Mary Ann Moon

Instead of fading as time passes, mental health problems, including posttraumatic stress disorder and depression, actually increase late in the year after combat veterans return from serving in Iraq, according to a report in the June issue of the Archives of General Psychiatry.

In a cross-sectional study of more than 13,000 returning veterans of ground combat, both PTSD and depression not only persisted, they actually increased between 3 months and 12 months after return from duty in Iraq.

“Despite efforts to systematically assess soldiers following deployment, dispel stigma, encourage treatment, and improve access to care, the prevalence rates … showed increases…. These data make clear that at 12 months, many combat soldiers have not psychologically recovered,” said Jeffrey L. Thomas, Ph.D., Walter Reed Army Institute of Research, Silver Spring, Md., and his associates.

PTSD and depression both were associated with increases in aggressive behaviors and misuse of alcohol in these patients, and half of those affected reported serious functional impairment. Since it is “a virtual certainty” that veterans who remain in the service will have to deploy again to combat zones—usually after 1 year of “dwell time” away from combat—“a sizable proportion” will be struggling with their symptoms when they redeploy, the investigators noted.

Dr. Thomas and his colleagues collected anonymous survey data from 4,933 active-duty soldiers at 3–4 months after they returned from ground combat, 4,024 active-duty soldiers at 12 months after return, 2,684 National Guard soldiers from ground combat units at 3–4 months after return, and 1,585 National Guard soldiers from the same ground combat units at 12 months after return.

The researchers assessed PTSD symptoms (collected on the 17-item PTSD Checklist) according to seven case definitions of the disorder, as well as depression symptoms (collected on the 9-item Patient Health Questionnaire) using three case definitions of depression.

From 8% to 14% of all soldiers reported serious functional impairment because of either PTSD or depression symptoms 1 year after returning from combat, Dr. Thomas and his colleagues said (Arch. Gen. Psychiatry 2010;67:614–23).

With the least stringent diagnostic criteria, PTSD prevalence 1 year after return from active combat ranged from 21% to 31%. With the most stringent criteria, which included only patients with high symptom rates and serious functional impairment, PTSD prevalence ranged from 6% to 11%.

The least stringent diagnostic criteria yielded a depression prevalence rate at 1 year from 12% to 16%; with the most stringent criteria, depression prevalence ranged from 5% to 8%.

National Guard soldiers had a higher prevalence of both disorders than did active-duty soldiers by all criteria and at all time points. The estimated prevalence of either depression or PTSD based on strict DSM-IV criteria was 23% for active-duty soldiers and 28% for National Guard soldiers at 1 year.

This difference is likely related to the fact that National Guard soldiers immediately return to civilian life upon return from combat duty, so they must make a more difficult adjustment, have less access to veterans' health care, and have less support from combat-exposed peers than active-duty soldiers who remain in the military, the investigators noted.

Comorbid aggression and alcohol misuse were common across all case definitions, with approximately half of soldiers who had PTSD or depression reporting that they had kicked or smashed something, slammed doors, threatened someone with physical violence, gotten into a fight, needed to cut down on their drinking, and had drunk more than they meant to since returning from combat.

“These findings indicate that it may be beneficial to screen for alcohol and aggressive behaviors when soldiers present for treatment of PTSD or depression,” Dr. Thomas and his associates said.

Disclosures: This study was supported by the U.S. Army Medical Research and Material Command, Fort Detrick, Md. No financial conflicts were reported.

Instead of fading as time passes, mental health problems, including posttraumatic stress disorder and depression, actually increase late in the year after combat veterans return from serving in Iraq, according to a report in the June issue of the Archives of General Psychiatry.

In a cross-sectional study of more than 13,000 returning veterans of ground combat, both PTSD and depression not only persisted, they actually increased between 3 months and 12 months after return from duty in Iraq.

“Despite efforts to systematically assess soldiers following deployment, dispel stigma, encourage treatment, and improve access to care, the prevalence rates … showed increases…. These data make clear that at 12 months, many combat soldiers have not psychologically recovered,” said Jeffrey L. Thomas, Ph.D., Walter Reed Army Institute of Research, Silver Spring, Md., and his associates.

PTSD and depression both were associated with increases in aggressive behaviors and misuse of alcohol in these patients, and half of those affected reported serious functional impairment. Since it is “a virtual certainty” that veterans who remain in the service will have to deploy again to combat zones—usually after 1 year of “dwell time” away from combat—“a sizable proportion” will be struggling with their symptoms when they redeploy, the investigators noted.

Dr. Thomas and his colleagues collected anonymous survey data from 4,933 active-duty soldiers at 3–4 months after they returned from ground combat, 4,024 active-duty soldiers at 12 months after return, 2,684 National Guard soldiers from ground combat units at 3–4 months after return, and 1,585 National Guard soldiers from the same ground combat units at 12 months after return.

The researchers assessed PTSD symptoms (collected on the 17-item PTSD Checklist) according to seven case definitions of the disorder, as well as depression symptoms (collected on the 9-item Patient Health Questionnaire) using three case definitions of depression.

From 8% to 14% of all soldiers reported serious functional impairment because of either PTSD or depression symptoms 1 year after returning from combat, Dr. Thomas and his colleagues said (Arch. Gen. Psychiatry 2010;67:614–23).

With the least stringent diagnostic criteria, PTSD prevalence 1 year after return from active combat ranged from 21% to 31%. With the most stringent criteria, which included only patients with high symptom rates and serious functional impairment, PTSD prevalence ranged from 6% to 11%.

The least stringent diagnostic criteria yielded a depression prevalence rate at 1 year from 12% to 16%; with the most stringent criteria, depression prevalence ranged from 5% to 8%.

National Guard soldiers had a higher prevalence of both disorders than did active-duty soldiers by all criteria and at all time points. The estimated prevalence of either depression or PTSD based on strict DSM-IV criteria was 23% for active-duty soldiers and 28% for National Guard soldiers at 1 year.

This difference is likely related to the fact that National Guard soldiers immediately return to civilian life upon return from combat duty, so they must make a more difficult adjustment, have less access to veterans' health care, and have less support from combat-exposed peers than active-duty soldiers who remain in the military, the investigators noted.

Comorbid aggression and alcohol misuse were common across all case definitions, with approximately half of soldiers who had PTSD or depression reporting that they had kicked or smashed something, slammed doors, threatened someone with physical violence, gotten into a fight, needed to cut down on their drinking, and had drunk more than they meant to since returning from combat.

“These findings indicate that it may be beneficial to screen for alcohol and aggressive behaviors when soldiers present for treatment of PTSD or depression,” Dr. Thomas and his associates said.

Disclosures: This study was supported by the U.S. Army Medical Research and Material Command, Fort Detrick, Md. No financial conflicts were reported.

Instead of fading as time passes, mental health problems, including posttraumatic stress disorder and depression, actually increase late in the year after combat veterans return from serving in Iraq, according to a report in the June issue of the Archives of General Psychiatry.

In a cross-sectional study of more than 13,000 returning veterans of ground combat, both PTSD and depression not only persisted, they actually increased between 3 months and 12 months after return from duty in Iraq.

“Despite efforts to systematically assess soldiers following deployment, dispel stigma, encourage treatment, and improve access to care, the prevalence rates … showed increases…. These data make clear that at 12 months, many combat soldiers have not psychologically recovered,” said Jeffrey L. Thomas, Ph.D., Walter Reed Army Institute of Research, Silver Spring, Md., and his associates.

PTSD and depression both were associated with increases in aggressive behaviors and misuse of alcohol in these patients, and half of those affected reported serious functional impairment. Since it is “a virtual certainty” that veterans who remain in the service will have to deploy again to combat zones—usually after 1 year of “dwell time” away from combat—“a sizable proportion” will be struggling with their symptoms when they redeploy, the investigators noted.

Dr. Thomas and his colleagues collected anonymous survey data from 4,933 active-duty soldiers at 3–4 months after they returned from ground combat, 4,024 active-duty soldiers at 12 months after return, 2,684 National Guard soldiers from ground combat units at 3–4 months after return, and 1,585 National Guard soldiers from the same ground combat units at 12 months after return.

The researchers assessed PTSD symptoms (collected on the 17-item PTSD Checklist) according to seven case definitions of the disorder, as well as depression symptoms (collected on the 9-item Patient Health Questionnaire) using three case definitions of depression.

From 8% to 14% of all soldiers reported serious functional impairment because of either PTSD or depression symptoms 1 year after returning from combat, Dr. Thomas and his colleagues said (Arch. Gen. Psychiatry 2010;67:614–23).

