Mary Ann Moon

A modest increase in protein content and a modest decrease in glycemic index values allowed study subjects to maintain a 10-kg weight loss better than did other dietary manipulations, according to a randomized trial reported in the Nov. 25 issue of the New England Journal of Medicine.

More subjects also were able to continue losing weight while consuming this combination of high-protein, low-glycemic-index foods, said Thomas Meinert Larsen, Ph.D., of the University of Copenhagen and his associates in the Diet, Obesity, and Genes (Diogenes) study.

The Diogenes study was designed to assess the efficacy of five different maintenance diets in preventing weight regain after obese subjects lost at least 8% of their body weight during an 8-week low-calorie diet. The maintenance diets all contained moderate amounts of fats (25%-30% of total energy consumed), all allowed unrestricted caloric intake, and all attempted to keep alcohol and fiber contents comparable, varying only in their protein content and glycemic indexes.

The study was conducted at research centers throughout Europe. A total of 773 subjects who achieved their target weight loss during the low-calorie-diet period were randomly assigned to continue a 26-week maintenance phase following a diet low in protein (13% of total energy consumed) with a low glycemic index; a diet low in protein with a high glycemic index; a diet high in protein (25% of total energy consumed) with a low glycemic index; a high-protein, high-glycemic index diet; or a control diet with moderate protein content and no guidelines regarding glycemic index (N. Engl. J. Med. 2010;363:2102-13).

The study subjects received dietary counseling every other week for 6 weeks, and then monthly thereafter. They were given recipes, cooking instructions, behavioral advice, and a teaching system to help them achieve the targeted composition of macronutrients. Periodically, they weighed their food and completed food diaries for 3 consecutive days to facilitate monitoring of adherence. Adherence declined in all groups toward the end of the study.

A total of 29% of the subjects dropped out of the study during this 6-month maintenance phase, a rate nearly 10% higher than expected. Nevertheless, the Diogenes participants "were probably a more adherent group than participants in other studies, since they had adhered sufficiently to the low-calorie diet for 8 weeks to lose at least 8% of their body weight," Dr. Larsen and his colleagues said.

"Despite issues of adherence, we believe that our results are generalizable to obese people, particularly if diets are facilitated by easy access to low-glycemic-index foods and a culture that supports these dietary changes," they added.

Weight regain was significantly higher in the low-protein groups and the high-glycemic-index groups. In contrast, both the high-protein and low-glycemic-index groups were more likely to maintain their weight loss and to lose an additional 5% of their body weight.

Only subjects assigned to the group with low-protein content and high glycemic index showed significant weight regain – a mean of almost 2 kg.

The study subjects reported no between-group differences in feelings of satiety, "though we suspect that the effects were too subtle to be subjectively perceived or measured with the use of visual analog scales," Dr. Larsen and his associates said.

These findings show that "even a modest increase in dietary protein or a modest reduction in glycemic-index values was sufficient to minimize weight regain and promote further weight loss in obese patients after a successful weight-loss diet," Dr. Larsen and his associates concluded.

This study was funded by the European Commission. Dr. Larsen and his colleagues reported ties to more than 100 food companies and numerous drug companies.

A modest increase in protein content and a modest decrease in glycemic index values allowed study subjects to maintain a 10-kg weight loss better than did other dietary manipulations, according to a randomized trial reported in the Nov. 25 issue of the New England Journal of Medicine.

More subjects also were able to continue losing weight while consuming this combination of high-protein, low-glycemic-index foods, said Thomas Meinert Larsen, Ph.D., of the University of Copenhagen and his associates in the Diet, Obesity, and Genes (Diogenes) study.

The Diogenes study was designed to assess the efficacy of five different maintenance diets in preventing weight regain after obese subjects lost at least 8% of their body weight during an 8-week low-calorie diet. The maintenance diets all contained moderate amounts of fats (25%-30% of total energy consumed), all allowed unrestricted caloric intake, and all attempted to keep alcohol and fiber contents comparable, varying only in their protein content and glycemic indexes.

The study was conducted at research centers throughout Europe. A total of 773 subjects who achieved their target weight loss during the low-calorie-diet period were randomly assigned to continue a 26-week maintenance phase following a diet low in protein (13% of total energy consumed) with a low glycemic index; a diet low in protein with a high glycemic index; a diet high in protein (25% of total energy consumed) with a low glycemic index; a high-protein, high-glycemic index diet; or a control diet with moderate protein content and no guidelines regarding glycemic index (N. Engl. J. Med. 2010;363:2102-13).

The study subjects received dietary counseling every other week for 6 weeks, and then monthly thereafter. They were given recipes, cooking instructions, behavioral advice, and a teaching system to help them achieve the targeted composition of macronutrients. Periodically, they weighed their food and completed food diaries for 3 consecutive days to facilitate monitoring of adherence. Adherence declined in all groups toward the end of the study.

A total of 29% of the subjects dropped out of the study during this 6-month maintenance phase, a rate nearly 10% higher than expected. Nevertheless, the Diogenes participants "were probably a more adherent group than participants in other studies, since they had adhered sufficiently to the low-calorie diet for 8 weeks to lose at least 8% of their body weight," Dr. Larsen and his colleagues said.

"Despite issues of adherence, we believe that our results are generalizable to obese people, particularly if diets are facilitated by easy access to low-glycemic-index foods and a culture that supports these dietary changes," they added.

Weight regain was significantly higher in the low-protein groups and the high-glycemic-index groups. In contrast, both the high-protein and low-glycemic-index groups were more likely to maintain their weight loss and to lose an additional 5% of their body weight.

Only subjects assigned to the group with low-protein content and high glycemic index showed significant weight regain – a mean of almost 2 kg.

The study subjects reported no between-group differences in feelings of satiety, "though we suspect that the effects were too subtle to be subjectively perceived or measured with the use of visual analog scales," Dr. Larsen and his associates said.

These findings show that "even a modest increase in dietary protein or a modest reduction in glycemic-index values was sufficient to minimize weight regain and promote further weight loss in obese patients after a successful weight-loss diet," Dr. Larsen and his associates concluded.

This study was funded by the European Commission. Dr. Larsen and his colleagues reported ties to more than 100 food companies and numerous drug companies.

A modest increase in protein content and a modest decrease in glycemic index values allowed study subjects to maintain a 10-kg weight loss better than did other dietary manipulations, according to a randomized trial reported in the Nov. 25 issue of the New England Journal of Medicine.

More subjects also were able to continue losing weight while consuming this combination of high-protein, low-glycemic-index foods, said Thomas Meinert Larsen, Ph.D., of the University of Copenhagen and his associates in the Diet, Obesity, and Genes (Diogenes) study.

The Diogenes study was designed to assess the efficacy of five different maintenance diets in preventing weight regain after obese subjects lost at least 8% of their body weight during an 8-week low-calorie diet. The maintenance diets all contained moderate amounts of fats (25%-30% of total energy consumed), all allowed unrestricted caloric intake, and all attempted to keep alcohol and fiber contents comparable, varying only in their protein content and glycemic indexes.

The study was conducted at research centers throughout Europe. A total of 773 subjects who achieved their target weight loss during the low-calorie-diet period were randomly assigned to continue a 26-week maintenance phase following a diet low in protein (13% of total energy consumed) with a low glycemic index; a diet low in protein with a high glycemic index; a diet high in protein (25% of total energy consumed) with a low glycemic index; a high-protein, high-glycemic index diet; or a control diet with moderate protein content and no guidelines regarding glycemic index (N. Engl. J. Med. 2010;363:2102-13).

The study subjects received dietary counseling every other week for 6 weeks, and then monthly thereafter. They were given recipes, cooking instructions, behavioral advice, and a teaching system to help them achieve the targeted composition of macronutrients. Periodically, they weighed their food and completed food diaries for 3 consecutive days to facilitate monitoring of adherence. Adherence declined in all groups toward the end of the study.

A total of 29% of the subjects dropped out of the study during this 6-month maintenance phase, a rate nearly 10% higher than expected. Nevertheless, the Diogenes participants "were probably a more adherent group than participants in other studies, since they had adhered sufficiently to the low-calorie diet for 8 weeks to lose at least 8% of their body weight," Dr. Larsen and his colleagues said.

"Despite issues of adherence, we believe that our results are generalizable to obese people, particularly if diets are facilitated by easy access to low-glycemic-index foods and a culture that supports these dietary changes," they added.

Weight regain was significantly higher in the low-protein groups and the high-glycemic-index groups. In contrast, both the high-protein and low-glycemic-index groups were more likely to maintain their weight loss and to lose an additional 5% of their body weight.

Only subjects assigned to the group with low-protein content and high glycemic index showed significant weight regain – a mean of almost 2 kg.

The study subjects reported no between-group differences in feelings of satiety, "though we suspect that the effects were too subtle to be subjectively perceived or measured with the use of visual analog scales," Dr. Larsen and his associates said.

These findings show that "even a modest increase in dietary protein or a modest reduction in glycemic-index values was sufficient to minimize weight regain and promote further weight loss in obese patients after a successful weight-loss diet," Dr. Larsen and his associates concluded.

This study was funded by the European Commission. Dr. Larsen and his colleagues reported ties to more than 100 food companies and numerous drug companies.

Combined aerobic and resistance exercise training lowered hemoglobin A1c levels modestly in patients with type 2 diabetes, while either type of training alone did not, according to a report in the Nov. 24 issue of JAMA.

Patients who participated in the combined exercise also were able to decrease their hypoglycemic medication more often than were those who participated in either type of exercise alone, said Dr. Timothy S. Church of Pennington Biomedical Research Center at Louisiana State University, Baton Rouge, and his associates.

© sbm Hotting/Fotolia.com

The investigators assessed outcomes in 262 sedentary adults (mean age 56 years) with type 2 diabetes during a 9-month exercise intervention in which no attempt was made to alter patients’ diets, medication usage, or other lifestyle factors. The study subjects were randomly assigned to undergo aerobic training only (72 patients), resistance training only (73 patients), a combination of both (76 patients), or no exercise training (41 patients serving as a control group).

The interventions were specifically designed so that all study subjects would spend the same amount of time exercising – approximately 140 minutes per week. This ensured that any differences between the combined-exercise group and the other exercise groups could be attributed to the activity itself, rather than to an extended time spent exercising in the combination group.

All the interventions took place in a laboratory facility and were closely supervised. In addition, study subjects had monthly visits with a certified diabetes educator who reviewed fasting glucose records and measured weight and HbA1c levels from finger-prick blood samples.

The study population was ethnically diverse (44% African American) and included a relatively high proportion of women (63%). The mean duration of diabetes was 7 years and the mean BMI was 34.9. A total of 97% of the subjects were taking diabetes medications, including 18% taking insulin.

Compared with the control group, the combination exercise group showed an absolute decrease in HbA1c levels of 0.34%. Patients who performed resistance training only showed a 0.16% decrease and those who performed aerobic training only showed a 0.24% decrease, neither of which was statistically significant.

"An absolute decrease of 1% in HbA1c levels has been associated with a 15%-20% decrease in major cardiovascular disease events and 37% decrease in microvascular complications. Thus, our observed reduction [of 0.3%-0.4%] might be expected to produce a 5%-7% reduction in cardiovascular disease risk and a 12% reduction in microvascular complications," Dr. Church and his associates said (JAMA 2010;304:2253-62).

In a subgroup analysis confined only to subjects whose baseline HbA1c levels were 7% or higher, both the combination exercise group and the aerobic exercise group showed significant reductions in HbA1c, compared with the control group. In this subgroup of patients, such reductions could be expected to reduce cardiovascular disease events by 7%-10% and microvascular complications by 18%, they added.

All three intervention groups showed modest decreases in weight circumference, which were similar across the groups. Patients who did both aerobic and resistance training showed the largest decreases in diabetes medications.

"To our knowledge, this is the first large randomized trial involving individuals with type 2 diabetes to directly test exercise prescriptions that are consistent with the 2008 Physical Activity Guidelines of 500-1000 MET (metabolic equivalent tasks)-minutes per week combined with resistance training," the investigators noted.

