diverse California population, those who received pneumococcal vaccine did not have a lower risk of acute MI or stroke than did those who were unvaccinated.

Influenza vaccination has been shown to reduce the risk of MI, stroke, sudden cardiac death, cardiac hospitalization, and the need for revascularization, and similar results recently have been reported for vaccination against pneumococcus, said Hung Fu Tseng, Ph.D., of Kaiser Permanente Southern California, Pasadena, and his associates.

It is thought that respiratory infections can trigger an exaggerated inflammatory response that causes destabilization of atherosclerotic plaques and activation of the coagulation cascade.

To explore the possible protective effect of pneumococcal vaccine against MI and stroke, Dr. Tseng and his colleagues reviewed data from 84,170 men enrolled in the Kaiser health plan who were 45–69 years of age at baseline in 2000 and were followed through 2007.

There were 2,705 incident acute MIs and 1,134 incident strokes.

The rate of MI was 10.7 per 1,000 person-years in men who received at least one pneumococcal vaccination, compared with 6.1 per 1,000 person-years in men who had not received any pneumococcal vaccinations. The rate of stroke was 5.3 per 1,000 person-years in vaccinated men and 1.9 per 1,000 person-year in unvaccinated men.

“We found no evidence for an association between pneumococcal vaccine and reduced risk of acute MI or stroke” in the general study population. Moreover, there also was no protective effect in important subgroups such as smokers, men with diabetes, men with hypertension, and men with low cardiovascular risk (JAMA 2010;303:1699-706).

These results contrast with a well-publicized recent case-control study. Dr. Tseng's study was different in that it controlled for subjects' dietary habits, disease history, and lifestyle factors such as smoking and level of physical activity.

This study was funded by California Cancer Research Program and Kaiser Permanente. Dr. Tseng and his associates reported ties to Merck, the developer of a pneumococcal vaccine, and GlaxoSmithKline.

The MI rate was 10.7/1,000 person-years with vaccination and 6.1 without.

Source ©Pamela Moore/iStockphoto.com

The combined effect of smoking, excessive drinking, poor diet, and physical inactivity is “substantial” and significantly raises premature mortality from all causes, cardiovascular disease, and cancer, according to a U.K. prospective cohort study.

Compared with people who do not exhibit any of these poor lifestyle behaviors, those who exhibit all four are at threefold higher risk of dying prematurely from cardiovascular disease or cancer and at fourfold higher risk of dying prematurely from other causes, said Elisabeth Kvaavik, Ph.D., of the University of Oslo, and her associates.

The investigators assessed the combined influence of these health behaviors on 20-year mortality because almost all previous studies have examined only the individual effects. Since “poor lifestyle choices frequently coexist,” it is important to assess their combined impact on public health as well, they noted.

To do so, Dr. Kvaavik and her colleagues used data from a general survey of multiple health behaviors targeting the entire adult population of the United Kingdom. The survey began in 1984–1985. In this study, data for a subgroup of 4,886 men and women were assessed concerning self-reported smoking and alcohol drinking habits, leisure time exercise activities, and frequency of consuming fruits and vegetables.

During 20-year follow-up, there were 431 deaths from cardiovascular disease, 318 cancer deaths, and 331 deaths from other causes, for a total of 1,080 deaths.

Cumulative survival, adjusted for subject age at baseline and sex, was 96% for those who had none of the poor health behaviors measured, compared with 85% for those who had all four poor health behaviors. This rise in mortality risk was equivalent to an increase in chronological age of about 12 years, the researchers said (Arch. Intern. Med. 2010;170:711-8).

Compared with people who had no poor health behaviors, the risk of each cause of death rose as the number of poor health behaviors increased from one to four.

These findings suggest that “modest but achievable adjustments to lifestyle behaviors are likely to have a considerable impact at both the individual and population level,” Dr. Kvaavik and her associates wrote.

Disclosures: The U.K. survey was funded by the Health Promotion Research Trust. Dr. Kvaavik's study was supported by the Norwegian Research Council, the Medical Research Council (U.K.), Wellcome Trust, and the National Heart Foundation of Australia. No financial conflicts of interest were reported.

The combined effect of smoking, excessive drinking, poor diet, and physical inactivity is “substantial” and significantly raises premature mortality from all causes, cardiovascular disease, and cancer, according to a U.K. prospective cohort study.

Compared with people who do not exhibit any of these poor lifestyle behaviors, those who exhibit all four are at threefold higher risk of dying prematurely from cardiovascular disease or cancer and at fourfold higher risk of dying prematurely from other causes, said Elisabeth Kvaavik, Ph.D., of the University of Oslo, and her associates.

The investigators assessed the combined influence of these health behaviors on 20-year mortality because almost all previous studies have examined only the individual effects. Since “poor lifestyle choices frequently coexist,” it is important to assess their combined impact on public health as well, they noted.

To do so, Dr. Kvaavik and her colleagues used data from a general survey of multiple health behaviors targeting the entire adult population of the United Kingdom. The survey began in 1984–1985. In this study, data for a subgroup of 4,886 men and women were assessed concerning self-reported smoking and alcohol drinking habits, leisure time exercise activities, and frequency of consuming fruits and vegetables.