With the least stringent diagnostic criteria, PTSD prevalence 1 year after return from active combat ranged from 21% to 31%. With the most stringent criteria, which included only patients with high symptom rates and serious functional impairment, PTSD prevalence ranged from 6% to 11%.

The least stringent diagnostic criteria yielded a depression prevalence rate at 1 year from 12% to 16%; with the most stringent criteria, depression prevalence ranged from 5% to 8%.

National Guard soldiers had a higher prevalence of both disorders than did active-duty soldiers by all criteria and at all time points. The estimated prevalence of either depression or PTSD based on strict DSM-IV criteria was 23% for active-duty soldiers and 28% for National Guard soldiers at 1 year.

This difference is likely related to the fact that National Guard soldiers immediately return to civilian life upon return from combat duty, so they must make a more difficult adjustment, have less access to veterans' health care, and have less support from combat-exposed peers than active-duty soldiers who remain in the military, the investigators noted.

Comorbid aggression and alcohol misuse were common across all case definitions, with approximately half of soldiers who had PTSD or depression reporting that they had kicked or smashed something, slammed doors, threatened someone with physical violence, gotten into a fight, needed to cut down on their drinking, and had drunk more than they meant to since returning from combat.

“These findings indicate that it may be beneficial to screen for alcohol and aggressive behaviors when soldiers present for treatment of PTSD or depression,” Dr. Thomas and his associates said.

Disclosures: This study was supported by the U.S. Army Medical Research and Material Command, Fort Detrick, Md. No financial conflicts were reported.

Major Finding: After one year, mean systolic blood pressure was 7.3 mm Hg lower among the group visit patients compared with the usual care patients. Differences between the groups in terms of HbA_1c levels were not statistically significant.

Data Source: A randomized controlled trial.

Disclosures: The study was funded by the U.S. Department of Veterans Affairs Health Services Research and Development Service. No financial conflicts of interest were reported.

Compared with usual care, group medical visits produced meaningful improvement in blood pressure control but not diabetes control, according to a randomized controlled trial involving patients with both conditions.

The few randomized controlled trials of group medical clinics (GMCs) for diabetes patients have reported conflicting results, and no trials concerning GMCs for hypertension have been published, said Dr. David Edelman of Durham (N.C.) Veterans Affairs Medical Center and his associates.

In an editorial comment accompanying the report, Dr. Andrea Sikon and Dr. David L. Bronson of the Cleveland Clinic Foundation called shared appointments “an innovative alternative to the traditional patient-physician encounter.”

Since most such group clinics include time for private one-on-one consultation with the primary care physician and allot considerable time for patient education with professionals other than the physician, they have the potential to improve patient access to medical care, improve clinician productivity without adding to the existing workload, improve patient education, and improve “the bottom line for the practice,” Dr. Sikon and Dr. Bronson said (Ann. Intern. Med. 2010;152:745–6).

Dr. Edelman and his colleagues randomly assigned 239 patients with comorbid diabetes and hypertension at two VA medical centers to receive primary care as usual during individual visits or in group visits involving six to eight patients. A total of 211 patients completed the study.

Each GMC met every 2 months for approximately 90 minutes with the treatment team. At every GMC visit, patients' blood pressure was checked and home blood glucose values were collated so the treatment team could devise individualized plans for medication and lifestyle management for each patient. There also was an educational component during each group visit to address topics chosen by the patients.

Part of each GMC visit involved interaction with the entire group, and part involved a private consultation with the internist or pharmacist.

After 6 months, mean systolic blood pressure was 5.7 mm Hg lower in the GMC group than the usual care group, a significant difference. This benefit persisted throughout the study, and at 1 year, mean systolic BP was 7.3 mm Hg lower in the GMC group (Ann. Intern. Med. 2010;152:689–96).

This magnitude of treatment effect is similar to that reported in a large international clinical trial of antihypertensive and lipid-lowering medication, Dr. Edelman and his associates said.

Mean HbA_1c levels also were lower in the GMC group at both 6 months and 1 year, but the difference did not achieve statistical significance, they reported.

Control of diastolic blood pressure was a secondary outcome in this study. As with systolic BP, diastolic BP was significantly lower (by 3.8 mm Hg) in the GMC group than in the usual-care group.

Adverse events such as lightheadedness and falling during hypoglycemic episodes were significantly less frequent in the GMC group. The GMC patients also had 0.4 fewer visits to the emergency department per patient-year.

GMC care cost $460 a year per patient. “If found to be cost-effective and efficient, GMCs could be implemented in a wide range of settings and become important in the remodeling of long-term care in the United States,” they added.

Major Finding: After one year, mean systolic blood pressure was 7.3 mm Hg lower among the group visit patients compared with the usual care patients. Differences between the groups in terms of HbA_1c levels were not statistically significant.

Data Source: A randomized controlled trial.

Disclosures: The study was funded by the U.S. Department of Veterans Affairs Health Services Research and Development Service. No financial conflicts of interest were reported.

Compared with usual care, group medical visits produced meaningful improvement in blood pressure control but not diabetes control, according to a randomized controlled trial involving patients with both conditions.

The few randomized controlled trials of group medical clinics (GMCs) for diabetes patients have reported conflicting results, and no trials concerning GMCs for hypertension have been published, said Dr. David Edelman of Durham (N.C.) Veterans Affairs Medical Center and his associates.

In an editorial comment accompanying the report, Dr. Andrea Sikon and Dr. David L. Bronson of the Cleveland Clinic Foundation called shared appointments “an innovative alternative to the traditional patient-physician encounter.”

Since most such group clinics include time for private one-on-one consultation with the primary care physician and allot considerable time for patient education with professionals other than the physician, they have the potential to improve patient access to medical care, improve clinician productivity without adding to the existing workload, improve patient education, and improve “the bottom line for the practice,” Dr. Sikon and Dr. Bronson said (Ann. Intern. Med. 2010;152:745–6).

Dr. Edelman and his colleagues randomly assigned 239 patients with comorbid diabetes and hypertension at two VA medical centers to receive primary care as usual during individual visits or in group visits involving six to eight patients. A total of 211 patients completed the study.

Each GMC met every 2 months for approximately 90 minutes with the treatment team. At every GMC visit, patients' blood pressure was checked and home blood glucose values were collated so the treatment team could devise individualized plans for medication and lifestyle management for each patient. There also was an educational component during each group visit to address topics chosen by the patients.

Part of each GMC visit involved interaction with the entire group, and part involved a private consultation with the internist or pharmacist.

After 6 months, mean systolic blood pressure was 5.7 mm Hg lower in the GMC group than the usual care group, a significant difference. This benefit persisted throughout the study, and at 1 year, mean systolic BP was 7.3 mm Hg lower in the GMC group (Ann. Intern. Med. 2010;152:689–96).

This magnitude of treatment effect is similar to that reported in a large international clinical trial of antihypertensive and lipid-lowering medication, Dr. Edelman and his associates said.

Mean HbA_1c levels also were lower in the GMC group at both 6 months and 1 year, but the difference did not achieve statistical significance, they reported.

Control of diastolic blood pressure was a secondary outcome in this study. As with systolic BP, diastolic BP was significantly lower (by 3.8 mm Hg) in the GMC group than in the usual-care group.

Adverse events such as lightheadedness and falling during hypoglycemic episodes were significantly less frequent in the GMC group. The GMC patients also had 0.4 fewer visits to the emergency department per patient-year.

GMC care cost $460 a year per patient. “If found to be cost-effective and efficient, GMCs could be implemented in a wide range of settings and become important in the remodeling of long-term care in the United States,” they added.

Major Finding: After one year, mean systolic blood pressure was 7.3 mm Hg lower among the group visit patients compared with the usual care patients. Differences between the groups in terms of HbA_1c levels were not statistically significant.

Data Source: A randomized controlled trial.

Disclosures: The study was funded by the U.S. Department of Veterans Affairs Health Services Research and Development Service. No financial conflicts of interest were reported.

Compared with usual care, group medical visits produced meaningful improvement in blood pressure control but not diabetes control, according to a randomized controlled trial involving patients with both conditions.

The few randomized controlled trials of group medical clinics (GMCs) for diabetes patients have reported conflicting results, and no trials concerning GMCs for hypertension have been published, said Dr. David Edelman of Durham (N.C.) Veterans Affairs Medical Center and his associates.

In an editorial comment accompanying the report, Dr. Andrea Sikon and Dr. David L. Bronson of the Cleveland Clinic Foundation called shared appointments “an innovative alternative to the traditional patient-physician encounter.”

Since most such group clinics include time for private one-on-one consultation with the primary care physician and allot considerable time for patient education with professionals other than the physician, they have the potential to improve patient access to medical care, improve clinician productivity without adding to the existing workload, improve patient education, and improve “the bottom line for the practice,” Dr. Sikon and Dr. Bronson said (Ann. Intern. Med. 2010;152:745–6).