This study was supported by the National Institutes of Health. Dr. Church and his associates reported numerous ties to scientific, educational, and lay groups, as well as to makers of pharmaceuticals and medical devices.

Combined aerobic and resistance exercise training lowered hemoglobin A1c levels modestly in patients with type 2 diabetes, while either type of training alone did not, according to a report in the Nov. 24 issue of JAMA.

Patients who participated in the combined exercise also were able to decrease their hypoglycemic medication more often than were those who participated in either type of exercise alone, said Dr. Timothy S. Church of Pennington Biomedical Research Center at Louisiana State University, Baton Rouge, and his associates.

© sbm Hotting/Fotolia.com

The investigators assessed outcomes in 262 sedentary adults (mean age 56 years) with type 2 diabetes during a 9-month exercise intervention in which no attempt was made to alter patients’ diets, medication usage, or other lifestyle factors. The study subjects were randomly assigned to undergo aerobic training only (72 patients), resistance training only (73 patients), a combination of both (76 patients), or no exercise training (41 patients serving as a control group).

The interventions were specifically designed so that all study subjects would spend the same amount of time exercising – approximately 140 minutes per week. This ensured that any differences between the combined-exercise group and the other exercise groups could be attributed to the activity itself, rather than to an extended time spent exercising in the combination group.

All the interventions took place in a laboratory facility and were closely supervised. In addition, study subjects had monthly visits with a certified diabetes educator who reviewed fasting glucose records and measured weight and HbA1c levels from finger-prick blood samples.

The study population was ethnically diverse (44% African American) and included a relatively high proportion of women (63%). The mean duration of diabetes was 7 years and the mean BMI was 34.9. A total of 97% of the subjects were taking diabetes medications, including 18% taking insulin.

Compared with the control group, the combination exercise group showed an absolute decrease in HbA1c levels of 0.34%. Patients who performed resistance training only showed a 0.16% decrease and those who performed aerobic training only showed a 0.24% decrease, neither of which was statistically significant.

"An absolute decrease of 1% in HbA1c levels has been associated with a 15%-20% decrease in major cardiovascular disease events and 37% decrease in microvascular complications. Thus, our observed reduction [of 0.3%-0.4%] might be expected to produce a 5%-7% reduction in cardiovascular disease risk and a 12% reduction in microvascular complications," Dr. Church and his associates said (JAMA 2010;304:2253-62).

In a subgroup analysis confined only to subjects whose baseline HbA1c levels were 7% or higher, both the combination exercise group and the aerobic exercise group showed significant reductions in HbA1c, compared with the control group. In this subgroup of patients, such reductions could be expected to reduce cardiovascular disease events by 7%-10% and microvascular complications by 18%, they added.

All three intervention groups showed modest decreases in weight circumference, which were similar across the groups. Patients who did both aerobic and resistance training showed the largest decreases in diabetes medications.

"To our knowledge, this is the first large randomized trial involving individuals with type 2 diabetes to directly test exercise prescriptions that are consistent with the 2008 Physical Activity Guidelines of 500-1000 MET (metabolic equivalent tasks)-minutes per week combined with resistance training," the investigators noted.

This study was supported by the National Institutes of Health. Dr. Church and his associates reported numerous ties to scientific, educational, and lay groups, as well as to makers of pharmaceuticals and medical devices.

Combined aerobic and resistance exercise training lowered hemoglobin A1c levels modestly in patients with type 2 diabetes, while either type of training alone did not, according to a report in the Nov. 24 issue of JAMA.

Patients who participated in the combined exercise also were able to decrease their hypoglycemic medication more often than were those who participated in either type of exercise alone, said Dr. Timothy S. Church of Pennington Biomedical Research Center at Louisiana State University, Baton Rouge, and his associates.

© sbm Hotting/Fotolia.com

The investigators assessed outcomes in 262 sedentary adults (mean age 56 years) with type 2 diabetes during a 9-month exercise intervention in which no attempt was made to alter patients’ diets, medication usage, or other lifestyle factors. The study subjects were randomly assigned to undergo aerobic training only (72 patients), resistance training only (73 patients), a combination of both (76 patients), or no exercise training (41 patients serving as a control group).

The interventions were specifically designed so that all study subjects would spend the same amount of time exercising – approximately 140 minutes per week. This ensured that any differences between the combined-exercise group and the other exercise groups could be attributed to the activity itself, rather than to an extended time spent exercising in the combination group.

All the interventions took place in a laboratory facility and were closely supervised. In addition, study subjects had monthly visits with a certified diabetes educator who reviewed fasting glucose records and measured weight and HbA1c levels from finger-prick blood samples.

The study population was ethnically diverse (44% African American) and included a relatively high proportion of women (63%). The mean duration of diabetes was 7 years and the mean BMI was 34.9. A total of 97% of the subjects were taking diabetes medications, including 18% taking insulin.

Compared with the control group, the combination exercise group showed an absolute decrease in HbA1c levels of 0.34%. Patients who performed resistance training only showed a 0.16% decrease and those who performed aerobic training only showed a 0.24% decrease, neither of which was statistically significant.

"An absolute decrease of 1% in HbA1c levels has been associated with a 15%-20% decrease in major cardiovascular disease events and 37% decrease in microvascular complications. Thus, our observed reduction [of 0.3%-0.4%] might be expected to produce a 5%-7% reduction in cardiovascular disease risk and a 12% reduction in microvascular complications," Dr. Church and his associates said (JAMA 2010;304:2253-62).

In a subgroup analysis confined only to subjects whose baseline HbA1c levels were 7% or higher, both the combination exercise group and the aerobic exercise group showed significant reductions in HbA1c, compared with the control group. In this subgroup of patients, such reductions could be expected to reduce cardiovascular disease events by 7%-10% and microvascular complications by 18%, they added.

All three intervention groups showed modest decreases in weight circumference, which were similar across the groups. Patients who did both aerobic and resistance training showed the largest decreases in diabetes medications.

"To our knowledge, this is the first large randomized trial involving individuals with type 2 diabetes to directly test exercise prescriptions that are consistent with the 2008 Physical Activity Guidelines of 500-1000 MET (metabolic equivalent tasks)-minutes per week combined with resistance training," the investigators noted.

This study was supported by the National Institutes of Health. Dr. Church and his associates reported numerous ties to scientific, educational, and lay groups, as well as to makers of pharmaceuticals and medical devices.

Combined aerobic and resistance exercise training lowered hemoglobin A1c levels modestly in patients with type 2 diabetes, while either type of training alone did not, according to a report in the Nov. 24 issue of JAMA.

Patients who participated in the combined exercise also were able to decrease their hypoglycemic medication more often than were those who participated in either type of exercise alone, said Dr. Timothy S. Church of Pennington Biomedical Research Center at Louisiana State University, Baton Rouge, and his associates.

© sbm Hotting/Fotolia.com

The investigators assessed outcomes in 262 sedentary adults (mean age 56 years) with type 2 diabetes during a 9-month exercise intervention in which no attempt was made to alter patients’ diets, medication usage, or other lifestyle factors. The study subjects were randomly assigned to undergo aerobic training only (72 patients), resistance training only (73 patients), a combination of both (76 patients), or no exercise training (41 patients serving as a control group).

The interventions were specifically designed so that all study subjects would spend the same amount of time exercising – approximately 140 minutes per week. This ensured that any differences between the combined-exercise group and the other exercise groups could be attributed to the activity itself, rather than to an extended time spent exercising in the combination group.

All the interventions took place in a laboratory facility and were closely supervised. In addition, study subjects had monthly visits with a certified diabetes educator who reviewed fasting glucose records and measured weight and HbA1c levels from finger-prick blood samples.

The study population was ethnically diverse (44% African American) and included a relatively high proportion of women (63%). The mean duration of diabetes was 7 years and the mean BMI was 34.9. A total of 97% of the subjects were taking diabetes medications, including 18% taking insulin.

Compared with the control group, the combination exercise group showed an absolute decrease in HbA1c levels of 0.34%. Patients who performed resistance training only showed a 0.16% decrease and those who performed aerobic training only showed a 0.24% decrease, neither of which was statistically significant.

"An absolute decrease of 1% in HbA1c levels has been associated with a 15%-20% decrease in major cardiovascular disease events and 37% decrease in microvascular complications. Thus, our observed reduction [of 0.3%-0.4%] might be expected to produce a 5%-7% reduction in cardiovascular disease risk and a 12% reduction in microvascular complications," Dr. Church and his associates said (JAMA 2010;304:2253-62).

In a subgroup analysis confined only to subjects whose baseline HbA1c levels were 7% or higher, both the combination exercise group and the aerobic exercise group showed significant reductions in HbA1c, compared with the control group. In this subgroup of patients, such reductions could be expected to reduce cardiovascular disease events by 7%-10% and microvascular complications by 18%, they added.

All three intervention groups showed modest decreases in weight circumference, which were similar across the groups. Patients who did both aerobic and resistance training showed the largest decreases in diabetes medications.

"To our knowledge, this is the first large randomized trial involving individuals with type 2 diabetes to directly test exercise prescriptions that are consistent with the 2008 Physical Activity Guidelines of 500-1000 MET (metabolic equivalent tasks)-minutes per week combined with resistance training," the investigators noted.

This study was supported by the National Institutes of Health. Dr. Church and his associates reported numerous ties to scientific, educational, and lay groups, as well as to makers of pharmaceuticals and medical devices.

Combined aerobic and resistance exercise training lowered hemoglobin A1c levels modestly in patients with type 2 diabetes, while either type of training alone did not, according to a report in the Nov. 24 issue of JAMA.

Patients who participated in the combined exercise also were able to decrease their hypoglycemic medication more often than were those who participated in either type of exercise alone, said Dr. Timothy S. Church of Pennington Biomedical Research Center at Louisiana State University, Baton Rouge, and his associates.

© sbm Hotting/Fotolia.com

The investigators assessed outcomes in 262 sedentary adults (mean age 56 years) with type 2 diabetes during a 9-month exercise intervention in which no attempt was made to alter patients’ diets, medication usage, or other lifestyle factors. The study subjects were randomly assigned to undergo aerobic training only (72 patients), resistance training only (73 patients), a combination of both (76 patients), or no exercise training (41 patients serving as a control group).

The interventions were specifically designed so that all study subjects would spend the same amount of time exercising – approximately 140 minutes per week. This ensured that any differences between the combined-exercise group and the other exercise groups could be attributed to the activity itself, rather than to an extended time spent exercising in the combination group.

All the interventions took place in a laboratory facility and were closely supervised. In addition, study subjects had monthly visits with a certified diabetes educator who reviewed fasting glucose records and measured weight and HbA1c levels from finger-prick blood samples.

The study population was ethnically diverse (44% African American) and included a relatively high proportion of women (63%). The mean duration of diabetes was 7 years and the mean BMI was 34.9. A total of 97% of the subjects were taking diabetes medications, including 18% taking insulin.

Compared with the control group, the combination exercise group showed an absolute decrease in HbA1c levels of 0.34%. Patients who performed resistance training only showed a 0.16% decrease and those who performed aerobic training only showed a 0.24% decrease, neither of which was statistically significant.

"An absolute decrease of 1% in HbA1c levels has been associated with a 15%-20% decrease in major cardiovascular disease events and 37% decrease in microvascular complications. Thus, our observed reduction [of 0.3%-0.4%] might be expected to produce a 5%-7% reduction in cardiovascular disease risk and a 12% reduction in microvascular complications," Dr. Church and his associates said (JAMA 2010;304:2253-62).

In a subgroup analysis confined only to subjects whose baseline HbA1c levels were 7% or higher, both the combination exercise group and the aerobic exercise group showed significant reductions in HbA1c, compared with the control group. In this subgroup of patients, such reductions could be expected to reduce cardiovascular disease events by 7%-10% and microvascular complications by 18%, they added.