During 20-year follow-up, there were 431 deaths from cardiovascular disease, 318 cancer deaths, and 331 deaths from other causes, for a total of 1,080 deaths.

Cumulative survival, adjusted for subject age at baseline and sex, was 96% for those who had none of the poor health behaviors measured, compared with 85% for those who had all four poor health behaviors. This rise in mortality risk was equivalent to an increase in chronological age of about 12 years, the researchers said (Arch. Intern. Med. 2010;170:711-8).

Compared with people who had no poor health behaviors, the risk of each cause of death rose as the number of poor health behaviors increased from one to four.

These findings suggest that “modest but achievable adjustments to lifestyle behaviors are likely to have a considerable impact at both the individual and population level,” Dr. Kvaavik and her associates wrote.

Disclosures: The U.K. survey was funded by the Health Promotion Research Trust. Dr. Kvaavik's study was supported by the Norwegian Research Council, the Medical Research Council (U.K.), Wellcome Trust, and the National Heart Foundation of Australia. No financial conflicts of interest were reported.

The combined effect of smoking, excessive drinking, poor diet, and physical inactivity is “substantial” and significantly raises premature mortality from all causes, cardiovascular disease, and cancer, according to a U.K. prospective cohort study.

Compared with people who do not exhibit any of these poor lifestyle behaviors, those who exhibit all four are at threefold higher risk of dying prematurely from cardiovascular disease or cancer and at fourfold higher risk of dying prematurely from other causes, said Elisabeth Kvaavik, Ph.D., of the University of Oslo, and her associates.

The investigators assessed the combined influence of these health behaviors on 20-year mortality because almost all previous studies have examined only the individual effects. Since “poor lifestyle choices frequently coexist,” it is important to assess their combined impact on public health as well, they noted.

To do so, Dr. Kvaavik and her colleagues used data from a general survey of multiple health behaviors targeting the entire adult population of the United Kingdom. The survey began in 1984–1985. In this study, data for a subgroup of 4,886 men and women were assessed concerning self-reported smoking and alcohol drinking habits, leisure time exercise activities, and frequency of consuming fruits and vegetables.

During 20-year follow-up, there were 431 deaths from cardiovascular disease, 318 cancer deaths, and 331 deaths from other causes, for a total of 1,080 deaths.

Cumulative survival, adjusted for subject age at baseline and sex, was 96% for those who had none of the poor health behaviors measured, compared with 85% for those who had all four poor health behaviors. This rise in mortality risk was equivalent to an increase in chronological age of about 12 years, the researchers said (Arch. Intern. Med. 2010;170:711-8).

Compared with people who had no poor health behaviors, the risk of each cause of death rose as the number of poor health behaviors increased from one to four.

These findings suggest that “modest but achievable adjustments to lifestyle behaviors are likely to have a considerable impact at both the individual and population level,” Dr. Kvaavik and her associates wrote.

Disclosures: The U.K. survey was funded by the Health Promotion Research Trust. Dr. Kvaavik's study was supported by the Norwegian Research Council, the Medical Research Council (U.K.), Wellcome Trust, and the National Heart Foundation of Australia. No financial conflicts of interest were reported.

Major depressive disorder is markedly prevalent in patients with traumatic brain injury, developing in half of patients during the year after their injury.

This rate is nearly 8 times higher than that in the general population, and considerably higher than rates of 12% to 42% reported in previous high-quality studies, reported Charles H. Bombardier, Ph.D., and his associates at the University of Washington and Harborview Medical Center, Seattle.

The study enrolled consecutive patients admitted with complicated mild to severe TBI to a level 1 trauma center in 2001–2005. Most of the participants were men who had been injured in vehicular crashes and had sustained complicated mild injuries. Subjects were assessed using the Patient Health Questionnaire (PHQ) depression and anxiety modules at baseline, monthly for 6 months, and bimonthly thereafter for 1 year. At 12 months, they were assessed using the European Quality of Life measure.

A total of 297 patients (53%) met criteria for MDD at some time during that interval (7% in the general population). This also is higher than the rates reported in previous studies of TBI, perhaps because frequent assessments were conducted, and the investigators were able to capture the cases with transient (1-month) major depressive episodes.

In addition, the sample was characterized by high rates of depression-related risk factors such as alcohol dependence and other preinjury mental health diagnoses, Dr. Bombardier and his colleagues said (JAMA 2010;303:1938–45).

The median duration of depression was 4 months. There was no difference in the rate of depression between patients with mild TBI and those with severe TBI.

About half of the patients who developed depression did so within 3 months of their injury. This finding challenges the idea that poor awareness of impairment precludes depressive reactions during the first 6 months after injury. It also suggests that clinicians should act quickly to identify and treat depression, or even to prevent it.

About 16% of the subjects were depressed when they sustained the traumatic injury; another 27% had a history of depression but weren't depressed when injured. The investigators said the study results might not be generalizable because it was conducted at a single level 1 trauma center in the northwest region of the United States.

The National Center for Medical Rehabilitation Research and the National Institutes of Health supported the study. Dr. Bombardier owns stock in Pfizer Inc.

Major depressive disorder is markedly prevalent in patients with traumatic brain injury, developing in half of patients during the year after their injury.

