Mary Ann Moon

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 have reported.

“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 randomized to receive adjuvant or neoadjuvant chemotherapy alone or chemotherapy plus intramuscular 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 FSH.

Women with hormone-sensitive 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 26% for chemotherapy alone, compared with 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 just 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 50% of the chemotherapy-only group, compared with 63% 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 3 pregnancies (1 full-term, 1 premature delivery, and 1 voluntary abortion) in the chemotherapy plus triptorelin group were reported,” the 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.

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Approach With Caution

The findings of Del Mastro and associates are “intriguing, and represent an important and encouraging addition to the study of ovarian preservation for women in this difficult situation,” wrote Dr. Hope S. Rugo and Dr. Mitchell P. Rosen.

However, it would be premature to advocate the routine use of GnRH analogues for these patients of childbearing age who are facing early menopause.

“Given that patients with hormone receptor–positive disease in the current study who had evidence of ovarian recovery were immediately suppressed without data on long-term recovery and that breast cancer outcome data are not available, and given as well the potential adverse effects on disease outcome, the use of GnRH agonists concomitant with chemotherapy cannot be recommended as a standard treatment and should be approached with caution in women with hormone-sensitive disease,” they said.

HOPE S. RUGO, M.D., and MITCHELL P. ROSEN, M.D., are at the University of California, San Francisco. The university has received research funding from Pfizer, Novartis, Roche/Genentech, Abbott, Celgene, Merck, and Bristol-Meyers Squibb. Dr. Rugo reported receiving honoraria from Genomic Health. Dr. Rosen reported having no disclosures. These remarks were taken from their editorial accompanying Dr. Del Mastro's report (JAMA 2011;306:312-4).

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 have reported.

“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 randomized to receive adjuvant or neoadjuvant chemotherapy alone or chemotherapy plus intramuscular 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 FSH.

Women with hormone-sensitive 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 26% for chemotherapy alone, compared with 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 just 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 50% of the chemotherapy-only group, compared with 63% 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 3 pregnancies (1 full-term, 1 premature delivery, and 1 voluntary abortion) in the chemotherapy plus triptorelin group were reported,” the 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.

View on the News

Approach With Caution

The findings of Del Mastro and associates are “intriguing, and represent an important and encouraging addition to the study of ovarian preservation for women in this difficult situation,” wrote Dr. Hope S. Rugo and Dr. Mitchell P. Rosen.

However, it would be premature to advocate the routine use of GnRH analogues for these patients of childbearing age who are facing early menopause.

“Given that patients with hormone receptor–positive disease in the current study who had evidence of ovarian recovery were immediately suppressed without data on long-term recovery and that breast cancer outcome data are not available, and given as well the potential adverse effects on disease outcome, the use of GnRH agonists concomitant with chemotherapy cannot be recommended as a standard treatment and should be approached with caution in women with hormone-sensitive disease,” they said.

HOPE S. RUGO, M.D., and MITCHELL P. ROSEN, M.D., are at the University of California, San Francisco. The university has received research funding from Pfizer, Novartis, Roche/Genentech, Abbott, Celgene, Merck, and Bristol-Meyers Squibb. Dr. Rugo reported receiving honoraria from Genomic Health. Dr. Rosen reported having no disclosures. These remarks were taken from their editorial accompanying Dr. Del Mastro's report (JAMA 2011;306:312-4).

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 have reported.

“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 randomized to receive adjuvant or neoadjuvant chemotherapy alone or chemotherapy plus intramuscular 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 FSH.

Women with hormone-sensitive 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 26% for chemotherapy alone, compared with 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 just 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 50% of the chemotherapy-only group, compared with 63% 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 3 pregnancies (1 full-term, 1 premature delivery, and 1 voluntary abortion) in the chemotherapy plus triptorelin group were reported,” the 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.

View on the News

Approach With Caution

The findings of Del Mastro and associates are “intriguing, and represent an important and encouraging addition to the study of ovarian preservation for women in this difficult situation,” wrote Dr. Hope S. Rugo and Dr. Mitchell P. Rosen.

However, it would be premature to advocate the routine use of GnRH analogues for these patients of childbearing age who are facing early menopause.

“Given that patients with hormone receptor–positive disease in the current study who had evidence of ovarian recovery were immediately suppressed without data on long-term recovery and that breast cancer outcome data are not available, and given as well the potential adverse effects on disease outcome, the use of GnRH agonists concomitant with chemotherapy cannot be recommended as a standard treatment and should be approached with caution in women with hormone-sensitive disease,” they said.

HOPE S. RUGO, M.D., and MITCHELL P. ROSEN, M.D., are at the University of California, San Francisco. The university has received research funding from Pfizer, Novartis, Roche/Genentech, Abbott, Celgene, Merck, and Bristol-Meyers Squibb. Dr. Rugo reported receiving honoraria from Genomic Health. Dr. Rosen reported having no disclosures. These remarks were taken from their editorial accompanying Dr. Del Mastro's report (JAMA 2011;306:312-4).

Major Finding: Maternal use of SSRIs during pregnancy was associated with a twofold risk of autism in the exposed offspring, and SSRI use during the first trimester was associated with a threefold risk.

Data Source: A population-based case-control study examining the prenatal exposures to antidepressants of 298 children with ASD and 1,507 unaffected children.

Disclosures: This study was supported by the Kaiser Permanente Community Benefit Clinician Research Fund, and the Centers for Disease Control and Prevention. No relevant financial disclosures were reported.

Prenatal exposure to selective serotonin reuptake inhibitors, particularly during the first trimester, may “modestly” raise the risk of autism spectrum disorders, a preliminary study has shown.

“The fraction of cases of [autism spectrum disorders] that may be attributed to use of antidepressants by the mother during pregnancy is less than 3% in our population, and it is reasonable to conclude that prenatal SSRI exposure is very unlikely to be a major risk factor for ASD,” said Lisa A. Croen, Ph.D., of Kaiser Permanente Northern California, Oakland, and her associates.

“Although these findings indicate that maternal treatment with SSRIs during pregnancy may confer some risk to the fetus with regard to neurodevelopment, this potential risk must be balanced with the risk to the mother or the fetus of untreated mental health disorders,” they noted.

“We recommend that our findings be considered as preliminary and treated with caution, pending results from further studies designed to address the very complex question of whether prenatal exposure to SSRIs may be etiologically linked to later diagnoses of ASD in offspring,” the investigators added.

The study was a population-based case-control assessment of mothers' antidepressant use during pregnancy and the later diagnosis of ASD in their children. The sample was drawn from the Childhood Autism Perinatal Study, and it included 298 children with ASD and 1,507 unaffected controls matched for age, sex, and area of residence within Northern California.

Twenty case mothers (6.7%) and 50 control mothers (3.3%) had at least one prescription for an antidepressant during the year before the birth of the child. Most of these prescriptions – for 5% of the case mothers and 2.3% of the control mothers – were for SSRIs.

After the data were adjusted to account for maternal age, race/ethnicity, and education level and for the child's birth weight and sex, “we found an approximately twofold increased risk of ASD associated with treatment with SSRIs … and an approximately threefold increased risk associated with treatment during the first trimester,” Dr. Croen and her colleagues said (Arch. Gen. Psychiatry 2011 [doi:10.1001/archgenpsychiatry2011.73]).

Mothers of children later diagnosed as having ASD were twice as likely as other mothers to have had at least one antidepressant prescription during the year preceding the birth. In addition, mothers with a prescription for an antidepressant were more than twice as likely as other mothers to have a child who was later diagnosed as having ASD. No such associations were seen among women prescribed any non-SSRI antidepressants, but the number of women in that group was quite small.

The link between SSRIs and ASD risk remained robust in several further statistical analyses. It remained strong when the analysis was restricted to only term births, as well as when it was restricted to only cases in which only one child in the family was affected with ASD (“simplex” cases).

The correlation also remained strong regardless of the indication for which the mother took the drugs. Moreover, ASD risk did not correlate with a history of mental health disorders. These two findings indicate that the SSRIs themselves, not the underlying indications for taking the medications, were the relevant contributing factor, Dr. Croen and her associates said.

However, they cautioned that “despite the significant association, the number of women in this [study] population exposed to SSRIs was modest, and the proportion of children with ASD in this population that can be statistically attributed to SSRI exposure is quite low: 2.1% for exposure during the year before delivery, and 2.3% for exposure during the first trimester.”

There are several biologically plausible explanations for this link between SSRI exposure and ASD. Many studies have implicated serotonin abnormalities and anomalies in serotoninergic pathways in autism.

And several animal studies “suggest the possibility that prenatal exposure to SSRIs may operate directly on the developing brain, perhaps selectively in fetuses with abnormalities in serotonin-related genes,” they said.

“To our knowledge, our study is the first to directly examine antidepressant use during pregnancy as a potential risk factor for childhood ASD. A substantial strength of our study is our reliance on data documented in medical records and thus recorded at the time of diagnosis or treatment, avoiding potential biases associated with the mothers' recall after diagnosis of ASD in the children,” the investigators wrote.

Major Finding: Maternal use of SSRIs during pregnancy was associated with a twofold risk of autism in the exposed offspring, and SSRI use during the first trimester was associated with a threefold risk.

Data Source: A population-based case-control study examining the prenatal exposures to antidepressants of 298 children with ASD and 1,507 unaffected children.

Disclosures: This study was supported by the Kaiser Permanente Community Benefit Clinician Research Fund, and the Centers for Disease Control and Prevention. No relevant financial disclosures were reported.

Prenatal exposure to selective serotonin reuptake inhibitors, particularly during the first trimester, may “modestly” raise the risk of autism spectrum disorders, a preliminary study has shown.

“The fraction of cases of [autism spectrum disorders] that may be attributed to use of antidepressants by the mother during pregnancy is less than 3% in our population, and it is reasonable to conclude that prenatal SSRI exposure is very unlikely to be a major risk factor for ASD,” said Lisa A. Croen, Ph.D., of Kaiser Permanente Northern California, Oakland, and her associates.

“Although these findings indicate that maternal treatment with SSRIs during pregnancy may confer some risk to the fetus with regard to neurodevelopment, this potential risk must be balanced with the risk to the mother or the fetus of untreated mental health disorders,” they noted.

“We recommend that our findings be considered as preliminary and treated with caution, pending results from further studies designed to address the very complex question of whether prenatal exposure to SSRIs may be etiologically linked to later diagnoses of ASD in offspring,” the investigators added.

The study was a population-based case-control assessment of mothers' antidepressant use during pregnancy and the later diagnosis of ASD in their children. The sample was drawn from the Childhood Autism Perinatal Study, and it included 298 children with ASD and 1,507 unaffected controls matched for age, sex, and area of residence within Northern California.

Twenty case mothers (6.7%) and 50 control mothers (3.3%) had at least one prescription for an antidepressant during the year before the birth of the child. Most of these prescriptions – for 5% of the case mothers and 2.3% of the control mothers – were for SSRIs.

After the data were adjusted to account for maternal age, race/ethnicity, and education level and for the child's birth weight and sex, “we found an approximately twofold increased risk of ASD associated with treatment with SSRIs … and an approximately threefold increased risk associated with treatment during the first trimester,” Dr. Croen and her colleagues said (Arch. Gen. Psychiatry 2011 [doi:10.1001/archgenpsychiatry2011.73]).