All three intervention groups showed modest decreases in weight circumference, which were similar across the groups. Patients who did both aerobic and resistance training showed the largest decreases in diabetes medications.

"To our knowledge, this is the first large randomized trial involving individuals with type 2 diabetes to directly test exercise prescriptions that are consistent with the 2008 Physical Activity Guidelines of 500-1000 MET (metabolic equivalent tasks)-minutes per week combined with resistance training," the investigators noted.

This study was supported by the National Institutes of Health. Dr. Church and his associates reported numerous ties to scientific, educational, and lay groups, as well as to makers of pharmaceuticals and medical devices.

Combined aerobic and resistance exercise training lowered hemoglobin A1c levels modestly in patients with type 2 diabetes, while either type of training alone did not, according to a report in the Nov. 24 issue of JAMA.

Patients who participated in the combined exercise also were able to decrease their hypoglycemic medication more often than were those who participated in either type of exercise alone, said Dr. Timothy S. Church of Pennington Biomedical Research Center at Louisiana State University, Baton Rouge, and his associates.

© sbm Hotting/Fotolia.com

The investigators assessed outcomes in 262 sedentary adults (mean age 56 years) with type 2 diabetes during a 9-month exercise intervention in which no attempt was made to alter patients’ diets, medication usage, or other lifestyle factors. The study subjects were randomly assigned to undergo aerobic training only (72 patients), resistance training only (73 patients), a combination of both (76 patients), or no exercise training (41 patients serving as a control group).

The interventions were specifically designed so that all study subjects would spend the same amount of time exercising – approximately 140 minutes per week. This ensured that any differences between the combined-exercise group and the other exercise groups could be attributed to the activity itself, rather than to an extended time spent exercising in the combination group.

All the interventions took place in a laboratory facility and were closely supervised. In addition, study subjects had monthly visits with a certified diabetes educator who reviewed fasting glucose records and measured weight and HbA1c levels from finger-prick blood samples.

The study population was ethnically diverse (44% African American) and included a relatively high proportion of women (63%). The mean duration of diabetes was 7 years and the mean BMI was 34.9. A total of 97% of the subjects were taking diabetes medications, including 18% taking insulin.

Compared with the control group, the combination exercise group showed an absolute decrease in HbA1c levels of 0.34%. Patients who performed resistance training only showed a 0.16% decrease and those who performed aerobic training only showed a 0.24% decrease, neither of which was statistically significant.

"An absolute decrease of 1% in HbA1c levels has been associated with a 15%-20% decrease in major cardiovascular disease events and 37% decrease in microvascular complications. Thus, our observed reduction [of 0.3%-0.4%] might be expected to produce a 5%-7% reduction in cardiovascular disease risk and a 12% reduction in microvascular complications," Dr. Church and his associates said (JAMA 2010;304:2253-62).

In a subgroup analysis confined only to subjects whose baseline HbA1c levels were 7% or higher, both the combination exercise group and the aerobic exercise group showed significant reductions in HbA1c, compared with the control group. In this subgroup of patients, such reductions could be expected to reduce cardiovascular disease events by 7%-10% and microvascular complications by 18%, they added.

All three intervention groups showed modest decreases in weight circumference, which were similar across the groups. Patients who did both aerobic and resistance training showed the largest decreases in diabetes medications.

"To our knowledge, this is the first large randomized trial involving individuals with type 2 diabetes to directly test exercise prescriptions that are consistent with the 2008 Physical Activity Guidelines of 500-1000 MET (metabolic equivalent tasks)-minutes per week combined with resistance training," the investigators noted.

This study was supported by the National Institutes of Health. Dr. Church and his associates reported numerous ties to scientific, educational, and lay groups, as well as to makers of pharmaceuticals and medical devices.

For patients with suspected non–small-cell lung cancer, adding endosonography before surgical staging improves detection of mediastinal nodal metastases, thus reducing unnecessary thoracotomies by more than half, according to a report in the Nov. 24th issue of JAMA.

In addition, because endosonography is minimally invasive, adding this step doesn’t raise the rate of complications for staging procedures, said Dr. Jouke T. Annema of Leiden (the Netherlands) University Medical Center and associates.

The researchers compared surgical staging alone to endosonography followed by surgical staging because "at present it is not known whether initial mediastinal tissue staging of lung cancer by endosonography improves the detection of nodal metastases." Failure to detect such metastases during staging results in patients undergoing thoracotomy for tumor resection, only to have the thoracotomy aborted when unresectable or metastatic lung disease is discovered.

The investigators randomized 241 patients suspected of having resectable NSCLC, who were treated at four tertiary referral centers in Belgium, the Netherlands, and the United Kingdom. Patients were assigned to surgical staging alone, which is the current standard of care (118 subjects), or to endosonography followed by surgical staging (123 subjects).

The sensitivity of surgical staging alone was 79%. This improved to 94% when endosonography was combined with surgical staging, Dr. Annema and colleagues said (JAMA 2010;304:2245-52).

Mediastinal nodal metastases were found in 41 of 118 patients (35%) by surgical staging alone, compared with 62 of 123 patients (50%) by the combined approach. This means that there were 21 unnecessary thoracotomies with surgical staging alone, for a rate of 18%, compared with 9 with the combined approach, for a rate of 7%.

The complication rate was 6% for surgical staging, compared with 1% for endosonography.

These findings show that endosonography improves the sensitivity of surgical staging, halves the rate of unnecessary thoracotomy, and has a low complication rate. Because it also does not require general anesthesia and has been shown in previous studies to be cost effective as well as preferred by patients, "endosonography should be the first step for mediastinal nodal staging," the investigators said.

They added that all of the staging procedures in this study were performed in specialty centers by highly trained and experienced interventionists, so the applicability of the study findings to other settings is limited.

The study was supported in part by Hitachi Medical Systems, COOK, Olympus, the Zorgprogramma Oncologie Gent, the U.K. National Health Service R & D Health Technology Assessment Program, and the National Institute for Health Research Cambridge Biomedical Research Centre.

For patients with suspected non–small-cell lung cancer, adding endosonography before surgical staging improves detection of mediastinal nodal metastases, thus reducing unnecessary thoracotomies by more than half, according to a report in the Nov. 24th issue of JAMA.

In addition, because endosonography is minimally invasive, adding this step doesn’t raise the rate of complications for staging procedures, said Dr. Jouke T. Annema of Leiden (the Netherlands) University Medical Center and associates.

The researchers compared surgical staging alone to endosonography followed by surgical staging because "at present it is not known whether initial mediastinal tissue staging of lung cancer by endosonography improves the detection of nodal metastases." Failure to detect such metastases during staging results in patients undergoing thoracotomy for tumor resection, only to have the thoracotomy aborted when unresectable or metastatic lung disease is discovered.

The investigators randomized 241 patients suspected of having resectable NSCLC, who were treated at four tertiary referral centers in Belgium, the Netherlands, and the United Kingdom. Patients were assigned to surgical staging alone, which is the current standard of care (118 subjects), or to endosonography followed by surgical staging (123 subjects).

The sensitivity of surgical staging alone was 79%. This improved to 94% when endosonography was combined with surgical staging, Dr. Annema and colleagues said (JAMA 2010;304:2245-52).

Mediastinal nodal metastases were found in 41 of 118 patients (35%) by surgical staging alone, compared with 62 of 123 patients (50%) by the combined approach. This means that there were 21 unnecessary thoracotomies with surgical staging alone, for a rate of 18%, compared with 9 with the combined approach, for a rate of 7%.

The complication rate was 6% for surgical staging, compared with 1% for endosonography.

These findings show that endosonography improves the sensitivity of surgical staging, halves the rate of unnecessary thoracotomy, and has a low complication rate. Because it also does not require general anesthesia and has been shown in previous studies to be cost effective as well as preferred by patients, "endosonography should be the first step for mediastinal nodal staging," the investigators said.

They added that all of the staging procedures in this study were performed in specialty centers by highly trained and experienced interventionists, so the applicability of the study findings to other settings is limited.

The study was supported in part by Hitachi Medical Systems, COOK, Olympus, the Zorgprogramma Oncologie Gent, the U.K. National Health Service R & D Health Technology Assessment Program, and the National Institute for Health Research Cambridge Biomedical Research Centre.

For patients with suspected non–small-cell lung cancer, adding endosonography before surgical staging improves detection of mediastinal nodal metastases, thus reducing unnecessary thoracotomies by more than half, according to a report in the Nov. 24th issue of JAMA.

In addition, because endosonography is minimally invasive, adding this step doesn’t raise the rate of complications for staging procedures, said Dr. Jouke T. Annema of Leiden (the Netherlands) University Medical Center and associates.

The researchers compared surgical staging alone to endosonography followed by surgical staging because "at present it is not known whether initial mediastinal tissue staging of lung cancer by endosonography improves the detection of nodal metastases." Failure to detect such metastases during staging results in patients undergoing thoracotomy for tumor resection, only to have the thoracotomy aborted when unresectable or metastatic lung disease is discovered.

The investigators randomized 241 patients suspected of having resectable NSCLC, who were treated at four tertiary referral centers in Belgium, the Netherlands, and the United Kingdom. Patients were assigned to surgical staging alone, which is the current standard of care (118 subjects), or to endosonography followed by surgical staging (123 subjects).

The sensitivity of surgical staging alone was 79%. This improved to 94% when endosonography was combined with surgical staging, Dr. Annema and colleagues said (JAMA 2010;304:2245-52).

Mediastinal nodal metastases were found in 41 of 118 patients (35%) by surgical staging alone, compared with 62 of 123 patients (50%) by the combined approach. This means that there were 21 unnecessary thoracotomies with surgical staging alone, for a rate of 18%, compared with 9 with the combined approach, for a rate of 7%.

The complication rate was 6% for surgical staging, compared with 1% for endosonography.

These findings show that endosonography improves the sensitivity of surgical staging, halves the rate of unnecessary thoracotomy, and has a low complication rate. Because it also does not require general anesthesia and has been shown in previous studies to be cost effective as well as preferred by patients, "endosonography should be the first step for mediastinal nodal staging," the investigators said.

They added that all of the staging procedures in this study were performed in specialty centers by highly trained and experienced interventionists, so the applicability of the study findings to other settings is limited.

The study was supported in part by Hitachi Medical Systems, COOK, Olympus, the Zorgprogramma Oncologie Gent, the U.K. National Health Service R & D Health Technology Assessment Program, and the National Institute for Health Research Cambridge Biomedical Research Centre.

For patients with suspected non–small-cell lung cancer, adding endosonography before surgical staging improves detection of mediastinal nodal metastases, thus reducing unnecessary thoracotomies by more than half, according to a report in the Nov. 24th issue of JAMA.

In addition, because endosonography is minimally invasive, adding this step doesn’t raise the rate of complications for staging procedures, said Dr. Jouke T. Annema of Leiden (the Netherlands) University Medical Center and associates.

The researchers compared surgical staging alone to endosonography followed by surgical staging because "at present it is not known whether initial mediastinal tissue staging of lung cancer by endosonography improves the detection of nodal metastases." Failure to detect such metastases during staging results in patients undergoing thoracotomy for tumor resection, only to have the thoracotomy aborted when unresectable or metastatic lung disease is discovered.

The investigators randomized 241 patients suspected of having resectable NSCLC, who were treated at four tertiary referral centers in Belgium, the Netherlands, and the United Kingdom. Patients were assigned to surgical staging alone, which is the current standard of care (118 subjects), or to endosonography followed by surgical staging (123 subjects).

The sensitivity of surgical staging alone was 79%. This improved to 94% when endosonography was combined with surgical staging, Dr. Annema and colleagues said (JAMA 2010;304:2245-52).

Mediastinal nodal metastases were found in 41 of 118 patients (35%) by surgical staging alone, compared with 62 of 123 patients (50%) by the combined approach. This means that there were 21 unnecessary thoracotomies with surgical staging alone, for a rate of 18%, compared with 9 with the combined approach, for a rate of 7%.