This rate is nearly 8 times higher than that in the general population, and considerably higher than rates of 12% to 42% reported in previous high-quality studies, reported Charles H. Bombardier, Ph.D., and his associates at the University of Washington and Harborview Medical Center, Seattle.

The study enrolled consecutive patients admitted with complicated mild to severe TBI to a level 1 trauma center in 2001–2005. Most of the participants were men who had been injured in vehicular crashes and had sustained complicated mild injuries. Subjects were assessed using the Patient Health Questionnaire (PHQ) depression and anxiety modules at baseline, monthly for 6 months, and bimonthly thereafter for 1 year. At 12 months, they were assessed using the European Quality of Life measure.

A total of 297 patients (53%) met criteria for MDD at some time during that interval (7% in the general population). This also is higher than the rates reported in previous studies of TBI, perhaps because frequent assessments were conducted, and the investigators were able to capture the cases with transient (1-month) major depressive episodes.

In addition, the sample was characterized by high rates of depression-related risk factors such as alcohol dependence and other preinjury mental health diagnoses, Dr. Bombardier and his colleagues said (JAMA 2010;303:1938–45).

The median duration of depression was 4 months. There was no difference in the rate of depression between patients with mild TBI and those with severe TBI.

About half of the patients who developed depression did so within 3 months of their injury. This finding challenges the idea that poor awareness of impairment precludes depressive reactions during the first 6 months after injury. It also suggests that clinicians should act quickly to identify and treat depression, or even to prevent it.

About 16% of the subjects were depressed when they sustained the traumatic injury; another 27% had a history of depression but weren't depressed when injured. The investigators said the study results might not be generalizable because it was conducted at a single level 1 trauma center in the northwest region of the United States.

The National Center for Medical Rehabilitation Research and the National Institutes of Health supported the study. Dr. Bombardier owns stock in Pfizer Inc.

Major depressive disorder is markedly prevalent in patients with traumatic brain injury, developing in half of patients during the year after their injury.

This rate is nearly 8 times higher than that in the general population, and considerably higher than rates of 12% to 42% reported in previous high-quality studies, reported Charles H. Bombardier, Ph.D., and his associates at the University of Washington and Harborview Medical Center, Seattle.

The study enrolled consecutive patients admitted with complicated mild to severe TBI to a level 1 trauma center in 2001–2005. Most of the participants were men who had been injured in vehicular crashes and had sustained complicated mild injuries. Subjects were assessed using the Patient Health Questionnaire (PHQ) depression and anxiety modules at baseline, monthly for 6 months, and bimonthly thereafter for 1 year. At 12 months, they were assessed using the European Quality of Life measure.

A total of 297 patients (53%) met criteria for MDD at some time during that interval (7% in the general population). This also is higher than the rates reported in previous studies of TBI, perhaps because frequent assessments were conducted, and the investigators were able to capture the cases with transient (1-month) major depressive episodes.

In addition, the sample was characterized by high rates of depression-related risk factors such as alcohol dependence and other preinjury mental health diagnoses, Dr. Bombardier and his colleagues said (JAMA 2010;303:1938–45).

The median duration of depression was 4 months. There was no difference in the rate of depression between patients with mild TBI and those with severe TBI.

About half of the patients who developed depression did so within 3 months of their injury. This finding challenges the idea that poor awareness of impairment precludes depressive reactions during the first 6 months after injury. It also suggests that clinicians should act quickly to identify and treat depression, or even to prevent it.

About 16% of the subjects were depressed when they sustained the traumatic injury; another 27% had a history of depression but weren't depressed when injured. The investigators said the study results might not be generalizable because it was conducted at a single level 1 trauma center in the northwest region of the United States.

The National Center for Medical Rehabilitation Research and the National Institutes of Health supported the study. Dr. Bombardier owns stock in Pfizer Inc.

Use of proton pump inhibitors appears to increase the risk of recurrent Clostridium difficile infection and may even have a causal effect, according to two cohort studies.

In the first study, PPI use during treatment for an incident C. difficile infection was associated with a 42% higher risk of recurrent C. difficile infection. The second study showed a dose-response effect between increasing levels of acid suppression among inpatients taking PPIs and increasing risk for nosocomial C. difficile infection.

Neither study was designed to establish causality; a large randomized controlled trial would be prohibitively expensive and possibly unethical. But both of these studies add to the growing body of evidence linking PPIs with C. difficile infection, and their findings should prompt clinicians and hospitals to limit patients' exposure to PPI therapy, both groups of investigators noted.

In the first study, Dr. Amy Linsky of Boston Medical Center and her associates examined pharmacy and administrative databases for eight Veterans Affairs medical centers in New England. They identified 1,166 patients who began treatment for an index case of C. difficile during a 4-year period.

This included 527 patients (45%) who used an oral PPI at some time during the 14 days following diagnosis and 639 (55%) who did not use any PPIs during that interval. Omeprazole was the PPI used by 97% of patients who took one.

The primary end point was recurrent C. difficile infection during the 90 days following the incident diagnosis. This occurred in 25% of the PPI-exposed group, compared with 19% of the nonexposed group, a significant difference.

