Michele G. Sullivan

VIENNA — Posttraumatic stress disorder nearly doubled the risk of later dementia in large cohort of male veterans, a retrospective study has determined.

The finding points to the importance of close follow-up for veterans—or any patient—with symptoms of the stress-induced disorder, Dr. Kristine Yaffe said at the International Conference on Alzheimer's disease. “It's critical to follow patients with PTSD [posttraumatic stress disorder] and evaluate them early for dementia,” said Dr. Yaffe, director of the Memory Disorders Clinic at the San Francisco Veterans Administration Medical Center.

Dr. Yaffe studied the incidence of dementia in a retrospective cohort of 183,000 veterans in the Department of Veterans Affairs National Patient Care Database who did not have dementia at baseline enrollment (1997-2000). Most of the subjects (97%) were men; their mean age at baseline was 69 years. PTSD had been diagnosed in 53,155 of the subjects.

During a follow-up period from 2001 to 2007, the cumulative incidence of new-onset dementia was 11% for those veterans with PTSD and 7% for those without PTSD, a significant difference. The results did not change even when Dr. Yaffe excluded subjects with a history of traumatic brain injury, substance abuse, or depression. “Even after adjusting for demographics and medical and psychiatric comorbidities, PTSD patients in this study were still nearly twice as likely to develop incident dementia (hazard ratio 1.8) than veterans without PTSD,” she said at the meeting, which was sponsored by the Alzheimer's Association.

Dr. Yaffe could not speculate on the nature of the connection between PTSD and dementia. She said she did not have any potential conflicts of interest with regard to the study.

VIENNA — Posttraumatic stress disorder nearly doubled the risk of later dementia in large cohort of male veterans, a retrospective study has determined.

The finding points to the importance of close follow-up for veterans—or any patient—with symptoms of the stress-induced disorder, Dr. Kristine Yaffe said at the International Conference on Alzheimer's disease. “It's critical to follow patients with PTSD [posttraumatic stress disorder] and evaluate them early for dementia,” said Dr. Yaffe, director of the Memory Disorders Clinic at the San Francisco Veterans Administration Medical Center.

Dr. Yaffe studied the incidence of dementia in a retrospective cohort of 183,000 veterans in the Department of Veterans Affairs National Patient Care Database who did not have dementia at baseline enrollment (1997-2000). Most of the subjects (97%) were men; their mean age at baseline was 69 years. PTSD had been diagnosed in 53,155 of the subjects.

During a follow-up period from 2001 to 2007, the cumulative incidence of new-onset dementia was 11% for those veterans with PTSD and 7% for those without PTSD, a significant difference. The results did not change even when Dr. Yaffe excluded subjects with a history of traumatic brain injury, substance abuse, or depression. “Even after adjusting for demographics and medical and psychiatric comorbidities, PTSD patients in this study were still nearly twice as likely to develop incident dementia (hazard ratio 1.8) than veterans without PTSD,” she said at the meeting, which was sponsored by the Alzheimer's Association.

Dr. Yaffe could not speculate on the nature of the connection between PTSD and dementia. She said she did not have any potential conflicts of interest with regard to the study.

VIENNA — Posttraumatic stress disorder nearly doubled the risk of later dementia in large cohort of male veterans, a retrospective study has determined.

The finding points to the importance of close follow-up for veterans—or any patient—with symptoms of the stress-induced disorder, Dr. Kristine Yaffe said at the International Conference on Alzheimer's disease. “It's critical to follow patients with PTSD [posttraumatic stress disorder] and evaluate them early for dementia,” said Dr. Yaffe, director of the Memory Disorders Clinic at the San Francisco Veterans Administration Medical Center.

Dr. Yaffe studied the incidence of dementia in a retrospective cohort of 183,000 veterans in the Department of Veterans Affairs National Patient Care Database who did not have dementia at baseline enrollment (1997-2000). Most of the subjects (97%) were men; their mean age at baseline was 69 years. PTSD had been diagnosed in 53,155 of the subjects.

During a follow-up period from 2001 to 2007, the cumulative incidence of new-onset dementia was 11% for those veterans with PTSD and 7% for those without PTSD, a significant difference. The results did not change even when Dr. Yaffe excluded subjects with a history of traumatic brain injury, substance abuse, or depression. “Even after adjusting for demographics and medical and psychiatric comorbidities, PTSD patients in this study were still nearly twice as likely to develop incident dementia (hazard ratio 1.8) than veterans without PTSD,” she said at the meeting, which was sponsored by the Alzheimer's Association.

Dr. Yaffe could not speculate on the nature of the connection between PTSD and dementia. She said she did not have any potential conflicts of interest with regard to the study.

VIENNA — Statin treatment may reduce the risk of later dementia by more than 50%, a national Finnish study has determined.

“Disturbances in cholesterol metabolism have previously been linked to dementia development,” Dr. Alina Solomon wrote in a poster presented at the International Conference on Alzheimer's Disease. However, noted Dr. Solomon of the University of Kuopio, Finland, not all studies have concluded that statins confer a protective effect against dementia onset.

Dr. Solomon and her colleagues examined this question using data extracted from the national FINRISK study, a large, population-based survey of cardiovascular risk factors among Finnish citizens. The survey began in 1972 and is conducted every 5 years. Dr. Solomon's substudy of FINRISK included data on 17,257 citizens who were included in the 1997 and 2002 cohorts, and who were at least 60 years old in 1995, when statins became available in Finland.

By the study's end at 2007, 1,551 of the subjects had developed dementia and 15,706 had not. Only 18% of those who developed dementia had taken at least 1 year of statin therapy, while 37% of those who were dementia-free had taken a statin—a significant difference.

No significant associations were found between dementia and the use of other cholesterol-lowering medications, Dr. Solomon said, suggesting that “the effect of statins in dementia is partly independent of their cholesterol-lowering effect.”

Subjects who developed dementia also had significantly higher baseline total cholesterol and baseline systolic and diastolic blood pressure. But a multivariate regression model that controlled for age, gender, education, cholesterol, weight, and blood pressure still found that statins conferred a 57% risk reduction for dementia over the course of the study, Dr. Solomon said at the meeting, which was sponsored by the Alzheimer's Association.

Neither she nor her coinvestigators declared any conflict of interest.

VIENNA — Statin treatment may reduce the risk of later dementia by more than 50%, a national Finnish study has determined.

“Disturbances in cholesterol metabolism have previously been linked to dementia development,” Dr. Alina Solomon wrote in a poster presented at the International Conference on Alzheimer's Disease. However, noted Dr. Solomon of the University of Kuopio, Finland, not all studies have concluded that statins confer a protective effect against dementia onset.

Dr. Solomon and her colleagues examined this question using data extracted from the national FINRISK study, a large, population-based survey of cardiovascular risk factors among Finnish citizens. The survey began in 1972 and is conducted every 5 years. Dr. Solomon's substudy of FINRISK included data on 17,257 citizens who were included in the 1997 and 2002 cohorts, and who were at least 60 years old in 1995, when statins became available in Finland.

By the study's end at 2007, 1,551 of the subjects had developed dementia and 15,706 had not. Only 18% of those who developed dementia had taken at least 1 year of statin therapy, while 37% of those who were dementia-free had taken a statin—a significant difference.

No significant associations were found between dementia and the use of other cholesterol-lowering medications, Dr. Solomon said, suggesting that “the effect of statins in dementia is partly independent of their cholesterol-lowering effect.”

Subjects who developed dementia also had significantly higher baseline total cholesterol and baseline systolic and diastolic blood pressure. But a multivariate regression model that controlled for age, gender, education, cholesterol, weight, and blood pressure still found that statins conferred a 57% risk reduction for dementia over the course of the study, Dr. Solomon said at the meeting, which was sponsored by the Alzheimer's Association.

Neither she nor her coinvestigators declared any conflict of interest.

VIENNA — Statin treatment may reduce the risk of later dementia by more than 50%, a national Finnish study has determined.

“Disturbances in cholesterol metabolism have previously been linked to dementia development,” Dr. Alina Solomon wrote in a poster presented at the International Conference on Alzheimer's Disease. However, noted Dr. Solomon of the University of Kuopio, Finland, not all studies have concluded that statins confer a protective effect against dementia onset.

Dr. Solomon and her colleagues examined this question using data extracted from the national FINRISK study, a large, population-based survey of cardiovascular risk factors among Finnish citizens. The survey began in 1972 and is conducted every 5 years. Dr. Solomon's substudy of FINRISK included data on 17,257 citizens who were included in the 1997 and 2002 cohorts, and who were at least 60 years old in 1995, when statins became available in Finland.

By the study's end at 2007, 1,551 of the subjects had developed dementia and 15,706 had not. Only 18% of those who developed dementia had taken at least 1 year of statin therapy, while 37% of those who were dementia-free had taken a statin—a significant difference.