Dr. Edelman and his colleagues randomly assigned 239 patients with comorbid diabetes and hypertension at two VA medical centers to receive primary care as usual during individual visits or in group visits involving six to eight patients. A total of 211 patients completed the study.

Each GMC met every 2 months for approximately 90 minutes with the treatment team. At every GMC visit, patients' blood pressure was checked and home blood glucose values were collated so the treatment team could devise individualized plans for medication and lifestyle management for each patient. There also was an educational component during each group visit to address topics chosen by the patients.

Part of each GMC visit involved interaction with the entire group, and part involved a private consultation with the internist or pharmacist.

After 6 months, mean systolic blood pressure was 5.7 mm Hg lower in the GMC group than the usual care group, a significant difference. This benefit persisted throughout the study, and at 1 year, mean systolic BP was 7.3 mm Hg lower in the GMC group (Ann. Intern. Med. 2010;152:689–96).

This magnitude of treatment effect is similar to that reported in a large international clinical trial of antihypertensive and lipid-lowering medication, Dr. Edelman and his associates said.

Mean HbA_1c levels also were lower in the GMC group at both 6 months and 1 year, but the difference did not achieve statistical significance, they reported.

Control of diastolic blood pressure was a secondary outcome in this study. As with systolic BP, diastolic BP was significantly lower (by 3.8 mm Hg) in the GMC group than in the usual-care group.

Adverse events such as lightheadedness and falling during hypoglycemic episodes were significantly less frequent in the GMC group. The GMC patients also had 0.4 fewer visits to the emergency department per patient-year.

GMC care cost $460 a year per patient. “If found to be cost-effective and efficient, GMCs could be implemented in a wide range of settings and become important in the remodeling of long-term care in the United States,” they added.

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 researchers in Australia.

These risks were highest in the 3-month period immediately after each annual dose, said Kerrie M. Sanders, Ph.D., of the University of Melbourne and her associates.

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, they noted.

Dr. Sanders and her colleagues performed their single-center study in 2,256 white women aged 70 and older. 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 of falls and of fractures 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.

The reason for these counterproductive effects is not yet known, but it is possible that the once-a-year oral regimen—compared with either a regimen that divides the oral doses or one that uses intramuscular doses—is at fault. “It is reasonable to speculate that high serum levels of vitamin D or metabolites resulting from the large annual dose, subsequent decrease in the levels, or both might be causal,” Dr. Sanders and her associates wrote.

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,” they noted (JAMA 2010;303:1861–2).

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.

Contrary to expectations, annual high-dose vitamin D was tied to 15% more falls and 26% more fractures.

Source ©Joss/Fotolia.com

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 researchers in Australia.

These risks were highest in the 3-month period immediately after each annual dose, said Kerrie M. Sanders, Ph.D., of the University of Melbourne and her associates.

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, they noted.

Dr. Sanders and her colleagues performed their single-center study in 2,256 white women aged 70 and older. 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 of falls and of fractures 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.

The reason for these counterproductive effects is not yet known, but it is possible that the once-a-year oral regimen—compared with either a regimen that divides the oral doses or one that uses intramuscular doses—is at fault. “It is reasonable to speculate that high serum levels of vitamin D or metabolites resulting from the large annual dose, subsequent decrease in the levels, or both might be causal,” Dr. Sanders and her associates wrote.

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,” they noted (JAMA 2010;303:1861–2).

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.

Contrary to expectations, annual high-dose vitamin D was tied to 15% more falls and 26% more fractures.

Source ©Joss/Fotolia.com

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 researchers in Australia.

These risks were highest in the 3-month period immediately after each annual dose, said Kerrie M. Sanders, Ph.D., of the University of Melbourne and her associates.

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, they noted.

Dr. Sanders and her colleagues performed their single-center study in 2,256 white women aged 70 and older. 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 of falls and of fractures 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.

The reason for these counterproductive effects is not yet known, but it is possible that the once-a-year oral regimen—compared with either a regimen that divides the oral doses or one that uses intramuscular doses—is at fault. “It is reasonable to speculate that high serum levels of vitamin D or metabolites resulting from the large annual dose, subsequent decrease in the levels, or both might be causal,” Dr. Sanders and her associates wrote.

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,” they noted (JAMA 2010;303:1861–2).

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.

Contrary to expectations, annual high-dose vitamin D was tied to 15% more falls and 26% more fractures.

Source ©Joss/Fotolia.com

Patients with papillary thyroid cancers that are limited to that gland are likely to have a favorable outcome regardless of whether they undergo rapid definitive treatment or are simply observed for disease progression, researchers reported.

In an epidemiologic study using Surveillance, Epidemiology, and End Results (SEER) data on more than 35,000 papillary thyroid cancers (PTCs) diagnosed in 1973–2005, 20-year survival was 97% in patients who did not receive definitive treatment within 1 year, compared with 99%—“only 2% better”—in those who did, wrote Dr. Louise Davies of Veterans Affairs Medical Center, White River Junction, Vt., and her associates.

“Papillary thyroid cancers of any size that are confined to the thyroid gland, have no lymph node metastases at presentation, and do not show extraglandular extension are unlikely to result in death due to the cancer. Thus, clinicians and patients should feel comfortable considering the option to observe for a year or longer cancers that fall into this category,” the investigators said.

In an editorial, Dr. Erich M. Sturgis and Dr. Steven I. Sherman of the University of Texas M.D. Anderson Cancer Center, Houston, strongly disagreed with this conclusion, emphasizing that observation “should only be cautiously considered in the most carefully selected cases.” They added, “We would wonder whether the six people who died of their thyroid cancer in this real yet very selected … 'no treatment' group would have agreed that a statistically significant 2% difference in survival was not clinically relevant.”

Dr. Davies and her associates examined the natural history of untreated PTC using SEER data because the number of thyroid cancers detected using new technologies has tripled in the past 30 years, and there is still great uncertainty about whether and how to treat these mostly subclinical lesions.

They identified 35,663 cases of microscopically confirmed, localized PTC diagnosed during the 32-year study period. Only 440 patients (1.2%) did not undergo hemithyroidectomy or total thyroidectomy, with or without irradiation, within 1 year of diagnosis.

The reasons for the decision to forgo treatment were not available. In 216 of the 440 patients, definitive treatment was recommended but not done, and in 165 it was not recommended and not done. Treatment recommendations were not documented for the remaining 59 patients.

After mean follow-up of approximately 8 years for the treated group and 6 years for the untreated group, there was no significant difference between the proportion of thyroid cancer deaths that occurred in the treated group (161 of 35,223 patients, or 0.5%) and the untreated group (6 of 440 patients, or 1.4%). Long-term thyroid cancer–specific survival rates “were nearly identical” at 99% and 97%, respectively, the investigators said.

Survival was not affected by whether treatment had been recommended or not, Dr. Davies and her colleagues said (Arch. Otolaryngol. Head Neck Surg. 2010;136:440–4). In addition, cancer-specific survival was essentially the same whether patients underwent hemithyroidectomy or total thyroidectomy.

For patients with this form of cancer, “survival is so good that it is appropriate to consider whether the risk of complications outweighs the benefits of treatment during discussions about when and how to treat the disease. The risk of permanent hypoparathyroidism and significant damage to laryngeal function have been reported to range from 3% to 5% in large case series,” they noted.

In their invited commentary, Dr. Sturgis and Dr. Sherman disputed these conclusions, noting that readers will be “poorly informed and perhaps misinformed” by the authors' interpretation of their data (Arch. Otolaryngol. Head Neck Surg. 2010;136:444–6).

Disclosures: This study was supported in part by the Department of Veterans Affairs and the Robert Wood Johnson Faculty Scholars Program. No financial conflicts of interest were reported.

Patients with papillary thyroid cancers that are limited to that gland are likely to have a favorable outcome regardless of whether they undergo rapid definitive treatment or are simply observed for disease progression, researchers reported.

In an epidemiologic study using Surveillance, Epidemiology, and End Results (SEER) data on more than 35,000 papillary thyroid cancers (PTCs) diagnosed in 1973–2005, 20-year survival was 97% in patients who did not receive definitive treatment within 1 year, compared with 99%—“only 2% better”—in those who did, wrote Dr. Louise Davies of Veterans Affairs Medical Center, White River Junction, Vt., and her associates.

“Papillary thyroid cancers of any size that are confined to the thyroid gland, have no lymph node metastases at presentation, and do not show extraglandular extension are unlikely to result in death due to the cancer. Thus, clinicians and patients should feel comfortable considering the option to observe for a year or longer cancers that fall into this category,” the investigators said.