After the data were adjusted to account for patient age, antibiotic treatment, duration of hospitalization, and differences in baseline comorbidities and medications, there was a 42% increase in risk for recurrent C. difficile infection for patients taking PPIs, Dr. Linsky and her colleagues said (Arch. Intern. Med. 2010;170:772–8).

In the second study, Dr. Michael D. Howell of Beth Israel Deaconess Medical Center, Boston, and his associates performed a secondary analysis of data prospectively collected on 101,796 discharges from their center in 2004–2008. Nosocomial C. difficile infection had developed in 665 (0.7%) of these cases.

In unadjusted analysis, the risk of acquiring the infection rose from 0.3% with no exposure to PPIs to 0.9% with daily use of PPIs to 1.4% with more frequent than daily use of PPIs.

This dose-response effect persisted after the data were adjusted to account for patient age, comorbid conditions, and receipt of antibiotics. The odds ratios were 1 (reference) for no exposure to PPIs, 1.74 for daily exposure, and 2.36 for more frequent exposure to PPIs. This represents more than a 70% increase in the risk of developing nosocomial C. difficile if a patient is taking a daily PPI, and more than a doubling of the odds if a patient is taking the drugs more frequently, Dr. Howell and his colleagues said (Arch. Intern. Med. 2010;170:784–90).

The findings suggest that “we should expect at least 1 additional case of nosocomial C. difficile infection for every 533 patients who receive a daily PPI, after controlling for other risk factors,” they noted.

“Although this seems like a relatively large number-needed-to-harm, the magnitude of exposure is large. We found that 60% of patients received acid-suppressive therapy,” the researchers added.

Given the widespread use of PPIs and the millions of hospital discharges every year, “the number of potentially attributable nosocomial C. difficile cases in the United States numbers in the tens of thousands per year,” they noted.

This figure is particularly alarming because research has shown that PPIs are not strictly indicated for more than two-thirds of inpatients who receive them, Dr. Howell and his colleagues added.

Disclosures: Support for Dr. Linsky's study was provided by the VA Cooperative Studies Program and the VA Boston Healthcare System. No financial conflicts of interest were reported for either study.

Use of proton pump inhibitors appears to increase the risk of recurrent Clostridium difficile infection and may even have a causal effect, according to two cohort studies.

In the first study, PPI use during treatment for an incident C. difficile infection was associated with a 42% higher risk of recurrent C. difficile infection. The second study showed a dose-response effect between increasing levels of acid suppression among inpatients taking PPIs and increasing risk for nosocomial C. difficile infection.

Neither study was designed to establish causality; a large randomized controlled trial would be prohibitively expensive and possibly unethical. But both of these studies add to the growing body of evidence linking PPIs with C. difficile infection, and their findings should prompt clinicians and hospitals to limit patients' exposure to PPI therapy, both groups of investigators noted.

In the first study, Dr. Amy Linsky of Boston Medical Center and her associates examined pharmacy and administrative databases for eight Veterans Affairs medical centers in New England. They identified 1,166 patients who began treatment for an index case of C. difficile during a 4-year period.

This included 527 patients (45%) who used an oral PPI at some time during the 14 days following diagnosis and 639 (55%) who did not use any PPIs during that interval. Omeprazole was the PPI used by 97% of patients who took one.

The primary end point was recurrent C. difficile infection during the 90 days following the incident diagnosis. This occurred in 25% of the PPI-exposed group, compared with 19% of the nonexposed group, a significant difference.

After the data were adjusted to account for patient age, antibiotic treatment, duration of hospitalization, and differences in baseline comorbidities and medications, there was a 42% increase in risk for recurrent C. difficile infection for patients taking PPIs, Dr. Linsky and her colleagues said (Arch. Intern. Med. 2010;170:772–8).

In the second study, Dr. Michael D. Howell of Beth Israel Deaconess Medical Center, Boston, and his associates performed a secondary analysis of data prospectively collected on 101,796 discharges from their center in 2004–2008. Nosocomial C. difficile infection had developed in 665 (0.7%) of these cases.

In unadjusted analysis, the risk of acquiring the infection rose from 0.3% with no exposure to PPIs to 0.9% with daily use of PPIs to 1.4% with more frequent than daily use of PPIs.

This dose-response effect persisted after the data were adjusted to account for patient age, comorbid conditions, and receipt of antibiotics. The odds ratios were 1 (reference) for no exposure to PPIs, 1.74 for daily exposure, and 2.36 for more frequent exposure to PPIs. This represents more than a 70% increase in the risk of developing nosocomial C. difficile if a patient is taking a daily PPI, and more than a doubling of the odds if a patient is taking the drugs more frequently, Dr. Howell and his colleagues said (Arch. Intern. Med. 2010;170:784–90).

The findings suggest that “we should expect at least 1 additional case of nosocomial C. difficile infection for every 533 patients who receive a daily PPI, after controlling for other risk factors,” they noted.

“Although this seems like a relatively large number-needed-to-harm, the magnitude of exposure is large. We found that 60% of patients received acid-suppressive therapy,” the researchers added.

Given the widespread use of PPIs and the millions of hospital discharges every year, “the number of potentially attributable nosocomial C. difficile cases in the United States numbers in the tens of thousands per year,” they noted.

This figure is particularly alarming because research has shown that PPIs are not strictly indicated for more than two-thirds of inpatients who receive them, Dr. Howell and his colleagues added.