No significant associations were found between dementia and the use of other cholesterol-lowering medications, Dr. Solomon said, suggesting that “the effect of statins in dementia is partly independent of their cholesterol-lowering effect.”

Subjects who developed dementia also had significantly higher baseline total cholesterol and baseline systolic and diastolic blood pressure. But a multivariate regression model that controlled for age, gender, education, cholesterol, weight, and blood pressure still found that statins conferred a 57% risk reduction for dementia over the course of the study, Dr. Solomon said at the meeting, which was sponsored by the Alzheimer's Association.

Neither she nor her coinvestigators declared any conflict of interest.

CHICAGO — A noninvasive breath test that measures exhaled 13C-methacetin can accurately predict the risk of liver decompensation within up to 2 years.

With more confirmatory research, the test “could be used to give transplant priority to patients who are at risk of imminent decompensation, or to determine whether a cirrhotic patient has enough liver reserve to undergo a hepatic resection or other surgery,” Dr. Gadi Lalazar said at a press briefing at the annual Digestive Disease Week.

Currently, the Model for End-Stage Liver Disease (MELD) and Child-Pugh scores are the best ways to evaluate hepatic reserve in patients with chronic liver disease, said Dr. Lalazar of Hebrew University-Hadassah Medical Center, Jerusalem. But the scoring systems aren't foolproof. “MELD's main predictive power is only for up to 90 days, and we often see patients with similar MELD scores and very different disease courses—some will decompensate and die and some will not.”

The breath test is administered with a portable machine (Breath ID, manufactured by Exalenz Bioscience Ltd.). Patients fast for 8 hours before the test, then drink 150 mL of water containing 75 mg of methacetin. They wear a nasal cannula while hooked to the machine, which continuously collects and analyzes their breath for 60 minutes.

Methacetin is metabolized solely by healthy hepatocytes, Dr. Lalazar said. He described the process in a paper published earlier this year (World J. Gastro. 2009;15:966-72).

Preliminary studies found that the test reliably distinguished between early cirrhotic and noncirrhotic patients with 95% sensitivity and 97% specificity.

Dr. Lalazar and his colleagues examined the test's ability to predict death from liver failure over a 2-year period in a cohort of 575 patients with chronic liver disease. The patients' mean age was 48 years; 209 of them had cirrhosis. The mean MELD score at baseline was 9. Most of the group (67%) had hepatitis C infection. Patients were divided into risk groups according to their breath test results: low risk (342 patients), moderate risk (135), and high risk (98).

There were 25 deaths in the entire cohort over the 2-year follow-up period. When analyzed by the breath test risk levels, most of the deaths occurred in the high-risk group (15% of that group). Deaths occurred in 6% of the moderate-risk group and in 1% of the low-risk group. The relationship of death to risk group was consistent at every time point in the study. (See chart.)

The investigators then examined the rate of death in the subgroup of cirrhotic patients. The breath test identified 42 patients as low risk, 83 patients as moderate risk, and 84 as having a high risk. At 2 years, there was 1 death in the low-risk group, 7 in the moderate-risk group, and 14 in the high-risk group.

The machine is now being analyzed in a phase III U.S. trial for the detection of cirrhosis in patients with chronic liver disease (clinicaltrials.govNCT00736840

Dr. Lalazar said he had no financial interest in the company or any other potential conflict regarding the study.

Source ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — A noninvasive breath test that measures exhaled 13C-methacetin can accurately predict the risk of liver decompensation within up to 2 years.

With more confirmatory research, the test “could be used to give transplant priority to patients who are at risk of imminent decompensation, or to determine whether a cirrhotic patient has enough liver reserve to undergo a hepatic resection or other surgery,” Dr. Gadi Lalazar said at a press briefing at the annual Digestive Disease Week.

Currently, the Model for End-Stage Liver Disease (MELD) and Child-Pugh scores are the best ways to evaluate hepatic reserve in patients with chronic liver disease, said Dr. Lalazar of Hebrew University-Hadassah Medical Center, Jerusalem. But the scoring systems aren't foolproof. “MELD's main predictive power is only for up to 90 days, and we often see patients with similar MELD scores and very different disease courses—some will decompensate and die and some will not.”

The breath test is administered with a portable machine (Breath ID, manufactured by Exalenz Bioscience Ltd.). Patients fast for 8 hours before the test, then drink 150 mL of water containing 75 mg of methacetin. They wear a nasal cannula while hooked to the machine, which continuously collects and analyzes their breath for 60 minutes.

Methacetin is metabolized solely by healthy hepatocytes, Dr. Lalazar said. He described the process in a paper published earlier this year (World J. Gastro. 2009;15:966-72).

Preliminary studies found that the test reliably distinguished between early cirrhotic and noncirrhotic patients with 95% sensitivity and 97% specificity.

Dr. Lalazar and his colleagues examined the test's ability to predict death from liver failure over a 2-year period in a cohort of 575 patients with chronic liver disease. The patients' mean age was 48 years; 209 of them had cirrhosis. The mean MELD score at baseline was 9. Most of the group (67%) had hepatitis C infection. Patients were divided into risk groups according to their breath test results: low risk (342 patients), moderate risk (135), and high risk (98).

There were 25 deaths in the entire cohort over the 2-year follow-up period. When analyzed by the breath test risk levels, most of the deaths occurred in the high-risk group (15% of that group). Deaths occurred in 6% of the moderate-risk group and in 1% of the low-risk group. The relationship of death to risk group was consistent at every time point in the study. (See chart.)

The investigators then examined the rate of death in the subgroup of cirrhotic patients. The breath test identified 42 patients as low risk, 83 patients as moderate risk, and 84 as having a high risk. At 2 years, there was 1 death in the low-risk group, 7 in the moderate-risk group, and 14 in the high-risk group.

The machine is now being analyzed in a phase III U.S. trial for the detection of cirrhosis in patients with chronic liver disease (clinicaltrials.govNCT00736840

Dr. Lalazar said he had no financial interest in the company or any other potential conflict regarding the study.

Source ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — A noninvasive breath test that measures exhaled 13C-methacetin can accurately predict the risk of liver decompensation within up to 2 years.

With more confirmatory research, the test “could be used to give transplant priority to patients who are at risk of imminent decompensation, or to determine whether a cirrhotic patient has enough liver reserve to undergo a hepatic resection or other surgery,” Dr. Gadi Lalazar said at a press briefing at the annual Digestive Disease Week.

Currently, the Model for End-Stage Liver Disease (MELD) and Child-Pugh scores are the best ways to evaluate hepatic reserve in patients with chronic liver disease, said Dr. Lalazar of Hebrew University-Hadassah Medical Center, Jerusalem. But the scoring systems aren't foolproof. “MELD's main predictive power is only for up to 90 days, and we often see patients with similar MELD scores and very different disease courses—some will decompensate and die and some will not.”

The breath test is administered with a portable machine (Breath ID, manufactured by Exalenz Bioscience Ltd.). Patients fast for 8 hours before the test, then drink 150 mL of water containing 75 mg of methacetin. They wear a nasal cannula while hooked to the machine, which continuously collects and analyzes their breath for 60 minutes.

Methacetin is metabolized solely by healthy hepatocytes, Dr. Lalazar said. He described the process in a paper published earlier this year (World J. Gastro. 2009;15:966-72).

Preliminary studies found that the test reliably distinguished between early cirrhotic and noncirrhotic patients with 95% sensitivity and 97% specificity.

Dr. Lalazar and his colleagues examined the test's ability to predict death from liver failure over a 2-year period in a cohort of 575 patients with chronic liver disease. The patients' mean age was 48 years; 209 of them had cirrhosis. The mean MELD score at baseline was 9. Most of the group (67%) had hepatitis C infection. Patients were divided into risk groups according to their breath test results: low risk (342 patients), moderate risk (135), and high risk (98).

There were 25 deaths in the entire cohort over the 2-year follow-up period. When analyzed by the breath test risk levels, most of the deaths occurred in the high-risk group (15% of that group). Deaths occurred in 6% of the moderate-risk group and in 1% of the low-risk group. The relationship of death to risk group was consistent at every time point in the study. (See chart.)

The investigators then examined the rate of death in the subgroup of cirrhotic patients. The breath test identified 42 patients as low risk, 83 patients as moderate risk, and 84 as having a high risk. At 2 years, there was 1 death in the low-risk group, 7 in the moderate-risk group, and 14 in the high-risk group.

The machine is now being analyzed in a phase III U.S. trial for the detection of cirrhosis in patients with chronic liver disease (clinicaltrials.govNCT00736840

Dr. Lalazar said he had no financial interest in the company or any other potential conflict regarding the study.

Source ELSEVIER GLOBAL MEDICAL NEWS

For patients with at least one additional cardiovascular risk factor, tight blood pressure control seems to decrease the risk of developing left ventricular hypertrophy and other clinical cardiovascular events, a 2-year open-label trial has concluded.