Mothers of children later diagnosed as having ASD were twice as likely as other mothers to have had at least one antidepressant prescription during the year preceding the birth. In addition, mothers with a prescription for an antidepressant were more than twice as likely as other mothers to have a child who was later diagnosed as having ASD. No such associations were seen among women prescribed any non-SSRI antidepressants, but the number of women in that group was quite small.

The link between SSRIs and ASD risk remained robust in several further statistical analyses. It remained strong when the analysis was restricted to only term births, as well as when it was restricted to only cases in which only one child in the family was affected with ASD (“simplex” cases).

The correlation also remained strong regardless of the indication for which the mother took the drugs. Moreover, ASD risk did not correlate with a history of mental health disorders. These two findings indicate that the SSRIs themselves, not the underlying indications for taking the medications, were the relevant contributing factor, Dr. Croen and her associates said.

However, they cautioned that “despite the significant association, the number of women in this [study] population exposed to SSRIs was modest, and the proportion of children with ASD in this population that can be statistically attributed to SSRI exposure is quite low: 2.1% for exposure during the year before delivery, and 2.3% for exposure during the first trimester.”

There are several biologically plausible explanations for this link between SSRI exposure and ASD. Many studies have implicated serotonin abnormalities and anomalies in serotoninergic pathways in autism.

And several animal studies “suggest the possibility that prenatal exposure to SSRIs may operate directly on the developing brain, perhaps selectively in fetuses with abnormalities in serotonin-related genes,” they said.

“To our knowledge, our study is the first to directly examine antidepressant use during pregnancy as a potential risk factor for childhood ASD. A substantial strength of our study is our reliance on data documented in medical records and thus recorded at the time of diagnosis or treatment, avoiding potential biases associated with the mothers' recall after diagnosis of ASD in the children,” the investigators wrote.

Major Finding: Maternal use of SSRIs during pregnancy was associated with a twofold risk of autism in the exposed offspring, and SSRI use during the first trimester was associated with a threefold risk.

Data Source: A population-based case-control study examining the prenatal exposures to antidepressants of 298 children with ASD and 1,507 unaffected children.

Disclosures: This study was supported by the Kaiser Permanente Community Benefit Clinician Research Fund, and the Centers for Disease Control and Prevention. No relevant financial disclosures were reported.

Prenatal exposure to selective serotonin reuptake inhibitors, particularly during the first trimester, may “modestly” raise the risk of autism spectrum disorders, a preliminary study has shown.

“The fraction of cases of [autism spectrum disorders] that may be attributed to use of antidepressants by the mother during pregnancy is less than 3% in our population, and it is reasonable to conclude that prenatal SSRI exposure is very unlikely to be a major risk factor for ASD,” said Lisa A. Croen, Ph.D., of Kaiser Permanente Northern California, Oakland, and her associates.

“Although these findings indicate that maternal treatment with SSRIs during pregnancy may confer some risk to the fetus with regard to neurodevelopment, this potential risk must be balanced with the risk to the mother or the fetus of untreated mental health disorders,” they noted.

“We recommend that our findings be considered as preliminary and treated with caution, pending results from further studies designed to address the very complex question of whether prenatal exposure to SSRIs may be etiologically linked to later diagnoses of ASD in offspring,” the investigators added.

The study was a population-based case-control assessment of mothers' antidepressant use during pregnancy and the later diagnosis of ASD in their children. The sample was drawn from the Childhood Autism Perinatal Study, and it included 298 children with ASD and 1,507 unaffected controls matched for age, sex, and area of residence within Northern California.

Twenty case mothers (6.7%) and 50 control mothers (3.3%) had at least one prescription for an antidepressant during the year before the birth of the child. Most of these prescriptions – for 5% of the case mothers and 2.3% of the control mothers – were for SSRIs.

After the data were adjusted to account for maternal age, race/ethnicity, and education level and for the child's birth weight and sex, “we found an approximately twofold increased risk of ASD associated with treatment with SSRIs … and an approximately threefold increased risk associated with treatment during the first trimester,” Dr. Croen and her colleagues said (Arch. Gen. Psychiatry 2011 [doi:10.1001/archgenpsychiatry2011.73]).

Mothers of children later diagnosed as having ASD were twice as likely as other mothers to have had at least one antidepressant prescription during the year preceding the birth. In addition, mothers with a prescription for an antidepressant were more than twice as likely as other mothers to have a child who was later diagnosed as having ASD. No such associations were seen among women prescribed any non-SSRI antidepressants, but the number of women in that group was quite small.

The link between SSRIs and ASD risk remained robust in several further statistical analyses. It remained strong when the analysis was restricted to only term births, as well as when it was restricted to only cases in which only one child in the family was affected with ASD (“simplex” cases).

The correlation also remained strong regardless of the indication for which the mother took the drugs. Moreover, ASD risk did not correlate with a history of mental health disorders. These two findings indicate that the SSRIs themselves, not the underlying indications for taking the medications, were the relevant contributing factor, Dr. Croen and her associates said.

However, they cautioned that “despite the significant association, the number of women in this [study] population exposed to SSRIs was modest, and the proportion of children with ASD in this population that can be statistically attributed to SSRI exposure is quite low: 2.1% for exposure during the year before delivery, and 2.3% for exposure during the first trimester.”

There are several biologically plausible explanations for this link between SSRI exposure and ASD. Many studies have implicated serotonin abnormalities and anomalies in serotoninergic pathways in autism.

And several animal studies “suggest the possibility that prenatal exposure to SSRIs may operate directly on the developing brain, perhaps selectively in fetuses with abnormalities in serotonin-related genes,” they said.

“To our knowledge, our study is the first to directly examine antidepressant use during pregnancy as a potential risk factor for childhood ASD. A substantial strength of our study is our reliance on data documented in medical records and thus recorded at the time of diagnosis or treatment, avoiding potential biases associated with the mothers' recall after diagnosis of ASD in the children,” the investigators wrote.

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.

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.

“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 Health and Nutritional Examination 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.

These links 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.”

No financial conflicts of interest were reported.

View on the News

Food Sources Are Probably Best

Optimizing potassium intake in the general population is of great public health importance, but there are “important questions regarding potential unintended negative consequences,” said Dr. Lynn D. Silver and Dr. Thomas A. Farley.

It is unknown whether dietary or pharmacologic supplementation would have the same health benefits as potassium from traditional dietary sources. “Potassium in foods is accompanied by anions that are bicarbonate precursors, whereas potassium in pills and salt substitutes is generally potassium chloride,” they noted.

Potassium supplements may help some patients, but they would put many others at risk for hyperkalemia – chiefly people with diabetes, renal failure, or heart failure, and people who take ACE inhibitors or spironolactone. “It is crucial that we understand the interplay of sodium and potassium in the diet and how to optimize intake in an increasingly processed food supply without generating harm,” they said.

DR. SILVER and Dr. Farley are with the New York City Department of Health and Mental Hygiene and reported no conflicts of interest. These remarks were taken from their editorial accompanying Dr. Yang's report (Arch. Intern. Med. 2011;171:1191-2).

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.

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.

“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 Health and Nutritional Examination 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.

These links 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.”

No financial conflicts of interest were reported.

View on the News

Food Sources Are Probably Best

Optimizing potassium intake in the general population is of great public health importance, but there are “important questions regarding potential unintended negative consequences,” said Dr. Lynn D. Silver and Dr. Thomas A. Farley.

It is unknown whether dietary or pharmacologic supplementation would have the same health benefits as potassium from traditional dietary sources. “Potassium in foods is accompanied by anions that are bicarbonate precursors, whereas potassium in pills and salt substitutes is generally potassium chloride,” they noted.

Potassium supplements may help some patients, but they would put many others at risk for hyperkalemia – chiefly people with diabetes, renal failure, or heart failure, and people who take ACE inhibitors or spironolactone. “It is crucial that we understand the interplay of sodium and potassium in the diet and how to optimize intake in an increasingly processed food supply without generating harm,” they said.

DR. SILVER and Dr. Farley are with the New York City Department of Health and Mental Hygiene and reported no conflicts of interest. These remarks were taken from their editorial accompanying Dr. Yang's report (Arch. Intern. Med. 2011;171:1191-2).

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.

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.

“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 Health and Nutritional Examination 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.

These links 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.”

No financial conflicts of interest were reported.

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Food Sources Are Probably Best

Optimizing potassium intake in the general population is of great public health importance, but there are “important questions regarding potential unintended negative consequences,” said Dr. Lynn D. Silver and Dr. Thomas A. Farley.

It is unknown whether dietary or pharmacologic supplementation would have the same health benefits as potassium from traditional dietary sources. “Potassium in foods is accompanied by anions that are bicarbonate precursors, whereas potassium in pills and salt substitutes is generally potassium chloride,” they noted.

Potassium supplements may help some patients, but they would put many others at risk for hyperkalemia – chiefly people with diabetes, renal failure, or heart failure, and people who take ACE inhibitors or spironolactone. “It is crucial that we understand the interplay of sodium and potassium in the diet and how to optimize intake in an increasingly processed food supply without generating harm,” they said.

DR. SILVER and Dr. Farley are with the New York City Department of Health and Mental Hygiene and reported no conflicts of interest. These remarks were taken from their editorial accompanying Dr. Yang's report (Arch. Intern. Med. 2011;171:1191-2).

Parenting style and parents’ sense of helplessness in influencing their child’s behavior are both associated with adherence to treatment and metabolic control in adolescents who have type 1 diabetes, according to a report in the August issue of Diabetes Care.

In a study of 100 adolescents with type 1 diabetes and their mothers and fathers, these parenting factors remained significant predictors of the adolescents’ diabetic control even after the data were adjusted to account for potentially confounding factors, such as the child’s age and sex and the method of treatment, said Maayan Shorer, Ph.D., of the Schneider Children’s Medical Center of Israel, Petach Tikva, and her associates.

The investigators defined three mutually exclusive parenting styles as follows:

• An authoritative style is characterized by clear limits to the child that are set by the parents in a caring, noncoercive manner.

• A permissive style is characterized by few efforts by the parents to direct and limit the child’s behavior.

• An authoritarian style is characterized by a coercive, harsh, and punitive approach and parental attempts to control the child’s behavior.

In all, 100 adolescents aged 11-18 years (mean age, 14 years) were enrolled in the cross-sectional study, along with 79 mothers and 63 fathers. The 47 girls and 53 boys had been diagnosed as having type 1 diabetes at a mean of 4.9 years previously.

Most families (approximately 40%) reported high incomes, whereas 32% reported midrange and 28% reported low incomes. The parents were divorced in 11% of families.

A total of 32 adolescents used an insulin pump, and 68 used multiple daily insulin injections.

Each child, together with one parent, completed the Adherence to Diabetes Treatment Regimen Questionnaire, and parents completed the Parental Authority Questionnaire, the Parental Helplessness Questionnaire, and a questionnaire soliciting demographic information. Glycemic control was estimated by assessing each patient’s average HbA_1c value over the course of 1 year.