Disclosures: Support for Dr. Linsky's study was provided by the VA Cooperative Studies Program and the VA Boston Healthcare System. No financial conflicts of interest were reported for either study.

Use of proton pump inhibitors appears to increase the risk of recurrent Clostridium difficile infection and may even have a causal effect, according to two cohort studies.

In the first study, PPI use during treatment for an incident C. difficile infection was associated with a 42% higher risk of recurrent C. difficile infection. The second study showed a dose-response effect between increasing levels of acid suppression among inpatients taking PPIs and increasing risk for nosocomial C. difficile infection.

Neither study was designed to establish causality; a large randomized controlled trial would be prohibitively expensive and possibly unethical. But both of these studies add to the growing body of evidence linking PPIs with C. difficile infection, and their findings should prompt clinicians and hospitals to limit patients' exposure to PPI therapy, both groups of investigators noted.

In the first study, Dr. Amy Linsky of Boston Medical Center and her associates examined pharmacy and administrative databases for eight Veterans Affairs medical centers in New England. They identified 1,166 patients who began treatment for an index case of C. difficile during a 4-year period.

This included 527 patients (45%) who used an oral PPI at some time during the 14 days following diagnosis and 639 (55%) who did not use any PPIs during that interval. Omeprazole was the PPI used by 97% of patients who took one.

The primary end point was recurrent C. difficile infection during the 90 days following the incident diagnosis. This occurred in 25% of the PPI-exposed group, compared with 19% of the nonexposed group, a significant difference.

After the data were adjusted to account for patient age, antibiotic treatment, duration of hospitalization, and differences in baseline comorbidities and medications, there was a 42% increase in risk for recurrent C. difficile infection for patients taking PPIs, Dr. Linsky and her colleagues said (Arch. Intern. Med. 2010;170:772–8).

In the second study, Dr. Michael D. Howell of Beth Israel Deaconess Medical Center, Boston, and his associates performed a secondary analysis of data prospectively collected on 101,796 discharges from their center in 2004–2008. Nosocomial C. difficile infection had developed in 665 (0.7%) of these cases.

In unadjusted analysis, the risk of acquiring the infection rose from 0.3% with no exposure to PPIs to 0.9% with daily use of PPIs to 1.4% with more frequent than daily use of PPIs.

This dose-response effect persisted after the data were adjusted to account for patient age, comorbid conditions, and receipt of antibiotics. The odds ratios were 1 (reference) for no exposure to PPIs, 1.74 for daily exposure, and 2.36 for more frequent exposure to PPIs. This represents more than a 70% increase in the risk of developing nosocomial C. difficile if a patient is taking a daily PPI, and more than a doubling of the odds if a patient is taking the drugs more frequently, Dr. Howell and his colleagues said (Arch. Intern. Med. 2010;170:784–90).

The findings suggest that “we should expect at least 1 additional case of nosocomial C. difficile infection for every 533 patients who receive a daily PPI, after controlling for other risk factors,” they noted.

“Although this seems like a relatively large number-needed-to-harm, the magnitude of exposure is large. We found that 60% of patients received acid-suppressive therapy,” the researchers added.

Given the widespread use of PPIs and the millions of hospital discharges every year, “the number of potentially attributable nosocomial C. difficile cases in the United States numbers in the tens of thousands per year,” they noted.

This figure is particularly alarming because research has shown that PPIs are not strictly indicated for more than two-thirds of inpatients who receive them, Dr. Howell and his colleagues added.

Disclosures: Support for Dr. Linsky's study was provided by the VA Cooperative Studies Program and the VA Boston Healthcare System. No financial conflicts of interest were reported for either study.

Physical activity prevents weight gain in middle-aged and older women only if they are already of low or ideal weight, not in those with body mass indexes of 25 or more, according to a large 13-year study.

Even lighter women must sustain vigorous physical activity—1 hour or more of moderate-intensity activity every day, on average—to prevent weight gain over time. Women who exercise regularly but do so at lower intensity gain weight at the same rate as those who are inactive, said I-Min Lee, Sc.D., of Brigham and Women's Hospital, Boston, and her associates.

These findings imply that following federal and other recommendations advocating 150 minutes of physical activity per week isn't sufficient to prevent weight gain in most middle-aged women, although it may well provide other health benefits, the investigators noted.

Dr. Lee and her colleagues assessed weight changes associated with various levels of physical activity, they said, because different expert groups have recommended widely varying levels of activity. For example, the federal government, the American College of Sports Medicine, and the American Heart Association recommend a minimum of 150 minutes per week, while the Institute of Medicine suggests nearly three times that amount, 420 minutes per week, to avoid becoming overweight or obese.

The researchers examined the issue using data from the Women's Health Study, a prospective cohort study of healthy women who had a mean age of 54 years at baseline in 1992. The team assessed 34,079 of these subjects who have been followed up on periodically since the main portion of that study was concluded in 2004.

At baseline, approximately half the women were classified as inactive, performing less than 150 minutes per week of moderate-level physical activity such as brisk walking, running, bicycling, swimming, weight training, or aerobic dance or exercise. Another 29% performed an intermediate amount of physical activity, and 22% performed a high level, at 21 or more hours of such activity per week.