Although the findings need to be evaluated in a randomized controlled trial, they do lend credence to the idea that tight control of hypertension could benefit nondiabetic patients, just as it has been shown to benefit those with diabetes, Dr. Paolo Verdecchia and his colleagues wrote (Lancet 2009;374:525-33).

“Present evidence lends support to reduced thresholds of diastolic blood pressure in patients with type 2 diabetes,” wrote Dr. Verdecchia of the Hospital Santa Maria Misericordia, Perugia, Italy. However, recent European hypertension control guidelines emphasized the need for “urgent research” into just how low the target systolic blood pressure should be in the general population of hypertensive patients.

The Italian Study on the Cardiovascular Effects of Systolic Blood Pressure Control (Cardio-Sis) enrolled 1,111 nondiabetic patients aged 55 years and older who continued to have elevated systolic blood pressure (at least 150 mm Hg) despite 12 weeks of antihypertensive therapy. All patients had at least one additional cardiovascular risk factor.

Patients were randomized to either tight control (less than 130 mm Hg systolic pressure) or usual control (less than 140 mm Hg). Physicians were allowed to prescribe any antihypertensive therapy they deemed appropriate. In the tight-control group, one systolic reading of more than 130 mm Hg triggered more intensive treatment; in the usual control group, one reading of below 130 mm Hg triggered a down-titration of treatment.

The primary outcome was the prevalence of electrocardiographic left ventricular hypertrophy at 2 years. The secondary composite end point included all-cause mortality, heart attack, stroke, congestive heart failure, angina, and other cardiovascular events.

In both groups, the patients' mean age was 67 years. Their mean baseline systolic blood pressure was 163/90 mm Hg. About 20% were smokers and 76% had dyslipidemia.

At the study's end, systolic blood pressure had decreased by 28 mm Hg in the usual-control group and by 31 mm Hg in the tight-control group. The final end-of-study mean pressures were 136/79 in the usual-control group and 132/77 in the tight-control group.

The primary end point of left ventricular hypotrophy occurred in 17% of the usual-control group and 11% of the tight-control group—a significant difference. A more detailed analysis revealed that tight control significantly decreased the likelihood of hypertrophy at both 1 and 2 years (62% and 69%, respectively). However, usual control did not significantly reduce the risk at either time point (18% and 32%).

The composite secondary end point occurred in significantly more of the usual-control group than the tight-control group (9% vs. 5%). The difference was driven by more new-onset atrial fibrillation and coronary revascularization in the usual-control group. There were no significant differences in heart attack, heart failure, stroke, transient ischemic attack, or death.

Adverse reactions to drug therapy were rare, mild, and similar between groups. Patients in both groups generally needed more drugs to control their blood pressure as the study advanced. At baseline, all patients were taking a mean of two drug classes, but were up to three classes by years 1 and 2. Patients in the tight-control group were significantly more likely to get diuretics and angiotensin-receptor blockers than were those in the usual-care group, but the use of beta-blockers, calcium-channel blockers, and angiotensin-converting enzyme inhibitors was similar between the groups.

The study was funded by Boehringer-Ingelheim Pharmaceuticals Inc., Sanofi-Aventis, and Pfizer Inc. Several of the researchers disclosed having received lecture and consulting fees from those and other pharmaceutical companies.

For patients with at least one additional cardiovascular risk factor, tight blood pressure control seems to decrease the risk of developing left ventricular hypertrophy and other clinical cardiovascular events, a 2-year open-label trial has concluded.

Although the findings need to be evaluated in a randomized controlled trial, they do lend credence to the idea that tight control of hypertension could benefit nondiabetic patients, just as it has been shown to benefit those with diabetes, Dr. Paolo Verdecchia and his colleagues wrote (Lancet 2009;374:525-33).

“Present evidence lends support to reduced thresholds of diastolic blood pressure in patients with type 2 diabetes,” wrote Dr. Verdecchia of the Hospital Santa Maria Misericordia, Perugia, Italy. However, recent European hypertension control guidelines emphasized the need for “urgent research” into just how low the target systolic blood pressure should be in the general population of hypertensive patients.

The Italian Study on the Cardiovascular Effects of Systolic Blood Pressure Control (Cardio-Sis) enrolled 1,111 nondiabetic patients aged 55 years and older who continued to have elevated systolic blood pressure (at least 150 mm Hg) despite 12 weeks of antihypertensive therapy. All patients had at least one additional cardiovascular risk factor.

Patients were randomized to either tight control (less than 130 mm Hg systolic pressure) or usual control (less than 140 mm Hg). Physicians were allowed to prescribe any antihypertensive therapy they deemed appropriate. In the tight-control group, one systolic reading of more than 130 mm Hg triggered more intensive treatment; in the usual control group, one reading of below 130 mm Hg triggered a down-titration of treatment.

The primary outcome was the prevalence of electrocardiographic left ventricular hypertrophy at 2 years. The secondary composite end point included all-cause mortality, heart attack, stroke, congestive heart failure, angina, and other cardiovascular events.

In both groups, the patients' mean age was 67 years. Their mean baseline systolic blood pressure was 163/90 mm Hg. About 20% were smokers and 76% had dyslipidemia.

At the study's end, systolic blood pressure had decreased by 28 mm Hg in the usual-control group and by 31 mm Hg in the tight-control group. The final end-of-study mean pressures were 136/79 in the usual-control group and 132/77 in the tight-control group.

The primary end point of left ventricular hypotrophy occurred in 17% of the usual-control group and 11% of the tight-control group—a significant difference. A more detailed analysis revealed that tight control significantly decreased the likelihood of hypertrophy at both 1 and 2 years (62% and 69%, respectively). However, usual control did not significantly reduce the risk at either time point (18% and 32%).

The composite secondary end point occurred in significantly more of the usual-control group than the tight-control group (9% vs. 5%). The difference was driven by more new-onset atrial fibrillation and coronary revascularization in the usual-control group. There were no significant differences in heart attack, heart failure, stroke, transient ischemic attack, or death.

Adverse reactions to drug therapy were rare, mild, and similar between groups. Patients in both groups generally needed more drugs to control their blood pressure as the study advanced. At baseline, all patients were taking a mean of two drug classes, but were up to three classes by years 1 and 2. Patients in the tight-control group were significantly more likely to get diuretics and angiotensin-receptor blockers than were those in the usual-care group, but the use of beta-blockers, calcium-channel blockers, and angiotensin-converting enzyme inhibitors was similar between the groups.

The study was funded by Boehringer-Ingelheim Pharmaceuticals Inc., Sanofi-Aventis, and Pfizer Inc. Several of the researchers disclosed having received lecture and consulting fees from those and other pharmaceutical companies.

For patients with at least one additional cardiovascular risk factor, tight blood pressure control seems to decrease the risk of developing left ventricular hypertrophy and other clinical cardiovascular events, a 2-year open-label trial has concluded.

Although the findings need to be evaluated in a randomized controlled trial, they do lend credence to the idea that tight control of hypertension could benefit nondiabetic patients, just as it has been shown to benefit those with diabetes, Dr. Paolo Verdecchia and his colleagues wrote (Lancet 2009;374:525-33).

“Present evidence lends support to reduced thresholds of diastolic blood pressure in patients with type 2 diabetes,” wrote Dr. Verdecchia of the Hospital Santa Maria Misericordia, Perugia, Italy. However, recent European hypertension control guidelines emphasized the need for “urgent research” into just how low the target systolic blood pressure should be in the general population of hypertensive patients.

The Italian Study on the Cardiovascular Effects of Systolic Blood Pressure Control (Cardio-Sis) enrolled 1,111 nondiabetic patients aged 55 years and older who continued to have elevated systolic blood pressure (at least 150 mm Hg) despite 12 weeks of antihypertensive therapy. All patients had at least one additional cardiovascular risk factor.

Patients were randomized to either tight control (less than 130 mm Hg systolic pressure) or usual control (less than 140 mm Hg). Physicians were allowed to prescribe any antihypertensive therapy they deemed appropriate. In the tight-control group, one systolic reading of more than 130 mm Hg triggered more intensive treatment; in the usual control group, one reading of below 130 mm Hg triggered a down-titration of treatment.

The primary outcome was the prevalence of electrocardiographic left ventricular hypertrophy at 2 years. The secondary composite end point included all-cause mortality, heart attack, stroke, congestive heart failure, angina, and other cardiovascular events.

In both groups, the patients' mean age was 67 years. Their mean baseline systolic blood pressure was 163/90 mm Hg. About 20% were smokers and 76% had dyslipidemia.

At the study's end, systolic blood pressure had decreased by 28 mm Hg in the usual-control group and by 31 mm Hg in the tight-control group. The final end-of-study mean pressures were 136/79 in the usual-control group and 132/77 in the tight-control group.