The complication rate was 6% for surgical staging, compared with 1% for endosonography.

These findings show that endosonography improves the sensitivity of surgical staging, halves the rate of unnecessary thoracotomy, and has a low complication rate. Because it also does not require general anesthesia and has been shown in previous studies to be cost effective as well as preferred by patients, "endosonography should be the first step for mediastinal nodal staging," the investigators said.

They added that all of the staging procedures in this study were performed in specialty centers by highly trained and experienced interventionists, so the applicability of the study findings to other settings is limited.

The study was supported in part by Hitachi Medical Systems, COOK, Olympus, the Zorgprogramma Oncologie Gent, the U.K. National Health Service R & D Health Technology Assessment Program, and the National Institute for Health Research Cambridge Biomedical Research Centre.

For patients with suspected non–small-cell lung cancer, adding endosonography before surgical staging improves detection of mediastinal nodal metastases, thus reducing unnecessary thoracotomies by more than half, according to a report in the Nov. 24th issue of JAMA.

In addition, because endosonography is minimally invasive, adding this step doesn’t raise the rate of complications for staging procedures, said Dr. Jouke T. Annema of Leiden (the Netherlands) University Medical Center and associates.

The researchers compared surgical staging alone to endosonography followed by surgical staging because "at present it is not known whether initial mediastinal tissue staging of lung cancer by endosonography improves the detection of nodal metastases." Failure to detect such metastases during staging results in patients undergoing thoracotomy for tumor resection, only to have the thoracotomy aborted when unresectable or metastatic lung disease is discovered.

The investigators randomized 241 patients suspected of having resectable NSCLC, who were treated at four tertiary referral centers in Belgium, the Netherlands, and the United Kingdom. Patients were assigned to surgical staging alone, which is the current standard of care (118 subjects), or to endosonography followed by surgical staging (123 subjects).

The sensitivity of surgical staging alone was 79%. This improved to 94% when endosonography was combined with surgical staging, Dr. Annema and colleagues said (JAMA 2010;304:2245-52).

Mediastinal nodal metastases were found in 41 of 118 patients (35%) by surgical staging alone, compared with 62 of 123 patients (50%) by the combined approach. This means that there were 21 unnecessary thoracotomies with surgical staging alone, for a rate of 18%, compared with 9 with the combined approach, for a rate of 7%.

The complication rate was 6% for surgical staging, compared with 1% for endosonography.

These findings show that endosonography improves the sensitivity of surgical staging, halves the rate of unnecessary thoracotomy, and has a low complication rate. Because it also does not require general anesthesia and has been shown in previous studies to be cost effective as well as preferred by patients, "endosonography should be the first step for mediastinal nodal staging," the investigators said.

They added that all of the staging procedures in this study were performed in specialty centers by highly trained and experienced interventionists, so the applicability of the study findings to other settings is limited.

The study was supported in part by Hitachi Medical Systems, COOK, Olympus, the Zorgprogramma Oncologie Gent, the U.K. National Health Service R & D Health Technology Assessment Program, and the National Institute for Health Research Cambridge Biomedical Research Centre.

For patients with suspected non–small-cell lung cancer, adding endosonography before surgical staging improves detection of mediastinal nodal metastases, thus reducing unnecessary thoracotomies by more than half, according to a report in the Nov. 24th issue of JAMA.

In addition, because endosonography is minimally invasive, adding this step doesn’t raise the rate of complications for staging procedures, said Dr. Jouke T. Annema of Leiden (the Netherlands) University Medical Center and associates.

The researchers compared surgical staging alone to endosonography followed by surgical staging because "at present it is not known whether initial mediastinal tissue staging of lung cancer by endosonography improves the detection of nodal metastases." Failure to detect such metastases during staging results in patients undergoing thoracotomy for tumor resection, only to have the thoracotomy aborted when unresectable or metastatic lung disease is discovered.

The investigators randomized 241 patients suspected of having resectable NSCLC, who were treated at four tertiary referral centers in Belgium, the Netherlands, and the United Kingdom. Patients were assigned to surgical staging alone, which is the current standard of care (118 subjects), or to endosonography followed by surgical staging (123 subjects).

The sensitivity of surgical staging alone was 79%. This improved to 94% when endosonography was combined with surgical staging, Dr. Annema and colleagues said (JAMA 2010;304:2245-52).

Mediastinal nodal metastases were found in 41 of 118 patients (35%) by surgical staging alone, compared with 62 of 123 patients (50%) by the combined approach. This means that there were 21 unnecessary thoracotomies with surgical staging alone, for a rate of 18%, compared with 9 with the combined approach, for a rate of 7%.

The complication rate was 6% for surgical staging, compared with 1% for endosonography.

These findings show that endosonography improves the sensitivity of surgical staging, halves the rate of unnecessary thoracotomy, and has a low complication rate. Because it also does not require general anesthesia and has been shown in previous studies to be cost effective as well as preferred by patients, "endosonography should be the first step for mediastinal nodal staging," the investigators said.

They added that all of the staging procedures in this study were performed in specialty centers by highly trained and experienced interventionists, so the applicability of the study findings to other settings is limited.

The study was supported in part by Hitachi Medical Systems, COOK, Olympus, the Zorgprogramma Oncologie Gent, the U.K. National Health Service R & D Health Technology Assessment Program, and the National Institute for Health Research Cambridge Biomedical Research Centre.

The association between diabetes and depression is bidirectional in middle-age women, with the presence of either disease significantly raising the risk that the other also will develop, according to a report in the Nov. 22 issue of the Archives of Internal Medicine.

Moreover, diabetes raises the risk of depression, and depression raises the risk of diabetes, independently of other known risk factors such as adiposity that are common to both diseases, said An Pan, Ph.D., of Harvard School of Public Health, Boston, and his associates.

To date, "only a few" studies have examined the association between diabetes and depression simultaneously, and their results have been inconsistent. "Therefore, we took advantage of repeated measurements of lifestyle risk factors and disease occurrences during 10 years of follow-up in a large prospective cohort" – the Nurses’ Health Study – to address the bidirectional relationship.

The NHS involved female registered nurses residing in 11 states who were followed every 2 years via health questionnaires. Dr. Pan and his colleagues assessed a subset of 65,381 NHS participants who were aged 50-75 years in 1996 and were followed until 2006.

Depressive symptoms were categorized according to the women’s scores on the Mental Health Index 5, whether depression had been diagnosed by a physician and whether they used antidepressants. Diabetes was categorized as requiring no medications, only oral hypoglycemic agents, or insulin therapy.

During follow-up, 2,844 incident cases of diabetes were documented. The risk of developing diabetes was significantly higher in women who had depressive symptoms than in those who did not.

In addition, this rise in diabetes risk showed a "dose-response relationship" with worsening depressive symptoms, such that diabetes risk increased significantly as scores on the MHI-5 rose.

This association between depression and diabetes remained significant, although it was markedly attenuated, when the data were adjusted to account for body mass index (BMI) and lifestyle factors, particularly physical activity.

In a separate analysis of the same data, 7,415 study subjects developed incident clinical depression during follow-up. Compared with women who did not have diabetes, women with diabetes had a relative risk of developing clinical depression of 1.44, the investigators said (Arch. Intern. Med. 2010;170:1884-91).

Controlling for major comorbidities such as hypertension and coronary heart disease attenuated this association, but it remained significant.

In addition, the risk of developing clinical depression also showed a dose-response relationship with worsening diabetes symptoms. Women with diabetes who were not taking any medication had a relative risk of 1.36; those taking oral agents only had a relative risk of 1.42; and those taking insulin had a relative risk of 1.78 of developing clinical depression.

These findings show that depression and diabetes "are closely related to each other, and this reciprocal association also depends on the severity and treatment of each condition. All the associations were independent of sociodemographic, diet, and lifestyle factors," Dr. Pan and his associates said.

Since depression and diabetes both are highly prevalent in the middle-age and elderly populations, particularly among women, "proper lifestyle interventions including adequate weight management and regular physical activity are recommended to lower the risk of both conditions," they noted.

The reasons underlying the bidirectional association are not yet understood. It is possible that antidepressant use might be a contributing factor to diabetes risk. Antidepressants might exert some clinical effects on glucose homeostasis, and they are known to cause weight gain. However, the link between depression and diabetes was significant independent of BMI, so the possibility that antidepressants might exert some other metabolic effect warrants further investigation, the researchers said.

Alternatively, biochemical changes directly caused by diabetes or its treatment might contribute to depression. It also is possible that the stresses associated with chronic diabetes and its debilitating consequences also contribute to depression.

This study was somewhat limited in that the NHS cohort was 94% white, well educated, and well versed on health issues. The results might not be generalizable to other populations, they added.

This study was supported by the National Institutes of Health, the National Alliance for Research on Schizophrenia & Depression, and the Fonds de la recherche en santé du Québec. No financial conflicts of interest were reported.

The association between diabetes and depression is bidirectional in middle-age women, with the presence of either disease significantly raising the risk that the other also will develop, according to a report in the Nov. 22 issue of the Archives of Internal Medicine.

Moreover, diabetes raises the risk of depression, and depression raises the risk of diabetes, independently of other known risk factors such as adiposity that are common to both diseases, said An Pan, Ph.D., of Harvard School of Public Health, Boston, and his associates.

To date, "only a few" studies have examined the association between diabetes and depression simultaneously, and their results have been inconsistent. "Therefore, we took advantage of repeated measurements of lifestyle risk factors and disease occurrences during 10 years of follow-up in a large prospective cohort" – the Nurses’ Health Study – to address the bidirectional relationship.

The NHS involved female registered nurses residing in 11 states who were followed every 2 years via health questionnaires. Dr. Pan and his colleagues assessed a subset of 65,381 NHS participants who were aged 50-75 years in 1996 and were followed until 2006.

Depressive symptoms were categorized according to the women’s scores on the Mental Health Index 5, whether depression had been diagnosed by a physician and whether they used antidepressants. Diabetes was categorized as requiring no medications, only oral hypoglycemic agents, or insulin therapy.

During follow-up, 2,844 incident cases of diabetes were documented. The risk of developing diabetes was significantly higher in women who had depressive symptoms than in those who did not.

In addition, this rise in diabetes risk showed a "dose-response relationship" with worsening depressive symptoms, such that diabetes risk increased significantly as scores on the MHI-5 rose.

This association between depression and diabetes remained significant, although it was markedly attenuated, when the data were adjusted to account for body mass index (BMI) and lifestyle factors, particularly physical activity.

In a separate analysis of the same data, 7,415 study subjects developed incident clinical depression during follow-up. Compared with women who did not have diabetes, women with diabetes had a relative risk of developing clinical depression of 1.44, the investigators said (Arch. Intern. Med. 2010;170:1884-91).

Controlling for major comorbidities such as hypertension and coronary heart disease attenuated this association, but it remained significant.

In addition, the risk of developing clinical depression also showed a dose-response relationship with worsening diabetes symptoms. Women with diabetes who were not taking any medication had a relative risk of 1.36; those taking oral agents only had a relative risk of 1.42; and those taking insulin had a relative risk of 1.78 of developing clinical depression.

These findings show that depression and diabetes "are closely related to each other, and this reciprocal association also depends on the severity and treatment of each condition. All the associations were independent of sociodemographic, diet, and lifestyle factors," Dr. Pan and his associates said.

Since depression and diabetes both are highly prevalent in the middle-age and elderly populations, particularly among women, "proper lifestyle interventions including adequate weight management and regular physical activity are recommended to lower the risk of both conditions," they noted.

The reasons underlying the bidirectional association are not yet understood. It is possible that antidepressant use might be a contributing factor to diabetes risk. Antidepressants might exert some clinical effects on glucose homeostasis, and they are known to cause weight gain. However, the link between depression and diabetes was significant independent of BMI, so the possibility that antidepressants might exert some other metabolic effect warrants further investigation, the researchers said.