In an initial data analysis, all three groups showed similar patterns of weight gain over a mean 13 years of follow-up. The inactive group gained a mean of 0.12 kg and the intermediate group gained 0.11 kg, which was an insignificant difference.

Further analysis showed, however, that women starting with BMIs lower than 25 showed an inverse correlation between physical activity and weight gain (JAMA 2010;303:1173-9).

Another analysis examined the likelihood of gaining 2.3 kg or more over the course of 3 years. Again, there was no correlation between activity level and weight gain except in the subgroup of women with BMIs lower than 25. Only in those women did a high level of activity prevent weight gain.

Finally, an analysis of the subgroup of women of normal weight who maintained that weight throughout follow-up showed that they spent at least 60 minutes per day performing moderately intense activity.

These findings indicate that once women are overweight, “it may be too late” for physical activity to stave off further weight gain, the investigators said.

Disclosures: This study was supported by the National Institutes of Health. The authors reported no relevant financial conflicts of interest.

Once women are overweight, “it may be too late” for physical activity to stave off further weight gain.

Source ©Elena Korenbaum/iStockphoto.com

Physical activity prevents weight gain in middle-aged and older women only if they are already of low or ideal weight, not in those with body mass indexes of 25 or more, according to a large 13-year study.

Even lighter women must sustain vigorous physical activity—1 hour or more of moderate-intensity activity every day, on average—to prevent weight gain over time. Women who exercise regularly but do so at lower intensity gain weight at the same rate as those who are inactive, said I-Min Lee, Sc.D., of Brigham and Women's Hospital, Boston, and her associates.

These findings imply that following federal and other recommendations advocating 150 minutes of physical activity per week isn't sufficient to prevent weight gain in most middle-aged women, although it may well provide other health benefits, the investigators noted.

Dr. Lee and her colleagues assessed weight changes associated with various levels of physical activity, they said, because different expert groups have recommended widely varying levels of activity. For example, the federal government, the American College of Sports Medicine, and the American Heart Association recommend a minimum of 150 minutes per week, while the Institute of Medicine suggests nearly three times that amount, 420 minutes per week, to avoid becoming overweight or obese.

The researchers examined the issue using data from the Women's Health Study, a prospective cohort study of healthy women who had a mean age of 54 years at baseline in 1992. The team assessed 34,079 of these subjects who have been followed up on periodically since the main portion of that study was concluded in 2004.

At baseline, approximately half the women were classified as inactive, performing less than 150 minutes per week of moderate-level physical activity such as brisk walking, running, bicycling, swimming, weight training, or aerobic dance or exercise. Another 29% performed an intermediate amount of physical activity, and 22% performed a high level, at 21 or more hours of such activity per week.

In an initial data analysis, all three groups showed similar patterns of weight gain over a mean 13 years of follow-up. The inactive group gained a mean of 0.12 kg and the intermediate group gained 0.11 kg, which was an insignificant difference.

Further analysis showed, however, that women starting with BMIs lower than 25 showed an inverse correlation between physical activity and weight gain (JAMA 2010;303:1173-9).

Another analysis examined the likelihood of gaining 2.3 kg or more over the course of 3 years. Again, there was no correlation between activity level and weight gain except in the subgroup of women with BMIs lower than 25. Only in those women did a high level of activity prevent weight gain.

Finally, an analysis of the subgroup of women of normal weight who maintained that weight throughout follow-up showed that they spent at least 60 minutes per day performing moderately intense activity.

These findings indicate that once women are overweight, “it may be too late” for physical activity to stave off further weight gain, the investigators said.

Disclosures: This study was supported by the National Institutes of Health. The authors reported no relevant financial conflicts of interest.

Once women are overweight, “it may be too late” for physical activity to stave off further weight gain.

Source ©Elena Korenbaum/iStockphoto.com

Physical activity prevents weight gain in middle-aged and older women only if they are already of low or ideal weight, not in those with body mass indexes of 25 or more, according to a large 13-year study.

Even lighter women must sustain vigorous physical activity—1 hour or more of moderate-intensity activity every day, on average—to prevent weight gain over time. Women who exercise regularly but do so at lower intensity gain weight at the same rate as those who are inactive, said I-Min Lee, Sc.D., of Brigham and Women's Hospital, Boston, and her associates.

These findings imply that following federal and other recommendations advocating 150 minutes of physical activity per week isn't sufficient to prevent weight gain in most middle-aged women, although it may well provide other health benefits, the investigators noted.

Dr. Lee and her colleagues assessed weight changes associated with various levels of physical activity, they said, because different expert groups have recommended widely varying levels of activity. For example, the federal government, the American College of Sports Medicine, and the American Heart Association recommend a minimum of 150 minutes per week, while the Institute of Medicine suggests nearly three times that amount, 420 minutes per week, to avoid becoming overweight or obese.

The researchers examined the issue using data from the Women's Health Study, a prospective cohort study of healthy women who had a mean age of 54 years at baseline in 1992. The team assessed 34,079 of these subjects who have been followed up on periodically since the main portion of that study was concluded in 2004.