An authoritative parenting style, particularly among fathers, was associated with better adherence to treatment and glycemic control. In contrast, both permissive and authoritarian parenting styles were associated with poorer adherence and poorer outcome, Dr. Shorer and her colleagues said (Diabetes Care 2011;34:1735-6).

In addition, a greater sense of helplessness in influencing the child’s behavior, particularly among mothers, was associated with worse glycemic control.

The strong association between a father’s authoritativeness on the one hand and the adolescent’s better adherence and diabetes control on the other "highlights the importance of fathers’ involvement in children’s diabetes management," the researchers noted.

"Unfortunately, our clinical experience along with the empirical evidence suggests that compared with mothers, fathers tend to take a too-small role in their child’s diabetes management and exert fewer efforts at monitoring the child.

"We believe fathers should be more engaged in their child’s routine diabetes care, and to do so, specifically, by adopting an authoritative stance," they said.

These study findings spurred the investigators to perform a short-term prospective study, which is now underway, to assess whether improving parental authoritativeness skills will influence adolescents’ glycemic control.

The investigators reported no financial conflicts of interest.

Parenting style and parents’ sense of helplessness in influencing their child’s behavior are both associated with adherence to treatment and metabolic control in adolescents who have type 1 diabetes, according to a report in the August issue of Diabetes Care.

In a study of 100 adolescents with type 1 diabetes and their mothers and fathers, these parenting factors remained significant predictors of the adolescents’ diabetic control even after the data were adjusted to account for potentially confounding factors, such as the child’s age and sex and the method of treatment, said Maayan Shorer, Ph.D., of the Schneider Children’s Medical Center of Israel, Petach Tikva, and her associates.

The investigators defined three mutually exclusive parenting styles as follows:

• An authoritative style is characterized by clear limits to the child that are set by the parents in a caring, noncoercive manner.

• A permissive style is characterized by few efforts by the parents to direct and limit the child’s behavior.

• An authoritarian style is characterized by a coercive, harsh, and punitive approach and parental attempts to control the child’s behavior.

In all, 100 adolescents aged 11-18 years (mean age, 14 years) were enrolled in the cross-sectional study, along with 79 mothers and 63 fathers. The 47 girls and 53 boys had been diagnosed as having type 1 diabetes at a mean of 4.9 years previously.

Most families (approximately 40%) reported high incomes, whereas 32% reported midrange and 28% reported low incomes. The parents were divorced in 11% of families.

A total of 32 adolescents used an insulin pump, and 68 used multiple daily insulin injections.

Each child, together with one parent, completed the Adherence to Diabetes Treatment Regimen Questionnaire, and parents completed the Parental Authority Questionnaire, the Parental Helplessness Questionnaire, and a questionnaire soliciting demographic information. Glycemic control was estimated by assessing each patient’s average HbA_1c value over the course of 1 year.

An authoritative parenting style, particularly among fathers, was associated with better adherence to treatment and glycemic control. In contrast, both permissive and authoritarian parenting styles were associated with poorer adherence and poorer outcome, Dr. Shorer and her colleagues said (Diabetes Care 2011;34:1735-6).

In addition, a greater sense of helplessness in influencing the child’s behavior, particularly among mothers, was associated with worse glycemic control.

The strong association between a father’s authoritativeness on the one hand and the adolescent’s better adherence and diabetes control on the other "highlights the importance of fathers’ involvement in children’s diabetes management," the researchers noted.

"Unfortunately, our clinical experience along with the empirical evidence suggests that compared with mothers, fathers tend to take a too-small role in their child’s diabetes management and exert fewer efforts at monitoring the child.

"We believe fathers should be more engaged in their child’s routine diabetes care, and to do so, specifically, by adopting an authoritative stance," they said.

These study findings spurred the investigators to perform a short-term prospective study, which is now underway, to assess whether improving parental authoritativeness skills will influence adolescents’ glycemic control.

The investigators reported no financial conflicts of interest.

Parenting style and parents’ sense of helplessness in influencing their child’s behavior are both associated with adherence to treatment and metabolic control in adolescents who have type 1 diabetes, according to a report in the August issue of Diabetes Care.

In a study of 100 adolescents with type 1 diabetes and their mothers and fathers, these parenting factors remained significant predictors of the adolescents’ diabetic control even after the data were adjusted to account for potentially confounding factors, such as the child’s age and sex and the method of treatment, said Maayan Shorer, Ph.D., of the Schneider Children’s Medical Center of Israel, Petach Tikva, and her associates.

The investigators defined three mutually exclusive parenting styles as follows:

• An authoritative style is characterized by clear limits to the child that are set by the parents in a caring, noncoercive manner.

• A permissive style is characterized by few efforts by the parents to direct and limit the child’s behavior.

• An authoritarian style is characterized by a coercive, harsh, and punitive approach and parental attempts to control the child’s behavior.

In all, 100 adolescents aged 11-18 years (mean age, 14 years) were enrolled in the cross-sectional study, along with 79 mothers and 63 fathers. The 47 girls and 53 boys had been diagnosed as having type 1 diabetes at a mean of 4.9 years previously.

Most families (approximately 40%) reported high incomes, whereas 32% reported midrange and 28% reported low incomes. The parents were divorced in 11% of families.

A total of 32 adolescents used an insulin pump, and 68 used multiple daily insulin injections.

Each child, together with one parent, completed the Adherence to Diabetes Treatment Regimen Questionnaire, and parents completed the Parental Authority Questionnaire, the Parental Helplessness Questionnaire, and a questionnaire soliciting demographic information. Glycemic control was estimated by assessing each patient’s average HbA_1c value over the course of 1 year.

An authoritative parenting style, particularly among fathers, was associated with better adherence to treatment and glycemic control. In contrast, both permissive and authoritarian parenting styles were associated with poorer adherence and poorer outcome, Dr. Shorer and her colleagues said (Diabetes Care 2011;34:1735-6).

In addition, a greater sense of helplessness in influencing the child’s behavior, particularly among mothers, was associated with worse glycemic control.

The strong association between a father’s authoritativeness on the one hand and the adolescent’s better adherence and diabetes control on the other "highlights the importance of fathers’ involvement in children’s diabetes management," the researchers noted.

"Unfortunately, our clinical experience along with the empirical evidence suggests that compared with mothers, fathers tend to take a too-small role in their child’s diabetes management and exert fewer efforts at monitoring the child.

"We believe fathers should be more engaged in their child’s routine diabetes care, and to do so, specifically, by adopting an authoritative stance," they said.

These study findings spurred the investigators to perform a short-term prospective study, which is now underway, to assess whether improving parental authoritativeness skills will influence adolescents’ glycemic control.

The investigators reported no financial conflicts of interest.

Among patients with early-stage breast cancer whose sentinel nodes were negative for metastases on hematoxylin-eosin testing, a later finding of occult metastases using immunohistochemical staining did not impact survival, according to a report in the July 27 issue of JAMA.

Such occult sentinel node metastases were found in approximately 10% of more than 3,900 patients who participated in the Z0010 trial and whose sentinel node specimens had been tumor-negative on hematoxylin-eosin staining. Yet 5-year rates of overall survival were nearly identical – at just over 95% – between women who were found to have occult metastases and those who were not, said Dr. Armando E. Giuliano of the division of surgical oncology, John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, Calif., and his associates.

Occult metastases identified on immunohistochemical examination of bone marrow yielded conflicting results, so it wasn’t clear whether those metastases may impact survival.

Taken together, these findings show that routine immunohistochemical examination of both bone marrow and sentinel nodes that tested negative with hematoxylin-eosin staining are not clinically warranted for early-stage breast cancer, the investigators said.

The American College of Surgeons Oncology Group (ACOSOG) began the prospective, observational Z0010 trial in 1999 at 126 medical centers to examine the significance of occult metastases in lymph nodes and bone marrow among women undergoing breast-conserving surgery, sentinel lymph node dissection, and whole breast irradiation for T1 or T2 node-negative breast cancer. A total of 3,904 study subjects whose lymph nodes were hematoxylin-eosin negative were included in this analysis of Z0010 data.

Of these, 349 specimens (10.5%) were found to have occult metastases on immunohistochemical examination. Five-year overall survival was 95.7% for patients who had occult nodal metastases, which was not significantly different from the 95.1% rate for patients who did not.

Similarly, 5-year disease-free survival was 92.2% for patients who had occult nodal metastases, which was not significantly different from the 90.4% rate for patients who did not, Dr. Giuliano and his colleagues said (JAMA 2011;306:385-93).

The presence or absence of occult nodal metastases also had no impact on survival when the women were categorized according to adjuvant systemic therapy. Five-year overall survival was 96.3% without adjuvant systemic therapy and 95.7% with adjuvant systemic therapy for women who had occult metastases. Similarly, 5-year disease-free survival was 91.4% and 91%, respectively.

Bone marrow biopsy specimens were obtained in 3,413 patients, and immunocytochemistry revealed occult bone metastases in 104 women (3%). In the initial, univariable analysis, the presence of bone metastases appeared to reduce survival, but this association did not persist in multivariable analyses. Most likely, the small number of positive specimens in this study made it impossible to determine whether bone metastases truly impacted survival, the researchers said.

In the future, "improved techniques for isolating and detecting occult tumor cells may make their assessment in the bone marrow more efficient and feasible," they added.

The Z10010 study was supported by the National Institutes of Health and the American College of Surgeons Oncology Group (ACOSOG). Dr. Giuliano and his associates reported support from ACOSOG; three coauthors reported support from industry sources.

Among patients with early-stage breast cancer whose sentinel nodes were negative for metastases on hematoxylin-eosin testing, a later finding of occult metastases using immunohistochemical staining did not impact survival, according to a report in the July 27 issue of JAMA.

Such occult sentinel node metastases were found in approximately 10% of more than 3,900 patients who participated in the Z0010 trial and whose sentinel node specimens had been tumor-negative on hematoxylin-eosin staining. Yet 5-year rates of overall survival were nearly identical – at just over 95% – between women who were found to have occult metastases and those who were not, said Dr. Armando E. Giuliano of the division of surgical oncology, John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, Calif., and his associates.

Occult metastases identified on immunohistochemical examination of bone marrow yielded conflicting results, so it wasn’t clear whether those metastases may impact survival.

Taken together, these findings show that routine immunohistochemical examination of both bone marrow and sentinel nodes that tested negative with hematoxylin-eosin staining are not clinically warranted for early-stage breast cancer, the investigators said.

The American College of Surgeons Oncology Group (ACOSOG) began the prospective, observational Z0010 trial in 1999 at 126 medical centers to examine the significance of occult metastases in lymph nodes and bone marrow among women undergoing breast-conserving surgery, sentinel lymph node dissection, and whole breast irradiation for T1 or T2 node-negative breast cancer. A total of 3,904 study subjects whose lymph nodes were hematoxylin-eosin negative were included in this analysis of Z0010 data.

Of these, 349 specimens (10.5%) were found to have occult metastases on immunohistochemical examination. Five-year overall survival was 95.7% for patients who had occult nodal metastases, which was not significantly different from the 95.1% rate for patients who did not.