In an editorial, Dr. Erich M. Sturgis and Dr. Steven I. Sherman of the University of Texas M.D. Anderson Cancer Center, Houston, strongly disagreed with this conclusion, emphasizing that observation “should only be cautiously considered in the most carefully selected cases.” They added, “We would wonder whether the six people who died of their thyroid cancer in this real yet very selected … 'no treatment' group would have agreed that a statistically significant 2% difference in survival was not clinically relevant.”

Dr. Davies and her associates examined the natural history of untreated PTC using SEER data because the number of thyroid cancers detected using new technologies has tripled in the past 30 years, and there is still great uncertainty about whether and how to treat these mostly subclinical lesions.

They identified 35,663 cases of microscopically confirmed, localized PTC diagnosed during the 32-year study period. Only 440 patients (1.2%) did not undergo hemithyroidectomy or total thyroidectomy, with or without irradiation, within 1 year of diagnosis.

The reasons for the decision to forgo treatment were not available. In 216 of the 440 patients, definitive treatment was recommended but not done, and in 165 it was not recommended and not done. Treatment recommendations were not documented for the remaining 59 patients.

After mean follow-up of approximately 8 years for the treated group and 6 years for the untreated group, there was no significant difference between the proportion of thyroid cancer deaths that occurred in the treated group (161 of 35,223 patients, or 0.5%) and the untreated group (6 of 440 patients, or 1.4%). Long-term thyroid cancer–specific survival rates “were nearly identical” at 99% and 97%, respectively, the investigators said.

Survival was not affected by whether treatment had been recommended or not, Dr. Davies and her colleagues said (Arch. Otolaryngol. Head Neck Surg. 2010;136:440–4). In addition, cancer-specific survival was essentially the same whether patients underwent hemithyroidectomy or total thyroidectomy.

For patients with this form of cancer, “survival is so good that it is appropriate to consider whether the risk of complications outweighs the benefits of treatment during discussions about when and how to treat the disease. The risk of permanent hypoparathyroidism and significant damage to laryngeal function have been reported to range from 3% to 5% in large case series,” they noted.

In their invited commentary, Dr. Sturgis and Dr. Sherman disputed these conclusions, noting that readers will be “poorly informed and perhaps misinformed” by the authors' interpretation of their data (Arch. Otolaryngol. Head Neck Surg. 2010;136:444–6).

Disclosures: This study was supported in part by the Department of Veterans Affairs and the Robert Wood Johnson Faculty Scholars Program. No financial conflicts of interest were reported.

Patients with papillary thyroid cancers that are limited to that gland are likely to have a favorable outcome regardless of whether they undergo rapid definitive treatment or are simply observed for disease progression, researchers reported.

In an epidemiologic study using Surveillance, Epidemiology, and End Results (SEER) data on more than 35,000 papillary thyroid cancers (PTCs) diagnosed in 1973–2005, 20-year survival was 97% in patients who did not receive definitive treatment within 1 year, compared with 99%—“only 2% better”—in those who did, wrote Dr. Louise Davies of Veterans Affairs Medical Center, White River Junction, Vt., and her associates.

“Papillary thyroid cancers of any size that are confined to the thyroid gland, have no lymph node metastases at presentation, and do not show extraglandular extension are unlikely to result in death due to the cancer. Thus, clinicians and patients should feel comfortable considering the option to observe for a year or longer cancers that fall into this category,” the investigators said.

In an editorial, Dr. Erich M. Sturgis and Dr. Steven I. Sherman of the University of Texas M.D. Anderson Cancer Center, Houston, strongly disagreed with this conclusion, emphasizing that observation “should only be cautiously considered in the most carefully selected cases.” They added, “We would wonder whether the six people who died of their thyroid cancer in this real yet very selected … 'no treatment' group would have agreed that a statistically significant 2% difference in survival was not clinically relevant.”

Dr. Davies and her associates examined the natural history of untreated PTC using SEER data because the number of thyroid cancers detected using new technologies has tripled in the past 30 years, and there is still great uncertainty about whether and how to treat these mostly subclinical lesions.

They identified 35,663 cases of microscopically confirmed, localized PTC diagnosed during the 32-year study period. Only 440 patients (1.2%) did not undergo hemithyroidectomy or total thyroidectomy, with or without irradiation, within 1 year of diagnosis.

The reasons for the decision to forgo treatment were not available. In 216 of the 440 patients, definitive treatment was recommended but not done, and in 165 it was not recommended and not done. Treatment recommendations were not documented for the remaining 59 patients.

After mean follow-up of approximately 8 years for the treated group and 6 years for the untreated group, there was no significant difference between the proportion of thyroid cancer deaths that occurred in the treated group (161 of 35,223 patients, or 0.5%) and the untreated group (6 of 440 patients, or 1.4%). Long-term thyroid cancer–specific survival rates “were nearly identical” at 99% and 97%, respectively, the investigators said.

Survival was not affected by whether treatment had been recommended or not, Dr. Davies and her colleagues said (Arch. Otolaryngol. Head Neck Surg. 2010;136:440–4). In addition, cancer-specific survival was essentially the same whether patients underwent hemithyroidectomy or total thyroidectomy.

For patients with this form of cancer, “survival is so good that it is appropriate to consider whether the risk of complications outweighs the benefits of treatment during discussions about when and how to treat the disease. The risk of permanent hypoparathyroidism and significant damage to laryngeal function have been reported to range from 3% to 5% in large case series,” they noted.

In their invited commentary, Dr. Sturgis and Dr. Sherman disputed these conclusions, noting that readers will be “poorly informed and perhaps misinformed” by the authors' interpretation of their data (Arch. Otolaryngol. Head Neck Surg. 2010;136:444–6).

Disclosures: This study was supported in part by the Department of Veterans Affairs and the Robert Wood Johnson Faculty Scholars Program. No financial conflicts of interest were reported.

Obese and overweight patients do not appear to receive inferior health care, compared with normal-weight patients, according to an analysis of almost 70,000 patients.

In fact, patients with a higher body mass index may be more likely to undergo lipid screening and hemoglobin

A_1c testing; vaccination for influenza and pneumococcus; and screening for breast, colorectal, and cervical cancer, said Dr. Virginia W. Chang of the University of Pennsylvania, Philadelphia, and her associates.

They studied data from nationally representative samples of 36,122 Medicare beneficiaries and 33,550 Veterans Affairs patients. The prevalence of obesity was 20% in the Medicare group and 39% in the VA group. Eight quality-of-care measures were examined: whether diabetic patients received eye exams, lipid screening, and HbA_1c tests; whether appropriate patients received influenza and pneumococcal vaccines; and whether appropriate patients were offered mammography, Pap smears, and colorectal cancer screening.

Across all measures in both samples, “there was no instance in which obese or overweight individuals were estimated to have significantly lower odds of recommended care relative to normal-weight individuals,” the researchers wrote (JAMA 2010;303:1274-81).

“Our findings may not be generalizable to quality of care in younger populations,” the researchers noted.

The study was supported by the Veterans Health Administration and the Robert Wood Johnson Foundation. No financial conflicts were reported.

Obese and overweight patients do not appear to receive inferior health care, compared with normal-weight patients, according to an analysis of almost 70,000 patients.

In fact, patients with a higher body mass index may be more likely to undergo lipid screening and hemoglobin

A_1c testing; vaccination for influenza and pneumococcus; and screening for breast, colorectal, and cervical cancer, said Dr. Virginia W. Chang of the University of Pennsylvania, Philadelphia, and her associates.

They studied data from nationally representative samples of 36,122 Medicare beneficiaries and 33,550 Veterans Affairs patients. The prevalence of obesity was 20% in the Medicare group and 39% in the VA group. Eight quality-of-care measures were examined: whether diabetic patients received eye exams, lipid screening, and HbA_1c tests; whether appropriate patients received influenza and pneumococcal vaccines; and whether appropriate patients were offered mammography, Pap smears, and colorectal cancer screening.

Across all measures in both samples, “there was no instance in which obese or overweight individuals were estimated to have significantly lower odds of recommended care relative to normal-weight individuals,” the researchers wrote (JAMA 2010;303:1274-81).

“Our findings may not be generalizable to quality of care in younger populations,” the researchers noted.

The study was supported by the Veterans Health Administration and the Robert Wood Johnson Foundation. No financial conflicts were reported.

Obese and overweight patients do not appear to receive inferior health care, compared with normal-weight patients, according to an analysis of almost 70,000 patients.

In fact, patients with a higher body mass index may be more likely to undergo lipid screening and hemoglobin

A_1c testing; vaccination for influenza and pneumococcus; and screening for breast, colorectal, and cervical cancer, said Dr. Virginia W. Chang of the University of Pennsylvania, Philadelphia, and her associates.