The primary end point of left ventricular hypotrophy occurred in 17% of the usual-control group and 11% of the tight-control group—a significant difference. A more detailed analysis revealed that tight control significantly decreased the likelihood of hypertrophy at both 1 and 2 years (62% and 69%, respectively). However, usual control did not significantly reduce the risk at either time point (18% and 32%).

The composite secondary end point occurred in significantly more of the usual-control group than the tight-control group (9% vs. 5%). The difference was driven by more new-onset atrial fibrillation and coronary revascularization in the usual-control group. There were no significant differences in heart attack, heart failure, stroke, transient ischemic attack, or death.

Adverse reactions to drug therapy were rare, mild, and similar between groups. Patients in both groups generally needed more drugs to control their blood pressure as the study advanced. At baseline, all patients were taking a mean of two drug classes, but were up to three classes by years 1 and 2. Patients in the tight-control group were significantly more likely to get diuretics and angiotensin-receptor blockers than were those in the usual-care group, but the use of beta-blockers, calcium-channel blockers, and angiotensin-converting enzyme inhibitors was similar between the groups.

The study was funded by Boehringer-Ingelheim Pharmaceuticals Inc., Sanofi-Aventis, and Pfizer Inc. Several of the researchers disclosed having received lecture and consulting fees from those and other pharmaceutical companies.

The beta-blocker propranolol appears almost 100% effective in treating severe infantile hemangiomas, according to a French case series of 32 patients.

The group, led by Dr. Véronique Sans of Children's Hospital in Bordeaux, France, found that even life-threatening hemangiomas responded dramatically to propranolol treatment, with overnight color change and lesion softening after the first dose (2–3 mg/kg per day).

"Symptoms such as dyspnea and hemodynamic compromise [due to the lesions] regressed within 48 hours, and spontaneous ocular opening [in children with periorbital lesions] was possible within 7 days," wrote Dr. Sans and her colleagues (DOI:10.1542/peds.2008-3458

The observations in the paper are a fairly accurate representation of propranolol's remarkable effect on these lesions, Dr. Bernard Cohen said in an interview. Last July, after Dr. Sans' colleagues made an initial public report of their experience, Dr. Cohen began using propanolol as the first-line treatment for serious infantile hemangiomas in the pediatric vascular lesions clinic at Johns Hopkins Medical Center in Baltimore.

"I haven't used steroids in any of these children since then," said Dr. Cohen, director of pediatric dermatology at the center. He and his colleagues have so far treated 41 children with propanolol and will soon publish their own experience. Although they have not had quite the 100% success rate that the French group claims, Dr. Cohen said the drug is very effective, extremely safe, and can be given without the concerns for growth and immune response that come with steroid therapy.

"I think it works better than oral steroids, but it doesn't work for everyone," he said, adding that lesions on infants responded better to the treatment than lesions on children who were older than 1 year. "If lesions are causing a lot of [functional problems], propranolol does seem to shut them down, but it did not make a dramatic difference in every one of our patients. However, it is very safe—especially compared to oral steroids."

The French team observed serendipitously that beta-blockers used for hypertension in infants positively affected the growth of hemangiomas. In 2008, following that observation, they described their index case and 10 additional cases (N. Engl. J. Med. 2008: 358:2649–51).

The current report comprises 32 children (mean age 4 months) with severe hemangiomas. All of the lesions imposed either life-threatening symptoms or the risk of severe disfigurement.

Treatment consisted of a course of oral propranolol at a dose of 2–3 mg/kg per day, initiated in an inpatient setting so that clinicians could observe the child's reaction. Blood pressure and heart rate were monitored every hour during the first 6 hours of treatment. If no adverse events occurred, the child was sent home and re-evaluated after another 10 days, with monthly evaluations afterward, Dr. Sans and her associates said.

Most of the treatments (27) were early interventions on children aged 1–12 months. For these children, the goal was to decrease functional risk, serious symptoms, or cosmetic complications. The other five children were 18–48 months old; their treatment goal was functional risk or cosmetic risk. Thirteen of the children had received corticosteroids with no benefit.

Children who had ulcerated hemangiomas experienced complete healing within 2 months of therapy initiation. In the 11 children with ultrasound measurements, the 60-day exam showed a mean lesion thickness regression of 40%, with a lower resistivity index, indicating decreased vascular activity.

The 13 children who were taking steroids all discontinued treatment without rebound. Propranolol was discontinued in 6–14 months for the early-intervention cases and in 2–10 months for the later-intervention cases. It was restarted in two cases because of regrowth. The 12 patients with eyelid involvement experienced resolution of astigmatism and amblyopia at the end of therapy, the investigators reported.

Dr. Sans and her associates noted two adverse events. One patient had a decrease in blood pressure while sleeping, 3 hours after the first dose. Another patient discontinued propranolol after experiencing wheezing thought to be caused by allergic asthma.

The authors suggested that the optimal therapy for early intervention would be to give propranolol throughout the hemangioma's proliferative phase, usually from 4 to 12 months of age. For treatments commenced after the proliferative phase has concluded, the therapy should continue until maximum improvement is noted.

The overnight improvements of lesion softening and color change (from intense red to purple) indicated the drug's vasoconstrictive effect on the lesions' capillaries, Dr. Christine Léauté-Labrèze, also of Children's Hospital, said in the initial 2008 report.

Although Dr. Sans and her coauthors said they had no financial conflicts with regard to their paper, Dr. Léauté-Labrèze noted in the 2008 paper that she and her colleagues had applied for a patent for the use of propranolol on infantile hemangiomas. Dr. Léauté-Labrèze and her coauthors—Dr. Franck Boralevi, Dr. Eric Dumas de la Roque, and Dr. Alain Taïeb—who are with Children's Hospital, are also coauthors of Dr. Sans' paper.

Since switching to propranolol in July of last year, 'I haven't used steroids in any of these children.'

Source DR. COHEN

The beta-blocker propranolol appears almost 100% effective in treating severe infantile hemangiomas, according to a French case series of 32 patients.

The group, led by Dr. Véronique Sans of Children's Hospital in Bordeaux, France, found that even life-threatening hemangiomas responded dramatically to propranolol treatment, with overnight color change and lesion softening after the first dose (2–3 mg/kg per day).

"Symptoms such as dyspnea and hemodynamic compromise [due to the lesions] regressed within 48 hours, and spontaneous ocular opening [in children with periorbital lesions] was possible within 7 days," wrote Dr. Sans and her colleagues (DOI:10.1542/peds.2008-3458

The observations in the paper are a fairly accurate representation of propranolol's remarkable effect on these lesions, Dr. Bernard Cohen said in an interview. Last July, after Dr. Sans' colleagues made an initial public report of their experience, Dr. Cohen began using propanolol as the first-line treatment for serious infantile hemangiomas in the pediatric vascular lesions clinic at Johns Hopkins Medical Center in Baltimore.

"I haven't used steroids in any of these children since then," said Dr. Cohen, director of pediatric dermatology at the center. He and his colleagues have so far treated 41 children with propanolol and will soon publish their own experience. Although they have not had quite the 100% success rate that the French group claims, Dr. Cohen said the drug is very effective, extremely safe, and can be given without the concerns for growth and immune response that come with steroid therapy.

"I think it works better than oral steroids, but it doesn't work for everyone," he said, adding that lesions on infants responded better to the treatment than lesions on children who were older than 1 year. "If lesions are causing a lot of [functional problems], propranolol does seem to shut them down, but it did not make a dramatic difference in every one of our patients. However, it is very safe—especially compared to oral steroids."

The French team observed serendipitously that beta-blockers used for hypertension in infants positively affected the growth of hemangiomas. In 2008, following that observation, they described their index case and 10 additional cases (N. Engl. J. Med. 2008: 358:2649–51).

The current report comprises 32 children (mean age 4 months) with severe hemangiomas. All of the lesions imposed either life-threatening symptoms or the risk of severe disfigurement.

Treatment consisted of a course of oral propranolol at a dose of 2–3 mg/kg per day, initiated in an inpatient setting so that clinicians could observe the child's reaction. Blood pressure and heart rate were monitored every hour during the first 6 hours of treatment. If no adverse events occurred, the child was sent home and re-evaluated after another 10 days, with monthly evaluations afterward, Dr. Sans and her associates said.

Most of the treatments (27) were early interventions on children aged 1–12 months. For these children, the goal was to decrease functional risk, serious symptoms, or cosmetic complications. The other five children were 18–48 months old; their treatment goal was functional risk or cosmetic risk. Thirteen of the children had received corticosteroids with no benefit.

Children who had ulcerated hemangiomas experienced complete healing within 2 months of therapy initiation. In the 11 children with ultrasound measurements, the 60-day exam showed a mean lesion thickness regression of 40%, with a lower resistivity index, indicating decreased vascular activity.