Similarly, 5-year disease-free survival was 92.2% for patients who had occult nodal metastases, which was not significantly different from the 90.4% rate for patients who did not, Dr. Giuliano and his colleagues said (JAMA 2011;306:385-93).

The presence or absence of occult nodal metastases also had no impact on survival when the women were categorized according to adjuvant systemic therapy. Five-year overall survival was 96.3% without adjuvant systemic therapy and 95.7% with adjuvant systemic therapy for women who had occult metastases. Similarly, 5-year disease-free survival was 91.4% and 91%, respectively.

Bone marrow biopsy specimens were obtained in 3,413 patients, and immunocytochemistry revealed occult bone metastases in 104 women (3%). In the initial, univariable analysis, the presence of bone metastases appeared to reduce survival, but this association did not persist in multivariable analyses. Most likely, the small number of positive specimens in this study made it impossible to determine whether bone metastases truly impacted survival, the researchers said.

In the future, "improved techniques for isolating and detecting occult tumor cells may make their assessment in the bone marrow more efficient and feasible," they added.

The Z10010 study was supported by the National Institutes of Health and the American College of Surgeons Oncology Group (ACOSOG). Dr. Giuliano and his associates reported support from ACOSOG; three coauthors reported support from industry sources.

Among patients with early-stage breast cancer whose sentinel nodes were negative for metastases on hematoxylin-eosin testing, a later finding of occult metastases using immunohistochemical staining did not impact survival, according to a report in the July 27 issue of JAMA.

Such occult sentinel node metastases were found in approximately 10% of more than 3,900 patients who participated in the Z0010 trial and whose sentinel node specimens had been tumor-negative on hematoxylin-eosin staining. Yet 5-year rates of overall survival were nearly identical – at just over 95% – between women who were found to have occult metastases and those who were not, said Dr. Armando E. Giuliano of the division of surgical oncology, John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, Calif., and his associates.

Occult metastases identified on immunohistochemical examination of bone marrow yielded conflicting results, so it wasn’t clear whether those metastases may impact survival.

Taken together, these findings show that routine immunohistochemical examination of both bone marrow and sentinel nodes that tested negative with hematoxylin-eosin staining are not clinically warranted for early-stage breast cancer, the investigators said.

The American College of Surgeons Oncology Group (ACOSOG) began the prospective, observational Z0010 trial in 1999 at 126 medical centers to examine the significance of occult metastases in lymph nodes and bone marrow among women undergoing breast-conserving surgery, sentinel lymph node dissection, and whole breast irradiation for T1 or T2 node-negative breast cancer. A total of 3,904 study subjects whose lymph nodes were hematoxylin-eosin negative were included in this analysis of Z0010 data.

Of these, 349 specimens (10.5%) were found to have occult metastases on immunohistochemical examination. Five-year overall survival was 95.7% for patients who had occult nodal metastases, which was not significantly different from the 95.1% rate for patients who did not.

Similarly, 5-year disease-free survival was 92.2% for patients who had occult nodal metastases, which was not significantly different from the 90.4% rate for patients who did not, Dr. Giuliano and his colleagues said (JAMA 2011;306:385-93).

The presence or absence of occult nodal metastases also had no impact on survival when the women were categorized according to adjuvant systemic therapy. Five-year overall survival was 96.3% without adjuvant systemic therapy and 95.7% with adjuvant systemic therapy for women who had occult metastases. Similarly, 5-year disease-free survival was 91.4% and 91%, respectively.

Bone marrow biopsy specimens were obtained in 3,413 patients, and immunocytochemistry revealed occult bone metastases in 104 women (3%). In the initial, univariable analysis, the presence of bone metastases appeared to reduce survival, but this association did not persist in multivariable analyses. Most likely, the small number of positive specimens in this study made it impossible to determine whether bone metastases truly impacted survival, the researchers said.

In the future, "improved techniques for isolating and detecting occult tumor cells may make their assessment in the bone marrow more efficient and feasible," they added.

The Z10010 study was supported by the National Institutes of Health and the American College of Surgeons Oncology Group (ACOSOG). Dr. Giuliano and his associates reported support from ACOSOG; three coauthors reported support from industry sources.

Researchers have identified germline mutations in three genes that appear to be associated with Barrett's esophagus and esophageal adenocarcinoma, according to a report in the July 27 issue of JAMA.

The mutations, however, only accounted for a small proportion (11%) of cases of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) in this study. Mutations in the MSR1 gene accounted for 7% of cases, and mutations in either ASCC1 or CTHRC1 accounted for approximately 2% each, said Mohammed Orloff, Ph.D., of the Genomic Medicine Institute and Taussig Cancer Institute at the Cleveland Clinic, and his associates.

Most cases of BE and EAC are thought to be sporadic rather than inherited, but in the past few decades clustering of cases in some families has been observed, supporting the existence of predisposition genes as well, the authors explained.

"The discovery of germline mutations in a gene or genes that predispose to BE/EAC may have ramifications regarding cancer risk assessment, genetic counseling, premorbid diagnosis, and targeted surveillance and management, and also [may] add to the fundamental understanding of the pathophysiology of sporadic BE and EAC," they wrote.

Over the course of 5 years, the investigators performed a series of genetic studies that led to their discovery of these three germline mutations.

They began by recruiting 298 adults with histologically proven Barrett’s esophagus and/or esophageal adenocarcinoma, as well as families with two or more cases of these disorders, from 16 academic and community hospitals and clinics across the United States. They found and genotyped 21 pairs of siblings in which both siblings were affected and 11 pairs of siblings in which only one sibling was affected.

The researchers identified what appeared to be significant genomic regions in these subjects, then validated these "potentially interesting" regions and performed fine mapping in a separate series of 176 patients with BE and/or EAC and 200 ancestry-matched population control subjects, Dr. Orloff and his associates said. Only white patients of northern or western European descent were included.

The investigators integrated these results with publicly available data on somatic gene expression derived from 19 other affected patients to develop a list of 12 biologically plausible candidate genes to be scanned in more detail for germline mutations. This analysis showed that three candidate genes were significantly associated with BE or EAC (P less than .001 for each). The genes were MSR1 (macrophage scavenger receptor 1), ASCC1 (activating signal cointegrator 1 complex subunit 1), and CTHRC1 (collagen triple-helix repeat-containing 1).

A similar mutational analysis performed in a separate series of 58 cases obtained from outpatient endoscopy clinics confirmed these results.

"These three genes together accounted for 11% of our cases, reflecting what is normally considered a moderate- to high-penetrance genetic load for a disease," Dr. Orloff and his colleagues noted (JAMA 2011;306:410-19).

No mutations of these three genes were found in a pooled group of 264 control subjects.

"MSR1, on chromosome 8p22, encodes the class A macrophage scavenger receptor, which are macrophage-specific trimeric integral membrane glycoproteins implicated in many macrophage-associated, hormonal, and pathological processes, including inflammation, innate and adaptive immunity, oxidative stress, and apoptosis," they noted.

ASCC1 is thought to link inflammatory pathways to tumor suppression pathways. CTHRC1 is expressed in tissue repair processes; it may play a role in the host response to GERD and may predispose carriers to having decreased sphincter tone in the lower esophagus.

"In summary, germline mutations in MSR1, ASCC1, and CTHRC1 in patients with BE/EAC appear physiologically relevant to [these disorders], encoding proteins involved in apoptosis, innate immunity, polarity, and mobility that affect inflammatory and [other] pathways."

Larger studies are needed to determine whether genotyping to hunt for mutations in these genes and their variants would be useful in assessing people’s risk of developing BE or EAC, as well as in diagnosing the cancer earlier, when it is more responsive to treatment, the researchers said.

This study was funded in part by the M. Frank and Margaret Domiter Rudy Endowment of the Cleveland Clinic Taussig Cancer Institute and by grants from the National Cancer Institute and National Institutes of Health. No relevant financial conflicts of interest were reported.

Researchers have identified germline mutations in three genes that appear to be associated with Barrett's esophagus and esophageal adenocarcinoma, according to a report in the July 27 issue of JAMA.

The mutations, however, only accounted for a small proportion (11%) of cases of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) in this study. Mutations in the MSR1 gene accounted for 7% of cases, and mutations in either ASCC1 or CTHRC1 accounted for approximately 2% each, said Mohammed Orloff, Ph.D., of the Genomic Medicine Institute and Taussig Cancer Institute at the Cleveland Clinic, and his associates.

Most cases of BE and EAC are thought to be sporadic rather than inherited, but in the past few decades clustering of cases in some families has been observed, supporting the existence of predisposition genes as well, the authors explained.

"The discovery of germline mutations in a gene or genes that predispose to BE/EAC may have ramifications regarding cancer risk assessment, genetic counseling, premorbid diagnosis, and targeted surveillance and management, and also [may] add to the fundamental understanding of the pathophysiology of sporadic BE and EAC," they wrote.

Over the course of 5 years, the investigators performed a series of genetic studies that led to their discovery of these three germline mutations.

They began by recruiting 298 adults with histologically proven Barrett’s esophagus and/or esophageal adenocarcinoma, as well as families with two or more cases of these disorders, from 16 academic and community hospitals and clinics across the United States. They found and genotyped 21 pairs of siblings in which both siblings were affected and 11 pairs of siblings in which only one sibling was affected.

The researchers identified what appeared to be significant genomic regions in these subjects, then validated these "potentially interesting" regions and performed fine mapping in a separate series of 176 patients with BE and/or EAC and 200 ancestry-matched population control subjects, Dr. Orloff and his associates said. Only white patients of northern or western European descent were included.

The investigators integrated these results with publicly available data on somatic gene expression derived from 19 other affected patients to develop a list of 12 biologically plausible candidate genes to be scanned in more detail for germline mutations. This analysis showed that three candidate genes were significantly associated with BE or EAC (P less than .001 for each). The genes were MSR1 (macrophage scavenger receptor 1), ASCC1 (activating signal cointegrator 1 complex subunit 1), and CTHRC1 (collagen triple-helix repeat-containing 1).

A similar mutational analysis performed in a separate series of 58 cases obtained from outpatient endoscopy clinics confirmed these results.

"These three genes together accounted for 11% of our cases, reflecting what is normally considered a moderate- to high-penetrance genetic load for a disease," Dr. Orloff and his colleagues noted (JAMA 2011;306:410-19).

No mutations of these three genes were found in a pooled group of 264 control subjects.

"MSR1, on chromosome 8p22, encodes the class A macrophage scavenger receptor, which are macrophage-specific trimeric integral membrane glycoproteins implicated in many macrophage-associated, hormonal, and pathological processes, including inflammation, innate and adaptive immunity, oxidative stress, and apoptosis," they noted.

ASCC1 is thought to link inflammatory pathways to tumor suppression pathways. CTHRC1 is expressed in tissue repair processes; it may play a role in the host response to GERD and may predispose carriers to having decreased sphincter tone in the lower esophagus.

"In summary, germline mutations in MSR1, ASCC1, and CTHRC1 in patients with BE/EAC appear physiologically relevant to [these disorders], encoding proteins involved in apoptosis, innate immunity, polarity, and mobility that affect inflammatory and [other] pathways."