Alternatively, biochemical changes directly caused by diabetes or its treatment might contribute to depression. It also is possible that the stresses associated with chronic diabetes and its debilitating consequences also contribute to depression.

This study was somewhat limited in that the NHS cohort was 94% white, well educated, and well versed on health issues. The results might not be generalizable to other populations, they added.

This study was supported by the National Institutes of Health, the National Alliance for Research on Schizophrenia & Depression, and the Fonds de la recherche en santé du Québec. No financial conflicts of interest were reported.

The association between diabetes and depression is bidirectional in middle-age women, with the presence of either disease significantly raising the risk that the other also will develop, according to a report in the Nov. 22 issue of the Archives of Internal Medicine.

Moreover, diabetes raises the risk of depression, and depression raises the risk of diabetes, independently of other known risk factors such as adiposity that are common to both diseases, said An Pan, Ph.D., of Harvard School of Public Health, Boston, and his associates.

To date, "only a few" studies have examined the association between diabetes and depression simultaneously, and their results have been inconsistent. "Therefore, we took advantage of repeated measurements of lifestyle risk factors and disease occurrences during 10 years of follow-up in a large prospective cohort" – the Nurses’ Health Study – to address the bidirectional relationship.

The NHS involved female registered nurses residing in 11 states who were followed every 2 years via health questionnaires. Dr. Pan and his colleagues assessed a subset of 65,381 NHS participants who were aged 50-75 years in 1996 and were followed until 2006.

Depressive symptoms were categorized according to the women’s scores on the Mental Health Index 5, whether depression had been diagnosed by a physician and whether they used antidepressants. Diabetes was categorized as requiring no medications, only oral hypoglycemic agents, or insulin therapy.

During follow-up, 2,844 incident cases of diabetes were documented. The risk of developing diabetes was significantly higher in women who had depressive symptoms than in those who did not.

In addition, this rise in diabetes risk showed a "dose-response relationship" with worsening depressive symptoms, such that diabetes risk increased significantly as scores on the MHI-5 rose.

This association between depression and diabetes remained significant, although it was markedly attenuated, when the data were adjusted to account for body mass index (BMI) and lifestyle factors, particularly physical activity.

In a separate analysis of the same data, 7,415 study subjects developed incident clinical depression during follow-up. Compared with women who did not have diabetes, women with diabetes had a relative risk of developing clinical depression of 1.44, the investigators said (Arch. Intern. Med. 2010;170:1884-91).

Controlling for major comorbidities such as hypertension and coronary heart disease attenuated this association, but it remained significant.

In addition, the risk of developing clinical depression also showed a dose-response relationship with worsening diabetes symptoms. Women with diabetes who were not taking any medication had a relative risk of 1.36; those taking oral agents only had a relative risk of 1.42; and those taking insulin had a relative risk of 1.78 of developing clinical depression.

These findings show that depression and diabetes "are closely related to each other, and this reciprocal association also depends on the severity and treatment of each condition. All the associations were independent of sociodemographic, diet, and lifestyle factors," Dr. Pan and his associates said.

Since depression and diabetes both are highly prevalent in the middle-age and elderly populations, particularly among women, "proper lifestyle interventions including adequate weight management and regular physical activity are recommended to lower the risk of both conditions," they noted.

The reasons underlying the bidirectional association are not yet understood. It is possible that antidepressant use might be a contributing factor to diabetes risk. Antidepressants might exert some clinical effects on glucose homeostasis, and they are known to cause weight gain. However, the link between depression and diabetes was significant independent of BMI, so the possibility that antidepressants might exert some other metabolic effect warrants further investigation, the researchers said.

Alternatively, biochemical changes directly caused by diabetes or its treatment might contribute to depression. It also is possible that the stresses associated with chronic diabetes and its debilitating consequences also contribute to depression.

This study was somewhat limited in that the NHS cohort was 94% white, well educated, and well versed on health issues. The results might not be generalizable to other populations, they added.

This study was supported by the National Institutes of Health, the National Alliance for Research on Schizophrenia & Depression, and the Fonds de la recherche en santé du Québec. No financial conflicts of interest were reported.

The association between diabetes and depression is bidirectional in middle-age women, with the presence of either disease significantly raising the risk that the other also will develop, according to a report in the Nov. 22 issue of the Archives of Internal Medicine.

Moreover, diabetes raises the risk of depression, and depression raises the risk of diabetes, independently of other known risk factors such as adiposity that are common to both diseases, said An Pan, Ph.D., of Harvard School of Public Health, Boston, and his associates.

To date, "only a few" studies have examined the association between diabetes and depression simultaneously, and their results have been inconsistent. "Therefore, we took advantage of repeated measurements of lifestyle risk factors and disease occurrences during 10 years of follow-up in a large prospective cohort" – the Nurses’ Health Study – to address the bidirectional relationship.

The NHS involved female registered nurses residing in 11 states who were followed every 2 years via health questionnaires. Dr. Pan and his colleagues assessed a subset of 65,381 NHS participants who were aged 50-75 years in 1996 and were followed until 2006.

Depressive symptoms were categorized according to the women’s scores on the Mental Health Index 5, whether depression had been diagnosed by a physician and whether they used antidepressants. Diabetes was categorized as requiring no medications, only oral hypoglycemic agents, or insulin therapy.

During follow-up, 2,844 incident cases of diabetes were documented. The risk of developing diabetes was significantly higher in women who had depressive symptoms than in those who did not.

In addition, this rise in diabetes risk showed a "dose-response relationship" with worsening depressive symptoms, such that diabetes risk increased significantly as scores on the MHI-5 rose.

This association between depression and diabetes remained significant, although it was markedly attenuated, when the data were adjusted to account for body mass index (BMI) and lifestyle factors, particularly physical activity.

In a separate analysis of the same data, 7,415 study subjects developed incident clinical depression during follow-up. Compared with women who did not have diabetes, women with diabetes had a relative risk of developing clinical depression of 1.44, the investigators said (Arch. Intern. Med. 2010;170:1884-91).

Controlling for major comorbidities such as hypertension and coronary heart disease attenuated this association, but it remained significant.

In addition, the risk of developing clinical depression also showed a dose-response relationship with worsening diabetes symptoms. Women with diabetes who were not taking any medication had a relative risk of 1.36; those taking oral agents only had a relative risk of 1.42; and those taking insulin had a relative risk of 1.78 of developing clinical depression.

These findings show that depression and diabetes "are closely related to each other, and this reciprocal association also depends on the severity and treatment of each condition. All the associations were independent of sociodemographic, diet, and lifestyle factors," Dr. Pan and his associates said.

Since depression and diabetes both are highly prevalent in the middle-age and elderly populations, particularly among women, "proper lifestyle interventions including adequate weight management and regular physical activity are recommended to lower the risk of both conditions," they noted.

The reasons underlying the bidirectional association are not yet understood. It is possible that antidepressant use might be a contributing factor to diabetes risk. Antidepressants might exert some clinical effects on glucose homeostasis, and they are known to cause weight gain. However, the link between depression and diabetes was significant independent of BMI, so the possibility that antidepressants might exert some other metabolic effect warrants further investigation, the researchers said.

Alternatively, biochemical changes directly caused by diabetes or its treatment might contribute to depression. It also is possible that the stresses associated with chronic diabetes and its debilitating consequences also contribute to depression.

This study was somewhat limited in that the NHS cohort was 94% white, well educated, and well versed on health issues. The results might not be generalizable to other populations, they added.

This study was supported by the National Institutes of Health, the National Alliance for Research on Schizophrenia & Depression, and the Fonds de la recherche en santé du Québec. No financial conflicts of interest were reported.

The association between diabetes and depression is bidirectional in middle-age women, with the presence of either disease significantly raising the risk that the other also will develop, according to a report in the Nov. 22 issue of the Archives of Internal Medicine.

Moreover, diabetes raises the risk of depression, and depression raises the risk of diabetes, independently of other known risk factors such as adiposity that are common to both diseases, said An Pan, Ph.D., of Harvard School of Public Health, Boston, and his associates.

To date, "only a few" studies have examined the association between diabetes and depression simultaneously, and their results have been inconsistent. "Therefore, we took advantage of repeated measurements of lifestyle risk factors and disease occurrences during 10 years of follow-up in a large prospective cohort" – the Nurses’ Health Study – to address the bidirectional relationship.

The NHS involved female registered nurses residing in 11 states who were followed every 2 years via health questionnaires. Dr. Pan and his colleagues assessed a subset of 65,381 NHS participants who were aged 50-75 years in 1996 and were followed until 2006.

Depressive symptoms were categorized according to the women’s scores on the Mental Health Index 5, whether depression had been diagnosed by a physician and whether they used antidepressants. Diabetes was categorized as requiring no medications, only oral hypoglycemic agents, or insulin therapy.

During follow-up, 2,844 incident cases of diabetes were documented. The risk of developing diabetes was significantly higher in women who had depressive symptoms than in those who did not.

In addition, this rise in diabetes risk showed a "dose-response relationship" with worsening depressive symptoms, such that diabetes risk increased significantly as scores on the MHI-5 rose.

This association between depression and diabetes remained significant, although it was markedly attenuated, when the data were adjusted to account for body mass index (BMI) and lifestyle factors, particularly physical activity.

In a separate analysis of the same data, 7,415 study subjects developed incident clinical depression during follow-up. Compared with women who did not have diabetes, women with diabetes had a relative risk of developing clinical depression of 1.44, the investigators said (Arch. Intern. Med. 2010;170:1884-91).

Controlling for major comorbidities such as hypertension and coronary heart disease attenuated this association, but it remained significant.

In addition, the risk of developing clinical depression also showed a dose-response relationship with worsening diabetes symptoms. Women with diabetes who were not taking any medication had a relative risk of 1.36; those taking oral agents only had a relative risk of 1.42; and those taking insulin had a relative risk of 1.78 of developing clinical depression.

These findings show that depression and diabetes "are closely related to each other, and this reciprocal association also depends on the severity and treatment of each condition. All the associations were independent of sociodemographic, diet, and lifestyle factors," Dr. Pan and his associates said.

Since depression and diabetes both are highly prevalent in the middle-age and elderly populations, particularly among women, "proper lifestyle interventions including adequate weight management and regular physical activity are recommended to lower the risk of both conditions," they noted.

The reasons underlying the bidirectional association are not yet understood. It is possible that antidepressant use might be a contributing factor to diabetes risk. Antidepressants might exert some clinical effects on glucose homeostasis, and they are known to cause weight gain. However, the link between depression and diabetes was significant independent of BMI, so the possibility that antidepressants might exert some other metabolic effect warrants further investigation, the researchers said.

Alternatively, biochemical changes directly caused by diabetes or its treatment might contribute to depression. It also is possible that the stresses associated with chronic diabetes and its debilitating consequences also contribute to depression.

This study was somewhat limited in that the NHS cohort was 94% white, well educated, and well versed on health issues. The results might not be generalizable to other populations, they added.

This study was supported by the National Institutes of Health, the National Alliance for Research on Schizophrenia & Depression, and the Fonds de la recherche en santé du Québec. No financial conflicts of interest were reported.

The association between diabetes and depression is bidirectional in middle-age women, with the presence of either disease significantly raising the risk that the other also will develop, according to a report in the Nov. 22 issue of the Archives of Internal Medicine.

Moreover, diabetes raises the risk of depression, and depression raises the risk of diabetes, independently of other known risk factors such as adiposity that are common to both diseases, said An Pan, Ph.D., of Harvard School of Public Health, Boston, and his associates.

To date, "only a few" studies have examined the association between diabetes and depression simultaneously, and their results have been inconsistent. "Therefore, we took advantage of repeated measurements of lifestyle risk factors and disease occurrences during 10 years of follow-up in a large prospective cohort" – the Nurses’ Health Study – to address the bidirectional relationship.

The NHS involved female registered nurses residing in 11 states who were followed every 2 years via health questionnaires. Dr. Pan and his colleagues assessed a subset of 65,381 NHS participants who were aged 50-75 years in 1996 and were followed until 2006.