At baseline, approximately half the women were classified as inactive, performing less than 150 minutes per week of moderate-level physical activity such as brisk walking, running, bicycling, swimming, weight training, or aerobic dance or exercise. Another 29% performed an intermediate amount of physical activity, and 22% performed a high level, at 21 or more hours of such activity per week.

In an initial data analysis, all three groups showed similar patterns of weight gain over a mean 13 years of follow-up. The inactive group gained a mean of 0.12 kg and the intermediate group gained 0.11 kg, which was an insignificant difference.

Further analysis showed, however, that women starting with BMIs lower than 25 showed an inverse correlation between physical activity and weight gain (JAMA 2010;303:1173-9).

Another analysis examined the likelihood of gaining 2.3 kg or more over the course of 3 years. Again, there was no correlation between activity level and weight gain except in the subgroup of women with BMIs lower than 25. Only in those women did a high level of activity prevent weight gain.

Finally, an analysis of the subgroup of women of normal weight who maintained that weight throughout follow-up showed that they spent at least 60 minutes per day performing moderately intense activity.

These findings indicate that once women are overweight, “it may be too late” for physical activity to stave off further weight gain, the investigators said.

Disclosures: This study was supported by the National Institutes of Health. The authors reported no relevant financial conflicts of interest.

Once women are overweight, “it may be too late” for physical activity to stave off further weight gain.

Source ©Elena Korenbaum/iStockphoto.com

Adding the coronary artery calcium score to traditional risk factors significantly improved asymptomatic patients' risk classification for coronary heart disease, in an analysis of the Multi-Ethnic Study of Atherosclerosis.”

“Incorporation of an individual's CACS leads to a more refined estimation of future risk of CHD events than [do] traditional risk factors alone,” said Dr. Tamar S. Polonsky of Northwestern University, Chicago, and associates.

However, this finding “will need to be validated in additional populations” before CACS can be adopted into routine clinical practice, they noted. More importantly, it still hasn't been determined whether screening for subclinical disease using CACS actually improves patient outcomes, they cautioned.

In an editorial comment accompanying this report, Dr. John P.A. Ioannidis of the University of Ioannina (Greece) and Harvard School of Public Health, Boston, and Ioanna Tzoulaki, Ph.D., of Imperial College of Medicine, London, agreed that these study results, “no matter how promising, do not suffice to recommend this marker for widespread routine use.”

In addition to the clinical utility of obtaining the CACS, the considerable cost of the procedure and its potential harms due to radiation exposure must be thoroughly examined. “The evidence to date suggests that while CACS is a promising tool, the verdict is not yet in as to whether it is ready for routine use, and much more is still left to do,” wrote Dr. Ioannidis and Dr. Tzoulaki (JAMA 2010;303:1646-7).

Dr. Polonsky and colleagues assessed CACS using data from the Multi-Ethnic Study of Atherosclerosis, a cohort study of more than 6,800 white, black, Hispanic, and Chinese Americans aged 45-84 years who had no known cardiovascular disease at enrollment in 2000-2002. For their study, the investigators included 5,878 of these subjects who had undergone CT scanning for coronary calcium assessment at baseline and who had been followed every 9-12 months for a median of 6 years.

There were 209 CHD events during follow-up, including 96 MIs and 14 CHD deaths.

Adding CACS to the risk prediction model resulted in the reclassification of 26% of the sample. “Overall, 728 individuals in the entire cohort were reclassified to a higher risk category, with an event rate of 8.7%, and 814 were reclassified to a lower risk category, with an event rate of 2.7%,” Dr. Polonsky and her associates said (JAMA 2010;303:1610-6).

An important measure of a risk marker's usefulness “is whether it separates individuals into more clinically relevant risk categories. Ideally, a model would reclassify most of the individuals out of the intermediate-risk group and into the highest or lowest risk categories.”

Adding CACS to the risk prediction model placed 77% of the total study population into definitive highest-risk or lowest-risk categories, where treatment strategies are more straightforward, as opposed to the somewhat nebulous “intermediate risk” category. In comparison, only 69% of the study population was classified as highest or lowest risk when CACS was not added to the model.

A caveat: Patients in this study classified as low risk using CACS actually had an event rate that was higher than was predicted by the model. Therefore an important portion of patients thought to be at low risk did experience a coronary event. This study was supported by the National Heart, Lung, and Blood Institute and the National Center for Research Resources. Dr. Polonsky's associates reported receiving support from Pfizer and GE/Toshiba.

Adding the coronary artery calcium score to traditional risk factors significantly improved asymptomatic patients' risk classification for coronary heart disease, in an analysis of the Multi-Ethnic Study of Atherosclerosis.”

“Incorporation of an individual's CACS leads to a more refined estimation of future risk of CHD events than [do] traditional risk factors alone,” said Dr. Tamar S. Polonsky of Northwestern University, Chicago, and associates.

However, this finding “will need to be validated in additional populations” before CACS can be adopted into routine clinical practice, they noted. More importantly, it still hasn't been determined whether screening for subclinical disease using CACS actually improves patient outcomes, they cautioned.

In an editorial comment accompanying this report, Dr. John P.A. Ioannidis of the University of Ioannina (Greece) and Harvard School of Public Health, Boston, and Ioanna Tzoulaki, Ph.D., of Imperial College of Medicine, London, agreed that these study results, “no matter how promising, do not suffice to recommend this marker for widespread routine use.”