Larger studies are needed to determine whether genotyping to hunt for mutations in these genes and their variants would be useful in assessing people’s risk of developing BE or EAC, as well as in diagnosing the cancer earlier, when it is more responsive to treatment, the researchers said.

This study was funded in part by the M. Frank and Margaret Domiter Rudy Endowment of the Cleveland Clinic Taussig Cancer Institute and by grants from the National Cancer Institute and National Institutes of Health. No relevant financial conflicts of interest were reported.

Researchers have identified germline mutations in three genes that appear to be associated with Barrett's esophagus and esophageal adenocarcinoma, according to a report in the July 27 issue of JAMA.

The mutations, however, only accounted for a small proportion (11%) of cases of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) in this study. Mutations in the MSR1 gene accounted for 7% of cases, and mutations in either ASCC1 or CTHRC1 accounted for approximately 2% each, said Mohammed Orloff, Ph.D., of the Genomic Medicine Institute and Taussig Cancer Institute at the Cleveland Clinic, and his associates.

Most cases of BE and EAC are thought to be sporadic rather than inherited, but in the past few decades clustering of cases in some families has been observed, supporting the existence of predisposition genes as well, the authors explained.

"The discovery of germline mutations in a gene or genes that predispose to BE/EAC may have ramifications regarding cancer risk assessment, genetic counseling, premorbid diagnosis, and targeted surveillance and management, and also [may] add to the fundamental understanding of the pathophysiology of sporadic BE and EAC," they wrote.

Over the course of 5 years, the investigators performed a series of genetic studies that led to their discovery of these three germline mutations.

They began by recruiting 298 adults with histologically proven Barrett’s esophagus and/or esophageal adenocarcinoma, as well as families with two or more cases of these disorders, from 16 academic and community hospitals and clinics across the United States. They found and genotyped 21 pairs of siblings in which both siblings were affected and 11 pairs of siblings in which only one sibling was affected.

The researchers identified what appeared to be significant genomic regions in these subjects, then validated these "potentially interesting" regions and performed fine mapping in a separate series of 176 patients with BE and/or EAC and 200 ancestry-matched population control subjects, Dr. Orloff and his associates said. Only white patients of northern or western European descent were included.

The investigators integrated these results with publicly available data on somatic gene expression derived from 19 other affected patients to develop a list of 12 biologically plausible candidate genes to be scanned in more detail for germline mutations. This analysis showed that three candidate genes were significantly associated with BE or EAC (P less than .001 for each). The genes were MSR1 (macrophage scavenger receptor 1), ASCC1 (activating signal cointegrator 1 complex subunit 1), and CTHRC1 (collagen triple-helix repeat-containing 1).

A similar mutational analysis performed in a separate series of 58 cases obtained from outpatient endoscopy clinics confirmed these results.

"These three genes together accounted for 11% of our cases, reflecting what is normally considered a moderate- to high-penetrance genetic load for a disease," Dr. Orloff and his colleagues noted (JAMA 2011;306:410-19).

No mutations of these three genes were found in a pooled group of 264 control subjects.

"MSR1, on chromosome 8p22, encodes the class A macrophage scavenger receptor, which are macrophage-specific trimeric integral membrane glycoproteins implicated in many macrophage-associated, hormonal, and pathological processes, including inflammation, innate and adaptive immunity, oxidative stress, and apoptosis," they noted.

ASCC1 is thought to link inflammatory pathways to tumor suppression pathways. CTHRC1 is expressed in tissue repair processes; it may play a role in the host response to GERD and may predispose carriers to having decreased sphincter tone in the lower esophagus.

"In summary, germline mutations in MSR1, ASCC1, and CTHRC1 in patients with BE/EAC appear physiologically relevant to [these disorders], encoding proteins involved in apoptosis, innate immunity, polarity, and mobility that affect inflammatory and [other] pathways."

Larger studies are needed to determine whether genotyping to hunt for mutations in these genes and their variants would be useful in assessing people’s risk of developing BE or EAC, as well as in diagnosing the cancer earlier, when it is more responsive to treatment, the researchers said.

This study was funded in part by the M. Frank and Margaret Domiter Rudy Endowment of the Cleveland Clinic Taussig Cancer Institute and by grants from the National Cancer Institute and National Institutes of Health. No relevant financial conflicts of interest were reported.

Two interventions to improve the transition from hospital discharge to home care, and to thereby reduce readmissions, were effective in the first attempts to implement them in real-world settings, according to separate reports in the July 25 issue of Archives of Internal Medicine.

Both interventions had been effective in the comparatively controlled conditions of several randomized controlled trials, but until now it wasn’t known whether that success would translate into real-world practice.

In the first report, a Medicare demonstration project following the Care Transitions Intervention (CTI) model was assessed in 257 adults in the Medicare fee-for-service program who were hospitalized for a variety of diagnoses at six Rhode Island medical centers during an 18-month period. The facilities included community hospitals, teaching hospitals, and a tertiary care center, and their size ranged from 129 to 719 beds, said Rachel Voss of Quality Partners of Rhode Island, the Medicare Quality Improvement Organization for Rhode Island, and her associates.

The CTI is a 1-month program designed to help patients on the verge of discharge and their families to manage their health more actively and to communicate more effectively with their providers. Nurses or social workers act as "coaches" who conduct a hospital visit, a home visit within 3 days of discharge, a phone visit within 7-10 days, and a final phone visit within 30 days.

At these visits, the coaches review a booklet in which patients record their health problems, medications, and questions for providers; troubleshoot problems with outpatient care; ensure patients understand the signs and symptoms of worsening of their condition before an emergency issue develops; and help patients locate other sources of continued support.

Before implementation of the CTI program, the average 30-day readmission rate at the six participating hospitals was 21%. In comparison, the rate was only 12.8% in patients who participated in the intervention.

The primary outcome measure of the study was the difference between the readmission rate among the study participants (12.8%) and a control group of similar patients who did not participate (20%). This represents a 36% reduction in readmissions with the intervention program, a significant decrease, Ms. Voss and her colleagues said (Arch. Intern. Med. 2011;171:1232-7).

One drawback revealed in this study was the lack of success in recruiting and retaining study patients willing to participate in the intervention. Only 55% of the patients who were approached agreed to participate, and the attrition rate among those who initially agreed to a home visit was 75%, the researchers noted.

The second report was a pilot study at a single medical center involving patients with heart failure, a disorder for which hospital readmission is particularly common. The 3-month intervention was a traditional care program (TCP) in which advanced practice nurses educated patients and families about symptoms and self-management strategies, improved communication patterns with care providers, and marshaled caregiver and community resources to facilitate adherence to treatment and improve quality of life.

It included at least eight home visits, beginning within 72 hours of hospital admission, as well as 24-hour phone availability.

A total of 140 Medicare fee-for-service patients with heart failure were eligible, and 56 enrolled in the study. Once again only 40% of eligible patients agreed to participate in the intervention, said Dr. Brett D. Stauffer of the Institute for Health Care Research and Improvement, Baylor Health Care System, Dallas, and his associates.

The 30-day readmission rate was 48% lower after the intervention was implemented than it had been before. No such reduction in readmissions was noted at other medical centers in the same area during the study period, Dr. Stauffer and his colleagues said.

Total direct costs were lower for patients who participated in the intervention than for those who did not; however, the cost of the intervention itself was not recovered by the hospital.

The hospital actually lost revenue by preventing readmissions, because under the current payment system, readmissions are fully reimbursed. If and when this payment system is revised as part of health care reform, both the individual patients and the hospital itself will save money in their efforts to keep patients healthy and out of the hospital, the investigators said.

Ms. Voss’s study was funded by the Centers for Medicare and Medicaid Services. Dr. Stauffer’s study was supported by the Baylor Health Care System, Dallas. Both research groups reported no financial conflicts of interest.

Two interventions to improve the transition from hospital discharge to home care, and to thereby reduce readmissions, were effective in the first attempts to implement them in real-world settings, according to separate reports in the July 25 issue of Archives of Internal Medicine.

Both interventions had been effective in the comparatively controlled conditions of several randomized controlled trials, but until now it wasn’t known whether that success would translate into real-world practice.

In the first report, a Medicare demonstration project following the Care Transitions Intervention (CTI) model was assessed in 257 adults in the Medicare fee-for-service program who were hospitalized for a variety of diagnoses at six Rhode Island medical centers during an 18-month period. The facilities included community hospitals, teaching hospitals, and a tertiary care center, and their size ranged from 129 to 719 beds, said Rachel Voss of Quality Partners of Rhode Island, the Medicare Quality Improvement Organization for Rhode Island, and her associates.

The CTI is a 1-month program designed to help patients on the verge of discharge and their families to manage their health more actively and to communicate more effectively with their providers. Nurses or social workers act as "coaches" who conduct a hospital visit, a home visit within 3 days of discharge, a phone visit within 7-10 days, and a final phone visit within 30 days.

At these visits, the coaches review a booklet in which patients record their health problems, medications, and questions for providers; troubleshoot problems with outpatient care; ensure patients understand the signs and symptoms of worsening of their condition before an emergency issue develops; and help patients locate other sources of continued support.

Before implementation of the CTI program, the average 30-day readmission rate at the six participating hospitals was 21%. In comparison, the rate was only 12.8% in patients who participated in the intervention.

The primary outcome measure of the study was the difference between the readmission rate among the study participants (12.8%) and a control group of similar patients who did not participate (20%). This represents a 36% reduction in readmissions with the intervention program, a significant decrease, Ms. Voss and her colleagues said (Arch. Intern. Med. 2011;171:1232-7).

One drawback revealed in this study was the lack of success in recruiting and retaining study patients willing to participate in the intervention. Only 55% of the patients who were approached agreed to participate, and the attrition rate among those who initially agreed to a home visit was 75%, the researchers noted.

The second report was a pilot study at a single medical center involving patients with heart failure, a disorder for which hospital readmission is particularly common. The 3-month intervention was a traditional care program (TCP) in which advanced practice nurses educated patients and families about symptoms and self-management strategies, improved communication patterns with care providers, and marshaled caregiver and community resources to facilitate adherence to treatment and improve quality of life.

It included at least eight home visits, beginning within 72 hours of hospital admission, as well as 24-hour phone availability.

A total of 140 Medicare fee-for-service patients with heart failure were eligible, and 56 enrolled in the study. Once again only 40% of eligible patients agreed to participate in the intervention, said Dr. Brett D. Stauffer of the Institute for Health Care Research and Improvement, Baylor Health Care System, Dallas, and his associates.

The 30-day readmission rate was 48% lower after the intervention was implemented than it had been before. No such reduction in readmissions was noted at other medical centers in the same area during the study period, Dr. Stauffer and his colleagues said.

Total direct costs were lower for patients who participated in the intervention than for those who did not; however, the cost of the intervention itself was not recovered by the hospital.

The hospital actually lost revenue by preventing readmissions, because under the current payment system, readmissions are fully reimbursed. If and when this payment system is revised as part of health care reform, both the individual patients and the hospital itself will save money in their efforts to keep patients healthy and out of the hospital, the investigators said.

