Mary Ann Moon

Constrictive bronchiolitis should be considered in all returning veterans who report exercise limitations due to dyspnea, according to the authors of a report in the July 21 issue of the New England Journal of Medicine.

Lung biopsies revealed diffuse constrictive bronchiolitis in 38 of 49 previously healthy soldiers who developed unexplained exertional dyspnea and diminished exercise tolerance after serving in Iraq or Afghanistan, said Dr. Matthew S. King of the division of pulmonary and critical care medicine, Meharry Medical College, Nashville, Tenn., and his associates (N. Engl. J. Med. 2011;365:222-30).

Although most of the 38 soldiers had been exposed to smoke from a sulfur-mine fire in northern Iraq, 10 reported no potentially toxic exposures – a "particular concern" given that the potential toxic exposures among those 10 may be similar to those of most troops who were deployed to Iraq and Afghanistan.

The rare disorder is a challenge to diagnose, especially in the absence of known predisposing conditions such as rheumatologic disorders, because patients often show low-normal pulmonary function and normal radiologic results.

During a recent 5-year period, the investigators evaluated 80 soldiers from one Kentucky military base who had persistent respiratory symptoms and exercise intolerance – an extensive assessment that included a detailed review of occupational and environmental exposures. A total of 49 were referred for video-assisted thorascopic lung biopsy by their treating physicians.

Of those 49, 38 were found to have diffuse constrictive bronchiolitis. The 35 men and 3 women had a median age of 33 years (range, 23 years to 44 years), and had served in a variety of positions. All had met the requirements of U.S. Army readiness testing wearing full combat gear before being deployed, but now became breathless after climbing a single flight of stairs.

Chest radiography had yielded normal findings in 37 of the soldiers, and high-resolution CT had done so in 25 soldiers. "Only a few soldiers had high-resolution CT showing the centrilobular nodules or expiratory air trapping that can be associated with constrictive bronchiolitis," the researchers said.

Spirometry results, lung volumes, and measures of carbon monoxide diffusing capacity had been normal in 13 of the soldiers, while another 19 had shown only isolated low carbon monoxide diffusing capacity.

All of the 30 soldiers who had undergone cardiopulmonary exercise testing showed mean levels of maximal oxygen consumption and an anaerobic threshold that were in the low-normal range. However, when compared with results for military control subjects rather than controls from the general population, their mean maximal oxygen consumption was significantly lower, and their anaerobic threshold was significantly reduced.

During biopsy, 37 of the 38 soldiers were found to have lacy black pigment on the visceral pleural surface, and specimens demonstrated polarizable material within the pigment. That is consistent with inhalation of particulate matter.

The biopsy specimens also showed mixed airway-wall inflammation and membranous bronchioles containing hypertrophic mural smooth muscle or fibrous thickening that narrowed the lumen in the small airways. That finding, too, is consistent with toxic inhalation.

Culturing the biopsy samples yielded negative results on all attempts to identify bacteria, fungus, or acid-fast bacilli, Dr. King and his colleagues said.

Of the 38 soldiers, 28 had been exposed to smoke from a sulfur-mine fire in northern Iraq, 33 had been exposed to dust storms, 24 to incinerated solid waste in large burn pits, and 18 to incinerated human waste. However, 10 solders reported no potentially toxic exposures at all.

"We expected that the finding of constrictive bronchiolitis would be limited to" the soldiers with prolonged exposure to toxic levels of sulfur dioxide from the sulfur-mine fire, the researchers explained. But soldiers without such exposure also developed the disorder.

"This group causes particular concern, since their potential toxic exposures are shared by most personnel who were deployed to Iraq and Afghanistan," the investigators noted. "These common exposures include open-air burn pits, in which solid waste was routinely incinerated in close proximity to living quarters, and desert dust storms of such severity that they obscured visibility.

"The presenting symptoms, smoking histories, evaluations, and biopsy samples of the 10 soldiers who did not report exposure to the sulfur-mine fire were indistinguishable from those of the 28 soldiers who did report such exposure," the researchers added.

Twenty-seven of the 38 soldiers responded to a follow-up survey in 2010. Nineteen had left the military with a "disabled" rating, while 8 were still serving "despite their inability to complete a 2-mile run within the regulation time." Twenty-two reported that their respiratory problems limited their job opportunities.

Since the case series was completed, nine more soldiers who presented to Dr. King and his associates have been diagnosed as having constrictive bronchiolitis, they noted.

The study was supported in part by the National Center for Research Resources. One of Dr. King’s associates reported ties to Actelion Pharmaceuticals.

Constrictive bronchiolitis should be considered in all returning veterans who report exercise limitations due to dyspnea, according to the authors of a report in the July 21 issue of the New England Journal of Medicine.

Lung biopsies revealed diffuse constrictive bronchiolitis in 38 of 49 previously healthy soldiers who developed unexplained exertional dyspnea and diminished exercise tolerance after serving in Iraq or Afghanistan, said Dr. Matthew S. King of the division of pulmonary and critical care medicine, Meharry Medical College, Nashville, Tenn., and his associates (N. Engl. J. Med. 2011;365:222-30).

Although most of the 38 soldiers had been exposed to smoke from a sulfur-mine fire in northern Iraq, 10 reported no potentially toxic exposures – a "particular concern" given that the potential toxic exposures among those 10 may be similar to those of most troops who were deployed to Iraq and Afghanistan.

The rare disorder is a challenge to diagnose, especially in the absence of known predisposing conditions such as rheumatologic disorders, because patients often show low-normal pulmonary function and normal radiologic results.

During a recent 5-year period, the investigators evaluated 80 soldiers from one Kentucky military base who had persistent respiratory symptoms and exercise intolerance – an extensive assessment that included a detailed review of occupational and environmental exposures. A total of 49 were referred for video-assisted thorascopic lung biopsy by their treating physicians.

Of those 49, 38 were found to have diffuse constrictive bronchiolitis. The 35 men and 3 women had a median age of 33 years (range, 23 years to 44 years), and had served in a variety of positions. All had met the requirements of U.S. Army readiness testing wearing full combat gear before being deployed, but now became breathless after climbing a single flight of stairs.

Chest radiography had yielded normal findings in 37 of the soldiers, and high-resolution CT had done so in 25 soldiers. "Only a few soldiers had high-resolution CT showing the centrilobular nodules or expiratory air trapping that can be associated with constrictive bronchiolitis," the researchers said.

Spirometry results, lung volumes, and measures of carbon monoxide diffusing capacity had been normal in 13 of the soldiers, while another 19 had shown only isolated low carbon monoxide diffusing capacity.

All of the 30 soldiers who had undergone cardiopulmonary exercise testing showed mean levels of maximal oxygen consumption and an anaerobic threshold that were in the low-normal range. However, when compared with results for military control subjects rather than controls from the general population, their mean maximal oxygen consumption was significantly lower, and their anaerobic threshold was significantly reduced.

During biopsy, 37 of the 38 soldiers were found to have lacy black pigment on the visceral pleural surface, and specimens demonstrated polarizable material within the pigment. That is consistent with inhalation of particulate matter.

The biopsy specimens also showed mixed airway-wall inflammation and membranous bronchioles containing hypertrophic mural smooth muscle or fibrous thickening that narrowed the lumen in the small airways. That finding, too, is consistent with toxic inhalation.

Culturing the biopsy samples yielded negative results on all attempts to identify bacteria, fungus, or acid-fast bacilli, Dr. King and his colleagues said.

Of the 38 soldiers, 28 had been exposed to smoke from a sulfur-mine fire in northern Iraq, 33 had been exposed to dust storms, 24 to incinerated solid waste in large burn pits, and 18 to incinerated human waste. However, 10 solders reported no potentially toxic exposures at all.

"We expected that the finding of constrictive bronchiolitis would be limited to" the soldiers with prolonged exposure to toxic levels of sulfur dioxide from the sulfur-mine fire, the researchers explained. But soldiers without such exposure also developed the disorder.

"This group causes particular concern, since their potential toxic exposures are shared by most personnel who were deployed to Iraq and Afghanistan," the investigators noted. "These common exposures include open-air burn pits, in which solid waste was routinely incinerated in close proximity to living quarters, and desert dust storms of such severity that they obscured visibility.

"The presenting symptoms, smoking histories, evaluations, and biopsy samples of the 10 soldiers who did not report exposure to the sulfur-mine fire were indistinguishable from those of the 28 soldiers who did report such exposure," the researchers added.

Twenty-seven of the 38 soldiers responded to a follow-up survey in 2010. Nineteen had left the military with a "disabled" rating, while 8 were still serving "despite their inability to complete a 2-mile run within the regulation time." Twenty-two reported that their respiratory problems limited their job opportunities.

Since the case series was completed, nine more soldiers who presented to Dr. King and his associates have been diagnosed as having constrictive bronchiolitis, they noted.

The study was supported in part by the National Center for Research Resources. One of Dr. King’s associates reported ties to Actelion Pharmaceuticals.

Constrictive bronchiolitis should be considered in all returning veterans who report exercise limitations due to dyspnea, according to the authors of a report in the July 21 issue of the New England Journal of Medicine.

Lung biopsies revealed diffuse constrictive bronchiolitis in 38 of 49 previously healthy soldiers who developed unexplained exertional dyspnea and diminished exercise tolerance after serving in Iraq or Afghanistan, said Dr. Matthew S. King of the division of pulmonary and critical care medicine, Meharry Medical College, Nashville, Tenn., and his associates (N. Engl. J. Med. 2011;365:222-30).

Although most of the 38 soldiers had been exposed to smoke from a sulfur-mine fire in northern Iraq, 10 reported no potentially toxic exposures – a "particular concern" given that the potential toxic exposures among those 10 may be similar to those of most troops who were deployed to Iraq and Afghanistan.

The rare disorder is a challenge to diagnose, especially in the absence of known predisposing conditions such as rheumatologic disorders, because patients often show low-normal pulmonary function and normal radiologic results.

During a recent 5-year period, the investigators evaluated 80 soldiers from one Kentucky military base who had persistent respiratory symptoms and exercise intolerance – an extensive assessment that included a detailed review of occupational and environmental exposures. A total of 49 were referred for video-assisted thorascopic lung biopsy by their treating physicians.

Of those 49, 38 were found to have diffuse constrictive bronchiolitis. The 35 men and 3 women had a median age of 33 years (range, 23 years to 44 years), and had served in a variety of positions. All had met the requirements of U.S. Army readiness testing wearing full combat gear before being deployed, but now became breathless after climbing a single flight of stairs.

Chest radiography had yielded normal findings in 37 of the soldiers, and high-resolution CT had done so in 25 soldiers. "Only a few soldiers had high-resolution CT showing the centrilobular nodules or expiratory air trapping that can be associated with constrictive bronchiolitis," the researchers said.

Spirometry results, lung volumes, and measures of carbon monoxide diffusing capacity had been normal in 13 of the soldiers, while another 19 had shown only isolated low carbon monoxide diffusing capacity.

All of the 30 soldiers who had undergone cardiopulmonary exercise testing showed mean levels of maximal oxygen consumption and an anaerobic threshold that were in the low-normal range. However, when compared with results for military control subjects rather than controls from the general population, their mean maximal oxygen consumption was significantly lower, and their anaerobic threshold was significantly reduced.

During biopsy, 37 of the 38 soldiers were found to have lacy black pigment on the visceral pleural surface, and specimens demonstrated polarizable material within the pigment. That is consistent with inhalation of particulate matter.

The biopsy specimens also showed mixed airway-wall inflammation and membranous bronchioles containing hypertrophic mural smooth muscle or fibrous thickening that narrowed the lumen in the small airways. That finding, too, is consistent with toxic inhalation.

Culturing the biopsy samples yielded negative results on all attempts to identify bacteria, fungus, or acid-fast bacilli, Dr. King and his colleagues said.

Of the 38 soldiers, 28 had been exposed to smoke from a sulfur-mine fire in northern Iraq, 33 had been exposed to dust storms, 24 to incinerated solid waste in large burn pits, and 18 to incinerated human waste. However, 10 solders reported no potentially toxic exposures at all.

"We expected that the finding of constrictive bronchiolitis would be limited to" the soldiers with prolonged exposure to toxic levels of sulfur dioxide from the sulfur-mine fire, the researchers explained. But soldiers without such exposure also developed the disorder.

"This group causes particular concern, since their potential toxic exposures are shared by most personnel who were deployed to Iraq and Afghanistan," the investigators noted. "These common exposures include open-air burn pits, in which solid waste was routinely incinerated in close proximity to living quarters, and desert dust storms of such severity that they obscured visibility.

"The presenting symptoms, smoking histories, evaluations, and biopsy samples of the 10 soldiers who did not report exposure to the sulfur-mine fire were indistinguishable from those of the 28 soldiers who did report such exposure," the researchers added.

Twenty-seven of the 38 soldiers responded to a follow-up survey in 2010. Nineteen had left the military with a "disabled" rating, while 8 were still serving "despite their inability to complete a 2-mile run within the regulation time." Twenty-two reported that their respiratory problems limited their job opportunities.

Since the case series was completed, nine more soldiers who presented to Dr. King and his associates have been diagnosed as having constrictive bronchiolitis, they noted.

The study was supported in part by the National Center for Research Resources. One of Dr. King’s associates reported ties to Actelion Pharmaceuticals.

Taking the GnRH analogue triptorelin during chemotherapy led to a 17% absolute reduction in the occurrence of early menopause in young women with early-stage breast cancer, investigators reported in the July 20 issue of JAMA.