The 13 children who were taking steroids all discontinued treatment without rebound. Propranolol was discontinued in 6–14 months for the early-intervention cases and in 2–10 months for the later-intervention cases. It was restarted in two cases because of regrowth. The 12 patients with eyelid involvement experienced resolution of astigmatism and amblyopia at the end of therapy, the investigators reported.

Dr. Sans and her associates noted two adverse events. One patient had a decrease in blood pressure while sleeping, 3 hours after the first dose. Another patient discontinued propranolol after experiencing wheezing thought to be caused by allergic asthma.

The authors suggested that the optimal therapy for early intervention would be to give propranolol throughout the hemangioma's proliferative phase, usually from 4 to 12 months of age. For treatments commenced after the proliferative phase has concluded, the therapy should continue until maximum improvement is noted.

The overnight improvements of lesion softening and color change (from intense red to purple) indicated the drug's vasoconstrictive effect on the lesions' capillaries, Dr. Christine Léauté-Labrèze, also of Children's Hospital, said in the initial 2008 report.

Although Dr. Sans and her coauthors said they had no financial conflicts with regard to their paper, Dr. Léauté-Labrèze noted in the 2008 paper that she and her colleagues had applied for a patent for the use of propranolol on infantile hemangiomas. Dr. Léauté-Labrèze and her coauthors—Dr. Franck Boralevi, Dr. Eric Dumas de la Roque, and Dr. Alain Taïeb—who are with Children's Hospital, are also coauthors of Dr. Sans' paper.

Since switching to propranolol in July of last year, 'I haven't used steroids in any of these children.'

Source DR. COHEN

The beta-blocker propranolol appears almost 100% effective in treating severe infantile hemangiomas, according to a French case series of 32 patients.

The group, led by Dr. Véronique Sans of Children's Hospital in Bordeaux, France, found that even life-threatening hemangiomas responded dramatically to propranolol treatment, with overnight color change and lesion softening after the first dose (2–3 mg/kg per day).

"Symptoms such as dyspnea and hemodynamic compromise [due to the lesions] regressed within 48 hours, and spontaneous ocular opening [in children with periorbital lesions] was possible within 7 days," wrote Dr. Sans and her colleagues (DOI:10.1542/peds.2008-3458

The observations in the paper are a fairly accurate representation of propranolol's remarkable effect on these lesions, Dr. Bernard Cohen said in an interview. Last July, after Dr. Sans' colleagues made an initial public report of their experience, Dr. Cohen began using propanolol as the first-line treatment for serious infantile hemangiomas in the pediatric vascular lesions clinic at Johns Hopkins Medical Center in Baltimore.

"I haven't used steroids in any of these children since then," said Dr. Cohen, director of pediatric dermatology at the center. He and his colleagues have so far treated 41 children with propanolol and will soon publish their own experience. Although they have not had quite the 100% success rate that the French group claims, Dr. Cohen said the drug is very effective, extremely safe, and can be given without the concerns for growth and immune response that come with steroid therapy.

"I think it works better than oral steroids, but it doesn't work for everyone," he said, adding that lesions on infants responded better to the treatment than lesions on children who were older than 1 year. "If lesions are causing a lot of [functional problems], propranolol does seem to shut them down, but it did not make a dramatic difference in every one of our patients. However, it is very safe—especially compared to oral steroids."

The French team observed serendipitously that beta-blockers used for hypertension in infants positively affected the growth of hemangiomas. In 2008, following that observation, they described their index case and 10 additional cases (N. Engl. J. Med. 2008: 358:2649–51).

The current report comprises 32 children (mean age 4 months) with severe hemangiomas. All of the lesions imposed either life-threatening symptoms or the risk of severe disfigurement.

Treatment consisted of a course of oral propranolol at a dose of 2–3 mg/kg per day, initiated in an inpatient setting so that clinicians could observe the child's reaction. Blood pressure and heart rate were monitored every hour during the first 6 hours of treatment. If no adverse events occurred, the child was sent home and re-evaluated after another 10 days, with monthly evaluations afterward, Dr. Sans and her associates said.

Most of the treatments (27) were early interventions on children aged 1–12 months. For these children, the goal was to decrease functional risk, serious symptoms, or cosmetic complications. The other five children were 18–48 months old; their treatment goal was functional risk or cosmetic risk. Thirteen of the children had received corticosteroids with no benefit.

Children who had ulcerated hemangiomas experienced complete healing within 2 months of therapy initiation. In the 11 children with ultrasound measurements, the 60-day exam showed a mean lesion thickness regression of 40%, with a lower resistivity index, indicating decreased vascular activity.

The 13 children who were taking steroids all discontinued treatment without rebound. Propranolol was discontinued in 6–14 months for the early-intervention cases and in 2–10 months for the later-intervention cases. It was restarted in two cases because of regrowth. The 12 patients with eyelid involvement experienced resolution of astigmatism and amblyopia at the end of therapy, the investigators reported.

Dr. Sans and her associates noted two adverse events. One patient had a decrease in blood pressure while sleeping, 3 hours after the first dose. Another patient discontinued propranolol after experiencing wheezing thought to be caused by allergic asthma.

The authors suggested that the optimal therapy for early intervention would be to give propranolol throughout the hemangioma's proliferative phase, usually from 4 to 12 months of age. For treatments commenced after the proliferative phase has concluded, the therapy should continue until maximum improvement is noted.

The overnight improvements of lesion softening and color change (from intense red to purple) indicated the drug's vasoconstrictive effect on the lesions' capillaries, Dr. Christine Léauté-Labrèze, also of Children's Hospital, said in the initial 2008 report.

Although Dr. Sans and her coauthors said they had no financial conflicts with regard to their paper, Dr. Léauté-Labrèze noted in the 2008 paper that she and her colleagues had applied for a patent for the use of propranolol on infantile hemangiomas. Dr. Léauté-Labrèze and her coauthors—Dr. Franck Boralevi, Dr. Eric Dumas de la Roque, and Dr. Alain Taïeb—who are with Children's Hospital, are also coauthors of Dr. Sans' paper.

Since switching to propranolol in July of last year, 'I haven't used steroids in any of these children.'

Source DR. COHEN

WASHINGTON — Most women susceptible to fragility fractures fail to appreciate those risks, even if they have been told by a physician that they have osteoporosis, a large international survey-based study has concluded.

“We found a remarkable failure of many women to perceive that these clear-cut factors are putting them at increased risk for a fracture,” said Dr. Ethel Siris, an investigator for GLOW (Global Longitudinal Study of Osteoporosis in Women).

GLOW included more than 60,000 postmenopausal women who were recruited from 706 physician practices in 10 countries. The women completed questionnaires on demographic and medical information, risk factors for fragility fracture, any personal history of and treatment for osteoporosis, and health and functional status.

Comparing themselves with women of the same age, 64% of subjects with risk factors for fracture did not perceive themselves at increased risk, Dr. Siris said in an interview. Even more surprising, she said, 55% of women who had been told by a physician that they had osteoporosis thought that they were not at increased risk.

Women with other risk factors displayed a similar ignorance, Dr. Siris noted. Of women whose mother had experienced a hip fracture, 74% thought they were at a lower fracture risk than their peers or had a similar risk, as did 74% of those with a low body mass index, 80% of current smokers, 77% of those who frequently consumed alcohol, 61% of those taking corticosteroids, and 71% of those with rheumatoid arthritis.

The replies were consistent across countries, she said at an international symposium sponsored by the National Osteoporosis Foundation. “There is apparently a worldwide problem with communicating these ideas to patients.”

The failure to appreciate the implications of fracture risk may help account for the “lousy adherence” to osteoporosis therapy, said Dr. Siris, director of the osteoporosis center at Columbia University, New York.

Dr. Siris disclosed that she has received consulting fees for her time working on GLOW from Sanofi-Aventis and Procter & Gamble Co., which funded the project.

WASHINGTON — Most women susceptible to fragility fractures fail to appreciate those risks, even if they have been told by a physician that they have osteoporosis, a large international survey-based study has concluded.

“We found a remarkable failure of many women to perceive that these clear-cut factors are putting them at increased risk for a fracture,” said Dr. Ethel Siris, an investigator for GLOW (Global Longitudinal Study of Osteoporosis in Women).

GLOW included more than 60,000 postmenopausal women who were recruited from 706 physician practices in 10 countries. The women completed questionnaires on demographic and medical information, risk factors for fragility fracture, any personal history of and treatment for osteoporosis, and health and functional status.

Comparing themselves with women of the same age, 64% of subjects with risk factors for fracture did not perceive themselves at increased risk, Dr. Siris said in an interview. Even more surprising, she said, 55% of women who had been told by a physician that they had osteoporosis thought that they were not at increased risk.