They studied data from nationally representative samples of 36,122 Medicare beneficiaries and 33,550 Veterans Affairs patients. The prevalence of obesity was 20% in the Medicare group and 39% in the VA group. Eight quality-of-care measures were examined: whether diabetic patients received eye exams, lipid screening, and HbA_1c tests; whether appropriate patients received influenza and pneumococcal vaccines; and whether appropriate patients were offered mammography, Pap smears, and colorectal cancer screening.

Across all measures in both samples, “there was no instance in which obese or overweight individuals were estimated to have significantly lower odds of recommended care relative to normal-weight individuals,” the researchers wrote (JAMA 2010;303:1274-81).

“Our findings may not be generalizable to quality of care in younger populations,” the researchers noted.

The study was supported by the Veterans Health Administration and the Robert Wood Johnson Foundation. No financial conflicts were reported.

Treatment with vitamin A analogues such as isotretinoin and acitretin does not increase fracture risk, according to findings from a nationwide Danish case-control study.

Of all fractures sustained in a single year, no form of systemic or topical vitamin A analogues was associated with fracture risk at any skeletal site, said Dr. Peter Vestergaard and his associates at Aarhus (Denmark) University Hospital.

Previous research has yielded conflicting results. Some studies have found that high-dose therapy is related to an increased risk of fracture and adverse bone changes, including hyperostosis, hypercalcemia, impaired bone turnover, and decreased bone mineral density, while other studies have found no such association.

The results of this large population-based study show that “even very large daily doses of 14 mg of vitamin A analogues (equivalent to 14,000 micrograms of retinol equivalents per day) were not associated with an increased risk of fractures. It thus seems that vitamin A analogues are safe in terms of fractures, even at very high doses,” Dr. Vestergaard and his colleagues wrote (Arch. Dermatol. 2010;146:478-82).

They used data from 124,655 cases of fracture that occurred in 2000 and 373,962 control cases matched for age and sex. The data were adjusted to account for the severity of the underlying disease requiring treatment with vitamin A analogues, as well as for the concomitant use of drugs known to affect fracture risk, such as corticosteroids and antiepileptic agents.

There was no association between any form of vitamin A analogue and fracture risk at any site. Moreover, no trend was found between increasing dose or increasing duration of treatment and any fracture risk, the investigators reported.

There also was no association with fracture risk when the use of individual vitamin A analogues was analyzed.

“Even though some studies have reported a decreased BMD with high doses of vitamin A as retinol in dietary intake or as supplements, the decrease may not have been of such magnitude that it altered bone biomechanical competence,” Dr. Vestergaard and his associates noted.

In an editorial accompanying the report, Dr. John J. DiGiovanna of Brown University, Providence, noted that these results are particularly reassuring because the investigators examined “a large population of humans treated under real therapeutic conditions” and because the end point (fracture) was clinically important.

The main weakness of the study was that it could not completely account for potentially confounding factors such as smoking habits, body mass index, vitamin D status, and sun exposure, he wrote (Arch. Dermatol. 2010; 146:551-3).

“While it is reassuring to see this evidence of retinoid drug safety in relation to bone demineralization in a large population, the treatment of patients must rely on personalized prescription. Sound measures for good skeletal health, including adequate nutrition (especially vitamin D and calcium, etc.) and healthy physical activity, should be encouraged.

“Monitoring may be indicated for individuals with a family or personal history of osteoporosis, advanced age, and exposure to agents known to cause demineralization, and possibly those requiring long-term or high-dose retinoid drug therapy,” Dr. DiGiovanna added.

This study was supported by the Danish Medical Research Council. Dr. Vestergaard reported receiving support from Servier, Bayer Pharmaceuticals, Eli Lilly and Company, Novartis, and Sanofi-Aventis. Dr. DiGiovanna reported receiving support from Basilea, Hoffman La Roche, Allergan, and Cipher Pharmaceuticals.

Treatment with vitamin A analogues such as isotretinoin and acitretin does not increase fracture risk, according to findings from a nationwide Danish case-control study.

Of all fractures sustained in a single year, no form of systemic or topical vitamin A analogues was associated with fracture risk at any skeletal site, said Dr. Peter Vestergaard and his associates at Aarhus (Denmark) University Hospital.

Previous research has yielded conflicting results. Some studies have found that high-dose therapy is related to an increased risk of fracture and adverse bone changes, including hyperostosis, hypercalcemia, impaired bone turnover, and decreased bone mineral density, while other studies have found no such association.

The results of this large population-based study show that “even very large daily doses of 14 mg of vitamin A analogues (equivalent to 14,000 micrograms of retinol equivalents per day) were not associated with an increased risk of fractures. It thus seems that vitamin A analogues are safe in terms of fractures, even at very high doses,” Dr. Vestergaard and his colleagues wrote (Arch. Dermatol. 2010;146:478-82).

They used data from 124,655 cases of fracture that occurred in 2000 and 373,962 control cases matched for age and sex. The data were adjusted to account for the severity of the underlying disease requiring treatment with vitamin A analogues, as well as for the concomitant use of drugs known to affect fracture risk, such as corticosteroids and antiepileptic agents.

There was no association between any form of vitamin A analogue and fracture risk at any site. Moreover, no trend was found between increasing dose or increasing duration of treatment and any fracture risk, the investigators reported.

There also was no association with fracture risk when the use of individual vitamin A analogues was analyzed.

“Even though some studies have reported a decreased BMD with high doses of vitamin A as retinol in dietary intake or as supplements, the decrease may not have been of such magnitude that it altered bone biomechanical competence,” Dr. Vestergaard and his associates noted.

In an editorial accompanying the report, Dr. John J. DiGiovanna of Brown University, Providence, noted that these results are particularly reassuring because the investigators examined “a large population of humans treated under real therapeutic conditions” and because the end point (fracture) was clinically important.

The main weakness of the study was that it could not completely account for potentially confounding factors such as smoking habits, body mass index, vitamin D status, and sun exposure, he wrote (Arch. Dermatol. 2010; 146:551-3).

“While it is reassuring to see this evidence of retinoid drug safety in relation to bone demineralization in a large population, the treatment of patients must rely on personalized prescription. Sound measures for good skeletal health, including adequate nutrition (especially vitamin D and calcium, etc.) and healthy physical activity, should be encouraged.

“Monitoring may be indicated for individuals with a family or personal history of osteoporosis, advanced age, and exposure to agents known to cause demineralization, and possibly those requiring long-term or high-dose retinoid drug therapy,” Dr. DiGiovanna added.

This study was supported by the Danish Medical Research Council. Dr. Vestergaard reported receiving support from Servier, Bayer Pharmaceuticals, Eli Lilly and Company, Novartis, and Sanofi-Aventis. Dr. DiGiovanna reported receiving support from Basilea, Hoffman La Roche, Allergan, and Cipher Pharmaceuticals.

Treatment with vitamin A analogues such as isotretinoin and acitretin does not increase fracture risk, according to findings from a nationwide Danish case-control study.

Of all fractures sustained in a single year, no form of systemic or topical vitamin A analogues was associated with fracture risk at any skeletal site, said Dr. Peter Vestergaard and his associates at Aarhus (Denmark) University Hospital.

Previous research has yielded conflicting results. Some studies have found that high-dose therapy is related to an increased risk of fracture and adverse bone changes, including hyperostosis, hypercalcemia, impaired bone turnover, and decreased bone mineral density, while other studies have found no such association.

The results of this large population-based study show that “even very large daily doses of 14 mg of vitamin A analogues (equivalent to 14,000 micrograms of retinol equivalents per day) were not associated with an increased risk of fractures. It thus seems that vitamin A analogues are safe in terms of fractures, even at very high doses,” Dr. Vestergaard and his colleagues wrote (Arch. Dermatol. 2010;146:478-82).

They used data from 124,655 cases of fracture that occurred in 2000 and 373,962 control cases matched for age and sex. The data were adjusted to account for the severity of the underlying disease requiring treatment with vitamin A analogues, as well as for the concomitant use of drugs known to affect fracture risk, such as corticosteroids and antiepileptic agents.

There was no association between any form of vitamin A analogue and fracture risk at any site. Moreover, no trend was found between increasing dose or increasing duration of treatment and any fracture risk, the investigators reported.

There also was no association with fracture risk when the use of individual vitamin A analogues was analyzed.

“Even though some studies have reported a decreased BMD with high doses of vitamin A as retinol in dietary intake or as supplements, the decrease may not have been of such magnitude that it altered bone biomechanical competence,” Dr. Vestergaard and his associates noted.