Depressive symptoms were categorized according to the women’s scores on the Mental Health Index 5, whether depression had been diagnosed by a physician and whether they used antidepressants. Diabetes was categorized as requiring no medications, only oral hypoglycemic agents, or insulin therapy.

During follow-up, 2,844 incident cases of diabetes were documented. The risk of developing diabetes was significantly higher in women who had depressive symptoms than in those who did not.

In addition, this rise in diabetes risk showed a "dose-response relationship" with worsening depressive symptoms, such that diabetes risk increased significantly as scores on the MHI-5 rose.

This association between depression and diabetes remained significant, although it was markedly attenuated, when the data were adjusted to account for body mass index (BMI) and lifestyle factors, particularly physical activity.

In a separate analysis of the same data, 7,415 study subjects developed incident clinical depression during follow-up. Compared with women who did not have diabetes, women with diabetes had a relative risk of developing clinical depression of 1.44, the investigators said (Arch. Intern. Med. 2010;170:1884-91).

Controlling for major comorbidities such as hypertension and coronary heart disease attenuated this association, but it remained significant.

In addition, the risk of developing clinical depression also showed a dose-response relationship with worsening diabetes symptoms. Women with diabetes who were not taking any medication had a relative risk of 1.36; those taking oral agents only had a relative risk of 1.42; and those taking insulin had a relative risk of 1.78 of developing clinical depression.

These findings show that depression and diabetes "are closely related to each other, and this reciprocal association also depends on the severity and treatment of each condition. All the associations were independent of sociodemographic, diet, and lifestyle factors," Dr. Pan and his associates said.

Since depression and diabetes both are highly prevalent in the middle-age and elderly populations, particularly among women, "proper lifestyle interventions including adequate weight management and regular physical activity are recommended to lower the risk of both conditions," they noted.

The reasons underlying the bidirectional association are not yet understood. It is possible that antidepressant use might be a contributing factor to diabetes risk. Antidepressants might exert some clinical effects on glucose homeostasis, and they are known to cause weight gain. However, the link between depression and diabetes was significant independent of BMI, so the possibility that antidepressants might exert some other metabolic effect warrants further investigation, the researchers said.

Alternatively, biochemical changes directly caused by diabetes or its treatment might contribute to depression. It also is possible that the stresses associated with chronic diabetes and its debilitating consequences also contribute to depression.

This study was somewhat limited in that the NHS cohort was 94% white, well educated, and well versed on health issues. The results might not be generalizable to other populations, they added.

This study was supported by the National Institutes of Health, the National Alliance for Research on Schizophrenia & Depression, and the Fonds de la recherche en santé du Québec. No financial conflicts of interest were reported.

Patients taking dual antiplatelet therapy have a high frequency of minor hemorrhage and should be taught to anticipate and recognize such events, according to the results of a large, retrospective analysis reported in the Nov. 22 issue of Archives of Internal Medicine.

Otherwise, patients caught unawares may overreact to minor hemorrhage and discontinue the antiplatelet therapy abruptly, jeopardizing their health, wrote Nadine Shehab, Pharm.D., of the Centers for Disease Control and Prevention, Atlanta, and her associates.

Until now there have been few data on the real-world risks of dual antiplatelet therapy "outside the rigorous controlled settings of clinical trials," the researchers said. So their finding that patients on dual antiplatelet therapy visit an emergency department for acute hemorrhage with a similar frequency as that of patients on warfarin will likely come as a surprise to many clinicians.

"We used nationally representative surveillance data ... to describe the frequency, rates, and nature of emergency department (ED) visits for hemorrhagic and other related adverse events attributed to clopidogrel plus aspirin therapy. To gain a better understanding of the magnitude and scope of these types of adverse events, we placed these data in the context of similar data for warfarin, an agent with a related adverse-event profile," they said.

Based on data from adult ED visits to a probability sample of 63 hospitals across the United States between 2006 and 2009, the investigators estimated that there are 7,654 visits every year for hemorrhage-related adverse events among patients taking dual antiplatelet therapy, and that almost all of these involve acute hemorrhage.

In comparison, the number of ED visits for hemorrhage-related adverse events among patients taking warfarin was estimated to be nearly 8 times higher (60,575) – a reasonable difference given that warfarin is prescribed so much more often than is dual antiplatelet therapy. However, ED visits for patients on warfarin often did not involve acute hemorrhage; rather, these patients often visited the ED because of abnormalities in laboratory coagulation variables such as an elevated INR, or for evaluation of potential hemorrhage from a fall or injury, or for toxic effects unrelated to hemorrhage.

"When only ED visits involving acute hemorrhages were considered, the difference [between dual antiplatelet therapy users and warfarin users] was not statistically significant," Dr. Shehab and her colleagues said.

An estimated 60% of ED visits for dual-antiplatelet users involved only epistaxis, skin, or other minor hemorrhages, such as bleeding from the mouth, small cuts, bruising, petechiae, and ecchymosis. Even though the immediate harm from such adverse events is not severe, patients find it very concerning and have been shown to discontinue antiplatelet therapy prematurely after such "nuisance" bleeding.

In contrast, warfarin users tend to be more familiar with minor hemorrhages and less likely to seek ED treatment for them.

Clinicians should be made aware of the large number of patients on dual antiplatelet therapy who mistakenly consider such events to be emergencies. Clinicians also should provide patients with both avoidance and management strategies for such hemorrhages. And they should make sure patients know to anticipate these events, recognize them, seek more appropriate treatment, and, most importantly, not stop antiplatelet therapy abruptly, Dr. Shehab and her associates said (Arch. Intern. Med. 2010;170:1926-33).

Even though most of the ED visits for dual-antiplatelet users involved only minor hemorrhage, a substantial portion – nearly one-third – of visits did involve bleeding severe enough to require hospitalization, including life-threatening pulmonary or CNS hemorrhages, the investigators noted.

When the analysis was restricted only to ED visits for acute hemorrhage, "the risk of clopidogrel plus aspirin-related ED visits resulting in hospitalization was not significantly different from that for warfarin." In addition, almost one-third of clopidogrel plus aspirin-related ED visits were for gastrointestinal tract hemorrhages, and the proportion of patients hospitalized for such bleeding was similar between antiplatelet users and warfarin users.

This is particularly concerning because there are several strategies for managing GI hemorrhages in warfarin users (including careful dose titration, INR monitoring, and patient education) but "few similar interventions for mitigating bleeding harm from antiplatelet medication," Dr. Shehab and her colleagues said.

Overall, the study findings indicate that the hemorrhagic risks with dual antiplatelet therapy are substantial, and that both clinicians and patients "need to approach that risk with vigilance," they added.

This study was supported by the Centers for Disease Control and Prevention. No financial conflicts of interest were reported.

Patients taking dual antiplatelet therapy have a high frequency of minor hemorrhage and should be taught to anticipate and recognize such events, according to the results of a large, retrospective analysis reported in the Nov. 22 issue of Archives of Internal Medicine.

Otherwise, patients caught unawares may overreact to minor hemorrhage and discontinue the antiplatelet therapy abruptly, jeopardizing their health, wrote Nadine Shehab, Pharm.D., of the Centers for Disease Control and Prevention, Atlanta, and her associates.

Until now there have been few data on the real-world risks of dual antiplatelet therapy "outside the rigorous controlled settings of clinical trials," the researchers said. So their finding that patients on dual antiplatelet therapy visit an emergency department for acute hemorrhage with a similar frequency as that of patients on warfarin will likely come as a surprise to many clinicians.

"We used nationally representative surveillance data ... to describe the frequency, rates, and nature of emergency department (ED) visits for hemorrhagic and other related adverse events attributed to clopidogrel plus aspirin therapy. To gain a better understanding of the magnitude and scope of these types of adverse events, we placed these data in the context of similar data for warfarin, an agent with a related adverse-event profile," they said.

Based on data from adult ED visits to a probability sample of 63 hospitals across the United States between 2006 and 2009, the investigators estimated that there are 7,654 visits every year for hemorrhage-related adverse events among patients taking dual antiplatelet therapy, and that almost all of these involve acute hemorrhage.

In comparison, the number of ED visits for hemorrhage-related adverse events among patients taking warfarin was estimated to be nearly 8 times higher (60,575) – a reasonable difference given that warfarin is prescribed so much more often than is dual antiplatelet therapy. However, ED visits for patients on warfarin often did not involve acute hemorrhage; rather, these patients often visited the ED because of abnormalities in laboratory coagulation variables such as an elevated INR, or for evaluation of potential hemorrhage from a fall or injury, or for toxic effects unrelated to hemorrhage.

"When only ED visits involving acute hemorrhages were considered, the difference [between dual antiplatelet therapy users and warfarin users] was not statistically significant," Dr. Shehab and her colleagues said.

An estimated 60% of ED visits for dual-antiplatelet users involved only epistaxis, skin, or other minor hemorrhages, such as bleeding from the mouth, small cuts, bruising, petechiae, and ecchymosis. Even though the immediate harm from such adverse events is not severe, patients find it very concerning and have been shown to discontinue antiplatelet therapy prematurely after such "nuisance" bleeding.

In contrast, warfarin users tend to be more familiar with minor hemorrhages and less likely to seek ED treatment for them.

Clinicians should be made aware of the large number of patients on dual antiplatelet therapy who mistakenly consider such events to be emergencies. Clinicians also should provide patients with both avoidance and management strategies for such hemorrhages. And they should make sure patients know to anticipate these events, recognize them, seek more appropriate treatment, and, most importantly, not stop antiplatelet therapy abruptly, Dr. Shehab and her associates said (Arch. Intern. Med. 2010;170:1926-33).

Even though most of the ED visits for dual-antiplatelet users involved only minor hemorrhage, a substantial portion – nearly one-third – of visits did involve bleeding severe enough to require hospitalization, including life-threatening pulmonary or CNS hemorrhages, the investigators noted.

When the analysis was restricted only to ED visits for acute hemorrhage, "the risk of clopidogrel plus aspirin-related ED visits resulting in hospitalization was not significantly different from that for warfarin." In addition, almost one-third of clopidogrel plus aspirin-related ED visits were for gastrointestinal tract hemorrhages, and the proportion of patients hospitalized for such bleeding was similar between antiplatelet users and warfarin users.

This is particularly concerning because there are several strategies for managing GI hemorrhages in warfarin users (including careful dose titration, INR monitoring, and patient education) but "few similar interventions for mitigating bleeding harm from antiplatelet medication," Dr. Shehab and her colleagues said.

Overall, the study findings indicate that the hemorrhagic risks with dual antiplatelet therapy are substantial, and that both clinicians and patients "need to approach that risk with vigilance," they added.

This study was supported by the Centers for Disease Control and Prevention. No financial conflicts of interest were reported.

Patients taking dual antiplatelet therapy have a high frequency of minor hemorrhage and should be taught to anticipate and recognize such events, according to the results of a large, retrospective analysis reported in the Nov. 22 issue of Archives of Internal Medicine.

Otherwise, patients caught unawares may overreact to minor hemorrhage and discontinue the antiplatelet therapy abruptly, jeopardizing their health, wrote Nadine Shehab, Pharm.D., of the Centers for Disease Control and Prevention, Atlanta, and her associates.

Until now there have been few data on the real-world risks of dual antiplatelet therapy "outside the rigorous controlled settings of clinical trials," the researchers said. So their finding that patients on dual antiplatelet therapy visit an emergency department for acute hemorrhage with a similar frequency as that of patients on warfarin will likely come as a surprise to many clinicians.

"We used nationally representative surveillance data ... to describe the frequency, rates, and nature of emergency department (ED) visits for hemorrhagic and other related adverse events attributed to clopidogrel plus aspirin therapy. To gain a better understanding of the magnitude and scope of these types of adverse events, we placed these data in the context of similar data for warfarin, an agent with a related adverse-event profile," they said.