Women with other risk factors displayed a similar ignorance, Dr. Siris noted. Of women whose mother had experienced a hip fracture, 74% thought they were at a lower fracture risk than their peers or had a similar risk, as did 74% of those with a low body mass index, 80% of current smokers, 77% of those who frequently consumed alcohol, 61% of those taking corticosteroids, and 71% of those with rheumatoid arthritis.

The replies were consistent across countries, she said at an international symposium sponsored by the National Osteoporosis Foundation. “There is apparently a worldwide problem with communicating these ideas to patients.”

The failure to appreciate the implications of fracture risk may help account for the “lousy adherence” to osteoporosis therapy, said Dr. Siris, director of the osteoporosis center at Columbia University, New York.

Dr. Siris disclosed that she has received consulting fees for her time working on GLOW from Sanofi-Aventis and Procter & Gamble Co., which funded the project.

WASHINGTON — Most women susceptible to fragility fractures fail to appreciate those risks, even if they have been told by a physician that they have osteoporosis, a large international survey-based study has concluded.

“We found a remarkable failure of many women to perceive that these clear-cut factors are putting them at increased risk for a fracture,” said Dr. Ethel Siris, an investigator for GLOW (Global Longitudinal Study of Osteoporosis in Women).

GLOW included more than 60,000 postmenopausal women who were recruited from 706 physician practices in 10 countries. The women completed questionnaires on demographic and medical information, risk factors for fragility fracture, any personal history of and treatment for osteoporosis, and health and functional status.

Comparing themselves with women of the same age, 64% of subjects with risk factors for fracture did not perceive themselves at increased risk, Dr. Siris said in an interview. Even more surprising, she said, 55% of women who had been told by a physician that they had osteoporosis thought that they were not at increased risk.

Women with other risk factors displayed a similar ignorance, Dr. Siris noted. Of women whose mother had experienced a hip fracture, 74% thought they were at a lower fracture risk than their peers or had a similar risk, as did 74% of those with a low body mass index, 80% of current smokers, 77% of those who frequently consumed alcohol, 61% of those taking corticosteroids, and 71% of those with rheumatoid arthritis.

The replies were consistent across countries, she said at an international symposium sponsored by the National Osteoporosis Foundation. “There is apparently a worldwide problem with communicating these ideas to patients.”

The failure to appreciate the implications of fracture risk may help account for the “lousy adherence” to osteoporosis therapy, said Dr. Siris, director of the osteoporosis center at Columbia University, New York.

Dr. Siris disclosed that she has received consulting fees for her time working on GLOW from Sanofi-Aventis and Procter & Gamble Co., which funded the project.

CHICAGO — Thiopurine therapy appears to prevent colorectal neoplasias in patients with long-term, extensive inflammatory bowel disease, reducing the risk of cancer or high-grade dysplasia by more than 70%.

The finding from a large French prospective cohort study casts a new light on the usual concern about the immunosuppressive effect of thiopurine, Dr. Philippe Seksik said at the annual Digestive Disease Week.

“Thiopurines could increase the risk of colorectal cancer via their immunosuppressive effect, or through their anti-inflammatory effect, [they] could reduce the risk of colorectal cancer,” said Dr. Seksik of Saint-Antoine Hospital, Paris. “Our data raise the hypothesis that the anti-inflammatory effect of thiopurines on colonic mucosa has a much greater impact on the risk of colorectal cancer than the putative deleterious effect of its drug-induced immunosuppression.”

Dr. Seksik and his colleagues examined the risk of colorectal cancer in CESAME, a cross-sectional French cohort study that prospectively assesses the risk of cancers in patients with irritable bowel diseases. The study recruited 19,500 patients from 2004 to 2005, and followed them through December 2007.

The patients' mean age at recruitment was 40 years (range, 1-96 years). The mean duration of the disease was 8 years, although again, the range was very wide, including a disease duration of up to 65 years. In all, 11,760 patients (60%) had Crohn's disease; of these, 15% had long-standing extensive colitis, defined as a disease duration of more than 10 years with more than 50% of the colonic mucosa involved. The remaining 40% of the cohort had ulcerative colitis or an unclassified inflammatory bowel disease; of these, 37% had long-standing extensive colitis.

In the entire cohort, there were 36 incident cases of colorectal cancer and 21 high-grade dysplasias. Among only those patients with long-standing extensive co-litis, there were 21 new cancers and 8 high-grade dysplasias.

At study inclusion, 36% of the patients were on immunosuppressive therapy. Of those, 30% were taking azathioprine or 6-mercaptopurine, 4% were taking methotrexate, and 5% were taking a tumor necrosis factor antagonist. Among all thiopurine-exposed patients, there were nine incident cases of co-lorectal cancer and three cases of high-grade dysplasia. Among only those with long-standing colitis, there were five co-lorectal cancers and one case of high-grade dysplasia.

The investigators performed a multivariate analysis examining the risk of colorectal neoplasia associated with sex, age, disease duration, and extensive co-litis. The presence of extensive colitis significantly increased patients' risk of neoplasia sevenfold, compared with the expected number of cases obtained from the national French cancer registries.

When the team examined the association between thiopurine therapy and neoplasia, they found a nonsignificant risk reduction of 43%, compared with patients who had never taken a thio-purine. The effect was much more powerful when the analysis was restricted to those with long-standing extensive colitis; thiopurine exposure reduced the risk of new neoplasia by 72%—a 3.5-fold decrease from the rate seen in thio-purine-naive patients.

Researchers are still uncertain about the mechanism of protection, Dr. Seksik said. “The protective effect could be due to a nonspecific anti-inflammatory effect, or it could be a drug-specific, antineoplastic action on the inflammation-dysplasia-cancer sequence.”

Dr. Seksik reported that he had no relevant financial disclosures.

In those with long-standing extensive colitis, thiopurine reduced the risk of new neoplasia by 72%.

Source DR. SEKSIK

CHICAGO — Thiopurine therapy appears to prevent colorectal neoplasias in patients with long-term, extensive inflammatory bowel disease, reducing the risk of cancer or high-grade dysplasia by more than 70%.

The finding from a large French prospective cohort study casts a new light on the usual concern about the immunosuppressive effect of thiopurine, Dr. Philippe Seksik said at the annual Digestive Disease Week.

“Thiopurines could increase the risk of colorectal cancer via their immunosuppressive effect, or through their anti-inflammatory effect, [they] could reduce the risk of colorectal cancer,” said Dr. Seksik of Saint-Antoine Hospital, Paris. “Our data raise the hypothesis that the anti-inflammatory effect of thiopurines on colonic mucosa has a much greater impact on the risk of colorectal cancer than the putative deleterious effect of its drug-induced immunosuppression.”

Dr. Seksik and his colleagues examined the risk of colorectal cancer in CESAME, a cross-sectional French cohort study that prospectively assesses the risk of cancers in patients with irritable bowel diseases. The study recruited 19,500 patients from 2004 to 2005, and followed them through December 2007.

The patients' mean age at recruitment was 40 years (range, 1-96 years). The mean duration of the disease was 8 years, although again, the range was very wide, including a disease duration of up to 65 years. In all, 11,760 patients (60%) had Crohn's disease; of these, 15% had long-standing extensive colitis, defined as a disease duration of more than 10 years with more than 50% of the colonic mucosa involved. The remaining 40% of the cohort had ulcerative colitis or an unclassified inflammatory bowel disease; of these, 37% had long-standing extensive colitis.

In the entire cohort, there were 36 incident cases of colorectal cancer and 21 high-grade dysplasias. Among only those patients with long-standing extensive co-litis, there were 21 new cancers and 8 high-grade dysplasias.

At study inclusion, 36% of the patients were on immunosuppressive therapy. Of those, 30% were taking azathioprine or 6-mercaptopurine, 4% were taking methotrexate, and 5% were taking a tumor necrosis factor antagonist. Among all thiopurine-exposed patients, there were nine incident cases of co-lorectal cancer and three cases of high-grade dysplasia. Among only those with long-standing colitis, there were five co-lorectal cancers and one case of high-grade dysplasia.

The investigators performed a multivariate analysis examining the risk of colorectal neoplasia associated with sex, age, disease duration, and extensive co-litis. The presence of extensive colitis significantly increased patients' risk of neoplasia sevenfold, compared with the expected number of cases obtained from the national French cancer registries.

When the team examined the association between thiopurine therapy and neoplasia, they found a nonsignificant risk reduction of 43%, compared with patients who had never taken a thio-purine. The effect was much more powerful when the analysis was restricted to those with long-standing extensive colitis; thiopurine exposure reduced the risk of new neoplasia by 72%—a 3.5-fold decrease from the rate seen in thio-purine-naive patients.

Researchers are still uncertain about the mechanism of protection, Dr. Seksik said. “The protective effect could be due to a nonspecific anti-inflammatory effect, or it could be a drug-specific, antineoplastic action on the inflammation-dysplasia-cancer sequence.”