"Our results suggest that temporarily suppressing ovarian function by administering triptorelin reduces the incidence of chemotherapy-induced early menopause. This treatment can therefore be offered to premenopausal patients with breast cancer who wish to decrease the risk of permanent ovarian failure associated with chemotherapy," wrote Dr. Lucia Del Mastro of Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy, and her associates.

In what they described as the largest phase III study to examine this issue, the investigators assessed 281 women aged 18-45 years who were treated for stage I, II, or III breast cancer at 16 Italian medical centers. The patients were randomly assigned to receive adjuvant or neoadjuvant chemotherapy alone or chemotherapy plus IM triptorelin, and were followed for 1 year to compare the incidence of early menopause.

For this open-label trial, early menopause was defined as no resumption of menstrual activity and postmenopausal levels of follicle-stimulating hormone (FSH).

Women with hormone-senstive tumors were also given tamoxifen for 5 years following the end of chemotherapy. Those whose ovarian function returned during the follow-up year also received triptorelin every 4 weeks until ovarian function had been suppressed for at least 2 years, to optimize their chance of eradicating the breast cancer.

The rate of early menopause was 25.9% for chemotherapy alone, compared with 8.9% for the addition of triptorelin, an absolute decrease of 17%. The number of patients who needed to take triptorelin to prevent one case of early menopause was only six, Dr. Del Mastro and her colleagues wrote (JAMA 2011;306:269-76).

Moreover, in a multivariate analysis, the only factor found to significantly reduce the development of premature menopause was the use of triptorelin.

In a secondary analysis of a subgroup of 260 patients, menses resumed in 49.6% of the chemotherapy-only group, compared with 63.3% of the chemotherapy-plus-triptorelin group. The median time to resumption of menses was 6.7 months with the addition of triptorelin, but was not reached in the women who received chemotherapy alone.

"There was no difference in the incidence of selected toxicities that may have been partly related to the use of triptorelin," they added.

Longer follow-up is needed to assess the long-term maintenance of ovarian function and preservation of fertility in these patients. However, "at the time of the last annual follow-up, 1 full-term pregnancy in the chemotherapy-alone group and three pregnancies (one full-term, one premature delivery, and one voluntary abortion) in the chemotherapy plus triptorelin group were reported," Dr. Del Mastro and fellow researchers said.

In addition, longer follow-up is necessary to assess the effectiveness of the breast cancer therapy. So far, it doesn’t appear that adding triptorelin interferes with chemotherapy’s effects. There have been 27 breast cancer recurrences (13 with chemotherapy alone and 14 with the addition of triptorelin) and 11 deaths (3 in the chemotherapy-alone group, 8 in the chemotherapy plus triptorelin group), the researchers said.

The mechanisms by which GnRH analogues may preserve ovarian function "are not fully understood but may include the interruption of FSH secretion, a decrease in utero-ovarian perfusion, the activation of GnRH receptors, the up-regulation of intragonadal antiapoptotic molecules such as sphingosine-1-phosphate, or the protection of undifferentiated germ-line stem cells," they noted.

Taking the GnRH analogue triptorelin during chemotherapy led to a 17% absolute reduction in the occurrence of early menopause in young women with early-stage breast cancer, investigators reported in the July 20 issue of JAMA.

"Our results suggest that temporarily suppressing ovarian function by administering triptorelin reduces the incidence of chemotherapy-induced early menopause. This treatment can therefore be offered to premenopausal patients with breast cancer who wish to decrease the risk of permanent ovarian failure associated with chemotherapy," wrote Dr. Lucia Del Mastro of Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy, and her associates.

In what they described as the largest phase III study to examine this issue, the investigators assessed 281 women aged 18-45 years who were treated for stage I, II, or III breast cancer at 16 Italian medical centers. The patients were randomly assigned to receive adjuvant or neoadjuvant chemotherapy alone or chemotherapy plus IM triptorelin, and were followed for 1 year to compare the incidence of early menopause.

For this open-label trial, early menopause was defined as no resumption of menstrual activity and postmenopausal levels of follicle-stimulating hormone (FSH).

Women with hormone-senstive tumors were also given tamoxifen for 5 years following the end of chemotherapy. Those whose ovarian function returned during the follow-up year also received triptorelin every 4 weeks until ovarian function had been suppressed for at least 2 years, to optimize their chance of eradicating the breast cancer.

The rate of early menopause was 25.9% for chemotherapy alone, compared with 8.9% for the addition of triptorelin, an absolute decrease of 17%. The number of patients who needed to take triptorelin to prevent one case of early menopause was only six, Dr. Del Mastro and her colleagues wrote (JAMA 2011;306:269-76).

Moreover, in a multivariate analysis, the only factor found to significantly reduce the development of premature menopause was the use of triptorelin.

In a secondary analysis of a subgroup of 260 patients, menses resumed in 49.6% of the chemotherapy-only group, compared with 63.3% of the chemotherapy-plus-triptorelin group. The median time to resumption of menses was 6.7 months with the addition of triptorelin, but was not reached in the women who received chemotherapy alone.

"There was no difference in the incidence of selected toxicities that may have been partly related to the use of triptorelin," they added.

Longer follow-up is needed to assess the long-term maintenance of ovarian function and preservation of fertility in these patients. However, "at the time of the last annual follow-up, 1 full-term pregnancy in the chemotherapy-alone group and three pregnancies (one full-term, one premature delivery, and one voluntary abortion) in the chemotherapy plus triptorelin group were reported," Dr. Del Mastro and fellow researchers said.

In addition, longer follow-up is necessary to assess the effectiveness of the breast cancer therapy. So far, it doesn’t appear that adding triptorelin interferes with chemotherapy’s effects. There have been 27 breast cancer recurrences (13 with chemotherapy alone and 14 with the addition of triptorelin) and 11 deaths (3 in the chemotherapy-alone group, 8 in the chemotherapy plus triptorelin group), the researchers said.

The mechanisms by which GnRH analogues may preserve ovarian function "are not fully understood but may include the interruption of FSH secretion, a decrease in utero-ovarian perfusion, the activation of GnRH receptors, the up-regulation of intragonadal antiapoptotic molecules such as sphingosine-1-phosphate, or the protection of undifferentiated germ-line stem cells," they noted.

Taking the GnRH analogue triptorelin during chemotherapy led to a 17% absolute reduction in the occurrence of early menopause in young women with early-stage breast cancer, investigators reported in the July 20 issue of JAMA.

"Our results suggest that temporarily suppressing ovarian function by administering triptorelin reduces the incidence of chemotherapy-induced early menopause. This treatment can therefore be offered to premenopausal patients with breast cancer who wish to decrease the risk of permanent ovarian failure associated with chemotherapy," wrote Dr. Lucia Del Mastro of Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy, and her associates.

In what they described as the largest phase III study to examine this issue, the investigators assessed 281 women aged 18-45 years who were treated for stage I, II, or III breast cancer at 16 Italian medical centers. The patients were randomly assigned to receive adjuvant or neoadjuvant chemotherapy alone or chemotherapy plus IM triptorelin, and were followed for 1 year to compare the incidence of early menopause.

For this open-label trial, early menopause was defined as no resumption of menstrual activity and postmenopausal levels of follicle-stimulating hormone (FSH).

Women with hormone-senstive tumors were also given tamoxifen for 5 years following the end of chemotherapy. Those whose ovarian function returned during the follow-up year also received triptorelin every 4 weeks until ovarian function had been suppressed for at least 2 years, to optimize their chance of eradicating the breast cancer.

The rate of early menopause was 25.9% for chemotherapy alone, compared with 8.9% for the addition of triptorelin, an absolute decrease of 17%. The number of patients who needed to take triptorelin to prevent one case of early menopause was only six, Dr. Del Mastro and her colleagues wrote (JAMA 2011;306:269-76).

Moreover, in a multivariate analysis, the only factor found to significantly reduce the development of premature menopause was the use of triptorelin.

In a secondary analysis of a subgroup of 260 patients, menses resumed in 49.6% of the chemotherapy-only group, compared with 63.3% of the chemotherapy-plus-triptorelin group. The median time to resumption of menses was 6.7 months with the addition of triptorelin, but was not reached in the women who received chemotherapy alone.

"There was no difference in the incidence of selected toxicities that may have been partly related to the use of triptorelin," they added.

Longer follow-up is needed to assess the long-term maintenance of ovarian function and preservation of fertility in these patients. However, "at the time of the last annual follow-up, 1 full-term pregnancy in the chemotherapy-alone group and three pregnancies (one full-term, one premature delivery, and one voluntary abortion) in the chemotherapy plus triptorelin group were reported," Dr. Del Mastro and fellow researchers said.

In addition, longer follow-up is necessary to assess the effectiveness of the breast cancer therapy. So far, it doesn’t appear that adding triptorelin interferes with chemotherapy’s effects. There have been 27 breast cancer recurrences (13 with chemotherapy alone and 14 with the addition of triptorelin) and 11 deaths (3 in the chemotherapy-alone group, 8 in the chemotherapy plus triptorelin group), the researchers said.

The mechanisms by which GnRH analogues may preserve ovarian function "are not fully understood but may include the interruption of FSH secretion, a decrease in utero-ovarian perfusion, the activation of GnRH receptors, the up-regulation of intragonadal antiapoptotic molecules such as sphingosine-1-phosphate, or the protection of undifferentiated germ-line stem cells," they noted.

Physical activity appears to protect against cognitive impairment in the elderly, according to two separate studies reported online July 19 in the Archives of Internal Medicine.

In both studies, even light physical activity such as walking and doing housework were associated with better preservation of cognitive function than was inactivity, the investigators said.

Photo credit:  ©FotoW/iStockphoto

In the first study, researchers used an objective measure of activity energy expenditure to examine the relationship between even the lightest forms of activity and incident cognitive impairment in late life. Activity energy expenditure (AEE) captures energy expended on motions from fidgeting and changing posture to jogging and biking, said Laura E. Middleton, Ph.D., of the Heart and Stroke Foundation Centre for Stroke Recovery at the Sunnybrook Health Sciences Centre, Toronto, and her associates.

"It may be particularly important to capture low-intensity physical activity in elderly individuals, who are less likely to perform vigorous physical activity," they noted.

The AEE technique was used to assess a subgroup of 197 older white men and women (mean age, 75 years) who participated in the Health ABC (Aging and Body Composition) study. They were free of physical and cognitive impairment at baseline in 1998-1999. The participants’ global cognitive function was assessed using the 3MS, a brief test of orientation, concentration, language, praxis, immediate memory, and delayed memory.

During 2-5 years of follow-up, the likelihood of developing cognitive impairment was strongly associated with AEE in a dose-dependent fashion. The incidence of cognitive decline was 1.5% in subjects in the highest tertile of AEE, 4.5% among those in the middle tertile, and 16.9% in those in the lowest tertile of AEE.

This association remained robust through several further analyses, including one that controlled for factors known to influence activity level, such as fat-free body mass. In fact, the association between cognitive impairment and the simple daily motions of climbing stairs or caregiving was even stronger than that reported in previous studies for vigorous physical activity such as running, Dr. Middleton and her colleagues reported (Arch. Intern. Med. 2011 July 19 [doi:10.1001/archinternmed. 2011.277]).

In the second study, another group of researchers examined the association between physical activity and cognitive decline using data from a subgroup of 2,809 older women participating in the Women’s Antioxidant Cardiovascular Study. The study subjects were women health professionals aged 65 or older who had cardiovascular disease, three or more coronary risk factors, or a parent with a history of premature MI or CVD.

Cardiovascular disease and coronary risk factors markedly raise the risk of cognitive impairment. But previous studies that sought to determine whether physical activity would protect against such decline in these high-risk patients have yielded inconsistent and inconclusive results, said Marie-Noel Vercambre, Ph.D., of Mutuelle Generale de l’Education Nationale, Paris, and Brigham and Women’s Hospital, Boston, and her associates.

In this study, the women reported their physical activity and underwent a battery of cognitive tests by telephone interview every 2 years during approximately 6 years of follow-up. Greater physical activity was strongly and consistently associated with substantially slower cognitive decline. "Participating in the 2 highest quintiles of physical activity [the equivalent of walking 30 minutes per day at a brisk pace] was cognitively equivalent to being 5-7 years younger," Dr. Vercambre and her colleagues wrote.

"Most important, the association with total physical activity was not restricted to women engaged in vigorous exercise." Even women who never participated in any vigorous activity showed cognitive benefit from simple walking, they noted (Arch. Intern. Med. 2011 July 19 [doi:10.1001/archinternmed.2011.282]).

It is important to note that physical activity did not correlate with baseline vascular disease in these study subjects, so there was little chance that the findings were confounded by the severity of their CVD, the investigators added.

If these findings are confirmed in future research, "physical activity recommendations could yield substantial public health benefits, given the growing number of older persons with vascular conditions and their high risk of cognitive impairment," Dr. Vercambre and her associates wrote.

They added that several mechanisms may underlie physical activity’s protective effect on the brain. "Exercise may directly preserve neuronal structures by stimulating brain-derived neurotrophic factor and neuronal growth, possibly providing reserve against cognitive decline and dementia. Exercise may also have indirect effects by strengthening the underlying systems that support brain plasticity and helping to sustain the brain’s vascular health by beneficially influencing cardiovascular risk factors, promoting endothelial function, improving glucose and insulin regulation, and ensuring adequate cerebral perfusion.

"Furthermore, physical activity reduces inflammation, which is higher in those with vascular disease and impairs systemic and brain-specific growth factor signaling. Physical activity may also improve psychological well-being, which in turn may protect against decline in cognitive functioning," they wrote.

"I believe that these findings can inform practice and the advice that we give our aging patients," Dr. Eric B. Larson of Group Health Research Institute, Seattle, wrote in an invited commentary accompanying the reports (Arch. Intern. Med. 2011 July 19 [doi:10.1001/archinternmed.2011.273]).