Ms. Voss’s study was funded by the Centers for Medicare and Medicaid Services. Dr. Stauffer’s study was supported by the Baylor Health Care System, Dallas. Both research groups reported no financial conflicts of interest.

Two interventions to improve the transition from hospital discharge to home care, and to thereby reduce readmissions, were effective in the first attempts to implement them in real-world settings, according to separate reports in the July 25 issue of Archives of Internal Medicine.

Both interventions had been effective in the comparatively controlled conditions of several randomized controlled trials, but until now it wasn’t known whether that success would translate into real-world practice.

In the first report, a Medicare demonstration project following the Care Transitions Intervention (CTI) model was assessed in 257 adults in the Medicare fee-for-service program who were hospitalized for a variety of diagnoses at six Rhode Island medical centers during an 18-month period. The facilities included community hospitals, teaching hospitals, and a tertiary care center, and their size ranged from 129 to 719 beds, said Rachel Voss of Quality Partners of Rhode Island, the Medicare Quality Improvement Organization for Rhode Island, and her associates.

The CTI is a 1-month program designed to help patients on the verge of discharge and their families to manage their health more actively and to communicate more effectively with their providers. Nurses or social workers act as "coaches" who conduct a hospital visit, a home visit within 3 days of discharge, a phone visit within 7-10 days, and a final phone visit within 30 days.

At these visits, the coaches review a booklet in which patients record their health problems, medications, and questions for providers; troubleshoot problems with outpatient care; ensure patients understand the signs and symptoms of worsening of their condition before an emergency issue develops; and help patients locate other sources of continued support.

Before implementation of the CTI program, the average 30-day readmission rate at the six participating hospitals was 21%. In comparison, the rate was only 12.8% in patients who participated in the intervention.

The primary outcome measure of the study was the difference between the readmission rate among the study participants (12.8%) and a control group of similar patients who did not participate (20%). This represents a 36% reduction in readmissions with the intervention program, a significant decrease, Ms. Voss and her colleagues said (Arch. Intern. Med. 2011;171:1232-7).

One drawback revealed in this study was the lack of success in recruiting and retaining study patients willing to participate in the intervention. Only 55% of the patients who were approached agreed to participate, and the attrition rate among those who initially agreed to a home visit was 75%, the researchers noted.

The second report was a pilot study at a single medical center involving patients with heart failure, a disorder for which hospital readmission is particularly common. The 3-month intervention was a traditional care program (TCP) in which advanced practice nurses educated patients and families about symptoms and self-management strategies, improved communication patterns with care providers, and marshaled caregiver and community resources to facilitate adherence to treatment and improve quality of life.

It included at least eight home visits, beginning within 72 hours of hospital admission, as well as 24-hour phone availability.

A total of 140 Medicare fee-for-service patients with heart failure were eligible, and 56 enrolled in the study. Once again only 40% of eligible patients agreed to participate in the intervention, said Dr. Brett D. Stauffer of the Institute for Health Care Research and Improvement, Baylor Health Care System, Dallas, and his associates.

The 30-day readmission rate was 48% lower after the intervention was implemented than it had been before. No such reduction in readmissions was noted at other medical centers in the same area during the study period, Dr. Stauffer and his colleagues said.

Total direct costs were lower for patients who participated in the intervention than for those who did not; however, the cost of the intervention itself was not recovered by the hospital.

The hospital actually lost revenue by preventing readmissions, because under the current payment system, readmissions are fully reimbursed. If and when this payment system is revised as part of health care reform, both the individual patients and the hospital itself will save money in their efforts to keep patients healthy and out of the hospital, the investigators said.

Ms. Voss’s study was funded by the Centers for Medicare and Medicaid Services. Dr. Stauffer’s study was supported by the Baylor Health Care System, Dallas. Both research groups reported no financial conflicts of interest.

Cranberry capsules are less effective than prophylactic trimethoprim-sulfamethoxazole at preventing recurrent urinary tract infections in premenopausal women, according to a report in the July 25 issue of Archives of Internal Medicine.

However, the emergence of resistance to amoxicillin and the quinolones as well as to trimethoprim-sulfamethoxazole (TMP-SMX) was very rapid and affected approximately 90% of the women who took the antibiotic, compared with only 28% of those who took cranberry capsules. This adverse outcome must be balanced against the antibiotic’s greater effectiveness, said Dr. Marielle A. J. Beerepoot of the Academic Medical Center, Amsterdam, and her associates.

Photo courtesy Elenathewise/Fotolia.com.

"From clinical practice and during the recruitment phase of this study, we learned that many women are afraid of contracting drug-resistant bacteria using long-term antibiotic prophylaxis, and preferred either no or nonantibiotic prophylaxis. In those women, cranberry prophylaxis may be a useful alternative despite its lower effectiveness," they noted (Arch. Intern. Med. 2011;171:1270-8).

The investigators performed a randomized double-blind noninferiority trial to directly compare 1 year of prophylaxis with TMP-SMX (one 480-mg tablet once daily) against a capsule containing 500 mg cranberry extract (one capsule twice daily) for preventing recurrent UTI in 221 premenopausal women who had at least three UTIs during the previous year. The study subjects were treated at 10 medical centers across the Netherlands during a 2-year period and followed for 15 months, or 3 months after they stopped taking prophylaxis.

After 1 year of treatment, the mean number of clinical recurrences of UTI was 1.8 for TMP-SMX, compared with 4.0 for cranberry capsules. This difference exceeded the limit for noninferiority.

The proportion of women who developed at least one symptomatic UTI while on prophylaxis was 71.1% with TMP-SMX, compared with 78.2% with cranberry capsules. The median time to first recurrence was 8 months with TMP-SMX, compared with 4 months with cranberry capsules.

The median number of antibiotic prescriptions for UTI from the subjects’ primary care physicians during the study period was twice as high in the cranberry group (1) as in the TMP-SMX group (0.5). Nitrofurantoin was the drug most often prescribed for both groups, followed by norfloxacin.

Within 1 month of beginning antibiotic prophylaxis, the rate of resistance to TMP-SMX, TMP alone, and amoxicillin in samples of both urine and feces soared from 21%-28% to 73%-91%. Resistance rates returned to baseline within 3 months of discontinuing antibiotic prophylaxis.

The two interventions were equally well tolerated. "There were no statistically significant differences between the TMP-SMX and the cranberry groups in the percentages of patients with any or a specific adverse event or serious adverse event. In the TMP-SMX group, one woman had a serious adverse event (Stevens-Johnson syndrome) [that] led to her withdrawal [from the study]. There were no serious adverse events in the cranberry group," Dr. Beerepoot and her colleagues said.

This study was limited in that the dropout rate was quite high: only 54 of 110 women in the TMP-SMX group (49%) and only 45 of 111 women in the cranberry group (41%) completed the final assessment. However, these rates are in keeping with those of previous UTI trials with much shorter follow-up periods of 6 months or less, the investigators said.

The trial also was hampered by the fact that the optimal dosage of cranberry extract is still not known. A dose-finding study is now under way. In this study, the daily dose was equivalent to that in 75 mL of commercially available cranberry juice containing 27% cranberry, they noted.

This study was supported by the Netherlands Organisation for Health Research and Development. The cranberry and placebo capsules were provided by Springfield Nutraceuticals BV. Dr. Beerepoot reported no relevant financial disclosures.

Cranberry capsules are less effective than prophylactic trimethoprim-sulfamethoxazole at preventing recurrent urinary tract infections in premenopausal women, according to a report in the July 25 issue of Archives of Internal Medicine.

However, the emergence of resistance to amoxicillin and the quinolones as well as to trimethoprim-sulfamethoxazole (TMP-SMX) was very rapid and affected approximately 90% of the women who took the antibiotic, compared with only 28% of those who took cranberry capsules. This adverse outcome must be balanced against the antibiotic’s greater effectiveness, said Dr. Marielle A. J. Beerepoot of the Academic Medical Center, Amsterdam, and her associates.

Photo courtesy Elenathewise/Fotolia.com.

"From clinical practice and during the recruitment phase of this study, we learned that many women are afraid of contracting drug-resistant bacteria using long-term antibiotic prophylaxis, and preferred either no or nonantibiotic prophylaxis. In those women, cranberry prophylaxis may be a useful alternative despite its lower effectiveness," they noted (Arch. Intern. Med. 2011;171:1270-8).

The investigators performed a randomized double-blind noninferiority trial to directly compare 1 year of prophylaxis with TMP-SMX (one 480-mg tablet once daily) against a capsule containing 500 mg cranberry extract (one capsule twice daily) for preventing recurrent UTI in 221 premenopausal women who had at least three UTIs during the previous year. The study subjects were treated at 10 medical centers across the Netherlands during a 2-year period and followed for 15 months, or 3 months after they stopped taking prophylaxis.

After 1 year of treatment, the mean number of clinical recurrences of UTI was 1.8 for TMP-SMX, compared with 4.0 for cranberry capsules. This difference exceeded the limit for noninferiority.

The proportion of women who developed at least one symptomatic UTI while on prophylaxis was 71.1% with TMP-SMX, compared with 78.2% with cranberry capsules. The median time to first recurrence was 8 months with TMP-SMX, compared with 4 months with cranberry capsules.

The median number of antibiotic prescriptions for UTI from the subjects’ primary care physicians during the study period was twice as high in the cranberry group (1) as in the TMP-SMX group (0.5). Nitrofurantoin was the drug most often prescribed for both groups, followed by norfloxacin.

Within 1 month of beginning antibiotic prophylaxis, the rate of resistance to TMP-SMX, TMP alone, and amoxicillin in samples of both urine and feces soared from 21%-28% to 73%-91%. Resistance rates returned to baseline within 3 months of discontinuing antibiotic prophylaxis.

The two interventions were equally well tolerated. "There were no statistically significant differences between the TMP-SMX and the cranberry groups in the percentages of patients with any or a specific adverse event or serious adverse event. In the TMP-SMX group, one woman had a serious adverse event (Stevens-Johnson syndrome) [that] led to her withdrawal [from the study]. There were no serious adverse events in the cranberry group," Dr. Beerepoot and her colleagues said.

This study was limited in that the dropout rate was quite high: only 54 of 110 women in the TMP-SMX group (49%) and only 45 of 111 women in the cranberry group (41%) completed the final assessment. However, these rates are in keeping with those of previous UTI trials with much shorter follow-up periods of 6 months or less, the investigators said.

The trial also was hampered by the fact that the optimal dosage of cranberry extract is still not known. A dose-finding study is now under way. In this study, the daily dose was equivalent to that in 75 mL of commercially available cranberry juice containing 27% cranberry, they noted.

This study was supported by the Netherlands Organisation for Health Research and Development. The cranberry and placebo capsules were provided by Springfield Nutraceuticals BV. Dr. Beerepoot reported no relevant financial disclosures.

Cranberry capsules are less effective than prophylactic trimethoprim-sulfamethoxazole at preventing recurrent urinary tract infections in premenopausal women, according to a report in the July 25 issue of Archives of Internal Medicine.