Dr. Seksik reported that he had no relevant financial disclosures.

In those with long-standing extensive colitis, thiopurine reduced the risk of new neoplasia by 72%.

Source DR. SEKSIK

CHICAGO — Thiopurine therapy appears to prevent colorectal neoplasias in patients with long-term, extensive inflammatory bowel disease, reducing the risk of cancer or high-grade dysplasia by more than 70%.

The finding from a large French prospective cohort study casts a new light on the usual concern about the immunosuppressive effect of thiopurine, Dr. Philippe Seksik said at the annual Digestive Disease Week.

“Thiopurines could increase the risk of colorectal cancer via their immunosuppressive effect, or through their anti-inflammatory effect, [they] could reduce the risk of colorectal cancer,” said Dr. Seksik of Saint-Antoine Hospital, Paris. “Our data raise the hypothesis that the anti-inflammatory effect of thiopurines on colonic mucosa has a much greater impact on the risk of colorectal cancer than the putative deleterious effect of its drug-induced immunosuppression.”

Dr. Seksik and his colleagues examined the risk of colorectal cancer in CESAME, a cross-sectional French cohort study that prospectively assesses the risk of cancers in patients with irritable bowel diseases. The study recruited 19,500 patients from 2004 to 2005, and followed them through December 2007.

The patients' mean age at recruitment was 40 years (range, 1-96 years). The mean duration of the disease was 8 years, although again, the range was very wide, including a disease duration of up to 65 years. In all, 11,760 patients (60%) had Crohn's disease; of these, 15% had long-standing extensive colitis, defined as a disease duration of more than 10 years with more than 50% of the colonic mucosa involved. The remaining 40% of the cohort had ulcerative colitis or an unclassified inflammatory bowel disease; of these, 37% had long-standing extensive colitis.

In the entire cohort, there were 36 incident cases of colorectal cancer and 21 high-grade dysplasias. Among only those patients with long-standing extensive co-litis, there were 21 new cancers and 8 high-grade dysplasias.

At study inclusion, 36% of the patients were on immunosuppressive therapy. Of those, 30% were taking azathioprine or 6-mercaptopurine, 4% were taking methotrexate, and 5% were taking a tumor necrosis factor antagonist. Among all thiopurine-exposed patients, there were nine incident cases of co-lorectal cancer and three cases of high-grade dysplasia. Among only those with long-standing colitis, there were five co-lorectal cancers and one case of high-grade dysplasia.

The investigators performed a multivariate analysis examining the risk of colorectal neoplasia associated with sex, age, disease duration, and extensive co-litis. The presence of extensive colitis significantly increased patients' risk of neoplasia sevenfold, compared with the expected number of cases obtained from the national French cancer registries.

When the team examined the association between thiopurine therapy and neoplasia, they found a nonsignificant risk reduction of 43%, compared with patients who had never taken a thio-purine. The effect was much more powerful when the analysis was restricted to those with long-standing extensive colitis; thiopurine exposure reduced the risk of new neoplasia by 72%—a 3.5-fold decrease from the rate seen in thio-purine-naive patients.

Researchers are still uncertain about the mechanism of protection, Dr. Seksik said. “The protective effect could be due to a nonspecific anti-inflammatory effect, or it could be a drug-specific, antineoplastic action on the inflammation-dysplasia-cancer sequence.”

Dr. Seksik reported that he had no relevant financial disclosures.

In those with long-standing extensive colitis, thiopurine reduced the risk of new neoplasia by 72%.

Source DR. SEKSIK

CHICAGO — Although it is more expensive to administer, colorectal cancer screening with a fecal immunochemical test is less expensive in the long run than a guaiac-based test because it detects more high-risk lesions and thus prevents more cancers, a cost-analysis study has concluded.

The fecal immunochemical test (FIT) had better adherence rates and detected more high-risk adenomas than did the guaiac-based test, making it a much better option overall, Dr. Rodrigo Jover said at the annual Digestive Disease Week.

Positivity rates were 9.5% with the FIT and 2% with the guaiac test. “This provoked a huge difference in the detection rate of high-risk adenoma and cancer: 34 per 1,000 screened, compared with just 5 per 1,000,” said Dr. Jover of the Hospital General Universitario de Alicante, Spain.

Dr. Jover and his colleagues compared the first-round results of two regional colorectal cancer screening programs. The County of Valencia program invited 98,600 residents aged 50-69 years to be screened by mailing them a guaiac-based fecal occult blood test. The Region of Murcia program invited 35,700 residents of the same age to complete a FIT screen.

Dr. Jover had no relevant financial disclosures.

CHICAGO — Although it is more expensive to administer, colorectal cancer screening with a fecal immunochemical test is less expensive in the long run than a guaiac-based test because it detects more high-risk lesions and thus prevents more cancers, a cost-analysis study has concluded.

The fecal immunochemical test (FIT) had better adherence rates and detected more high-risk adenomas than did the guaiac-based test, making it a much better option overall, Dr. Rodrigo Jover said at the annual Digestive Disease Week.

Positivity rates were 9.5% with the FIT and 2% with the guaiac test. “This provoked a huge difference in the detection rate of high-risk adenoma and cancer: 34 per 1,000 screened, compared with just 5 per 1,000,” said Dr. Jover of the Hospital General Universitario de Alicante, Spain.

Dr. Jover and his colleagues compared the first-round results of two regional colorectal cancer screening programs. The County of Valencia program invited 98,600 residents aged 50-69 years to be screened by mailing them a guaiac-based fecal occult blood test. The Region of Murcia program invited 35,700 residents of the same age to complete a FIT screen.

Dr. Jover had no relevant financial disclosures.

CHICAGO — Although it is more expensive to administer, colorectal cancer screening with a fecal immunochemical test is less expensive in the long run than a guaiac-based test because it detects more high-risk lesions and thus prevents more cancers, a cost-analysis study has concluded.

The fecal immunochemical test (FIT) had better adherence rates and detected more high-risk adenomas than did the guaiac-based test, making it a much better option overall, Dr. Rodrigo Jover said at the annual Digestive Disease Week.

Positivity rates were 9.5% with the FIT and 2% with the guaiac test. “This provoked a huge difference in the detection rate of high-risk adenoma and cancer: 34 per 1,000 screened, compared with just 5 per 1,000,” said Dr. Jover of the Hospital General Universitario de Alicante, Spain.

Dr. Jover and his colleagues compared the first-round results of two regional colorectal cancer screening programs. The County of Valencia program invited 98,600 residents aged 50-69 years to be screened by mailing them a guaiac-based fecal occult blood test. The Region of Murcia program invited 35,700 residents of the same age to complete a FIT screen.

Dr. Jover had no relevant financial disclosures.

CHICAGO — Repeating a flexible sigmoidoscopy at 5 years instead of 3 years after an initial negative exam increases the risk of finding a cancer or advanced adenoma by 70%.

Men are particularly at risk when they delay the follow-up, Dr. Robert Schoen said at the annual Digestive Disease Week. “Not only did men have more neoplasias than women at the 5-year exam, but, when we compared the 3- and 5-year exams, the increase in yield was significantly greater in men than in women.”

The findings were seen in a subanalysis of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Initially, the trial protocol called for repeat flexible sigmoidoscopy 3 years after an initial negative exam. In 1998, the protocol changed to a 5-year follow-up period, said Dr. Schoen of the University of Pittsburgh.

The analysis included two cohorts: those whose repeat screenings took place after 3 years (9,000) and those whose repeat screenings took place after 5 years (24,000). None of the subjects had a polyp identified on their initial exam.

Overall, he said, significantly more 5-year exams were positive for a neoplasm (21% vs. 14%) than were 3-year exams. The crude number of cancers identified was not significantly different between the cohorts, but the number of cancers or advanced adenomas was (12/1,000 vs. 9/1,000 subjects). The crude rate of cancer or any adenoma also was significantly higher in the 5-year group (49/1,000 vs. 34/1,000).

In both cohorts, men were significantly more likely than women to have a neoplasm identified. But in a comparison of the 3- and 5-year exams, men also had a significantly higher change in the yield with the different follow-up times. (See chart.)

After controlling for age, gender, and history of a colon procedure at least 3 years before enrollment, the investigators found delaying the repeat exam to 5 years significantly increased the yield of a cancer or any adenoma by 70% and of cancer or an advanced adenoma by 47%.

Dr. Schoen had no financial disclosures relevant to the study.

Men were significantly more likely than women to have a neoplasm identified.

Source DR. SCHOEN

Source ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — Repeating a flexible sigmoidoscopy at 5 years instead of 3 years after an initial negative exam increases the risk of finding a cancer or advanced adenoma by 70%.

Men are particularly at risk when they delay the follow-up, Dr. Robert Schoen said at the annual Digestive Disease Week. “Not only did men have more neoplasias than women at the 5-year exam, but, when we compared the 3- and 5-year exams, the increase in yield was significantly greater in men than in women.”