"We can tell them that ongoing maintenance of physical activity is definitely worthwhile and likely of increasing benefit as they advance into old age."

Meanwhile, researchers should now turn toward developing ways to change behavior and promote habitual physical activity, especially in middle and late life, he added.

Dr. Middleton’s study was supported by the National Institute on Aging, the National Institute of Diabetes and Digestive and Kidney Diseases, the Canadian Institute of Health Research, the Alzheimer’s Association, and the American Federation of Aging Research. Dr. Vercambre’s study was supported by the National Institutes of Health, the Fondation Bettencourt-Schueller, and the American Heart Association. Dr. Larson is supported by the National Institute on Aging and reported no financial conflicts of interest. No authors in either study reported having any financial conflicts of interest.

Physical activity appears to protect against cognitive impairment in the elderly, according to two separate studies reported online July 19 in the Archives of Internal Medicine.

In both studies, even light physical activity such as walking and doing housework were associated with better preservation of cognitive function than was inactivity, the investigators said.

Photo credit:  ©FotoW/iStockphoto

In the first study, researchers used an objective measure of activity energy expenditure to examine the relationship between even the lightest forms of activity and incident cognitive impairment in late life. Activity energy expenditure (AEE) captures energy expended on motions from fidgeting and changing posture to jogging and biking, said Laura E. Middleton, Ph.D., of the Heart and Stroke Foundation Centre for Stroke Recovery at the Sunnybrook Health Sciences Centre, Toronto, and her associates.

"It may be particularly important to capture low-intensity physical activity in elderly individuals, who are less likely to perform vigorous physical activity," they noted.

The AEE technique was used to assess a subgroup of 197 older white men and women (mean age, 75 years) who participated in the Health ABC (Aging and Body Composition) study. They were free of physical and cognitive impairment at baseline in 1998-1999. The participants’ global cognitive function was assessed using the 3MS, a brief test of orientation, concentration, language, praxis, immediate memory, and delayed memory.

During 2-5 years of follow-up, the likelihood of developing cognitive impairment was strongly associated with AEE in a dose-dependent fashion. The incidence of cognitive decline was 1.5% in subjects in the highest tertile of AEE, 4.5% among those in the middle tertile, and 16.9% in those in the lowest tertile of AEE.

This association remained robust through several further analyses, including one that controlled for factors known to influence activity level, such as fat-free body mass. In fact, the association between cognitive impairment and the simple daily motions of climbing stairs or caregiving was even stronger than that reported in previous studies for vigorous physical activity such as running, Dr. Middleton and her colleagues reported (Arch. Intern. Med. 2011 July 19 [doi:10.1001/archinternmed. 2011.277]).

In the second study, another group of researchers examined the association between physical activity and cognitive decline using data from a subgroup of 2,809 older women participating in the Women’s Antioxidant Cardiovascular Study. The study subjects were women health professionals aged 65 or older who had cardiovascular disease, three or more coronary risk factors, or a parent with a history of premature MI or CVD.

Cardiovascular disease and coronary risk factors markedly raise the risk of cognitive impairment. But previous studies that sought to determine whether physical activity would protect against such decline in these high-risk patients have yielded inconsistent and inconclusive results, said Marie-Noel Vercambre, Ph.D., of Mutuelle Generale de l’Education Nationale, Paris, and Brigham and Women’s Hospital, Boston, and her associates.

In this study, the women reported their physical activity and underwent a battery of cognitive tests by telephone interview every 2 years during approximately 6 years of follow-up. Greater physical activity was strongly and consistently associated with substantially slower cognitive decline. "Participating in the 2 highest quintiles of physical activity [the equivalent of walking 30 minutes per day at a brisk pace] was cognitively equivalent to being 5-7 years younger," Dr. Vercambre and her colleagues wrote.

"Most important, the association with total physical activity was not restricted to women engaged in vigorous exercise." Even women who never participated in any vigorous activity showed cognitive benefit from simple walking, they noted (Arch. Intern. Med. 2011 July 19 [doi:10.1001/archinternmed.2011.282]).

It is important to note that physical activity did not correlate with baseline vascular disease in these study subjects, so there was little chance that the findings were confounded by the severity of their CVD, the investigators added.

If these findings are confirmed in future research, "physical activity recommendations could yield substantial public health benefits, given the growing number of older persons with vascular conditions and their high risk of cognitive impairment," Dr. Vercambre and her associates wrote.

They added that several mechanisms may underlie physical activity’s protective effect on the brain. "Exercise may directly preserve neuronal structures by stimulating brain-derived neurotrophic factor and neuronal growth, possibly providing reserve against cognitive decline and dementia. Exercise may also have indirect effects by strengthening the underlying systems that support brain plasticity and helping to sustain the brain’s vascular health by beneficially influencing cardiovascular risk factors, promoting endothelial function, improving glucose and insulin regulation, and ensuring adequate cerebral perfusion.

"Furthermore, physical activity reduces inflammation, which is higher in those with vascular disease and impairs systemic and brain-specific growth factor signaling. Physical activity may also improve psychological well-being, which in turn may protect against decline in cognitive functioning," they wrote.

"I believe that these findings can inform practice and the advice that we give our aging patients," Dr. Eric B. Larson of Group Health Research Institute, Seattle, wrote in an invited commentary accompanying the reports (Arch. Intern. Med. 2011 July 19 [doi:10.1001/archinternmed.2011.273]).

"We can tell them that ongoing maintenance of physical activity is definitely worthwhile and likely of increasing benefit as they advance into old age."

Meanwhile, researchers should now turn toward developing ways to change behavior and promote habitual physical activity, especially in middle and late life, he added.

Dr. Middleton’s study was supported by the National Institute on Aging, the National Institute of Diabetes and Digestive and Kidney Diseases, the Canadian Institute of Health Research, the Alzheimer’s Association, and the American Federation of Aging Research. Dr. Vercambre’s study was supported by the National Institutes of Health, the Fondation Bettencourt-Schueller, and the American Heart Association. Dr. Larson is supported by the National Institute on Aging and reported no financial conflicts of interest. No authors in either study reported having any financial conflicts of interest.

Physical activity appears to protect against cognitive impairment in the elderly, according to two separate studies reported online July 19 in the Archives of Internal Medicine.

In both studies, even light physical activity such as walking and doing housework were associated with better preservation of cognitive function than was inactivity, the investigators said.

Photo credit:  ©FotoW/iStockphoto

In the first study, researchers used an objective measure of activity energy expenditure to examine the relationship between even the lightest forms of activity and incident cognitive impairment in late life. Activity energy expenditure (AEE) captures energy expended on motions from fidgeting and changing posture to jogging and biking, said Laura E. Middleton, Ph.D., of the Heart and Stroke Foundation Centre for Stroke Recovery at the Sunnybrook Health Sciences Centre, Toronto, and her associates.

"It may be particularly important to capture low-intensity physical activity in elderly individuals, who are less likely to perform vigorous physical activity," they noted.

The AEE technique was used to assess a subgroup of 197 older white men and women (mean age, 75 years) who participated in the Health ABC (Aging and Body Composition) study. They were free of physical and cognitive impairment at baseline in 1998-1999. The participants’ global cognitive function was assessed using the 3MS, a brief test of orientation, concentration, language, praxis, immediate memory, and delayed memory.

During 2-5 years of follow-up, the likelihood of developing cognitive impairment was strongly associated with AEE in a dose-dependent fashion. The incidence of cognitive decline was 1.5% in subjects in the highest tertile of AEE, 4.5% among those in the middle tertile, and 16.9% in those in the lowest tertile of AEE.

This association remained robust through several further analyses, including one that controlled for factors known to influence activity level, such as fat-free body mass. In fact, the association between cognitive impairment and the simple daily motions of climbing stairs or caregiving was even stronger than that reported in previous studies for vigorous physical activity such as running, Dr. Middleton and her colleagues reported (Arch. Intern. Med. 2011 July 19 [doi:10.1001/archinternmed. 2011.277]).

In the second study, another group of researchers examined the association between physical activity and cognitive decline using data from a subgroup of 2,809 older women participating in the Women’s Antioxidant Cardiovascular Study. The study subjects were women health professionals aged 65 or older who had cardiovascular disease, three or more coronary risk factors, or a parent with a history of premature MI or CVD.

Cardiovascular disease and coronary risk factors markedly raise the risk of cognitive impairment. But previous studies that sought to determine whether physical activity would protect against such decline in these high-risk patients have yielded inconsistent and inconclusive results, said Marie-Noel Vercambre, Ph.D., of Mutuelle Generale de l’Education Nationale, Paris, and Brigham and Women’s Hospital, Boston, and her associates.

In this study, the women reported their physical activity and underwent a battery of cognitive tests by telephone interview every 2 years during approximately 6 years of follow-up. Greater physical activity was strongly and consistently associated with substantially slower cognitive decline. "Participating in the 2 highest quintiles of physical activity [the equivalent of walking 30 minutes per day at a brisk pace] was cognitively equivalent to being 5-7 years younger," Dr. Vercambre and her colleagues wrote.

"Most important, the association with total physical activity was not restricted to women engaged in vigorous exercise." Even women who never participated in any vigorous activity showed cognitive benefit from simple walking, they noted (Arch. Intern. Med. 2011 July 19 [doi:10.1001/archinternmed.2011.282]).

It is important to note that physical activity did not correlate with baseline vascular disease in these study subjects, so there was little chance that the findings were confounded by the severity of their CVD, the investigators added.

If these findings are confirmed in future research, "physical activity recommendations could yield substantial public health benefits, given the growing number of older persons with vascular conditions and their high risk of cognitive impairment," Dr. Vercambre and her associates wrote.

They added that several mechanisms may underlie physical activity’s protective effect on the brain. "Exercise may directly preserve neuronal structures by stimulating brain-derived neurotrophic factor and neuronal growth, possibly providing reserve against cognitive decline and dementia. Exercise may also have indirect effects by strengthening the underlying systems that support brain plasticity and helping to sustain the brain’s vascular health by beneficially influencing cardiovascular risk factors, promoting endothelial function, improving glucose and insulin regulation, and ensuring adequate cerebral perfusion.

"Furthermore, physical activity reduces inflammation, which is higher in those with vascular disease and impairs systemic and brain-specific growth factor signaling. Physical activity may also improve psychological well-being, which in turn may protect against decline in cognitive functioning," they wrote.

"I believe that these findings can inform practice and the advice that we give our aging patients," Dr. Eric B. Larson of Group Health Research Institute, Seattle, wrote in an invited commentary accompanying the reports (Arch. Intern. Med. 2011 July 19 [doi:10.1001/archinternmed.2011.273]).

"We can tell them that ongoing maintenance of physical activity is definitely worthwhile and likely of increasing benefit as they advance into old age."

Meanwhile, researchers should now turn toward developing ways to change behavior and promote habitual physical activity, especially in middle and late life, he added.

Dr. Middleton’s study was supported by the National Institute on Aging, the National Institute of Diabetes and Digestive and Kidney Diseases, the Canadian Institute of Health Research, the Alzheimer’s Association, and the American Federation of Aging Research. Dr. Vercambre’s study was supported by the National Institutes of Health, the Fondation Bettencourt-Schueller, and the American Heart Association. Dr. Larson is supported by the National Institute on Aging and reported no financial conflicts of interest. No authors in either study reported having any financial conflicts of interest.

Neither aspirin nor simvastatin improved outcomes for patients with pulmonary arterial hypertension in a phase II safety and efficacy trial published in Circulation and simultaneously presented at the annual meeting of the American Thoracic Society.

The primary end point of 6-minute walk distance did not increase after 6 months of aspirin therapy and actually decreased after 6 months of simvastatin therapy, indicating that neither agent should be used as an add-on therapy in PAH, said Dr. Steven M. Kawut of Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, and his associates.

A recent animal study showed that aspirin decreased pulmonary artery pressure, reduced right ventricular hypertrophy, and improved survival, and several recent studies showed that statins were effective in animal models of pulmonary hypertension. Dr. Kawut and his associates in the ASA-STAT Study Group designed their phase II clinical trial to test the safety and efficacy of both agents against matching placebos, intending to enroll 100 subjects with PAH.

The study, however, was terminated after only 65 subjects had been randomized because an interim analysis showed "a high likelihood of not rejecting the null hypothesis for the simvastatin arm even if fully recruited," they wrote. The investigators reported their findings for those 65 subjects.

The patients’ mean age was 50 years, and 86% were women. Approximately 52% had idiopathic PAH, 19% had PAH associated with systemic sclerosis, 15% had PAH associated with other connective tissue diseases, 9% had congenital systemic-to-pulmonary shunts, and 5% had heritable PAH.

The primary outcome measure was 6-minute walk distance after 6 months of treatment, after adjustment for 6-minute walk distance at baseline.

Patients who received aspirin therapy showed no improvement in this measure, compared with those who received placebo. They also showed no improvement in median Borg dyspnea scores after the walk test, in any scales of the SF-36, or in World Health Organization functional class. And there was no difference between the two groups in time to clinical worsening, Dr. Kawut and his associates said.

Similarly, patients who received simvastatin showed no improvement in 6-minute walk distance after 6 months of treatment, compared with those who received placebo. In fact, the active drug may have reduced this distance, although the number of subjects was not sufficient to detect a statistically significant difference. Moreover, the median Borg dyspnea scores after the walk test tended to be higher in subjects who took simvastatin than in those who took placebo, suggesting greater breathlessness.

As with aspirin, there were no differences on any scales of the SF-36 or in WHO functional class between the subjects who took simvastatin and those who took placebo (Circulation 2011 May 19 [doi:10.1161/CIRCULATIONAHA.110.015693]).