In addition to the clinical utility of obtaining the CACS, the considerable cost of the procedure and its potential harms due to radiation exposure must be thoroughly examined. “The evidence to date suggests that while CACS is a promising tool, the verdict is not yet in as to whether it is ready for routine use, and much more is still left to do,” wrote Dr. Ioannidis and Dr. Tzoulaki (JAMA 2010;303:1646-7).

Dr. Polonsky and colleagues assessed CACS using data from the Multi-Ethnic Study of Atherosclerosis, a cohort study of more than 6,800 white, black, Hispanic, and Chinese Americans aged 45-84 years who had no known cardiovascular disease at enrollment in 2000-2002. For their study, the investigators included 5,878 of these subjects who had undergone CT scanning for coronary calcium assessment at baseline and who had been followed every 9-12 months for a median of 6 years.

There were 209 CHD events during follow-up, including 96 MIs and 14 CHD deaths.

Adding CACS to the risk prediction model resulted in the reclassification of 26% of the sample. “Overall, 728 individuals in the entire cohort were reclassified to a higher risk category, with an event rate of 8.7%, and 814 were reclassified to a lower risk category, with an event rate of 2.7%,” Dr. Polonsky and her associates said (JAMA 2010;303:1610-6).

An important measure of a risk marker's usefulness “is whether it separates individuals into more clinically relevant risk categories. Ideally, a model would reclassify most of the individuals out of the intermediate-risk group and into the highest or lowest risk categories.”

Adding CACS to the risk prediction model placed 77% of the total study population into definitive highest-risk or lowest-risk categories, where treatment strategies are more straightforward, as opposed to the somewhat nebulous “intermediate risk” category. In comparison, only 69% of the study population was classified as highest or lowest risk when CACS was not added to the model.

A caveat: Patients in this study classified as low risk using CACS actually had an event rate that was higher than was predicted by the model. Therefore an important portion of patients thought to be at low risk did experience a coronary event. This study was supported by the National Heart, Lung, and Blood Institute and the National Center for Research Resources. Dr. Polonsky's associates reported receiving support from Pfizer and GE/Toshiba.

Adding the coronary artery calcium score to traditional risk factors significantly improved asymptomatic patients' risk classification for coronary heart disease, in an analysis of the Multi-Ethnic Study of Atherosclerosis.”

“Incorporation of an individual's CACS leads to a more refined estimation of future risk of CHD events than [do] traditional risk factors alone,” said Dr. Tamar S. Polonsky of Northwestern University, Chicago, and associates.

However, this finding “will need to be validated in additional populations” before CACS can be adopted into routine clinical practice, they noted. More importantly, it still hasn't been determined whether screening for subclinical disease using CACS actually improves patient outcomes, they cautioned.

In an editorial comment accompanying this report, Dr. John P.A. Ioannidis of the University of Ioannina (Greece) and Harvard School of Public Health, Boston, and Ioanna Tzoulaki, Ph.D., of Imperial College of Medicine, London, agreed that these study results, “no matter how promising, do not suffice to recommend this marker for widespread routine use.”

In addition to the clinical utility of obtaining the CACS, the considerable cost of the procedure and its potential harms due to radiation exposure must be thoroughly examined. “The evidence to date suggests that while CACS is a promising tool, the verdict is not yet in as to whether it is ready for routine use, and much more is still left to do,” wrote Dr. Ioannidis and Dr. Tzoulaki (JAMA 2010;303:1646-7).

Dr. Polonsky and colleagues assessed CACS using data from the Multi-Ethnic Study of Atherosclerosis, a cohort study of more than 6,800 white, black, Hispanic, and Chinese Americans aged 45-84 years who had no known cardiovascular disease at enrollment in 2000-2002. For their study, the investigators included 5,878 of these subjects who had undergone CT scanning for coronary calcium assessment at baseline and who had been followed every 9-12 months for a median of 6 years.

There were 209 CHD events during follow-up, including 96 MIs and 14 CHD deaths.

Adding CACS to the risk prediction model resulted in the reclassification of 26% of the sample. “Overall, 728 individuals in the entire cohort were reclassified to a higher risk category, with an event rate of 8.7%, and 814 were reclassified to a lower risk category, with an event rate of 2.7%,” Dr. Polonsky and her associates said (JAMA 2010;303:1610-6).

An important measure of a risk marker's usefulness “is whether it separates individuals into more clinically relevant risk categories. Ideally, a model would reclassify most of the individuals out of the intermediate-risk group and into the highest or lowest risk categories.”

Adding CACS to the risk prediction model placed 77% of the total study population into definitive highest-risk or lowest-risk categories, where treatment strategies are more straightforward, as opposed to the somewhat nebulous “intermediate risk” category. In comparison, only 69% of the study population was classified as highest or lowest risk when CACS was not added to the model.

A caveat: Patients in this study classified as low risk using CACS actually had an event rate that was higher than was predicted by the model. Therefore an important portion of patients thought to be at low risk did experience a coronary event. This study was supported by the National Heart, Lung, and Blood Institute and the National Center for Research Resources. Dr. Polonsky's associates reported receiving support from Pfizer and GE/Toshiba.