However, the emergence of resistance to amoxicillin and the quinolones as well as to trimethoprim-sulfamethoxazole (TMP-SMX) was very rapid and affected approximately 90% of the women who took the antibiotic, compared with only 28% of those who took cranberry capsules. This adverse outcome must be balanced against the antibiotic’s greater effectiveness, said Dr. Marielle A. J. Beerepoot of the Academic Medical Center, Amsterdam, and her associates.

Photo courtesy Elenathewise/Fotolia.com.

"From clinical practice and during the recruitment phase of this study, we learned that many women are afraid of contracting drug-resistant bacteria using long-term antibiotic prophylaxis, and preferred either no or nonantibiotic prophylaxis. In those women, cranberry prophylaxis may be a useful alternative despite its lower effectiveness," they noted (Arch. Intern. Med. 2011;171:1270-8).

The investigators performed a randomized double-blind noninferiority trial to directly compare 1 year of prophylaxis with TMP-SMX (one 480-mg tablet once daily) against a capsule containing 500 mg cranberry extract (one capsule twice daily) for preventing recurrent UTI in 221 premenopausal women who had at least three UTIs during the previous year. The study subjects were treated at 10 medical centers across the Netherlands during a 2-year period and followed for 15 months, or 3 months after they stopped taking prophylaxis.

After 1 year of treatment, the mean number of clinical recurrences of UTI was 1.8 for TMP-SMX, compared with 4.0 for cranberry capsules. This difference exceeded the limit for noninferiority.

The proportion of women who developed at least one symptomatic UTI while on prophylaxis was 71.1% with TMP-SMX, compared with 78.2% with cranberry capsules. The median time to first recurrence was 8 months with TMP-SMX, compared with 4 months with cranberry capsules.

The median number of antibiotic prescriptions for UTI from the subjects’ primary care physicians during the study period was twice as high in the cranberry group (1) as in the TMP-SMX group (0.5). Nitrofurantoin was the drug most often prescribed for both groups, followed by norfloxacin.

Within 1 month of beginning antibiotic prophylaxis, the rate of resistance to TMP-SMX, TMP alone, and amoxicillin in samples of both urine and feces soared from 21%-28% to 73%-91%. Resistance rates returned to baseline within 3 months of discontinuing antibiotic prophylaxis.

The two interventions were equally well tolerated. "There were no statistically significant differences between the TMP-SMX and the cranberry groups in the percentages of patients with any or a specific adverse event or serious adverse event. In the TMP-SMX group, one woman had a serious adverse event (Stevens-Johnson syndrome) [that] led to her withdrawal [from the study]. There were no serious adverse events in the cranberry group," Dr. Beerepoot and her colleagues said.

This study was limited in that the dropout rate was quite high: only 54 of 110 women in the TMP-SMX group (49%) and only 45 of 111 women in the cranberry group (41%) completed the final assessment. However, these rates are in keeping with those of previous UTI trials with much shorter follow-up periods of 6 months or less, the investigators said.

The trial also was hampered by the fact that the optimal dosage of cranberry extract is still not known. A dose-finding study is now under way. In this study, the daily dose was equivalent to that in 75 mL of commercially available cranberry juice containing 27% cranberry, they noted.

This study was supported by the Netherlands Organisation for Health Research and Development. The cranberry and placebo capsules were provided by Springfield Nutraceuticals BV. Dr. Beerepoot reported no relevant financial disclosures.

The rate of coronary artery bypass grafting performed in U.S. hospitals declined by approximately one-third between 2001 and 2008, according to an analysis of the Agency for Healthcare Research and Quality database.

During the same period, the rate of percutaneous coronary interventions (PCIs) showed a far more modest decrease.

"Our data imply a sizeable shift in cardiovascular clinical practice patterns away from surgical treatment toward percutaneous, catheter-based interventions," said Andrew J. Epstein, Ph.D., of the Philadelphia Veterans Affairs? Center for Health Equity Research and Promotion and the University of Pennsylvania, and his associates.

Given that coronary artery bypass grafting remains the better choice for patients with previously untreated three-vessel or left main coronary artery disease, according to the results of the SYNTAX trial (N. Engl. J. Med. 2009;360:961-72), it appears that CABG is being underused, the authors wrote.

It seems likely that in recent years, "patients who would have been optimally treated with CABG surgery were instead treated with PCI," they noted.

To assess temporal trends in coronary revascularization procedures, the investigators examined a nationally representative sample of hospitalization claims using an Agency for Healthcare Research and Quality database.

The database includes discharge data from approximately 1,000 nonfederal hospitals in 42 states, which covers 20% of U.S. hospitals and allows accurate estimates for the entire population of hospitalized patients, regardless of payer or insurance status.

Between 2001 and 2008, the total number of coronary revascularizations decreased "modestly," by approximately 15%.

There was a "substantial," statistically significant, 38% decrease in the annual rate of CABG surgery, from 1,742 per million adults in the first year of the study period to 1,081 per million in the final year.

This decline was roughly linear throughout the 8-year study period, suggesting that it "was not triggered by any single event occurring during the past decade, such as the introduction of competing technologies, advances in CABG surgical techniques, publication of clinical trials, or issuance of clinical guidelines."

CABG procedures decreased across all sex, age, racial, and regional subgroups.

In contrast, the PCI rate remained fairly constant, showing a "modest" 4% decrease from 3,827 per million adults per year in the first year of the study to 3,667 in the final year.

"Projected to the entire U.S. population, these rate changes implied that 130,000 fewer CABG surgeries were performed in 2008 compared to 2001," Dr. Epstein and his colleagues noted (JAMA 2011;305:1769-76).

The data did not allow the researchers to distinguish which patients may have been more appropriate candidates for CABG than for PCI, so "it cannot be known with certainty whether physicians were increasingly substituting PCI for CABG surgery during the past decade. ... [But] our findings suggest the possibility that several thousand patients who underwent PCI in 2008 would have undergone CABG surgery had patterns of care not changed markedly," they said.

The preferences of patients were also not discernible from the data, lead investigator Dr. Peter W. Groeneveld said in an interview. "However, if patient preference [for PCI vs. CABG] was the driving factor, there would have to be some reason that PCI was even more preferable to patients in 2008 than it was in 2001.

This scenario seems unlikely since the procedures haven?t changed that much," said Dr. Groeneveld, assistant professor of medicine at the University of Pennsylvania and staff physician at the Philadelphia Veterans Affairs Medical Center.

Another important finding was that during this interval, the number of hospitals providing CABG increased. Combined with the drop in the number of CABG surgeries, this resulted in a 28% decline in the median caseload per hospital, "and a substantial increase in the number of hospitals that provided fewer than 100 CABG surgeries per year."

Whether or not low-volume centers inherently have worse CABG outcomes can be debated, but either way "our findings highlight the increasing role of low-volume hospitals in the provision of CABG surgery," Dr. Epstein and his associates said.

The final trend in coronary revascularizations revealed in these data was the marked surge in PCI procedures using drug-eluting stents soon after two devices were approved by the Food and Drug Administration in 2003.

By mid-2005, 90% of PCI procedures involved drug-eluting stents, reflecting "a high level of clinician enthusiasm" for the devices.

This peak was soon followed by a marked decline after the publication of safety concerns such as late in-stent thrombosis, "as well as increasing clinician awareness of the imperative for ... adherence to long-duration antiplatelet therapy."

By the beginning of 2008, only 61% of PCI procedures involved placement of drug-eluting stents, but that rate increased steadily during that year, which also saw the adoption of second-generation stents that carried lower restenosis rates.

"An important implication of this volatility is that thousands of patients may have received drug-eluting stents during the peak years who would have received bare-metal stents [in later years].

"Whether these patients were appropriately treated ... during these years of ?high enthusiasm? for drug-eluting stents is uncertain," the investigators noted.

This study was supported by the National Heart, Lung, and Blood Institute; the Agency for Healthcare Research and Quality; and the Pennsylvania Department of Health. ☐

The rate of coronary artery bypass grafting performed in U.S. hospitals declined by approximately one-third between 2001 and 2008, according to an analysis of the Agency for Healthcare Research and Quality database.

During the same period, the rate of percutaneous coronary interventions (PCIs) showed a far more modest decrease.

"Our data imply a sizeable shift in cardiovascular clinical practice patterns away from surgical treatment toward percutaneous, catheter-based interventions," said Andrew J. Epstein, Ph.D., of the Philadelphia Veterans Affairs? Center for Health Equity Research and Promotion and the University of Pennsylvania, and his associates.

Given that coronary artery bypass grafting remains the better choice for patients with previously untreated three-vessel or left main coronary artery disease, according to the results of the SYNTAX trial (N. Engl. J. Med. 2009;360:961-72), it appears that CABG is being underused, the authors wrote.

It seems likely that in recent years, "patients who would have been optimally treated with CABG surgery were instead treated with PCI," they noted.

To assess temporal trends in coronary revascularization procedures, the investigators examined a nationally representative sample of hospitalization claims using an Agency for Healthcare Research and Quality database.

The database includes discharge data from approximately 1,000 nonfederal hospitals in 42 states, which covers 20% of U.S. hospitals and allows accurate estimates for the entire population of hospitalized patients, regardless of payer or insurance status.

Between 2001 and 2008, the total number of coronary revascularizations decreased "modestly," by approximately 15%.

There was a "substantial," statistically significant, 38% decrease in the annual rate of CABG surgery, from 1,742 per million adults in the first year of the study period to 1,081 per million in the final year.

This decline was roughly linear throughout the 8-year study period, suggesting that it "was not triggered by any single event occurring during the past decade, such as the introduction of competing technologies, advances in CABG surgical techniques, publication of clinical trials, or issuance of clinical guidelines."

CABG procedures decreased across all sex, age, racial, and regional subgroups.

In contrast, the PCI rate remained fairly constant, showing a "modest" 4% decrease from 3,827 per million adults per year in the first year of the study to 3,667 in the final year.

"Projected to the entire U.S. population, these rate changes implied that 130,000 fewer CABG surgeries were performed in 2008 compared to 2001," Dr. Epstein and his colleagues noted (JAMA 2011;305:1769-76).

The data did not allow the researchers to distinguish which patients may have been more appropriate candidates for CABG than for PCI, so "it cannot be known with certainty whether physicians were increasingly substituting PCI for CABG surgery during the past decade. ... [But] our findings suggest the possibility that several thousand patients who underwent PCI in 2008 would have undergone CABG surgery had patterns of care not changed markedly," they said.

The preferences of patients were also not discernible from the data, lead investigator Dr. Peter W. Groeneveld said in an interview. "However, if patient preference [for PCI vs. CABG] was the driving factor, there would have to be some reason that PCI was even more preferable to patients in 2008 than it was in 2001.

This scenario seems unlikely since the procedures haven?t changed that much," said Dr. Groeneveld, assistant professor of medicine at the University of Pennsylvania and staff physician at the Philadelphia Veterans Affairs Medical Center.

Another important finding was that during this interval, the number of hospitals providing CABG increased. Combined with the drop in the number of CABG surgeries, this resulted in a 28% decline in the median caseload per hospital, "and a substantial increase in the number of hospitals that provided fewer than 100 CABG surgeries per year."