"There was a possible increased risk of major bleeding associated with aspirin use," they noted, but again, the number of subjects was not sufficient to make this determination definitively.

"On the basis of these findings, neither drug can be recommended for the treatment of PAH," Dr. Kawut and his colleagues said.

The study was funded by the National Institutes of Health and the National Center for Research Resources. Aspirin and matching placebo were provided free of charge by Bayer Healthcare. Additional support was provided by Merck. Dr. Kawut and his associates reported ties to numerous industry sources.

Neither aspirin nor simvastatin improved outcomes for patients with pulmonary arterial hypertension in a phase II safety and efficacy trial published in Circulation and simultaneously presented at the annual meeting of the American Thoracic Society.

The primary end point of 6-minute walk distance did not increase after 6 months of aspirin therapy and actually decreased after 6 months of simvastatin therapy, indicating that neither agent should be used as an add-on therapy in PAH, said Dr. Steven M. Kawut of Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, and his associates.

A recent animal study showed that aspirin decreased pulmonary artery pressure, reduced right ventricular hypertrophy, and improved survival, and several recent studies showed that statins were effective in animal models of pulmonary hypertension. Dr. Kawut and his associates in the ASA-STAT Study Group designed their phase II clinical trial to test the safety and efficacy of both agents against matching placebos, intending to enroll 100 subjects with PAH.

The study, however, was terminated after only 65 subjects had been randomized because an interim analysis showed "a high likelihood of not rejecting the null hypothesis for the simvastatin arm even if fully recruited," they wrote. The investigators reported their findings for those 65 subjects.

The patients’ mean age was 50 years, and 86% were women. Approximately 52% had idiopathic PAH, 19% had PAH associated with systemic sclerosis, 15% had PAH associated with other connective tissue diseases, 9% had congenital systemic-to-pulmonary shunts, and 5% had heritable PAH.

The primary outcome measure was 6-minute walk distance after 6 months of treatment, after adjustment for 6-minute walk distance at baseline.

Patients who received aspirin therapy showed no improvement in this measure, compared with those who received placebo. They also showed no improvement in median Borg dyspnea scores after the walk test, in any scales of the SF-36, or in World Health Organization functional class. And there was no difference between the two groups in time to clinical worsening, Dr. Kawut and his associates said.

Similarly, patients who received simvastatin showed no improvement in 6-minute walk distance after 6 months of treatment, compared with those who received placebo. In fact, the active drug may have reduced this distance, although the number of subjects was not sufficient to detect a statistically significant difference. Moreover, the median Borg dyspnea scores after the walk test tended to be higher in subjects who took simvastatin than in those who took placebo, suggesting greater breathlessness.

As with aspirin, there were no differences on any scales of the SF-36 or in WHO functional class between the subjects who took simvastatin and those who took placebo (Circulation 2011 May 19 [doi:10.1161/CIRCULATIONAHA.110.015693]).

"There was a possible increased risk of major bleeding associated with aspirin use," they noted, but again, the number of subjects was not sufficient to make this determination definitively.

"On the basis of these findings, neither drug can be recommended for the treatment of PAH," Dr. Kawut and his colleagues said.

The study was funded by the National Institutes of Health and the National Center for Research Resources. Aspirin and matching placebo were provided free of charge by Bayer Healthcare. Additional support was provided by Merck. Dr. Kawut and his associates reported ties to numerous industry sources.

Neither aspirin nor simvastatin improved outcomes for patients with pulmonary arterial hypertension in a phase II safety and efficacy trial published in Circulation and simultaneously presented at the annual meeting of the American Thoracic Society.

The primary end point of 6-minute walk distance did not increase after 6 months of aspirin therapy and actually decreased after 6 months of simvastatin therapy, indicating that neither agent should be used as an add-on therapy in PAH, said Dr. Steven M. Kawut of Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, and his associates.

A recent animal study showed that aspirin decreased pulmonary artery pressure, reduced right ventricular hypertrophy, and improved survival, and several recent studies showed that statins were effective in animal models of pulmonary hypertension. Dr. Kawut and his associates in the ASA-STAT Study Group designed their phase II clinical trial to test the safety and efficacy of both agents against matching placebos, intending to enroll 100 subjects with PAH.

The study, however, was terminated after only 65 subjects had been randomized because an interim analysis showed "a high likelihood of not rejecting the null hypothesis for the simvastatin arm even if fully recruited," they wrote. The investigators reported their findings for those 65 subjects.

The patients’ mean age was 50 years, and 86% were women. Approximately 52% had idiopathic PAH, 19% had PAH associated with systemic sclerosis, 15% had PAH associated with other connective tissue diseases, 9% had congenital systemic-to-pulmonary shunts, and 5% had heritable PAH.

The primary outcome measure was 6-minute walk distance after 6 months of treatment, after adjustment for 6-minute walk distance at baseline.

Patients who received aspirin therapy showed no improvement in this measure, compared with those who received placebo. They also showed no improvement in median Borg dyspnea scores after the walk test, in any scales of the SF-36, or in World Health Organization functional class. And there was no difference between the two groups in time to clinical worsening, Dr. Kawut and his associates said.

Similarly, patients who received simvastatin showed no improvement in 6-minute walk distance after 6 months of treatment, compared with those who received placebo. In fact, the active drug may have reduced this distance, although the number of subjects was not sufficient to detect a statistically significant difference. Moreover, the median Borg dyspnea scores after the walk test tended to be higher in subjects who took simvastatin than in those who took placebo, suggesting greater breathlessness.

As with aspirin, there were no differences on any scales of the SF-36 or in WHO functional class between the subjects who took simvastatin and those who took placebo (Circulation 2011 May 19 [doi:10.1161/CIRCULATIONAHA.110.015693]).

"There was a possible increased risk of major bleeding associated with aspirin use," they noted, but again, the number of subjects was not sufficient to make this determination definitively.

"On the basis of these findings, neither drug can be recommended for the treatment of PAH," Dr. Kawut and his colleagues said.

The study was funded by the National Institutes of Health and the National Center for Research Resources. Aspirin and matching placebo were provided free of charge by Bayer Healthcare. Additional support was provided by Merck. Dr. Kawut and his associates reported ties to numerous industry sources.

Adding short-term androgen-deprivation therapy before and during conventional radiotherapy for early localized prostate cancer confers a modest but significant increase in 10-year survival, according to a new report in the July 14 issue of the New England Journal of Medicine.

The strategy also halves disease-specific 10-year mortality, reduces the rate of biochemical failure (recurrence of elevated PSA), cuts the incidence of distant metastases, and decreases the rate of positive findings on repeat prostate biopsy after 2 years, said Dr. Christopher U. Jones of Radiological Associates of Sacramento and his associates in this Radiation Therapy Oncology Group (RTOG) phase III clinical trial.

These benefits were most pronounced for men deemed to be at intermediate risk at diagnosis, they noted.

The RTOG initiated the international randomized trial because little is known about the role of short-term androgen-deprivation therapy (ADT) for nonbulky localized tumors. Study subjects comprised 1,979 men with stage T1b, T1c, T2a, or T2b prostate adenocarcinomas and an initial PSA level of 20 ng per milliliter or lower.

Patients were randomly assigned to standard radiotherapy alone (992 subjects) or radiotherapy plus three-times-daily flutamide and either subcutaneous goserelin or intramuscular leuprolide beginning 2 months before initiation of radiotherapy and continuing through 2 months of radiotherapy (987 subjects).

The primary end point was overall survival after a sufficiently long interval had passed to allow for recurrence of this often indolent cancer. The 10-year overall survival was 62% with added ADT, compared with 57% with radiotherapy alone.

The 10-year disease-specific mortality was 4% with combined therapy and 8% with radiotherapy alone. The 10-year rate of biochemical failure was 26% with combined therapy and 41% with radiotherapy alone. The 10-year cumulative incidence of distant metastases was 6% with combined therapy and 8% with radiotherapy alone.

Approximately 45% of the study population underwent repeat prostate biopsy after 2 years. Persistent cancer was detected in 20% of the specimens from men who had received radiotherapy plus ADT, compared with 39% of the men who had received radiotherapy alone.

A subgroup analysis showed that adding ADT to radiotherapy was most beneficial for men who had been considered to be at intermediate risk at baseline; they comprised slightly more than half of the study subjects. In this subgroup of 524 men who received combination therapy, 10-year overall survival was 61% (vs. 54% in the 544 intermediate-risk men who received radiotherapy alone) and 10-year disease-specific mortality was 3% (vs. 10%).

Low-risk men did not show these benefits when ADT was added to radiotherapy, but ADT did significantly decrease the incidence of biochemical failure and the rate of positive results on repeat biopsy in low-risk men. "It is conceivable that in patients with indolent disease, longer follow-up is required to show a benefit with respect to the disease-specific mortality and overall survival rates," Dr. Jones and his colleagues said (N. Engl. J. Med. 2011;365:107-18).

For the small number of subjects (11% of both study groups) considered to be at high risk at baseline, adding short-term ADT to radiotherapy did not appear to be beneficial. This comparison, however, may have been underpowered. It also may be that, as previous clinical trials have suggested, more than 4 months of ADT is required for maximum benefit in this population, the investigators added.

In all, 395 of the study subjects were black, and black men showed similar benefits from short-term ADT as did white men. Adding ADT decreased the 10-year disease-specific mortality from 7% to 5% and cut the 10-year rate of biochemical failure from 40% to 19% in black men. Overall survival was worse among black men compared with white, but disease-specific mortality was similar.

Acute and late radiation-induced toxic effects were similar between subjects who received radiotherapy alone and those who received radiotherapy plus ADT. The rate of grade 3 or higher toxic effects related to ADT was less than 5%.

Given that the addition of ADT may not be as beneficial for low-risk patients, the treatment’s toxic effects, which do affect quality of life, may tip the balance against using this approach in low-risk men. Hot flashes and erectile dysfunction were more common with ADT, and previous studies have suggested that such erectile dysfunction may be less responsive to interventions than after radiotherapy alone. Moreover, other studies have reported that even short-term ADT can cause measurable muscle loss, fat accumulation, decreased insulin sensitivity, and increases in cholesterol and triglyceride levels, Dr. Jones and his associates said.

They noted that radiotherapy techniques have changed somewhat since this study was initiated, and intensity-modulated radiotherapy, low-dose-rate brachytherapy, and high-dose-rate brachytherapy now allow "the safe delivery of higher doses of radiation than was possible when this study was conducted." The value of adding short-term ADT to these techniques is not yet known but is currently being studied in another RTOG clinical trial, they said.

The study was supported by the National Cancer Institute and no commercial support was provided. Dr. Jones’ associates reported ties to Amgen, Ferring, GlaxoSmithKline, Eli Lilly, Calypso Medical, and Varian.

Adding short-term androgen-deprivation therapy before and during conventional radiotherapy for early localized prostate cancer confers a modest but significant increase in 10-year survival, according to a new report in the July 14 issue of the New England Journal of Medicine.

The strategy also halves disease-specific 10-year mortality, reduces the rate of biochemical failure (recurrence of elevated PSA), cuts the incidence of distant metastases, and decreases the rate of positive findings on repeat prostate biopsy after 2 years, said Dr. Christopher U. Jones of Radiological Associates of Sacramento and his associates in this Radiation Therapy Oncology Group (RTOG) phase III clinical trial.

These benefits were most pronounced for men deemed to be at intermediate risk at diagnosis, they noted.

The RTOG initiated the international randomized trial because little is known about the role of short-term androgen-deprivation therapy (ADT) for nonbulky localized tumors. Study subjects comprised 1,979 men with stage T1b, T1c, T2a, or T2b prostate adenocarcinomas and an initial PSA level of 20 ng per milliliter or lower.

Patients were randomly assigned to standard radiotherapy alone (992 subjects) or radiotherapy plus three-times-daily flutamide and either subcutaneous goserelin or intramuscular leuprolide beginning 2 months before initiation of radiotherapy and continuing through 2 months of radiotherapy (987 subjects).

The primary end point was overall survival after a sufficiently long interval had passed to allow for recurrence of this often indolent cancer. The 10-year overall survival was 62% with added ADT, compared with 57% with radiotherapy alone.

The 10-year disease-specific mortality was 4% with combined therapy and 8% with radiotherapy alone. The 10-year rate of biochemical failure was 26% with combined therapy and 41% with radiotherapy alone. The 10-year cumulative incidence of distant metastases was 6% with combined therapy and 8% with radiotherapy alone.

Approximately 45% of the study population underwent repeat prostate biopsy after 2 years. Persistent cancer was detected in 20% of the specimens from men who had received radiotherapy plus ADT, compared with 39% of the men who had received radiotherapy alone.

A subgroup analysis showed that adding ADT to radiotherapy was most beneficial for men who had been considered to be at intermediate risk at baseline; they comprised slightly more than half of the study subjects. In this subgroup of 524 men who received combination therapy, 10-year overall survival was 61% (vs. 54% in the 544 intermediate-risk men who received radiotherapy alone) and 10-year disease-specific mortality was 3% (vs. 10%).

Low-risk men did not show these benefits when ADT was added to radiotherapy, but ADT did significantly decrease the incidence of biochemical failure and the rate of positive results on repeat biopsy in low-risk men. "It is conceivable that in patients with indolent disease, longer follow-up is required to show a benefit with respect to the disease-specific mortality and overall survival rates," Dr. Jones and his colleagues said (N. Engl. J. Med. 2011;365:107-18).