Based on data from adult ED visits to a probability sample of 63 hospitals across the United States between 2006 and 2009, the investigators estimated that there are 7,654 visits every year for hemorrhage-related adverse events among patients taking dual antiplatelet therapy, and that almost all of these involve acute hemorrhage.

In comparison, the number of ED visits for hemorrhage-related adverse events among patients taking warfarin was estimated to be nearly 8 times higher (60,575) – a reasonable difference given that warfarin is prescribed so much more often than is dual antiplatelet therapy. However, ED visits for patients on warfarin often did not involve acute hemorrhage; rather, these patients often visited the ED because of abnormalities in laboratory coagulation variables such as an elevated INR, or for evaluation of potential hemorrhage from a fall or injury, or for toxic effects unrelated to hemorrhage.

"When only ED visits involving acute hemorrhages were considered, the difference [between dual antiplatelet therapy users and warfarin users] was not statistically significant," Dr. Shehab and her colleagues said.

An estimated 60% of ED visits for dual-antiplatelet users involved only epistaxis, skin, or other minor hemorrhages, such as bleeding from the mouth, small cuts, bruising, petechiae, and ecchymosis. Even though the immediate harm from such adverse events is not severe, patients find it very concerning and have been shown to discontinue antiplatelet therapy prematurely after such "nuisance" bleeding.

In contrast, warfarin users tend to be more familiar with minor hemorrhages and less likely to seek ED treatment for them.

Clinicians should be made aware of the large number of patients on dual antiplatelet therapy who mistakenly consider such events to be emergencies. Clinicians also should provide patients with both avoidance and management strategies for such hemorrhages. And they should make sure patients know to anticipate these events, recognize them, seek more appropriate treatment, and, most importantly, not stop antiplatelet therapy abruptly, Dr. Shehab and her associates said (Arch. Intern. Med. 2010;170:1926-33).

Even though most of the ED visits for dual-antiplatelet users involved only minor hemorrhage, a substantial portion – nearly one-third – of visits did involve bleeding severe enough to require hospitalization, including life-threatening pulmonary or CNS hemorrhages, the investigators noted.

When the analysis was restricted only to ED visits for acute hemorrhage, "the risk of clopidogrel plus aspirin-related ED visits resulting in hospitalization was not significantly different from that for warfarin." In addition, almost one-third of clopidogrel plus aspirin-related ED visits were for gastrointestinal tract hemorrhages, and the proportion of patients hospitalized for such bleeding was similar between antiplatelet users and warfarin users.

This is particularly concerning because there are several strategies for managing GI hemorrhages in warfarin users (including careful dose titration, INR monitoring, and patient education) but "few similar interventions for mitigating bleeding harm from antiplatelet medication," Dr. Shehab and her colleagues said.

Overall, the study findings indicate that the hemorrhagic risks with dual antiplatelet therapy are substantial, and that both clinicians and patients "need to approach that risk with vigilance," they added.

This study was supported by the Centers for Disease Control and Prevention. No financial conflicts of interest were reported.

Patients taking dual antiplatelet therapy have a high frequency of minor hemorrhage and should be taught to anticipate and recognize such events, according to the results of a large, retrospective analysis reported in the Nov. 22 issue of Archives of Internal Medicine.

Otherwise, patients caught unawares may overreact to minor hemorrhage and discontinue the antiplatelet therapy abruptly, jeopardizing their health, wrote Nadine Shehab, Pharm.D., of the Centers for Disease Control and Prevention, Atlanta, and her associates.

Until now there have been few data on the real-world risks of dual antiplatelet therapy "outside the rigorous controlled settings of clinical trials," the researchers said. So their finding that patients on dual antiplatelet therapy visit an emergency department for acute hemorrhage with a similar frequency as that of patients on warfarin will likely come as a surprise to many clinicians.

"We used nationally representative surveillance data ... to describe the frequency, rates, and nature of emergency department (ED) visits for hemorrhagic and other related adverse events attributed to clopidogrel plus aspirin therapy. To gain a better understanding of the magnitude and scope of these types of adverse events, we placed these data in the context of similar data for warfarin, an agent with a related adverse-event profile," they said.

Based on data from adult ED visits to a probability sample of 63 hospitals across the United States between 2006 and 2009, the investigators estimated that there are 7,654 visits every year for hemorrhage-related adverse events among patients taking dual antiplatelet therapy, and that almost all of these involve acute hemorrhage.

In comparison, the number of ED visits for hemorrhage-related adverse events among patients taking warfarin was estimated to be nearly 8 times higher (60,575) – a reasonable difference given that warfarin is prescribed so much more often than is dual antiplatelet therapy. However, ED visits for patients on warfarin often did not involve acute hemorrhage; rather, these patients often visited the ED because of abnormalities in laboratory coagulation variables such as an elevated INR, or for evaluation of potential hemorrhage from a fall or injury, or for toxic effects unrelated to hemorrhage.

"When only ED visits involving acute hemorrhages were considered, the difference [between dual antiplatelet therapy users and warfarin users] was not statistically significant," Dr. Shehab and her colleagues said.

An estimated 60% of ED visits for dual-antiplatelet users involved only epistaxis, skin, or other minor hemorrhages, such as bleeding from the mouth, small cuts, bruising, petechiae, and ecchymosis. Even though the immediate harm from such adverse events is not severe, patients find it very concerning and have been shown to discontinue antiplatelet therapy prematurely after such "nuisance" bleeding.

In contrast, warfarin users tend to be more familiar with minor hemorrhages and less likely to seek ED treatment for them.

Clinicians should be made aware of the large number of patients on dual antiplatelet therapy who mistakenly consider such events to be emergencies. Clinicians also should provide patients with both avoidance and management strategies for such hemorrhages. And they should make sure patients know to anticipate these events, recognize them, seek more appropriate treatment, and, most importantly, not stop antiplatelet therapy abruptly, Dr. Shehab and her associates said (Arch. Intern. Med. 2010;170:1926-33).

Even though most of the ED visits for dual-antiplatelet users involved only minor hemorrhage, a substantial portion – nearly one-third – of visits did involve bleeding severe enough to require hospitalization, including life-threatening pulmonary or CNS hemorrhages, the investigators noted.

When the analysis was restricted only to ED visits for acute hemorrhage, "the risk of clopidogrel plus aspirin-related ED visits resulting in hospitalization was not significantly different from that for warfarin." In addition, almost one-third of clopidogrel plus aspirin-related ED visits were for gastrointestinal tract hemorrhages, and the proportion of patients hospitalized for such bleeding was similar between antiplatelet users and warfarin users.

This is particularly concerning because there are several strategies for managing GI hemorrhages in warfarin users (including careful dose titration, INR monitoring, and patient education) but "few similar interventions for mitigating bleeding harm from antiplatelet medication," Dr. Shehab and her colleagues said.

Overall, the study findings indicate that the hemorrhagic risks with dual antiplatelet therapy are substantial, and that both clinicians and patients "need to approach that risk with vigilance," they added.

This study was supported by the Centers for Disease Control and Prevention. No financial conflicts of interest were reported.

Patients taking dual antiplatelet therapy have a high frequency of minor hemorrhage and should be taught to anticipate and recognize such events, according to the results of a large, retrospective analysis reported in the Nov. 22 issue of Archives of Internal Medicine.

Otherwise, patients caught unawares may overreact to minor hemorrhage and discontinue the antiplatelet therapy abruptly, jeopardizing their health, wrote Nadine Shehab, Pharm.D., of the Centers for Disease Control and Prevention, Atlanta, and her associates.

Until now there have been few data on the real-world risks of dual antiplatelet therapy "outside the rigorous controlled settings of clinical trials," the researchers said. So their finding that patients on dual antiplatelet therapy visit an emergency department for acute hemorrhage with a similar frequency as that of patients on warfarin will likely come as a surprise to many clinicians.

"We used nationally representative surveillance data ... to describe the frequency, rates, and nature of emergency department (ED) visits for hemorrhagic and other related adverse events attributed to clopidogrel plus aspirin therapy. To gain a better understanding of the magnitude and scope of these types of adverse events, we placed these data in the context of similar data for warfarin, an agent with a related adverse-event profile," they said.

Based on data from adult ED visits to a probability sample of 63 hospitals across the United States between 2006 and 2009, the investigators estimated that there are 7,654 visits every year for hemorrhage-related adverse events among patients taking dual antiplatelet therapy, and that almost all of these involve acute hemorrhage.

In comparison, the number of ED visits for hemorrhage-related adverse events among patients taking warfarin was estimated to be nearly 8 times higher (60,575) – a reasonable difference given that warfarin is prescribed so much more often than is dual antiplatelet therapy. However, ED visits for patients on warfarin often did not involve acute hemorrhage; rather, these patients often visited the ED because of abnormalities in laboratory coagulation variables such as an elevated INR, or for evaluation of potential hemorrhage from a fall or injury, or for toxic effects unrelated to hemorrhage.

"When only ED visits involving acute hemorrhages were considered, the difference [between dual antiplatelet therapy users and warfarin users] was not statistically significant," Dr. Shehab and her colleagues said.

An estimated 60% of ED visits for dual-antiplatelet users involved only epistaxis, skin, or other minor hemorrhages, such as bleeding from the mouth, small cuts, bruising, petechiae, and ecchymosis. Even though the immediate harm from such adverse events is not severe, patients find it very concerning and have been shown to discontinue antiplatelet therapy prematurely after such "nuisance" bleeding.

In contrast, warfarin users tend to be more familiar with minor hemorrhages and less likely to seek ED treatment for them.

Clinicians should be made aware of the large number of patients on dual antiplatelet therapy who mistakenly consider such events to be emergencies. Clinicians also should provide patients with both avoidance and management strategies for such hemorrhages. And they should make sure patients know to anticipate these events, recognize them, seek more appropriate treatment, and, most importantly, not stop antiplatelet therapy abruptly, Dr. Shehab and her associates said (Arch. Intern. Med. 2010;170:1926-33).

Even though most of the ED visits for dual-antiplatelet users involved only minor hemorrhage, a substantial portion – nearly one-third – of visits did involve bleeding severe enough to require hospitalization, including life-threatening pulmonary or CNS hemorrhages, the investigators noted.

When the analysis was restricted only to ED visits for acute hemorrhage, "the risk of clopidogrel plus aspirin-related ED visits resulting in hospitalization was not significantly different from that for warfarin." In addition, almost one-third of clopidogrel plus aspirin-related ED visits were for gastrointestinal tract hemorrhages, and the proportion of patients hospitalized for such bleeding was similar between antiplatelet users and warfarin users.

This is particularly concerning because there are several strategies for managing GI hemorrhages in warfarin users (including careful dose titration, INR monitoring, and patient education) but "few similar interventions for mitigating bleeding harm from antiplatelet medication," Dr. Shehab and her colleagues said.

Overall, the study findings indicate that the hemorrhagic risks with dual antiplatelet therapy are substantial, and that both clinicians and patients "need to approach that risk with vigilance," they added.

This study was supported by the Centers for Disease Control and Prevention. No financial conflicts of interest were reported.

Patients taking dual antiplatelet therapy have a high frequency of minor hemorrhage and should be taught to anticipate and recognize such events, according to the results of a large, retrospective analysis reported in the Nov. 22 issue of Archives of Internal Medicine.

Otherwise, patients caught unawares may overreact to minor hemorrhage and discontinue the antiplatelet therapy abruptly, jeopardizing their health, wrote Nadine Shehab, Pharm.D., of the Centers for Disease Control and Prevention, Atlanta, and her associates.

Until now there have been few data on the real-world risks of dual antiplatelet therapy "outside the rigorous controlled settings of clinical trials," the researchers said. So their finding that patients on dual antiplatelet therapy visit an emergency department for acute hemorrhage with a similar frequency as that of patients on warfarin will likely come as a surprise to many clinicians.

"We used nationally representative surveillance data ... to describe the frequency, rates, and nature of emergency department (ED) visits for hemorrhagic and other related adverse events attributed to clopidogrel plus aspirin therapy. To gain a better understanding of the magnitude and scope of these types of adverse events, we placed these data in the context of similar data for warfarin, an agent with a related adverse-event profile," they said.