In an editorial accompanying the report, Dr. John J. DiGiovanna of Brown University, Providence, noted that these results are particularly reassuring because the investigators examined “a large population of humans treated under real therapeutic conditions” and because the end point (fracture) was clinically important.

The main weakness of the study was that it could not completely account for potentially confounding factors such as smoking habits, body mass index, vitamin D status, and sun exposure, he wrote (Arch. Dermatol. 2010; 146:551-3).

“While it is reassuring to see this evidence of retinoid drug safety in relation to bone demineralization in a large population, the treatment of patients must rely on personalized prescription. Sound measures for good skeletal health, including adequate nutrition (especially vitamin D and calcium, etc.) and healthy physical activity, should be encouraged.

“Monitoring may be indicated for individuals with a family or personal history of osteoporosis, advanced age, and exposure to agents known to cause demineralization, and possibly those requiring long-term or high-dose retinoid drug therapy,” Dr. DiGiovanna added.

This study was supported by the Danish Medical Research Council. Dr. Vestergaard reported receiving support from Servier, Bayer Pharmaceuticals, Eli Lilly and Company, Novartis, and Sanofi-Aventis. Dr. DiGiovanna reported receiving support from Basilea, Hoffman La Roche, Allergan, and Cipher Pharmaceuticals.

The use of proton pump inhibitors does not 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 did not 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).

Although these findings leave many questions unresolved, “based on the accumulation of evidence, it is prudent for clinicians to periodically reevaluate the need for long-term PPI therapy,” the investigators said.

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,” they added.

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).

“We should offer treatments other than PPIs for functional dyspepsia, prescribe short courses of PPI treatment (after disclosure of possible risks and benefits), and consider a trial of discontinuing PPI therapy in patients who are asymptomatic.

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

The WHI Program was funded by the National Heart, Lung, and Blood Institute.

Dr. Gray reported no financial conflicts of interest. 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 does not 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 did not 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).

Although these findings leave many questions unresolved, “based on the accumulation of evidence, it is prudent for clinicians to periodically reevaluate the need for long-term PPI therapy,” the investigators said.

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,” they added.

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).

“We should offer treatments other than PPIs for functional dyspepsia, prescribe short courses of PPI treatment (after disclosure of possible risks and benefits), and consider a trial of discontinuing PPI therapy in patients who are asymptomatic.

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

The WHI Program was funded by the National Heart, Lung, and Blood Institute.

Dr. Gray reported no financial conflicts of interest. 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 does not 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 did not 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).

Although these findings leave many questions unresolved, “based on the accumulation of evidence, it is prudent for clinicians to periodically reevaluate the need for long-term PPI therapy,” the investigators said.

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,” they added.

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).

“We should offer treatments other than PPIs for functional dyspepsia, prescribe short courses of PPI treatment (after disclosure of possible risks and benefits), and consider a trial of discontinuing PPI therapy in patients who are asymptomatic.

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

The WHI Program was funded by the National Heart, Lung, and Blood Institute.

Dr. Gray reported no financial conflicts of interest. 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.

Everolimus-eluting coronary stents produced a 38% relative reduction in the 1-year rate of target-lesion failure and a 45% relative reduction in target-lesion revascularization, compared with paclitaxel-eluting stents, according to randomized study.

In what the researchers described as the only clinical trial to date that was large enough to establish the superiority of one drug-eluting stent over another, the primary end point of target-lesion failure 1 year after percutaneous coronary intervention was 4.2% with everolimus-eluting stents, compared with 6.8% with paclitaxel-eluting stents, a significant difference.

The everolimus-eluting stent (Xience V, Abbott Vascular) also was superior with respect to the secondary end point of ischemia-driven target-lesion revascularization at 1 year, with a 2.5% rate of this outcome, compared with a significantly higher 4.6% rate for the paclitaxel-eluting stent (Taxus Express, Boston Scientific), said Dr. Gregg W. Stone of Columbia University, New York, and his associates in the Abbott-sponsored SPIRIT IV study.

However, the rates of cardiac death and of death from all causes were not significantly different between the two stents. This may be due in part to the low mortality in both groups after just 1 year. Longer follow-up “will determine whether these differences are durable or increase over time,” the investigators said.

In addition, the everolimus-eluting stent did not show superiority in patients with diabetes—a major subgroup that accounts for a significant portion of stent procedures, they noted.

Dr. Stone and his colleagues compared the two devices in 3,687 patients, including 1,185 with diabetes, who underwent PCI at 66 U.S. medical centers in 2006–2008. These study subjects had up to three untreated coronary artery lesions that were as long as 28 mm, in vessels with a diameter of 2.5–3.75 mm.

The subjects were randomly assigned to receive everolimus-eluting stents (2,458 patients) or paclitaxel-eluting stents (1,229 patients) and were followed for 1 year.

The everolimus-eluting stent was superior regarding target-lesion failure and ischemia-driven target lesion revascularization; it was noninferior to the paclitaxel-eluting stent in the secondary end point of cardiac death or target-vessel myocardial infarction.

The everolimus-eluting stent also was superior in the secondary end point of preventing stent thrombosis, with a 1-year rate of 0.85%, compared with a 1.10% rate for the paclitaxel-eluting stent group. This represents a relative reduction of 75%, Dr. Stone and his associates wrote (N. Engl. J. Med. 2010; 362:1663–74).

These findings were consistent across 11 subgroups of patients, regardless of patient symptoms or smoking, hypertension, or cholesterol status; the number of lesions treated; which coronary vessels were involved; and the dimensions of the lesions or the vessels.

The sole exception was the large subgroup of diabetic patients, in whom there were no significant differences in outcomes between the two stents. A discrepancy in outcomes has been reported previously for diabetic patients receiving stents, and “suggests that the mechanisms of restenosis or the response to antiproliferative agents may vary in patients with insulin resistance or deficiency,” the researchers noted.

The SPIRIT IV trial was sponsored by Abbott Vascular. Dr. Stone reported ties to Abbott, Boston Scientific, Osprey Medical, InfraReDx, Reva Medical, Merck, CoreValve, St. Jude Medical, Edwards, and numerous other pharmaceutical and device companies.

Everolimus-eluting coronary stents produced a 38% relative reduction in the 1-year rate of target-lesion failure and a 45% relative reduction in target-lesion revascularization, compared with paclitaxel-eluting stents, according to randomized study.

In what the researchers described as the only clinical trial to date that was large enough to establish the superiority of one drug-eluting stent over another, the primary end point of target-lesion failure 1 year after percutaneous coronary intervention was 4.2% with everolimus-eluting stents, compared with 6.8% with paclitaxel-eluting stents, a significant difference.

The everolimus-eluting stent (Xience V, Abbott Vascular) also was superior with respect to the secondary end point of ischemia-driven target-lesion revascularization at 1 year, with a 2.5% rate of this outcome, compared with a significantly higher 4.6% rate for the paclitaxel-eluting stent (Taxus Express, Boston Scientific), said Dr. Gregg W. Stone of Columbia University, New York, and his associates in the Abbott-sponsored SPIRIT IV study.

However, the rates of cardiac death and of death from all causes were not significantly different between the two stents. This may be due in part to the low mortality in both groups after just 1 year. Longer follow-up “will determine whether these differences are durable or increase over time,” the investigators said.

In addition, the everolimus-eluting stent did not show superiority in patients with diabetes—a major subgroup that accounts for a significant portion of stent procedures, they noted.

Dr. Stone and his colleagues compared the two devices in 3,687 patients, including 1,185 with diabetes, who underwent PCI at 66 U.S. medical centers in 2006–2008. These study subjects had up to three untreated coronary artery lesions that were as long as 28 mm, in vessels with a diameter of 2.5–3.75 mm.

The subjects were randomly assigned to receive everolimus-eluting stents (2,458 patients) or paclitaxel-eluting stents (1,229 patients) and were followed for 1 year.

The everolimus-eluting stent was superior regarding target-lesion failure and ischemia-driven target lesion revascularization; it was noninferior to the paclitaxel-eluting stent in the secondary end point of cardiac death or target-vessel myocardial infarction.

The everolimus-eluting stent also was superior in the secondary end point of preventing stent thrombosis, with a 1-year rate of 0.85%, compared with a 1.10% rate for the paclitaxel-eluting stent group. This represents a relative reduction of 75%, Dr. Stone and his associates wrote (N. Engl. J. Med. 2010; 362:1663–74).

These findings were consistent across 11 subgroups of patients, regardless of patient symptoms or smoking, hypertension, or cholesterol status; the number of lesions treated; which coronary vessels were involved; and the dimensions of the lesions or the vessels.