Whether or not low-volume centers inherently have worse CABG outcomes can be debated, but either way "our findings highlight the increasing role of low-volume hospitals in the provision of CABG surgery," Dr. Epstein and his associates said.

The final trend in coronary revascularizations revealed in these data was the marked surge in PCI procedures using drug-eluting stents soon after two devices were approved by the Food and Drug Administration in 2003.

By mid-2005, 90% of PCI procedures involved drug-eluting stents, reflecting "a high level of clinician enthusiasm" for the devices.

This peak was soon followed by a marked decline after the publication of safety concerns such as late in-stent thrombosis, "as well as increasing clinician awareness of the imperative for ... adherence to long-duration antiplatelet therapy."

By the beginning of 2008, only 61% of PCI procedures involved placement of drug-eluting stents, but that rate increased steadily during that year, which also saw the adoption of second-generation stents that carried lower restenosis rates.

"An important implication of this volatility is that thousands of patients may have received drug-eluting stents during the peak years who would have received bare-metal stents [in later years].

"Whether these patients were appropriately treated ... during these years of ?high enthusiasm? for drug-eluting stents is uncertain," the investigators noted.

This study was supported by the National Heart, Lung, and Blood Institute; the Agency for Healthcare Research and Quality; and the Pennsylvania Department of Health. ☐

The rate of coronary artery bypass grafting performed in U.S. hospitals declined by approximately one-third between 2001 and 2008, according to an analysis of the Agency for Healthcare Research and Quality database.

During the same period, the rate of percutaneous coronary interventions (PCIs) showed a far more modest decrease.

"Our data imply a sizeable shift in cardiovascular clinical practice patterns away from surgical treatment toward percutaneous, catheter-based interventions," said Andrew J. Epstein, Ph.D., of the Philadelphia Veterans Affairs? Center for Health Equity Research and Promotion and the University of Pennsylvania, and his associates.

Given that coronary artery bypass grafting remains the better choice for patients with previously untreated three-vessel or left main coronary artery disease, according to the results of the SYNTAX trial (N. Engl. J. Med. 2009;360:961-72), it appears that CABG is being underused, the authors wrote.

It seems likely that in recent years, "patients who would have been optimally treated with CABG surgery were instead treated with PCI," they noted.

To assess temporal trends in coronary revascularization procedures, the investigators examined a nationally representative sample of hospitalization claims using an Agency for Healthcare Research and Quality database.

The database includes discharge data from approximately 1,000 nonfederal hospitals in 42 states, which covers 20% of U.S. hospitals and allows accurate estimates for the entire population of hospitalized patients, regardless of payer or insurance status.

Between 2001 and 2008, the total number of coronary revascularizations decreased "modestly," by approximately 15%.

There was a "substantial," statistically significant, 38% decrease in the annual rate of CABG surgery, from 1,742 per million adults in the first year of the study period to 1,081 per million in the final year.

This decline was roughly linear throughout the 8-year study period, suggesting that it "was not triggered by any single event occurring during the past decade, such as the introduction of competing technologies, advances in CABG surgical techniques, publication of clinical trials, or issuance of clinical guidelines."

CABG procedures decreased across all sex, age, racial, and regional subgroups.

In contrast, the PCI rate remained fairly constant, showing a "modest" 4% decrease from 3,827 per million adults per year in the first year of the study to 3,667 in the final year.

"Projected to the entire U.S. population, these rate changes implied that 130,000 fewer CABG surgeries were performed in 2008 compared to 2001," Dr. Epstein and his colleagues noted (JAMA 2011;305:1769-76).

The data did not allow the researchers to distinguish which patients may have been more appropriate candidates for CABG than for PCI, so "it cannot be known with certainty whether physicians were increasingly substituting PCI for CABG surgery during the past decade. ... [But] our findings suggest the possibility that several thousand patients who underwent PCI in 2008 would have undergone CABG surgery had patterns of care not changed markedly," they said.

The preferences of patients were also not discernible from the data, lead investigator Dr. Peter W. Groeneveld said in an interview. "However, if patient preference [for PCI vs. CABG] was the driving factor, there would have to be some reason that PCI was even more preferable to patients in 2008 than it was in 2001.

This scenario seems unlikely since the procedures haven?t changed that much," said Dr. Groeneveld, assistant professor of medicine at the University of Pennsylvania and staff physician at the Philadelphia Veterans Affairs Medical Center.

Another important finding was that during this interval, the number of hospitals providing CABG increased. Combined with the drop in the number of CABG surgeries, this resulted in a 28% decline in the median caseload per hospital, "and a substantial increase in the number of hospitals that provided fewer than 100 CABG surgeries per year."

Whether or not low-volume centers inherently have worse CABG outcomes can be debated, but either way "our findings highlight the increasing role of low-volume hospitals in the provision of CABG surgery," Dr. Epstein and his associates said.

The final trend in coronary revascularizations revealed in these data was the marked surge in PCI procedures using drug-eluting stents soon after two devices were approved by the Food and Drug Administration in 2003.

By mid-2005, 90% of PCI procedures involved drug-eluting stents, reflecting "a high level of clinician enthusiasm" for the devices.

This peak was soon followed by a marked decline after the publication of safety concerns such as late in-stent thrombosis, "as well as increasing clinician awareness of the imperative for ... adherence to long-duration antiplatelet therapy."

By the beginning of 2008, only 61% of PCI procedures involved placement of drug-eluting stents, but that rate increased steadily during that year, which also saw the adoption of second-generation stents that carried lower restenosis rates.

"An important implication of this volatility is that thousands of patients may have received drug-eluting stents during the peak years who would have received bare-metal stents [in later years].

"Whether these patients were appropriately treated ... during these years of ?high enthusiasm? for drug-eluting stents is uncertain," the investigators noted.

This study was supported by the National Heart, Lung, and Blood Institute; the Agency for Healthcare Research and Quality; and the Pennsylvania Department of Health. ☐

Contrary to clinical practice guidelines and simple logic, most patients who have stable coronary artery disease are not given optimal medical therapy before undergoing percutaneous coronary intervention, according to a recent study reported in JAMA.

In March 2007, "the most definitive randomized trial" comparing percutaneous coronary intervention (PCI) to optimal medical therapy, determined that PCI is no more effective than drug treatment at preventing MI or death in stable CAD. But even with this evidence, there was little change in the pattern of stable CAD patients going straight to PCI, said Dr. William B. Borden of Weill Cornell Medical College in New York, and his associates.

Dr. Borden and his colleagues assessed the practice patterns regarding the use of optimal medical therapy before and after PCI using data obtained from the national CathPCI Registry.

The researchers examined a 19-month interval occurring before publication of the trial results of Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) (N. Engl. J. Med. 2007;356:1503-16) and a 24-month period occuring afterward, to determine whether physicians had been inspired to transfer those findings into clinical practice.

The study population comprised 467,211 patients treated at 1,013 U.S. hospitals, which constituted about 28% of the total CathPCI population during the study period.

Optimal medical therapy was defined as being prescribed aspirin, a beta-blocker, and a statin before PCI and being prescribed aspirin or thienopyridine, a beta-blocker, a statin, and an ACE inhibitor or angiotensin receptor blocker after PCI, or having specific contraindications to these medications.

Overall, fewer than half of PCI patients ? 45% ? received optimal medical therapy before undergoing PCI. Current guidelines recommend maximizing medical therapy because that often relieves symptoms, obviating the need for PCI.

The rates of optimal medical therapy increased only slightly after publication of the COURAGE results, from 43% to 45%. This increase "was of little clinical significance," the investigators said (JAMA 2011:305:1882-9).

Dr. Borden disclosed ties to the pharmaceutical Kowa Company.

Contrary to clinical practice guidelines and simple logic, most patients who have stable coronary artery disease are not given optimal medical therapy before undergoing percutaneous coronary intervention, according to a recent study reported in JAMA.

In March 2007, "the most definitive randomized trial" comparing percutaneous coronary intervention (PCI) to optimal medical therapy, determined that PCI is no more effective than drug treatment at preventing MI or death in stable CAD. But even with this evidence, there was little change in the pattern of stable CAD patients going straight to PCI, said Dr. William B. Borden of Weill Cornell Medical College in New York, and his associates.

Dr. Borden and his colleagues assessed the practice patterns regarding the use of optimal medical therapy before and after PCI using data obtained from the national CathPCI Registry.

The researchers examined a 19-month interval occurring before publication of the trial results of Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) (N. Engl. J. Med. 2007;356:1503-16) and a 24-month period occuring afterward, to determine whether physicians had been inspired to transfer those findings into clinical practice.

The study population comprised 467,211 patients treated at 1,013 U.S. hospitals, which constituted about 28% of the total CathPCI population during the study period.

Optimal medical therapy was defined as being prescribed aspirin, a beta-blocker, and a statin before PCI and being prescribed aspirin or thienopyridine, a beta-blocker, a statin, and an ACE inhibitor or angiotensin receptor blocker after PCI, or having specific contraindications to these medications.

Overall, fewer than half of PCI patients ? 45% ? received optimal medical therapy before undergoing PCI. Current guidelines recommend maximizing medical therapy because that often relieves symptoms, obviating the need for PCI.

The rates of optimal medical therapy increased only slightly after publication of the COURAGE results, from 43% to 45%. This increase "was of little clinical significance," the investigators said (JAMA 2011:305:1882-9).

Dr. Borden disclosed ties to the pharmaceutical Kowa Company.

Contrary to clinical practice guidelines and simple logic, most patients who have stable coronary artery disease are not given optimal medical therapy before undergoing percutaneous coronary intervention, according to a recent study reported in JAMA.

In March 2007, "the most definitive randomized trial" comparing percutaneous coronary intervention (PCI) to optimal medical therapy, determined that PCI is no more effective than drug treatment at preventing MI or death in stable CAD. But even with this evidence, there was little change in the pattern of stable CAD patients going straight to PCI, said Dr. William B. Borden of Weill Cornell Medical College in New York, and his associates.

Dr. Borden and his colleagues assessed the practice patterns regarding the use of optimal medical therapy before and after PCI using data obtained from the national CathPCI Registry.

The researchers examined a 19-month interval occurring before publication of the trial results of Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) (N. Engl. J. Med. 2007;356:1503-16) and a 24-month period occuring afterward, to determine whether physicians had been inspired to transfer those findings into clinical practice.

The study population comprised 467,211 patients treated at 1,013 U.S. hospitals, which constituted about 28% of the total CathPCI population during the study period.

Optimal medical therapy was defined as being prescribed aspirin, a beta-blocker, and a statin before PCI and being prescribed aspirin or thienopyridine, a beta-blocker, a statin, and an ACE inhibitor or angiotensin receptor blocker after PCI, or having specific contraindications to these medications.

Overall, fewer than half of PCI patients ? 45% ? received optimal medical therapy before undergoing PCI. Current guidelines recommend maximizing medical therapy because that often relieves symptoms, obviating the need for PCI.

The rates of optimal medical therapy increased only slightly after publication of the COURAGE results, from 43% to 45%. This increase "was of little clinical significance," the investigators said (JAMA 2011:305:1882-9).

Dr. Borden disclosed ties to the pharmaceutical Kowa Company.