For the small number of subjects (11% of both study groups) considered to be at high risk at baseline, adding short-term ADT to radiotherapy did not appear to be beneficial. This comparison, however, may have been underpowered. It also may be that, as previous clinical trials have suggested, more than 4 months of ADT is required for maximum benefit in this population, the investigators added.

In all, 395 of the study subjects were black, and black men showed similar benefits from short-term ADT as did white men. Adding ADT decreased the 10-year disease-specific mortality from 7% to 5% and cut the 10-year rate of biochemical failure from 40% to 19% in black men. Overall survival was worse among black men compared with white, but disease-specific mortality was similar.

Acute and late radiation-induced toxic effects were similar between subjects who received radiotherapy alone and those who received radiotherapy plus ADT. The rate of grade 3 or higher toxic effects related to ADT was less than 5%.

Given that the addition of ADT may not be as beneficial for low-risk patients, the treatment’s toxic effects, which do affect quality of life, may tip the balance against using this approach in low-risk men. Hot flashes and erectile dysfunction were more common with ADT, and previous studies have suggested that such erectile dysfunction may be less responsive to interventions than after radiotherapy alone. Moreover, other studies have reported that even short-term ADT can cause measurable muscle loss, fat accumulation, decreased insulin sensitivity, and increases in cholesterol and triglyceride levels, Dr. Jones and his associates said.

They noted that radiotherapy techniques have changed somewhat since this study was initiated, and intensity-modulated radiotherapy, low-dose-rate brachytherapy, and high-dose-rate brachytherapy now allow "the safe delivery of higher doses of radiation than was possible when this study was conducted." The value of adding short-term ADT to these techniques is not yet known but is currently being studied in another RTOG clinical trial, they said.

The study was supported by the National Cancer Institute and no commercial support was provided. Dr. Jones’ associates reported ties to Amgen, Ferring, GlaxoSmithKline, Eli Lilly, Calypso Medical, and Varian.

Adding short-term androgen-deprivation therapy before and during conventional radiotherapy for early localized prostate cancer confers a modest but significant increase in 10-year survival, according to a new report in the July 14 issue of the New England Journal of Medicine.

The strategy also halves disease-specific 10-year mortality, reduces the rate of biochemical failure (recurrence of elevated PSA), cuts the incidence of distant metastases, and decreases the rate of positive findings on repeat prostate biopsy after 2 years, said Dr. Christopher U. Jones of Radiological Associates of Sacramento and his associates in this Radiation Therapy Oncology Group (RTOG) phase III clinical trial.

These benefits were most pronounced for men deemed to be at intermediate risk at diagnosis, they noted.

The RTOG initiated the international randomized trial because little is known about the role of short-term androgen-deprivation therapy (ADT) for nonbulky localized tumors. Study subjects comprised 1,979 men with stage T1b, T1c, T2a, or T2b prostate adenocarcinomas and an initial PSA level of 20 ng per milliliter or lower.

Patients were randomly assigned to standard radiotherapy alone (992 subjects) or radiotherapy plus three-times-daily flutamide and either subcutaneous goserelin or intramuscular leuprolide beginning 2 months before initiation of radiotherapy and continuing through 2 months of radiotherapy (987 subjects).

The primary end point was overall survival after a sufficiently long interval had passed to allow for recurrence of this often indolent cancer. The 10-year overall survival was 62% with added ADT, compared with 57% with radiotherapy alone.

The 10-year disease-specific mortality was 4% with combined therapy and 8% with radiotherapy alone. The 10-year rate of biochemical failure was 26% with combined therapy and 41% with radiotherapy alone. The 10-year cumulative incidence of distant metastases was 6% with combined therapy and 8% with radiotherapy alone.

Approximately 45% of the study population underwent repeat prostate biopsy after 2 years. Persistent cancer was detected in 20% of the specimens from men who had received radiotherapy plus ADT, compared with 39% of the men who had received radiotherapy alone.

A subgroup analysis showed that adding ADT to radiotherapy was most beneficial for men who had been considered to be at intermediate risk at baseline; they comprised slightly more than half of the study subjects. In this subgroup of 524 men who received combination therapy, 10-year overall survival was 61% (vs. 54% in the 544 intermediate-risk men who received radiotherapy alone) and 10-year disease-specific mortality was 3% (vs. 10%).

Low-risk men did not show these benefits when ADT was added to radiotherapy, but ADT did significantly decrease the incidence of biochemical failure and the rate of positive results on repeat biopsy in low-risk men. "It is conceivable that in patients with indolent disease, longer follow-up is required to show a benefit with respect to the disease-specific mortality and overall survival rates," Dr. Jones and his colleagues said (N. Engl. J. Med. 2011;365:107-18).

For the small number of subjects (11% of both study groups) considered to be at high risk at baseline, adding short-term ADT to radiotherapy did not appear to be beneficial. This comparison, however, may have been underpowered. It also may be that, as previous clinical trials have suggested, more than 4 months of ADT is required for maximum benefit in this population, the investigators added.

In all, 395 of the study subjects were black, and black men showed similar benefits from short-term ADT as did white men. Adding ADT decreased the 10-year disease-specific mortality from 7% to 5% and cut the 10-year rate of biochemical failure from 40% to 19% in black men. Overall survival was worse among black men compared with white, but disease-specific mortality was similar.

Acute and late radiation-induced toxic effects were similar between subjects who received radiotherapy alone and those who received radiotherapy plus ADT. The rate of grade 3 or higher toxic effects related to ADT was less than 5%.

Given that the addition of ADT may not be as beneficial for low-risk patients, the treatment’s toxic effects, which do affect quality of life, may tip the balance against using this approach in low-risk men. Hot flashes and erectile dysfunction were more common with ADT, and previous studies have suggested that such erectile dysfunction may be less responsive to interventions than after radiotherapy alone. Moreover, other studies have reported that even short-term ADT can cause measurable muscle loss, fat accumulation, decreased insulin sensitivity, and increases in cholesterol and triglyceride levels, Dr. Jones and his associates said.

They noted that radiotherapy techniques have changed somewhat since this study was initiated, and intensity-modulated radiotherapy, low-dose-rate brachytherapy, and high-dose-rate brachytherapy now allow "the safe delivery of higher doses of radiation than was possible when this study was conducted." The value of adding short-term ADT to these techniques is not yet known but is currently being studied in another RTOG clinical trial, they said.

The study was supported by the National Cancer Institute and no commercial support was provided. Dr. Jones’ associates reported ties to Amgen, Ferring, GlaxoSmithKline, Eli Lilly, Calypso Medical, and Varian.

In a pilot study designed to tease out placebo effects from genuine clinical responses, asthma patients rated albuterol and two placebo interventions as effective, yet only the albuterol objectively improved forced expiratory volume in 1 second, according to a report in the July 14 issue of the New England Journal of Medicine.

The 46 study subjects also rated both placebo interventions as superior to a no-intervention control situation, even though the objective forced expiratory volume in 1 second (FEV₁) response was nearly identical in all three, said Dr. Michael E. Wechsler of the division of pulmonary and critical care medicine, Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and his associates.

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"Even though there was a large, objective drug effect (mean percent improvement in FEV₁, 20%) that was nearly three times the effect of the two placebos and the no-intervention control (mean percent improvement in FEV₁, approximately 7% for all three), patients could not reliably detect the difference between this robust effect of the active drug and the effects of inhaled placebo and sham acupuncture (mean subjective improvement reported by all patients, regardless of intervention, ranged between 45% and 50%)," they wrote.

These findings suggest that asthma patients poorly perceive changes in FEV₁ and that subjective assessments in clinical studies of asthma are severely limited. "Furthermore, it can justly be asserted that for self-appraised symptoms, placebos can have a powerful effect," Dr. Wechsler and his colleagues said.

Their results may also have important implications for placebo effects in general, not just in asthma patients. "Although effective medications target and modulate objective biologic features, the mere ritual of treatment may affect patients’ self-monitoring and subjective experience of their disease," the investigators said.

They chose asthma patients as ideal subjects for this pilot study of placebo effects because repeated objective lung-function assessments can be performed over a short period of time. "We compared acute changes in lung function that occurred after repeated administration of four interventions: a masked bronchodilator (inhaled albuterol), two different types of placebo (an inert inhaler and a validated sham acupuncture needle), and a [waiting] period of no intervention."

A total of 46 adults with stable, mild to moderate asthma who had experience using inhalers were enrolled. They were assigned to each of the four interventions in random order on four separate occasions, 3-7 days apart. On each occasion, they underwent spirometry at baseline and at 20-minute intervals for 2 hours following the intervention. The study subjects documented their subjective treatment responses using a 10-point visual analog scale.

The mean percent improvement in FEV₁ was 20.1% for inhaled albuterol, compared with 7.5% for inhaled placebo, 7.3% for sham acupuncture, and 7.1% for the no-intervention control situation of sitting in a waiting room. This constitutes a "significant" and "large" difference between active and nonactive interventions.

Moreover, using a standard definition of treatment response (12% or greater improvement in FEV₁), patients using the albuterol inhaler responded 77% of the time, while those using the placebo inhaler responded 24% of the time, those using sham acupuncture responded 20% of the time, and those using no intervention responded 18% of the time, Dr. Wechsler and his associates said (N. Engl. J. Med. 2011;365:119-26).

However, the subjects’ assessments did not reflect these results. They reported a 50% improvement in asthma symptoms with inhaled albuterol, a 45% improvement with inhaled placebo, and a 46% improvement with sham acupuncture, compared with a significantly lower 21% improvement with no intervention.

Patients were asked whether they thought they had received active or placebo interventions. Most believed all the interventions except sitting in a waiting room were active. A total of 73% believed the albuterol was active, 66% believed the placebo inhaler was active, and "a remarkable" 85% believed the sham acupuncture was active.

The study findings complement those of a recent trial in which placebo given with "enhanced expectations" – such as deceptive remarks that subjects were receiving a powerful medication – had no effect on objective outcomes but did increase subjective response.

Dr. Wechsler and his colleagues said their results suggest that "subjective improvement in asthma should be interpreted with caution and that objective outcomes should be more heavily relied on for optimal asthma care."

But this interpretation can be questioned. Dr. Wechsler and his colleagues concluded that asthma patients’ reports were "unreliable" because "they reported improvement when there was none – that is, the subjective experiences were simply wrong because they ignored objective facts as measured by FEV₁," Daniel E. Moerman, Ph.D., wrote in an editorial accompanying Dr. Wechsler’s report (N. Engl. J. Med. 2011;365:171-2).

"It is the subjective symptoms that brought these patients to medical care in the first place. They came because they were wheezing and felt suffocated, not because they had a reduced FEV₁," noted Dr. Moerman of the University of Michigan, Dearborn.

For subjective and functional conditions, including migraine, back pain, depression, asthma, inflammatory bowel disease, many autoimmune disorders, and any condition defined by its symptoms, "a patient-centered approach requires that patient-preferred outcomes trump the judgment of the physician.

"Under these conditions, inert pills can be as useful as ‘real’ ones; two inert pills can work better than one; colorful inert pills can work better than plain ones; and injections can work better than pills," wrote Dr. Moerman.

Dr. Wechsler’s study was supported by the National Center for Complementary and Alternative Medicine. Dr. Wechsler and his associates reported ties to numerous industry sources. Dr. Moerman reported no financial conflicts.

In a pilot study designed to tease out placebo effects from genuine clinical responses, asthma patients rated albuterol and two placebo interventions as effective, yet only the albuterol objectively improved forced expiratory volume in 1 second, according to a report in the July 14 issue of the New England Journal of Medicine.

The 46 study subjects also rated both placebo interventions as superior to a no-intervention control situation, even though the objective forced expiratory volume in 1 second (FEV₁) response was nearly identical in all three, said Dr. Michael E. Wechsler of the division of pulmonary and critical care medicine, Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and his associates.

(c) Monkey Business/Fotolia.com

"Even though there was a large, objective drug effect (mean percent improvement in FEV₁, 20%) that was nearly three times the effect of the two placebos and the no-intervention control (mean percent improvement in FEV₁, approximately 7% for all three), patients could not reliably detect the difference between this robust effect of the active drug and the effects of inhaled placebo and sham acupuncture (mean subjective improvement reported by all patients, regardless of intervention, ranged between 45% and 50%)," they wrote.

These findings suggest that asthma patients poorly perceive changes in FEV₁ and that subjective assessments in clinical studies of asthma are severely limited. "Furthermore, it can justly be asserted that for self-appraised symptoms, placebos can have a powerful effect," Dr. Wechsler and his colleagues said.

Their results may also have important implications for placebo effects in general, not just in asthma patients. "Although effective medications target and modulate objective biologic features, the mere ritual of treatment may affect patients’ self-monitoring and subjective experience of their disease," the investigators said.

They chose asthma patients as ideal subjects for this pilot study of placebo effects because repeated objective lung-function assessments can be performed over a short period of time. "We compared acute changes in lung function that occurred after repeated administration of four interventions: a masked bronchodilator (inhaled albuterol), two different types of placebo (an inert inhaler and a validated sham acupuncture needle), and a [waiting] period of no intervention."

A total of 46 adults with stable, mild to moderate asthma who had experience using inhalers were enrolled. They were assigned to each of the four interventions in random order on four separate occasions, 3-7 days apart. On each occasion, they underwent spirometry at baseline and at 20-minute intervals for 2 hours following the intervention. The study subjects documented their subjective treatment responses using a 10-point visual analog scale.

The mean percent improvement in FEV₁ was 20.1% for inhaled albuterol, compared with 7.5% for inhaled placebo, 7.3% for sham acupuncture, and 7.1% for the no-intervention control situation of sitting in a waiting room. This constitutes a "significant" and "large" difference between active and nonactive interventions.