The sole exception was the large subgroup of diabetic patients, in whom there were no significant differences in outcomes between the two stents. A discrepancy in outcomes has been reported previously for diabetic patients receiving stents, and “suggests that the mechanisms of restenosis or the response to antiproliferative agents may vary in patients with insulin resistance or deficiency,” the researchers noted.

The SPIRIT IV trial was sponsored by Abbott Vascular. Dr. Stone reported ties to Abbott, Boston Scientific, Osprey Medical, InfraReDx, Reva Medical, Merck, CoreValve, St. Jude Medical, Edwards, and numerous other pharmaceutical and device companies.

Everolimus-eluting coronary stents produced a 38% relative reduction in the 1-year rate of target-lesion failure and a 45% relative reduction in target-lesion revascularization, compared with paclitaxel-eluting stents, according to randomized study.

In what the researchers described as the only clinical trial to date that was large enough to establish the superiority of one drug-eluting stent over another, the primary end point of target-lesion failure 1 year after percutaneous coronary intervention was 4.2% with everolimus-eluting stents, compared with 6.8% with paclitaxel-eluting stents, a significant difference.

The everolimus-eluting stent (Xience V, Abbott Vascular) also was superior with respect to the secondary end point of ischemia-driven target-lesion revascularization at 1 year, with a 2.5% rate of this outcome, compared with a significantly higher 4.6% rate for the paclitaxel-eluting stent (Taxus Express, Boston Scientific), said Dr. Gregg W. Stone of Columbia University, New York, and his associates in the Abbott-sponsored SPIRIT IV study.

However, the rates of cardiac death and of death from all causes were not significantly different between the two stents. This may be due in part to the low mortality in both groups after just 1 year. Longer follow-up “will determine whether these differences are durable or increase over time,” the investigators said.

In addition, the everolimus-eluting stent did not show superiority in patients with diabetes—a major subgroup that accounts for a significant portion of stent procedures, they noted.

Dr. Stone and his colleagues compared the two devices in 3,687 patients, including 1,185 with diabetes, who underwent PCI at 66 U.S. medical centers in 2006–2008. These study subjects had up to three untreated coronary artery lesions that were as long as 28 mm, in vessels with a diameter of 2.5–3.75 mm.

The subjects were randomly assigned to receive everolimus-eluting stents (2,458 patients) or paclitaxel-eluting stents (1,229 patients) and were followed for 1 year.

The everolimus-eluting stent was superior regarding target-lesion failure and ischemia-driven target lesion revascularization; it was noninferior to the paclitaxel-eluting stent in the secondary end point of cardiac death or target-vessel myocardial infarction.

The everolimus-eluting stent also was superior in the secondary end point of preventing stent thrombosis, with a 1-year rate of 0.85%, compared with a 1.10% rate for the paclitaxel-eluting stent group. This represents a relative reduction of 75%, Dr. Stone and his associates wrote (N. Engl. J. Med. 2010; 362:1663–74).

These findings were consistent across 11 subgroups of patients, regardless of patient symptoms or smoking, hypertension, or cholesterol status; the number of lesions treated; which coronary vessels were involved; and the dimensions of the lesions or the vessels.

The sole exception was the large subgroup of diabetic patients, in whom there were no significant differences in outcomes between the two stents. A discrepancy in outcomes has been reported previously for diabetic patients receiving stents, and “suggests that the mechanisms of restenosis or the response to antiproliferative agents may vary in patients with insulin resistance or deficiency,” the researchers noted.

The SPIRIT IV trial was sponsored by Abbott Vascular. Dr. Stone reported ties to Abbott, Boston Scientific, Osprey Medical, InfraReDx, Reva Medical, Merck, CoreValve, St. Jude Medical, Edwards, and numerous other pharmaceutical and device companies.

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

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, particularly influenza and pneumococcal pneumonia, can trigger an exaggerated inflammatory response that causes destabilization of atherosclerotic plaques, activation of the coagulation cascade, and vascular thrombosis.

To explore the possible protective effect of pneumococcal vaccine against MI and stroke, Dr. Tseng and his colleagues reviewed data collected as part of a cohort study of men's health, which involved 84,170 subjects enrolled in the Kaiser health plan who were aged 45–69 years at baseline in 2000 and who were followed through 2007.

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

“With adjustment for the propensity score, 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 the findings from 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. His study also adjusted for the fact that older men who receive the pneumococcal vaccine are more likely to get vaccinated because they have chronic conditions that heighten their risk for MI and stroke, the researchers noted.

The California Cancer Research Program and Kaiser Permanente funded the study. Dr. Tseng and associates reported ties to Merck, maker of a pneumococcal vaccine, and GlaxoSmithKline.

In a study of older men that controlled for dietary habits, disease history, and lifestyle factors, pneumococcal vaccines did not show a protective effect against MI or stroke.

Source Pamela Moore/iStockphoto.com

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

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, particularly influenza and pneumococcal pneumonia, can trigger an exaggerated inflammatory response that causes destabilization of atherosclerotic plaques, activation of the coagulation cascade, and vascular thrombosis.

To explore the possible protective effect of pneumococcal vaccine against MI and stroke, Dr. Tseng and his colleagues reviewed data collected as part of a cohort study of men's health, which involved 84,170 subjects enrolled in the Kaiser health plan who were aged 45–69 years at baseline in 2000 and who were followed through 2007.

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

“With adjustment for the propensity score, 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 the findings from 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. His study also adjusted for the fact that older men who receive the pneumococcal vaccine are more likely to get vaccinated because they have chronic conditions that heighten their risk for MI and stroke, the researchers noted.

The California Cancer Research Program and Kaiser Permanente funded the study. Dr. Tseng and associates reported ties to Merck, maker of a pneumococcal vaccine, and GlaxoSmithKline.

In a study of older men that controlled for dietary habits, disease history, and lifestyle factors, pneumococcal vaccines did not show a protective effect against MI or stroke.

Source Pamela Moore/iStockphoto.com

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

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, particularly influenza and pneumococcal pneumonia, can trigger an exaggerated inflammatory response that causes destabilization of atherosclerotic plaques, activation of the coagulation cascade, and vascular thrombosis.

To explore the possible protective effect of pneumococcal vaccine against MI and stroke, Dr. Tseng and his colleagues reviewed data collected as part of a cohort study of men's health, which involved 84,170 subjects enrolled in the Kaiser health plan who were aged 45–69 years at baseline in 2000 and who were followed through 2007.

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

“With adjustment for the propensity score, 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 the findings from 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. His study also adjusted for the fact that older men who receive the pneumococcal vaccine are more likely to get vaccinated because they have chronic conditions that heighten their risk for MI and stroke, the researchers noted.

The California Cancer Research Program and Kaiser Permanente funded the study. Dr. Tseng and associates reported ties to Merck, maker of a pneumococcal vaccine, and GlaxoSmithKline.

In a study of older men that controlled for dietary habits, disease history, and lifestyle factors, pneumococcal vaccines did not show a protective effect against MI or stroke.

Source Pamela Moore/iStockphoto.com

Major Finding: Mean FEV₁ was 2.13 at baseline and 2.22 at 6 months with the active drug, compared with 2.12 at baseline and 2.20 at 6 months with placebo.

Data Source: A 6-month placebo-controlled study of azithromycin in 263 relatively healthy children and adolescents with CF who had negative cultures for P. aeruginosa.

Disclosures: CF Foundation Therapeutics Inc. funded the study, and Pfizer Inc. supplied the azithromycin and the placebo. Dr. Saiman reported ties to Pfizer Inc., maker of azithromycin, and Aridis Pharmaceuticals LLC, Bayer, CF Foundation Therapeutics Inc., Chiesi Pharmaceuticals Inc., Gilead Sciences Inc., Johnson & Johnson, Mpex Pharmaceuticals Inc., Novartis, SmithKline Beecham Inc., and Transave Inc.

A 6-month course of azithromycin did not improve lung function in children and adolescents who had mild cystic fibrosis without Pseudomonas aeruginosa infection, according to a report.

The antibiotic failed to achieve the primary end point of improvement in forced expiratory volume in 1 second (FEV₁) in a randomized controlled trial of 263 CF patients with mild disease, and it also did not decrease the need for intravenous or inhaled antibiotics or for hospitalization.

However, azithromycin achieved the exploratory end points of reducing pulmonary exacerbations, preventing initiation of other oral antibiotics, and increasing thin patients' weight and body mass index.

“Further studies of azithromycin are warranted to further investigate its potential use in this population,” said Dr. Lisa Saiman of the pediatrics department at Columbia University, New York, and her associates (JAMA 2010;303:1707-15).

Azithromycin has both antimicrobial and anti-inflammatory activity, although its exact mechanism of action in CF is not yet known. It is recommended as chronic therapy for CF patients infected with P. aeruginosa, but its use in children who do not have P. aeruginosa has not been well studied.