Based on data from adult ED visits to a probability sample of 63 hospitals across the United States between 2006 and 2009, the investigators estimated that there are 7,654 visits every year for hemorrhage-related adverse events among patients taking dual antiplatelet therapy, and that almost all of these involve acute hemorrhage.

In comparison, the number of ED visits for hemorrhage-related adverse events among patients taking warfarin was estimated to be nearly 8 times higher (60,575) – a reasonable difference given that warfarin is prescribed so much more often than is dual antiplatelet therapy. However, ED visits for patients on warfarin often did not involve acute hemorrhage; rather, these patients often visited the ED because of abnormalities in laboratory coagulation variables such as an elevated INR, or for evaluation of potential hemorrhage from a fall or injury, or for toxic effects unrelated to hemorrhage.

"When only ED visits involving acute hemorrhages were considered, the difference [between dual antiplatelet therapy users and warfarin users] was not statistically significant," Dr. Shehab and her colleagues said.

An estimated 60% of ED visits for dual-antiplatelet users involved only epistaxis, skin, or other minor hemorrhages, such as bleeding from the mouth, small cuts, bruising, petechiae, and ecchymosis. Even though the immediate harm from such adverse events is not severe, patients find it very concerning and have been shown to discontinue antiplatelet therapy prematurely after such "nuisance" bleeding.

In contrast, warfarin users tend to be more familiar with minor hemorrhages and less likely to seek ED treatment for them.

Clinicians should be made aware of the large number of patients on dual antiplatelet therapy who mistakenly consider such events to be emergencies. Clinicians also should provide patients with both avoidance and management strategies for such hemorrhages. And they should make sure patients know to anticipate these events, recognize them, seek more appropriate treatment, and, most importantly, not stop antiplatelet therapy abruptly, Dr. Shehab and her associates said (Arch. Intern. Med. 2010;170:1926-33).

Even though most of the ED visits for dual-antiplatelet users involved only minor hemorrhage, a substantial portion – nearly one-third – of visits did involve bleeding severe enough to require hospitalization, including life-threatening pulmonary or CNS hemorrhages, the investigators noted.

When the analysis was restricted only to ED visits for acute hemorrhage, "the risk of clopidogrel plus aspirin-related ED visits resulting in hospitalization was not significantly different from that for warfarin." In addition, almost one-third of clopidogrel plus aspirin-related ED visits were for gastrointestinal tract hemorrhages, and the proportion of patients hospitalized for such bleeding was similar between antiplatelet users and warfarin users.

This is particularly concerning because there are several strategies for managing GI hemorrhages in warfarin users (including careful dose titration, INR monitoring, and patient education) but "few similar interventions for mitigating bleeding harm from antiplatelet medication," Dr. Shehab and her colleagues said.

Overall, the study findings indicate that the hemorrhagic risks with dual antiplatelet therapy are substantial, and that both clinicians and patients "need to approach that risk with vigilance," they added.

This study was supported by the Centers for Disease Control and Prevention. No financial conflicts of interest were reported.

Findings from a systematic review of the literature published through July 2010 will support the new acute otitis media practice guidelines now being prepared by the American Academy of Pediatrics, according to a report in the Nov. 17 issue of JAMA.

Experts looked to the latest results on AOM diagnosis, the changing microbial epidemiology associated with introduction of the heptavalent pneumococcal conjugate vaccine (PCV7) vaccine, the decision about whether to treat with antibiotics, and the comparative effectiveness of various antibiotics to inform the upcoming AAP practice guideline – an update of their 2001 study that was the basis of the 2004 AAP–American Academy of Family Physicians joint practice guideline on AOM, said Dr. Tumaini R. Coker of the University of California, Los Angeles, and the RAND Corp., Los Angeles, and her associates.

They included 80 articles used in the previous systematic review and 55 published since that time, reviewing both randomized controlled trials and observational studies (JAMA 2010;304:2161-9). Among their findings were the following:

• Otoscopic signs of inflammation (redness) and effusion (bulging or immobile tympanic membrane) are strongly associated with accurate diagnosis of AOM, while the importance of clinical symptoms is "less convincing."

"Perhaps the most important way to improve diagnosis is to increase clinicians’ ability to recognize and rely on key otoscopic findings," Dr. Coker and her colleagues said.

• AOM microbiology has shifted significantly since the introduction of PCV7, with Haemophilus influenzae becoming more prevalent and Streptococcus pneumoniae becoming less so. However, a recent study indicates that this balance may be shifting back again "because of an increase in the proportion of AOM with nonvaccine S. pneumoniae serotypes." Clinicians must stay current with microbial trends, especially given the recent approval of PCV13, the researchers said.

• Immediate ampicillin/amoxicillin treatment has a modest advantage over delayed antibiotic therapy or placebo, but also is more likely to cause diarrhea and rash. "Of 100 average-risk children with AOM, approximately 80 would likely get better within 3 days without antibiotics. If all were treated with immediate ampicillin/amoxicillin, an additional 12 would likely improve, but 3-10 children would develop rash and 5-10 would develop diarrhea. Clinicians need to weigh these risks (including possible long-term effects on antibiotic resistance) before prescribing immediate antibiotics for uncomplicated AOM," the investigators said.

• Most antibiotics have similar clinical efficacy in children at average risk who have uncomplicated AOM. "We found no evidence of the superiority of any other antibiotic over amoxicillin," they noted.

In particular, there is no evidence to support first-line use of more expensive antibiotics such as cefdinir or cefixime. In a given year, cefdinir is prescribed at 14% of the estimated 8 million physician visits for AOM, according to an analysis of data from the National Ambulatory Medical Care Survey. Assuming that such prescription is appropriate in approximately half of these cases because of a penicillin allergy, if physicians prescribed amoxicillin instead of cefdinir in the other half of cases, annual savings would exceed $34 million, Dr. Coker and her associates said.

This study was supported by the Agency for Healthcare Research and Quality. One of Dr. Coker’s associates reported selling Pfizer stock at the start of the study.

Findings from a systematic review of the literature published through July 2010 will support the new acute otitis media practice guidelines now being prepared by the American Academy of Pediatrics, according to a report in the Nov. 17 issue of JAMA.

Experts looked to the latest results on AOM diagnosis, the changing microbial epidemiology associated with introduction of the heptavalent pneumococcal conjugate vaccine (PCV7) vaccine, the decision about whether to treat with antibiotics, and the comparative effectiveness of various antibiotics to inform the upcoming AAP practice guideline – an update of their 2001 study that was the basis of the 2004 AAP–American Academy of Family Physicians joint practice guideline on AOM, said Dr. Tumaini R. Coker of the University of California, Los Angeles, and the RAND Corp., Los Angeles, and her associates.

They included 80 articles used in the previous systematic review and 55 published since that time, reviewing both randomized controlled trials and observational studies (JAMA 2010;304:2161-9). Among their findings were the following:

• Otoscopic signs of inflammation (redness) and effusion (bulging or immobile tympanic membrane) are strongly associated with accurate diagnosis of AOM, while the importance of clinical symptoms is "less convincing."

"Perhaps the most important way to improve diagnosis is to increase clinicians’ ability to recognize and rely on key otoscopic findings," Dr. Coker and her colleagues said.

• AOM microbiology has shifted significantly since the introduction of PCV7, with Haemophilus influenzae becoming more prevalent and Streptococcus pneumoniae becoming less so. However, a recent study indicates that this balance may be shifting back again "because of an increase in the proportion of AOM with nonvaccine S. pneumoniae serotypes." Clinicians must stay current with microbial trends, especially given the recent approval of PCV13, the researchers said.

• Immediate ampicillin/amoxicillin treatment has a modest advantage over delayed antibiotic therapy or placebo, but also is more likely to cause diarrhea and rash. "Of 100 average-risk children with AOM, approximately 80 would likely get better within 3 days without antibiotics. If all were treated with immediate ampicillin/amoxicillin, an additional 12 would likely improve, but 3-10 children would develop rash and 5-10 would develop diarrhea. Clinicians need to weigh these risks (including possible long-term effects on antibiotic resistance) before prescribing immediate antibiotics for uncomplicated AOM," the investigators said.

• Most antibiotics have similar clinical efficacy in children at average risk who have uncomplicated AOM. "We found no evidence of the superiority of any other antibiotic over amoxicillin," they noted.

In particular, there is no evidence to support first-line use of more expensive antibiotics such as cefdinir or cefixime. In a given year, cefdinir is prescribed at 14% of the estimated 8 million physician visits for AOM, according to an analysis of data from the National Ambulatory Medical Care Survey. Assuming that such prescription is appropriate in approximately half of these cases because of a penicillin allergy, if physicians prescribed amoxicillin instead of cefdinir in the other half of cases, annual savings would exceed $34 million, Dr. Coker and her associates said.

This study was supported by the Agency for Healthcare Research and Quality. One of Dr. Coker’s associates reported selling Pfizer stock at the start of the study.

Findings from a systematic review of the literature published through July 2010 will support the new acute otitis media practice guidelines now being prepared by the American Academy of Pediatrics, according to a report in the Nov. 17 issue of JAMA.

Experts looked to the latest results on AOM diagnosis, the changing microbial epidemiology associated with introduction of the heptavalent pneumococcal conjugate vaccine (PCV7) vaccine, the decision about whether to treat with antibiotics, and the comparative effectiveness of various antibiotics to inform the upcoming AAP practice guideline – an update of their 2001 study that was the basis of the 2004 AAP–American Academy of Family Physicians joint practice guideline on AOM, said Dr. Tumaini R. Coker of the University of California, Los Angeles, and the RAND Corp., Los Angeles, and her associates.

They included 80 articles used in the previous systematic review and 55 published since that time, reviewing both randomized controlled trials and observational studies (JAMA 2010;304:2161-9). Among their findings were the following:

• Otoscopic signs of inflammation (redness) and effusion (bulging or immobile tympanic membrane) are strongly associated with accurate diagnosis of AOM, while the importance of clinical symptoms is "less convincing."

"Perhaps the most important way to improve diagnosis is to increase clinicians’ ability to recognize and rely on key otoscopic findings," Dr. Coker and her colleagues said.

• AOM microbiology has shifted significantly since the introduction of PCV7, with Haemophilus influenzae becoming more prevalent and Streptococcus pneumoniae becoming less so. However, a recent study indicates that this balance may be shifting back again "because of an increase in the proportion of AOM with nonvaccine S. pneumoniae serotypes." Clinicians must stay current with microbial trends, especially given the recent approval of PCV13, the researchers said.

• Immediate ampicillin/amoxicillin treatment has a modest advantage over delayed antibiotic therapy or placebo, but also is more likely to cause diarrhea and rash. "Of 100 average-risk children with AOM, approximately 80 would likely get better within 3 days without antibiotics. If all were treated with immediate ampicillin/amoxicillin, an additional 12 would likely improve, but 3-10 children would develop rash and 5-10 would develop diarrhea. Clinicians need to weigh these risks (including possible long-term effects on antibiotic resistance) before prescribing immediate antibiotics for uncomplicated AOM," the investigators said.

• Most antibiotics have similar clinical efficacy in children at average risk who have uncomplicated AOM. "We found no evidence of the superiority of any other antibiotic over amoxicillin," they noted.

In particular, there is no evidence to support first-line use of more expensive antibiotics such as cefdinir or cefixime. In a given year, cefdinir is prescribed at 14% of the estimated 8 million physician visits for AOM, according to an analysis of data from the National Ambulatory Medical Care Survey. Assuming that such prescription is appropriate in approximately half of these cases because of a penicillin allergy, if physicians prescribed amoxicillin instead of cefdinir in the other half of cases, annual savings would exceed $34 million, Dr. Coker and her associates said.

This study was supported by the Agency for Healthcare Research and Quality. One of Dr. Coker’s associates reported selling Pfizer stock at the start of the study.