Moreover, using a standard definition of treatment response (12% or greater improvement in FEV₁), patients using the albuterol inhaler responded 77% of the time, while those using the placebo inhaler responded 24% of the time, those using sham acupuncture responded 20% of the time, and those using no intervention responded 18% of the time, Dr. Wechsler and his associates said (N. Engl. J. Med. 2011;365:119-26).

However, the subjects’ assessments did not reflect these results. They reported a 50% improvement in asthma symptoms with inhaled albuterol, a 45% improvement with inhaled placebo, and a 46% improvement with sham acupuncture, compared with a significantly lower 21% improvement with no intervention.

Patients were asked whether they thought they had received active or placebo interventions. Most believed all the interventions except sitting in a waiting room were active. A total of 73% believed the albuterol was active, 66% believed the placebo inhaler was active, and "a remarkable" 85% believed the sham acupuncture was active.

The study findings complement those of a recent trial in which placebo given with "enhanced expectations" – such as deceptive remarks that subjects were receiving a powerful medication – had no effect on objective outcomes but did increase subjective response.

Dr. Wechsler and his colleagues said their results suggest that "subjective improvement in asthma should be interpreted with caution and that objective outcomes should be more heavily relied on for optimal asthma care."

But this interpretation can be questioned. Dr. Wechsler and his colleagues concluded that asthma patients’ reports were "unreliable" because "they reported improvement when there was none – that is, the subjective experiences were simply wrong because they ignored objective facts as measured by FEV₁," Daniel E. Moerman, Ph.D., wrote in an editorial accompanying Dr. Wechsler’s report (N. Engl. J. Med. 2011;365:171-2).

"It is the subjective symptoms that brought these patients to medical care in the first place. They came because they were wheezing and felt suffocated, not because they had a reduced FEV₁," noted Dr. Moerman of the University of Michigan, Dearborn.

For subjective and functional conditions, including migraine, back pain, depression, asthma, inflammatory bowel disease, many autoimmune disorders, and any condition defined by its symptoms, "a patient-centered approach requires that patient-preferred outcomes trump the judgment of the physician.

"Under these conditions, inert pills can be as useful as ‘real’ ones; two inert pills can work better than one; colorful inert pills can work better than plain ones; and injections can work better than pills," wrote Dr. Moerman.

Dr. Wechsler’s study was supported by the National Center for Complementary and Alternative Medicine. Dr. Wechsler and his associates reported ties to numerous industry sources. Dr. Moerman reported no financial conflicts.

In a pilot study designed to tease out placebo effects from genuine clinical responses, asthma patients rated albuterol and two placebo interventions as effective, yet only the albuterol objectively improved forced expiratory volume in 1 second, according to a report in the July 14 issue of the New England Journal of Medicine.

The 46 study subjects also rated both placebo interventions as superior to a no-intervention control situation, even though the objective forced expiratory volume in 1 second (FEV₁) response was nearly identical in all three, said Dr. Michael E. Wechsler of the division of pulmonary and critical care medicine, Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and his associates.

(c) Monkey Business/Fotolia.com

"Even though there was a large, objective drug effect (mean percent improvement in FEV₁, 20%) that was nearly three times the effect of the two placebos and the no-intervention control (mean percent improvement in FEV₁, approximately 7% for all three), patients could not reliably detect the difference between this robust effect of the active drug and the effects of inhaled placebo and sham acupuncture (mean subjective improvement reported by all patients, regardless of intervention, ranged between 45% and 50%)," they wrote.

These findings suggest that asthma patients poorly perceive changes in FEV₁ and that subjective assessments in clinical studies of asthma are severely limited. "Furthermore, it can justly be asserted that for self-appraised symptoms, placebos can have a powerful effect," Dr. Wechsler and his colleagues said.

Their results may also have important implications for placebo effects in general, not just in asthma patients. "Although effective medications target and modulate objective biologic features, the mere ritual of treatment may affect patients’ self-monitoring and subjective experience of their disease," the investigators said.

They chose asthma patients as ideal subjects for this pilot study of placebo effects because repeated objective lung-function assessments can be performed over a short period of time. "We compared acute changes in lung function that occurred after repeated administration of four interventions: a masked bronchodilator (inhaled albuterol), two different types of placebo (an inert inhaler and a validated sham acupuncture needle), and a [waiting] period of no intervention."

A total of 46 adults with stable, mild to moderate asthma who had experience using inhalers were enrolled. They were assigned to each of the four interventions in random order on four separate occasions, 3-7 days apart. On each occasion, they underwent spirometry at baseline and at 20-minute intervals for 2 hours following the intervention. The study subjects documented their subjective treatment responses using a 10-point visual analog scale.

The mean percent improvement in FEV₁ was 20.1% for inhaled albuterol, compared with 7.5% for inhaled placebo, 7.3% for sham acupuncture, and 7.1% for the no-intervention control situation of sitting in a waiting room. This constitutes a "significant" and "large" difference between active and nonactive interventions.

Moreover, using a standard definition of treatment response (12% or greater improvement in FEV₁), patients using the albuterol inhaler responded 77% of the time, while those using the placebo inhaler responded 24% of the time, those using sham acupuncture responded 20% of the time, and those using no intervention responded 18% of the time, Dr. Wechsler and his associates said (N. Engl. J. Med. 2011;365:119-26).

However, the subjects’ assessments did not reflect these results. They reported a 50% improvement in asthma symptoms with inhaled albuterol, a 45% improvement with inhaled placebo, and a 46% improvement with sham acupuncture, compared with a significantly lower 21% improvement with no intervention.

Patients were asked whether they thought they had received active or placebo interventions. Most believed all the interventions except sitting in a waiting room were active. A total of 73% believed the albuterol was active, 66% believed the placebo inhaler was active, and "a remarkable" 85% believed the sham acupuncture was active.

The study findings complement those of a recent trial in which placebo given with "enhanced expectations" – such as deceptive remarks that subjects were receiving a powerful medication – had no effect on objective outcomes but did increase subjective response.

Dr. Wechsler and his colleagues said their results suggest that "subjective improvement in asthma should be interpreted with caution and that objective outcomes should be more heavily relied on for optimal asthma care."

But this interpretation can be questioned. Dr. Wechsler and his colleagues concluded that asthma patients’ reports were "unreliable" because "they reported improvement when there was none – that is, the subjective experiences were simply wrong because they ignored objective facts as measured by FEV₁," Daniel E. Moerman, Ph.D., wrote in an editorial accompanying Dr. Wechsler’s report (N. Engl. J. Med. 2011;365:171-2).

"It is the subjective symptoms that brought these patients to medical care in the first place. They came because they were wheezing and felt suffocated, not because they had a reduced FEV₁," noted Dr. Moerman of the University of Michigan, Dearborn.

For subjective and functional conditions, including migraine, back pain, depression, asthma, inflammatory bowel disease, many autoimmune disorders, and any condition defined by its symptoms, "a patient-centered approach requires that patient-preferred outcomes trump the judgment of the physician.

"Under these conditions, inert pills can be as useful as ‘real’ ones; two inert pills can work better than one; colorful inert pills can work better than plain ones; and injections can work better than pills," wrote Dr. Moerman.

Dr. Wechsler’s study was supported by the National Center for Complementary and Alternative Medicine. Dr. Wechsler and his associates reported ties to numerous industry sources. Dr. Moerman reported no financial conflicts.

A patient’s family history for breast and colorectal cancer changes substantially during early and middle adulthood, and making appropriate referrals for cancer screening requires keeping up to date with those changes, according to a report in the July 13 JAMA.

Overall, the percentage of patients who should be referred for screening because their family history puts them at high risk increases as much as threefold between the ages of 30 and 50, so family histories should be updated at least every 5-10 years, according to Argyrios Ziogas, Ph.D., of the University of California, Irvine, Genetic Epidemiology Research Institute and his associates (JAMA 2011;306:172-8).

"It is estimated that 22% of individuals have a family history that suggests familial or hereditary predisposition to cancer." However, until now, little has been studied regarding clinically relevant changes in family history over time.

"If a patient’s family history is not updated during early and middle adulthood, the opportunity may be missed to intervene with earlier or more intensive screening that maximizes the likelihood of detecting cancer at an early, treatable stage," they noted.

Previous research has documented that most primary care patients do not receive adequate assessment of familial cancer risks. Primary care physicians are likely to collect family history data at a patient’s first office visit, but do not adequately update that information in later visits. This is particularly important given that primary physicians are often the first – or only – caregivers to collect family health histories, and they are also the main source of referral for cancer screening, Dr. Ziogas and his colleagues said.

To determine how often family cancer histories should be updated, the researchers assessed how often patients’ family histories of breast and colorectal cancer changed throughout adulthood. They analyzed data on 16,724 subjects (plus 11,323 of their relatives) who were enrolled in the Cancer Genetics Network, a national U.S. registry established by the National Cancer Institute in 1998 for people with family histories of cancer.

The investigators performed one retrospective analysis of family histories, beginning on the day the subject enrolled in the registry and extending back to their birth, as well as one prospective analysis of family histories beginning on the day of enrollment and extending forward until the latest follow-up survey, a mean of 8 years later.

The retrospective analysis showed that at age 30 years, only 2% of the subjects would have met criteria for early colonoscopy screening based on their family history of colorectal cancer. But by age 50 years, this percentage increased to 7%, and by age 70, it increased to 11%.

Similarly, the retrospective analysis showed that only 7% of women at age 30 years would have met criteria for enhanced MRI scanning (rather than mammography) based on their family history of breast cancer, but that the percentage increased to 11% at age 50 and to 13% at ages 60 and older.

In the prospective analyses, 1% of the subjects had substantial changes in their family histories of colorectal cancer every 10 years, which would switch them from a low-risk to a high-risk category eligible for enhanced screening. Similarly, 3% of women had substantial changes in their family histories of breast cancer every 10 years, which would switch them from a low-risk to a high-risk category eligible for MRI scanning.

Overall, "we found a 5% chance that an individual’s colorectal cancer screening recommendation would change between ages 30 and 50 years based on family history and that 4% of women would become candidates for MRI screening," Dr. Ziogas and his associates wrote.

"We ... recommend that family history should be updated at least every 5-10 years to appropriately inform recommendations for cancer screening," they said.

This study was supported by the National Cancer Institute. No financial conflicts of interest were reported.

A patient’s family history for breast and colorectal cancer changes substantially during early and middle adulthood, and making appropriate referrals for cancer screening requires keeping up to date with those changes, according to a report in the July 13 JAMA.

Overall, the percentage of patients who should be referred for screening because their family history puts them at high risk increases as much as threefold between the ages of 30 and 50, so family histories should be updated at least every 5-10 years, according to Argyrios Ziogas, Ph.D., of the University of California, Irvine, Genetic Epidemiology Research Institute and his associates (JAMA 2011;306:172-8).

"It is estimated that 22% of individuals have a family history that suggests familial or hereditary predisposition to cancer." However, until now, little has been studied regarding clinically relevant changes in family history over time.

"If a patient’s family history is not updated during early and middle adulthood, the opportunity may be missed to intervene with earlier or more intensive screening that maximizes the likelihood of detecting cancer at an early, treatable stage," they noted.

Previous research has documented that most primary care patients do not receive adequate assessment of familial cancer risks. Primary care physicians are likely to collect family history data at a patient’s first office visit, but do not adequately update that information in later visits. This is particularly important given that primary physicians are often the first – or only – caregivers to collect family health histories, and they are also the main source of referral for cancer screening, Dr. Ziogas and his colleagues said.

To determine how often family cancer histories should be updated, the researchers assessed how often patients’ family histories of breast and colorectal cancer changed throughout adulthood. They analyzed data on 16,724 subjects (plus 11,323 of their relatives) who were enrolled in the Cancer Genetics Network, a national U.S. registry established by the National Cancer Institute in 1998 for people with family histories of cancer.

The investigators performed one retrospective analysis of family histories, beginning on the day the subject enrolled in the registry and extending back to their birth, as well as one prospective analysis of family histories beginning on the day of enrollment and extending forward until the latest follow-up survey, a mean of 8 years later.

The retrospective analysis showed that at age 30 years, only 2% of the subjects would have met criteria for early colonoscopy screening based on their family history of colorectal cancer. But by age 50 years, this percentage increased to 7%, and by age 70, it increased to 11%.

Similarly, the retrospective analysis showed that only 7% of women at age 30 years would have met criteria for enhanced MRI scanning (rather than mammography) based on their family history of breast cancer, but that the percentage increased to 11% at age 50 and to 13% at ages 60 and older.

In the prospective analyses, 1% of the subjects had substantial changes in their family histories of colorectal cancer every 10 years, which would switch them from a low-risk to a high-risk category eligible for enhanced screening. Similarly, 3% of women had substantial changes in their family histories of breast cancer every 10 years, which would switch them from a low-risk to a high-risk category eligible for MRI scanning.

Overall, "we found a 5% chance that an individual’s colorectal cancer screening recommendation would change between ages 30 and 50 years based on family history and that 4% of women would become candidates for MRI screening," Dr. Ziogas and his associates wrote.

"We ... recommend that family history should be updated at least every 5-10 years to appropriately inform recommendations for cancer screening," they said.

This study was supported by the National Cancer Institute. No financial conflicts of interest were reported.

A patient’s family history for breast and colorectal cancer changes substantially during early and middle adulthood, and making appropriate referrals for cancer screening requires keeping up to date with those changes, according to a report in the July 13 JAMA.

Overall, the percentage of patients who should be referred for screening because their family history puts them at high risk increases as much as threefold between the ages of 30 and 50, so family histories should be updated at least every 5-10 years, according to Argyrios Ziogas, Ph.D., of the University of California, Irvine, Genetic Epidemiology Research Institute and his associates (JAMA 2011;306:172-8).