Dr. Saiman and her colleagues assessed the drug in relatively healthy CF patients aged 6-18 years who had an FEV₁ of at least 50% predicted and had negative cultures for P. aeruginosa. The study subjects were treated between 2007 and 2009 at 40 centers accredited for CF care throughout the United States and Canada.

The patients were randomly assigned to receive 2-3 daily azithromycin tablets (131 patients) or a matching placebo (132 patients) for 168 days, and were closely followed for 196 days. Adherence in the treatment and placebo groups was 90% and 91%, respectively, and only eight participants (five on active treatment and three on placebo) withdrew from the study.

Azithromycin did not improve FEV₁, compared with placebo. Mean FEV₁ was 2.13 at baseline and 2.22 at 6 months with the active drug, compared with 2.12 at baseline and 2.20 at 6 months with placebo. Similarly, azithromycin failed to improve other indicators of pulmonary function, such as forced vital capacity and forced midexpiratory flow rate. There were no differences between the treatment and placebo groups in the number of hospitalizations or the need for IV or inhaled antibiotics.

However, azithromycin decreased the number of pulmonary exacerbations by nearly half and the need for new oral antibiotics by 27%, compared with placebo. It was also associated with a significant weight gain (0.58 kg) and a significant increase in body mass index (0.34 units).

The drug was well tolerated, producing no increase in the rates of nausea, diarrhea, wheezing, and serious or nonserious adverse events, compared with placebo.

The only significant differences between the two groups in treatment-emergent pathogens were found with macrolide-resistant Staphylococcus aureus and Haemophilus influenzae. Azithromycin users had 27% and 7% more emergence of those organisms, respectively, than did placebo participants.

Major Finding: Mean FEV₁ was 2.13 at baseline and 2.22 at 6 months with the active drug, compared with 2.12 at baseline and 2.20 at 6 months with placebo.

Data Source: A 6-month placebo-controlled study of azithromycin in 263 relatively healthy children and adolescents with CF who had negative cultures for P. aeruginosa.

Disclosures: CF Foundation Therapeutics Inc. funded the study, and Pfizer Inc. supplied the azithromycin and the placebo. Dr. Saiman reported ties to Pfizer Inc., maker of azithromycin, and Aridis Pharmaceuticals LLC, Bayer, CF Foundation Therapeutics Inc., Chiesi Pharmaceuticals Inc., Gilead Sciences Inc., Johnson & Johnson, Mpex Pharmaceuticals Inc., Novartis, SmithKline Beecham Inc., and Transave Inc.

A 6-month course of azithromycin did not improve lung function in children and adolescents who had mild cystic fibrosis without Pseudomonas aeruginosa infection, according to a report.

The antibiotic failed to achieve the primary end point of improvement in forced expiratory volume in 1 second (FEV₁) in a randomized controlled trial of 263 CF patients with mild disease, and it also did not decrease the need for intravenous or inhaled antibiotics or for hospitalization.

However, azithromycin achieved the exploratory end points of reducing pulmonary exacerbations, preventing initiation of other oral antibiotics, and increasing thin patients' weight and body mass index.

“Further studies of azithromycin are warranted to further investigate its potential use in this population,” said Dr. Lisa Saiman of the pediatrics department at Columbia University, New York, and her associates (JAMA 2010;303:1707-15).

Azithromycin has both antimicrobial and anti-inflammatory activity, although its exact mechanism of action in CF is not yet known. It is recommended as chronic therapy for CF patients infected with P. aeruginosa, but its use in children who do not have P. aeruginosa has not been well studied.

Dr. Saiman and her colleagues assessed the drug in relatively healthy CF patients aged 6-18 years who had an FEV₁ of at least 50% predicted and had negative cultures for P. aeruginosa. The study subjects were treated between 2007 and 2009 at 40 centers accredited for CF care throughout the United States and Canada.

The patients were randomly assigned to receive 2-3 daily azithromycin tablets (131 patients) or a matching placebo (132 patients) for 168 days, and were closely followed for 196 days. Adherence in the treatment and placebo groups was 90% and 91%, respectively, and only eight participants (five on active treatment and three on placebo) withdrew from the study.

Azithromycin did not improve FEV₁, compared with placebo. Mean FEV₁ was 2.13 at baseline and 2.22 at 6 months with the active drug, compared with 2.12 at baseline and 2.20 at 6 months with placebo. Similarly, azithromycin failed to improve other indicators of pulmonary function, such as forced vital capacity and forced midexpiratory flow rate. There were no differences between the treatment and placebo groups in the number of hospitalizations or the need for IV or inhaled antibiotics.

However, azithromycin decreased the number of pulmonary exacerbations by nearly half and the need for new oral antibiotics by 27%, compared with placebo. It was also associated with a significant weight gain (0.58 kg) and a significant increase in body mass index (0.34 units).

The drug was well tolerated, producing no increase in the rates of nausea, diarrhea, wheezing, and serious or nonserious adverse events, compared with placebo.

The only significant differences between the two groups in treatment-emergent pathogens were found with macrolide-resistant Staphylococcus aureus and Haemophilus influenzae. Azithromycin users had 27% and 7% more emergence of those organisms, respectively, than did placebo participants.

Major Finding: Mean FEV₁ was 2.13 at baseline and 2.22 at 6 months with the active drug, compared with 2.12 at baseline and 2.20 at 6 months with placebo.

Data Source: A 6-month placebo-controlled study of azithromycin in 263 relatively healthy children and adolescents with CF who had negative cultures for P. aeruginosa.

Disclosures: CF Foundation Therapeutics Inc. funded the study, and Pfizer Inc. supplied the azithromycin and the placebo. Dr. Saiman reported ties to Pfizer Inc., maker of azithromycin, and Aridis Pharmaceuticals LLC, Bayer, CF Foundation Therapeutics Inc., Chiesi Pharmaceuticals Inc., Gilead Sciences Inc., Johnson & Johnson, Mpex Pharmaceuticals Inc., Novartis, SmithKline Beecham Inc., and Transave Inc.

A 6-month course of azithromycin did not improve lung function in children and adolescents who had mild cystic fibrosis without Pseudomonas aeruginosa infection, according to a report.

The antibiotic failed to achieve the primary end point of improvement in forced expiratory volume in 1 second (FEV₁) in a randomized controlled trial of 263 CF patients with mild disease, and it also did not decrease the need for intravenous or inhaled antibiotics or for hospitalization.

However, azithromycin achieved the exploratory end points of reducing pulmonary exacerbations, preventing initiation of other oral antibiotics, and increasing thin patients' weight and body mass index.

“Further studies of azithromycin are warranted to further investigate its potential use in this population,” said Dr. Lisa Saiman of the pediatrics department at Columbia University, New York, and her associates (JAMA 2010;303:1707-15).

Azithromycin has both antimicrobial and anti-inflammatory activity, although its exact mechanism of action in CF is not yet known. It is recommended as chronic therapy for CF patients infected with P. aeruginosa, but its use in children who do not have P. aeruginosa has not been well studied.

Dr. Saiman and her colleagues assessed the drug in relatively healthy CF patients aged 6-18 years who had an FEV₁ of at least 50% predicted and had negative cultures for P. aeruginosa. The study subjects were treated between 2007 and 2009 at 40 centers accredited for CF care throughout the United States and Canada.

The patients were randomly assigned to receive 2-3 daily azithromycin tablets (131 patients) or a matching placebo (132 patients) for 168 days, and were closely followed for 196 days. Adherence in the treatment and placebo groups was 90% and 91%, respectively, and only eight participants (five on active treatment and three on placebo) withdrew from the study.

Azithromycin did not improve FEV₁, compared with placebo. Mean FEV₁ was 2.13 at baseline and 2.22 at 6 months with the active drug, compared with 2.12 at baseline and 2.20 at 6 months with placebo. Similarly, azithromycin failed to improve other indicators of pulmonary function, such as forced vital capacity and forced midexpiratory flow rate. There were no differences between the treatment and placebo groups in the number of hospitalizations or the need for IV or inhaled antibiotics.

However, azithromycin decreased the number of pulmonary exacerbations by nearly half and the need for new oral antibiotics by 27%, compared with placebo. It was also associated with a significant weight gain (0.58 kg) and a significant increase in body mass index (0.34 units).

The drug was well tolerated, producing no increase in the rates of nausea, diarrhea, wheezing, and serious or nonserious adverse events, compared with placebo.

The only significant differences between the two groups in treatment-emergent pathogens were found with macrolide-resistant Staphylococcus aureus and Haemophilus influenzae. Azithromycin users had 27% and 7% more emergence of those organisms, respectively, than did placebo participants.