"It is estimated that 22% of individuals have a family history that suggests familial or hereditary predisposition to cancer." However, until now, little has been studied regarding clinically relevant changes in family history over time.

"If a patient’s family history is not updated during early and middle adulthood, the opportunity may be missed to intervene with earlier or more intensive screening that maximizes the likelihood of detecting cancer at an early, treatable stage," they noted.

Previous research has documented that most primary care patients do not receive adequate assessment of familial cancer risks. Primary care physicians are likely to collect family history data at a patient’s first office visit, but do not adequately update that information in later visits. This is particularly important given that primary physicians are often the first – or only – caregivers to collect family health histories, and they are also the main source of referral for cancer screening, Dr. Ziogas and his colleagues said.

To determine how often family cancer histories should be updated, the researchers assessed how often patients’ family histories of breast and colorectal cancer changed throughout adulthood. They analyzed data on 16,724 subjects (plus 11,323 of their relatives) who were enrolled in the Cancer Genetics Network, a national U.S. registry established by the National Cancer Institute in 1998 for people with family histories of cancer.

The investigators performed one retrospective analysis of family histories, beginning on the day the subject enrolled in the registry and extending back to their birth, as well as one prospective analysis of family histories beginning on the day of enrollment and extending forward until the latest follow-up survey, a mean of 8 years later.

The retrospective analysis showed that at age 30 years, only 2% of the subjects would have met criteria for early colonoscopy screening based on their family history of colorectal cancer. But by age 50 years, this percentage increased to 7%, and by age 70, it increased to 11%.

Similarly, the retrospective analysis showed that only 7% of women at age 30 years would have met criteria for enhanced MRI scanning (rather than mammography) based on their family history of breast cancer, but that the percentage increased to 11% at age 50 and to 13% at ages 60 and older.

In the prospective analyses, 1% of the subjects had substantial changes in their family histories of colorectal cancer every 10 years, which would switch them from a low-risk to a high-risk category eligible for enhanced screening. Similarly, 3% of women had substantial changes in their family histories of breast cancer every 10 years, which would switch them from a low-risk to a high-risk category eligible for MRI scanning.

Overall, "we found a 5% chance that an individual’s colorectal cancer screening recommendation would change between ages 30 and 50 years based on family history and that 4% of women would become candidates for MRI screening," Dr. Ziogas and his associates wrote.

"We ... recommend that family history should be updated at least every 5-10 years to appropriately inform recommendations for cancer screening," they said.

This study was supported by the National Cancer Institute. No financial conflicts of interest were reported.

'"Late" percutaneous coronary intervention for total coronary occlusions more than 24 hours after MI is still commonplace, even though clinical practice guidelines recommend against it, according to an analysis of the CathPCI registry published online July 11 in Archives of Internal Medicine.

This finding, from an analysis of national trends in PCI use before and after these guidelines were changed in 2007, has two implications: First, it shows that "many stable patients with recent MI and persistent infarct artery occlusion continue to undergo a costly and ineffective procedure."

In addition, it shows that "a large public, scientific, and human patient investment in the generation of robust clinical evidence has yet to broadly influence U.S. practice," said Dr. Marc W. Deyell of the division of cardiology, University of British Columbia, Vancouver, and his associates.

The investigators analyzed data from the National Cardiovascular Data Registry and its CathPCI Registry, the largest clinical catheterization database in the country, to assess whether publication of the Occluded Artery Trial (OAT) in 2006 and the resulting change in clinical practice guidelines in 2007 succeeded in decreasing the inappropriate use of PCI. The randomized, controlled OAT, funded by the National Heart, Lung, and Blood Institute, concluded that PCI of totally occluded infarct-related arteries more than 24 hours after MI failed to reduce rates of mortality, reinfarction, and heart failure, and that its "small" beneficial effect on angina and quality of life was not durable.

The strength of the evidence in OAT compelled the American College of Cardiology/American Heart Association to update three sets of guidelines: those on unstable angina and non–ST-segment elevation MI, on ST-segment elevation MI, and on PCI.

The analysis by Dr. Deyell and his colleagues covered PCI performed in 896 U.S. hospitals in 11,083 patients before publication of the OAT findings, 7,838 patients after that publication but before the guidelines were revised, and 9,859 patients after the guidelines were revised.

There were no differences in rates of late PCI across these three intervals, they said (Arch. Intern. Med. 2011 July 11 [doi:10.1001/archinternmed.2011.315]).

Rates of late PCI also did not decline in any of the subgroups of patients studied, regardless of the presence of heart failure symptoms at presentation, the type of insurance, the geographical region, the type of hospital, or whether patients had experienced STEMI or non-STEMI.

"PCI for total occlusions identified after MI among patients similar to those enrolled in the OAT continues to be performed in a considerable proportion of patients," the researchers said.

The reasons why the updated guidelines have not been incorporated into practice are unclear.

"Cardiologists and interventionalists have been quick to incorporate the results of positive clinical device trials and related guideline recommendations in the past, and to respond to trials reporting clinically significant safety concerns." However, OAT was a "negative" trial and "did not demonstrate excessive harm from PCI, apart from a trend toward increased reinfarction."

"Physicians may be less likely to alter their practice based on negative results, especially when there are important competing factors," they noted.

This study was supported by the American College of Cardiology Foundation’s National Cardiovascular Data Registry and the National Heart, Lung, and Blood Institute. No financial conflicts of interest were reported.

'"Late" percutaneous coronary intervention for total coronary occlusions more than 24 hours after MI is still commonplace, even though clinical practice guidelines recommend against it, according to an analysis of the CathPCI registry published online July 11 in Archives of Internal Medicine.

This finding, from an analysis of national trends in PCI use before and after these guidelines were changed in 2007, has two implications: First, it shows that "many stable patients with recent MI and persistent infarct artery occlusion continue to undergo a costly and ineffective procedure."

In addition, it shows that "a large public, scientific, and human patient investment in the generation of robust clinical evidence has yet to broadly influence U.S. practice," said Dr. Marc W. Deyell of the division of cardiology, University of British Columbia, Vancouver, and his associates.

The investigators analyzed data from the National Cardiovascular Data Registry and its CathPCI Registry, the largest clinical catheterization database in the country, to assess whether publication of the Occluded Artery Trial (OAT) in 2006 and the resulting change in clinical practice guidelines in 2007 succeeded in decreasing the inappropriate use of PCI. The randomized, controlled OAT, funded by the National Heart, Lung, and Blood Institute, concluded that PCI of totally occluded infarct-related arteries more than 24 hours after MI failed to reduce rates of mortality, reinfarction, and heart failure, and that its "small" beneficial effect on angina and quality of life was not durable.

The strength of the evidence in OAT compelled the American College of Cardiology/American Heart Association to update three sets of guidelines: those on unstable angina and non–ST-segment elevation MI, on ST-segment elevation MI, and on PCI.

The analysis by Dr. Deyell and his colleagues covered PCI performed in 896 U.S. hospitals in 11,083 patients before publication of the OAT findings, 7,838 patients after that publication but before the guidelines were revised, and 9,859 patients after the guidelines were revised.

There were no differences in rates of late PCI across these three intervals, they said (Arch. Intern. Med. 2011 July 11 [doi:10.1001/archinternmed.2011.315]).

Rates of late PCI also did not decline in any of the subgroups of patients studied, regardless of the presence of heart failure symptoms at presentation, the type of insurance, the geographical region, the type of hospital, or whether patients had experienced STEMI or non-STEMI.

"PCI for total occlusions identified after MI among patients similar to those enrolled in the OAT continues to be performed in a considerable proportion of patients," the researchers said.

The reasons why the updated guidelines have not been incorporated into practice are unclear.

"Cardiologists and interventionalists have been quick to incorporate the results of positive clinical device trials and related guideline recommendations in the past, and to respond to trials reporting clinically significant safety concerns." However, OAT was a "negative" trial and "did not demonstrate excessive harm from PCI, apart from a trend toward increased reinfarction."

"Physicians may be less likely to alter their practice based on negative results, especially when there are important competing factors," they noted.

This study was supported by the American College of Cardiology Foundation’s National Cardiovascular Data Registry and the National Heart, Lung, and Blood Institute. No financial conflicts of interest were reported.

'"Late" percutaneous coronary intervention for total coronary occlusions more than 24 hours after MI is still commonplace, even though clinical practice guidelines recommend against it, according to an analysis of the CathPCI registry published online July 11 in Archives of Internal Medicine.

This finding, from an analysis of national trends in PCI use before and after these guidelines were changed in 2007, has two implications: First, it shows that "many stable patients with recent MI and persistent infarct artery occlusion continue to undergo a costly and ineffective procedure."

In addition, it shows that "a large public, scientific, and human patient investment in the generation of robust clinical evidence has yet to broadly influence U.S. practice," said Dr. Marc W. Deyell of the division of cardiology, University of British Columbia, Vancouver, and his associates.

The investigators analyzed data from the National Cardiovascular Data Registry and its CathPCI Registry, the largest clinical catheterization database in the country, to assess whether publication of the Occluded Artery Trial (OAT) in 2006 and the resulting change in clinical practice guidelines in 2007 succeeded in decreasing the inappropriate use of PCI. The randomized, controlled OAT, funded by the National Heart, Lung, and Blood Institute, concluded that PCI of totally occluded infarct-related arteries more than 24 hours after MI failed to reduce rates of mortality, reinfarction, and heart failure, and that its "small" beneficial effect on angina and quality of life was not durable.

The strength of the evidence in OAT compelled the American College of Cardiology/American Heart Association to update three sets of guidelines: those on unstable angina and non–ST-segment elevation MI, on ST-segment elevation MI, and on PCI.

The analysis by Dr. Deyell and his colleagues covered PCI performed in 896 U.S. hospitals in 11,083 patients before publication of the OAT findings, 7,838 patients after that publication but before the guidelines were revised, and 9,859 patients after the guidelines were revised.

There were no differences in rates of late PCI across these three intervals, they said (Arch. Intern. Med. 2011 July 11 [doi:10.1001/archinternmed.2011.315]).

Rates of late PCI also did not decline in any of the subgroups of patients studied, regardless of the presence of heart failure symptoms at presentation, the type of insurance, the geographical region, the type of hospital, or whether patients had experienced STEMI or non-STEMI.

"PCI for total occlusions identified after MI among patients similar to those enrolled in the OAT continues to be performed in a considerable proportion of patients," the researchers said.

The reasons why the updated guidelines have not been incorporated into practice are unclear.

"Cardiologists and interventionalists have been quick to incorporate the results of positive clinical device trials and related guideline recommendations in the past, and to respond to trials reporting clinically significant safety concerns." However, OAT was a "negative" trial and "did not demonstrate excessive harm from PCI, apart from a trend toward increased reinfarction."

"Physicians may be less likely to alter their practice based on negative results, especially when there are important competing factors," they noted.

This study was supported by the American College of Cardiology Foundation’s National Cardiovascular Data Registry and the National Heart, Lung, and Blood Institute. No financial conflicts of interest were reported.

A high sodium-potassium ratio appears to indicate a significantly increased risk of cardiovascular disease, ischemic heart disease, and all-cause mortality in the general population, according to a report in Archives of Internal Medicine.

A high sodium-potassium ratio was more strongly related to mortality than was a high sodium level alone or a low potassium level alone in a study of a large, nationally representative sample of adults. In addition, the robust association was independent of age, sex, race/ethnicity, and other variables, said Quanhe Yang, Ph.D., of the office of public health genomics at the Centers for Disease Control and Prevention, Atlanta, and associates.

Photo credit: ©thumb/iStockphoto.com

"From a public health point of view, reduced sodium intake accompanied by increased potassium intake could achieve greater health benefits than restricting sodium alone," they noted (Arch. Intern. Med. 2011;171:1183-91).

The link between high sodium consumption and hypertension is fairly well known, but the public is less aware that low potassium levels are even more strongly related to hypertension. Several recent studies have suggested that the ratio of sodium to potassium is an even more important risk factor for hypertension and cardiovascular disease than either component alone.

Dr. Yang and colleagues analyzed these associations using data from the Third National Examination and Nutritional Health Survey (NHANES III). They estimated the usual dietary intakes of sodium and potassium at baseline for 12,267 adults participating in the survey, then determined the subjects’ mortality status during a median of 15 years of follow-up using the National Death Index.

During that time, there were 2,270 deaths, including 825 CVD deaths and 433 deaths from ischemic heart disease.

The risk of all-cause mortality increased linearly with increasing sodium-potassium ratio. The hazard ratio was 1.46 for the patients in the highest quartile of sodium-potassium ratio, compared with the lowest quartile.

A higher sodium-potassium ratio also was significantly associated with the risk of death from cardiovascular disease and from ischemic heart disease. The hazard ratios comparing the highest with the lowest quartiles were 1.46 for CVD mortality and 2.15 for ischemic heart disease mortality, the investigators said.

"We could not obtain the stable estimates for stroke mortality owing to the limited number of stroke deaths (139)," they added.

These associations were robust regardless of subjects’ sex, age, race/ethnicity, body mass index, hypertension status, physical activity level, or educational achievement.

"The observed stronger and more consistent association between the sodium-potassium ratio and mortality than between each nutrient separately and mortality may be due to complex interactions between potassium and sodium at cellular levels," the researchers said. "High sodium levels induce increased blood pressure and hypertension by stiffening endothelial cells, thickening and narrowing resistance arteries, and blocking nitric oxide synthesis, whereas higher potassium levels can counteract these effects by activating nitric oxide release."

The study findings indicate that public health recommendations "should emphasize simultaneous reduction in sodium intake and increase in potassium intake," Dr. Yang and associates said.

No financial conflicts of interest were reported.

A high sodium-potassium ratio appears to indicate a significantly increased risk of cardiovascular disease, ischemic heart disease, and all-cause mortality in the general population, according to a report in Archives of Internal Medicine.

A high sodium-potassium ratio was more strongly related to mortality than was a high sodium level alone or a low potassium level alone in a study of a large, nationally representative sample of adults. In addition, the robust association was independent of age, sex, race/ethnicity, and other variables, said Quanhe Yang, Ph.D., of the office of public health genomics at the Centers for Disease Control and Prevention, Atlanta, and associates.

Photo credit: ©thumb/iStockphoto.com

"From a public health point of view, reduced sodium intake accompanied by increased potassium intake could achieve greater health benefits than restricting sodium alone," they noted (Arch. Intern. Med. 2011;171:1183-91).

The link between high sodium consumption and hypertension is fairly well known, but the public is less aware that low potassium levels are even more strongly related to hypertension. Several recent studies have suggested that the ratio of sodium to potassium is an even more important risk factor for hypertension and cardiovascular disease than either component alone.

Dr. Yang and colleagues analyzed these associations using data from the Third National Examination and Nutritional Health Survey (NHANES III). They estimated the usual dietary intakes of sodium and potassium at baseline for 12,267 adults participating in the survey, then determined the subjects’ mortality status during a median of 15 years of follow-up using the National Death Index.

During that time, there were 2,270 deaths, including 825 CVD deaths and 433 deaths from ischemic heart disease.

The risk of all-cause mortality increased linearly with increasing sodium-potassium ratio. The hazard ratio was 1.46 for the patients in the highest quartile of sodium-potassium ratio, compared with the lowest quartile.

A higher sodium-potassium ratio also was significantly associated with the risk of death from cardiovascular disease and from ischemic heart disease. The hazard ratios comparing the highest with the lowest quartiles were 1.46 for CVD mortality and 2.15 for ischemic heart disease mortality, the investigators said.

"We could not obtain the stable estimates for stroke mortality owing to the limited number of stroke deaths (139)," they added.

These associations were robust regardless of subjects’ sex, age, race/ethnicity, body mass index, hypertension status, physical activity level, or educational achievement.

"The observed stronger and more consistent association between the sodium-potassium ratio and mortality than between each nutrient separately and mortality may be due to complex interactions between potassium and sodium at cellular levels," the researchers said. "High sodium levels induce increased blood pressure and hypertension by stiffening endothelial cells, thickening and narrowing resistance arteries, and blocking nitric oxide synthesis, whereas higher potassium levels can counteract these effects by activating nitric oxide release."

The study findings indicate that public health recommendations "should emphasize simultaneous reduction in sodium intake and increase in potassium intake," Dr. Yang and associates said.

No financial conflicts of interest were reported.

A high sodium-potassium ratio appears to indicate a significantly increased risk of cardiovascular disease, ischemic heart disease, and all-cause mortality in the general population, according to a report in Archives of Internal Medicine.

A high sodium-potassium ratio was more strongly related to mortality than was a high sodium level alone or a low potassium level alone in a study of a large, nationally representative sample of adults. In addition, the robust association was independent of age, sex, race/ethnicity, and other variables, said Quanhe Yang, Ph.D., of the office of public health genomics at the Centers for Disease Control and Prevention, Atlanta, and associates.

Photo credit: ©thumb/iStockphoto.com

"From a public health point of view, reduced sodium intake accompanied by increased potassium intake could achieve greater health benefits than restricting sodium alone," they noted (Arch. Intern. Med. 2011;171:1183-91).

The link between high sodium consumption and hypertension is fairly well known, but the public is less aware that low potassium levels are even more strongly related to hypertension. Several recent studies have suggested that the ratio of sodium to potassium is an even more important risk factor for hypertension and cardiovascular disease than either component alone.

Dr. Yang and colleagues analyzed these associations using data from the Third National Examination and Nutritional Health Survey (NHANES III). They estimated the usual dietary intakes of sodium and potassium at baseline for 12,267 adults participating in the survey, then determined the subjects’ mortality status during a median of 15 years of follow-up using the National Death Index.

During that time, there were 2,270 deaths, including 825 CVD deaths and 433 deaths from ischemic heart disease.

The risk of all-cause mortality increased linearly with increasing sodium-potassium ratio. The hazard ratio was 1.46 for the patients in the highest quartile of sodium-potassium ratio, compared with the lowest quartile.

A higher sodium-potassium ratio also was significantly associated with the risk of death from cardiovascular disease and from ischemic heart disease. The hazard ratios comparing the highest with the lowest quartiles were 1.46 for CVD mortality and 2.15 for ischemic heart disease mortality, the investigators said.

"We could not obtain the stable estimates for stroke mortality owing to the limited number of stroke deaths (139)," they added.

These associations were robust regardless of subjects’ sex, age, race/ethnicity, body mass index, hypertension status, physical activity level, or educational achievement.

"The observed stronger and more consistent association between the sodium-potassium ratio and mortality than between each nutrient separately and mortality may be due to complex interactions between potassium and sodium at cellular levels," the researchers said. "High sodium levels induce increased blood pressure and hypertension by stiffening endothelial cells, thickening and narrowing resistance arteries, and blocking nitric oxide synthesis, whereas higher potassium levels can counteract these effects by activating nitric oxide release."

The study findings indicate that public health recommendations "should emphasize simultaneous reduction in sodium intake and increase in potassium intake," Dr. Yang and associates said.

No financial conflicts of interest were reported.

A high sodium-potassium ratio appears to indicate a significantly increased risk of cardiovascular disease, ischemic heart disease, and all-cause mortality in the general population, according to a report in Archives of Internal Medicine.

A high sodium-potassium ratio was more strongly related to mortality than was a high sodium level alone or a low potassium level alone in a study of a large, nationally representative sample of adults. In addition, the robust association was independent of age, sex, race/ethnicity, and other variables, said Quanhe Yang, Ph.D., of the office of public health genomics at the Centers for Disease Control and Prevention, Atlanta, and associates.

Photo credit: ©thumb/iStockphoto.com

"From a public health point of view, reduced sodium intake accompanied by increased potassium intake could achieve greater health benefits than restricting sodium alone," they noted (Arch. Intern. Med. 2011;171:1183-91).

The link between high sodium consumption and hypertension is fairly well known, but the public is less aware that low potassium levels are even more strongly related to hypertension. Several recent studies have suggested that the ratio of sodium to potassium is an even more important risk factor for hypertension and cardiovascular disease than either component alone.

Dr. Yang and colleagues analyzed these associations using data from the Third National Examination and Nutritional Health Survey (NHANES III). They estimated the usual dietary intakes of sodium and potassium at baseline for 12,267 adults participating in the survey, then determined the subjects’ mortality status during a median of 15 years of follow-up using the National Death Index.

During that time, there were 2,270 deaths, including 825 CVD deaths and 433 deaths from ischemic heart disease.

The risk of all-cause mortality increased linearly with increasing sodium-potassium ratio. The hazard ratio was 1.46 for the patients in the highest quartile of sodium-potassium ratio, compared with the lowest quartile.

A higher sodium-potassium ratio also was significantly associated with the risk of death from cardiovascular disease and from ischemic heart disease. The hazard ratios comparing the highest with the lowest quartiles were 1.46 for CVD mortality and 2.15 for ischemic heart disease mortality, the investigators said.

"We could not obtain the stable estimates for stroke mortality owing to the limited number of stroke deaths (139)," they added.

These associations were robust regardless of subjects’ sex, age, race/ethnicity, body mass index, hypertension status, physical activity level, or educational achievement.

"The observed stronger and more consistent association between the sodium-potassium ratio and mortality than between each nutrient separately and mortality may be due to complex interactions between potassium and sodium at cellular levels," the researchers said. "High sodium levels induce increased blood pressure and hypertension by stiffening endothelial cells, thickening and narrowing resistance arteries, and blocking nitric oxide synthesis, whereas higher potassium levels can counteract these effects by activating nitric oxide release."

The study findings indicate that public health recommendations "should emphasize simultaneous reduction in sodium intake and increase in potassium intake," Dr. Yang and associates said.

No financial conflicts of interest were reported.

A high sodium-potassium ratio appears to indicate a significantly increased risk of cardiovascular disease, ischemic heart disease, and all-cause mortality in the general population, according to a report in Archives of Internal Medicine.

A high sodium-potassium ratio was more strongly related to mortality than was a high sodium level alone or a low potassium level alone in a study of a large, nationally representative sample of adults. In addition, the robust association was independent of age, sex, race/ethnicity, and other variables, said Quanhe Yang, Ph.D., of the office of public health genomics at the Centers for Disease Control and Prevention, Atlanta, and associates.

Photo credit: ©thumb/iStockphoto.com

"From a public health point of view, reduced sodium intake accompanied by increased potassium intake could achieve greater health benefits than restricting sodium alone," they noted (Arch. Intern. Med. 2011;171:1183-91).

The link between high sodium consumption and hypertension is fairly well known, but the public is less aware that low potassium levels are even more strongly related to hypertension. Several recent studies have suggested that the ratio of sodium to potassium is an even more important risk factor for hypertension and cardiovascular disease than either component alone.

Dr. Yang and colleagues analyzed these associations using data from the Third National Examination and Nutritional Health Survey (NHANES III). They estimated the usual dietary intakes of sodium and potassium at baseline for 12,267 adults participating in the survey, then determined the subjects’ mortality status during a median of 15 years of follow-up using the National Death Index.

During that time, there were 2,270 deaths, including 825 CVD deaths and 433 deaths from ischemic heart disease.

The risk of all-cause mortality increased linearly with increasing sodium-potassium ratio. The hazard ratio was 1.46 for the patients in the highest quartile of sodium-potassium ratio, compared with the lowest quartile.

A higher sodium-potassium ratio also was significantly associated with the risk of death from cardiovascular disease and from ischemic heart disease. The hazard ratios comparing the highest with the lowest quartiles were 1.46 for CVD mortality and 2.15 for ischemic heart disease mortality, the investigators said.

"We could not obtain the stable estimates for stroke mortality owing to the limited number of stroke deaths (139)," they added.

These associations were robust regardless of subjects’ sex, age, race/ethnicity, body mass index, hypertension status, physical activity level, or educational achievement.

"The observed stronger and more consistent association between the sodium-potassium ratio and mortality than between each nutrient separately and mortality may be due to complex interactions between potassium and sodium at cellular levels," the researchers said. "High sodium levels induce increased blood pressure and hypertension by stiffening endothelial cells, thickening and narrowing resistance arteries, and blocking nitric oxide synthesis, whereas higher potassium levels can counteract these effects by activating nitric oxide release."

The study findings indicate that public health recommendations "should emphasize simultaneous reduction in sodium intake and increase in potassium intake," Dr. Yang and associates said.

No financial conflicts of interest were reported.

A high sodium-potassium ratio appears to indicate a significantly increased risk of cardiovascular disease, ischemic heart disease, and all-cause mortality in the general population, according to a report in Archives of Internal Medicine.

A high sodium-potassium ratio was more strongly related to mortality than was a high sodium level alone or a low potassium level alone in a study of a large, nationally representative sample of adults. In addition, the robust association was independent of age, sex, race/ethnicity, and other variables, said Quanhe Yang, Ph.D., of the office of public health genomics at the Centers for Disease Control and Prevention, Atlanta, and associates.

Photo credit: ©thumb/iStockphoto.com

"From a public health point of view, reduced sodium intake accompanied by increased potassium intake could achieve greater health benefits than restricting sodium alone," they noted (Arch. Intern. Med. 2011;171:1183-91).

The link between high sodium consumption and hypertension is fairly well known, but the public is less aware that low potassium levels are even more strongly related to hypertension. Several recent studies have suggested that the ratio of sodium to potassium is an even more important risk factor for hypertension and cardiovascular disease than either component alone.

Dr. Yang and colleagues analyzed these associations using data from the Third National Examination and Nutritional Health Survey (NHANES III). They estimated the usual dietary intakes of sodium and potassium at baseline for 12,267 adults participating in the survey, then determined the subjects’ mortality status during a median of 15 years of follow-up using the National Death Index.

During that time, there were 2,270 deaths, including 825 CVD deaths and 433 deaths from ischemic heart disease.

The risk of all-cause mortality increased linearly with increasing sodium-potassium ratio. The hazard ratio was 1.46 for the patients in the highest quartile of sodium-potassium ratio, compared with the lowest quartile.

A higher sodium-potassium ratio also was significantly associated with the risk of death from cardiovascular disease and from ischemic heart disease. The hazard ratios comparing the highest with the lowest quartiles were 1.46 for CVD mortality and 2.15 for ischemic heart disease mortality, the investigators said.

"We could not obtain the stable estimates for stroke mortality owing to the limited number of stroke deaths (139)," they added.

These associations were robust regardless of subjects’ sex, age, race/ethnicity, body mass index, hypertension status, physical activity level, or educational achievement.

"The observed stronger and more consistent association between the sodium-potassium ratio and mortality than between each nutrient separately and mortality may be due to complex interactions between potassium and sodium at cellular levels," the researchers said. "High sodium levels induce increased blood pressure and hypertension by stiffening endothelial cells, thickening and narrowing resistance arteries, and blocking nitric oxide synthesis, whereas higher potassium levels can counteract these effects by activating nitric oxide release."

The study findings indicate that public health recommendations "should emphasize simultaneous reduction in sodium intake and increase in potassium intake," Dr. Yang and associates said.

No financial conflicts of interest were reported.