The findings were seen in a subanalysis of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Initially, the trial protocol called for repeat flexible sigmoidoscopy 3 years after an initial negative exam. In 1998, the protocol changed to a 5-year follow-up period, said Dr. Schoen of the University of Pittsburgh.

The analysis included two cohorts: those whose repeat screenings took place after 3 years (9,000) and those whose repeat screenings took place after 5 years (24,000). None of the subjects had a polyp identified on their initial exam.

Overall, he said, significantly more 5-year exams were positive for a neoplasm (21% vs. 14%) than were 3-year exams. The crude number of cancers identified was not significantly different between the cohorts, but the number of cancers or advanced adenomas was (12/1,000 vs. 9/1,000 subjects). The crude rate of cancer or any adenoma also was significantly higher in the 5-year group (49/1,000 vs. 34/1,000).

In both cohorts, men were significantly more likely than women to have a neoplasm identified. But in a comparison of the 3- and 5-year exams, men also had a significantly higher change in the yield with the different follow-up times. (See chart.)

After controlling for age, gender, and history of a colon procedure at least 3 years before enrollment, the investigators found delaying the repeat exam to 5 years significantly increased the yield of a cancer or any adenoma by 70% and of cancer or an advanced adenoma by 47%.

Dr. Schoen had no financial disclosures relevant to the study.

Men were significantly more likely than women to have a neoplasm identified.

Source DR. SCHOEN

Source ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — Repeating a flexible sigmoidoscopy at 5 years instead of 3 years after an initial negative exam increases the risk of finding a cancer or advanced adenoma by 70%.

Men are particularly at risk when they delay the follow-up, Dr. Robert Schoen said at the annual Digestive Disease Week. “Not only did men have more neoplasias than women at the 5-year exam, but, when we compared the 3- and 5-year exams, the increase in yield was significantly greater in men than in women.”

The findings were seen in a subanalysis of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Initially, the trial protocol called for repeat flexible sigmoidoscopy 3 years after an initial negative exam. In 1998, the protocol changed to a 5-year follow-up period, said Dr. Schoen of the University of Pittsburgh.

The analysis included two cohorts: those whose repeat screenings took place after 3 years (9,000) and those whose repeat screenings took place after 5 years (24,000). None of the subjects had a polyp identified on their initial exam.

Overall, he said, significantly more 5-year exams were positive for a neoplasm (21% vs. 14%) than were 3-year exams. The crude number of cancers identified was not significantly different between the cohorts, but the number of cancers or advanced adenomas was (12/1,000 vs. 9/1,000 subjects). The crude rate of cancer or any adenoma also was significantly higher in the 5-year group (49/1,000 vs. 34/1,000).

In both cohorts, men were significantly more likely than women to have a neoplasm identified. But in a comparison of the 3- and 5-year exams, men also had a significantly higher change in the yield with the different follow-up times. (See chart.)

After controlling for age, gender, and history of a colon procedure at least 3 years before enrollment, the investigators found delaying the repeat exam to 5 years significantly increased the yield of a cancer or any adenoma by 70% and of cancer or an advanced adenoma by 47%.

Dr. Schoen had no financial disclosures relevant to the study.

Men were significantly more likely than women to have a neoplasm identified.

Source DR. SCHOEN

Source ELSEVIER GLOBAL MEDICAL NEWS

VIENNA – A drink or two a day seems to protect against the development of dementia in cognitively normal elderly adults, a study suggests.

But moderate alcohol consumption doesn't improve thinking processes in those who already have mild cognitive impairment (MCI), and heavy drinking can tip the scales from mild impairment to dementia, Dr. Kaycee M. Sink said at the International Conference on Alzheimer's Disease.

“Our findings support current recommendations for alcohol consumption [of one drink per day for women and two for men], at least for older adults with normal cognition,” Dr. Sink said in an interview.

However, she warned, alcohol's brain benefit can't be used as an excuse to take up drinking at an advanced age. “The results of our study apply only to older adults who reported drinking alcohol at the start of the study. They can't be extrapolated to those who do not currently drink–that is, we cannot recommend that someone in his 70s or 80s start drinking alcohol to try to prevent dementia,” said Dr. Sink of Wake Forest University, Winston-Salem, N.C.

Dr. Sink and her colleagues based their study on data extracted from the Ginkgo Evaluation of Memory (GEM) study, which enrolled 3,069 participants aged 75 or older with normal cognition or mild cognitive impairment. They were randomized to twice-daily doses of either placebo or 120 mg of ginkgo extract. Although the extract was safe, it was not associated with any significant cognitive improvement (JAMA 2008;300:2253-62).

At baseline, the subjects' average age was 78 years; 2,587 were cognitively normal, and 482 had MCI. MCI was present in 20% of the alcohol abstainers and 12% of the consumers.

Subjects self-reported daily alcohol consumption as abstinent, light (1-7 drinks a week), moderate (8-14 drinks), or heavy (more than 14 drinks). Abstinence was reported by 43%, light drinking by 38%, moderate drinking by 9%, and heavy drinking by 10%.

There were 523 new cases of dementia during the 6-year follow-up period. After adjustment for demographics, smoking, medical comorbidities, depression, social activity, and baseline cognition, moderate alcohol consumption conferred a 37% reduction in the risk of dementia in those who were cognitively normal at baseline. But moderate drinking did not reduce the dementia risk for those who already had MCI at baseline.

Heavy drinking conferred a nonsignificant 18% risk reduction for cognitively normal subjects. But in those who already had MCI, heavy drinking significantly increased by 92% the risk of progression to dementia. “Heavy alcohol use is associated long-term toxic effects in the brain. In addition to the almost twofold increase in risk of progression to dementia for participants with MCI who drank heavily, we saw that even lesser amounts of alcohol were associated with greater declines in a measure of overall cognition over the 6-year study,” she said.

The protective mechanism of mild drinking remains a mystery, she said.

“We don't fully understand how alcohol may be protective against dementia,” said Dr. Sink. However, since for many people, MCI is a transition state between normal cognition and dementia, it may be that any protective benefits from moderate alcohol intake are too late once the process of cognitive impairment begins. Alternatively, the results could be consistent with the cognitive reserve hypothesis, in that those who are already declining aren't as resilient to neurotoxic effects of heavy alcohol use as cognitively normal older adults might be.”

Dr. Sink said she had no conflicts of interest with regard to the study.

'The results of our study apply only to older adults who reported drinking alcohol at the start of the study.'

Source DR. SINK

VIENNA – A drink or two a day seems to protect against the development of dementia in cognitively normal elderly adults, a study suggests.

But moderate alcohol consumption doesn't improve thinking processes in those who already have mild cognitive impairment (MCI), and heavy drinking can tip the scales from mild impairment to dementia, Dr. Kaycee M. Sink said at the International Conference on Alzheimer's Disease.

“Our findings support current recommendations for alcohol consumption [of one drink per day for women and two for men], at least for older adults with normal cognition,” Dr. Sink said in an interview.

However, she warned, alcohol's brain benefit can't be used as an excuse to take up drinking at an advanced age. “The results of our study apply only to older adults who reported drinking alcohol at the start of the study. They can't be extrapolated to those who do not currently drink–that is, we cannot recommend that someone in his 70s or 80s start drinking alcohol to try to prevent dementia,” said Dr. Sink of Wake Forest University, Winston-Salem, N.C.

Dr. Sink and her colleagues based their study on data extracted from the Ginkgo Evaluation of Memory (GEM) study, which enrolled 3,069 participants aged 75 or older with normal cognition or mild cognitive impairment. They were randomized to twice-daily doses of either placebo or 120 mg of ginkgo extract. Although the extract was safe, it was not associated with any significant cognitive improvement (JAMA 2008;300:2253-62).

At baseline, the subjects' average age was 78 years; 2,587 were cognitively normal, and 482 had MCI. MCI was present in 20% of the alcohol abstainers and 12% of the consumers.

Subjects self-reported daily alcohol consumption as abstinent, light (1-7 drinks a week), moderate (8-14 drinks), or heavy (more than 14 drinks). Abstinence was reported by 43%, light drinking by 38%, moderate drinking by 9%, and heavy drinking by 10%.

There were 523 new cases of dementia during the 6-year follow-up period. After adjustment for demographics, smoking, medical comorbidities, depression, social activity, and baseline cognition, moderate alcohol consumption conferred a 37% reduction in the risk of dementia in those who were cognitively normal at baseline. But moderate drinking did not reduce the dementia risk for those who already had MCI at baseline.

Heavy drinking conferred a nonsignificant 18% risk reduction for cognitively normal subjects. But in those who already had MCI, heavy drinking significantly increased by 92% the risk of progression to dementia. “Heavy alcohol use is associated long-term toxic effects in the brain. In addition to the almost twofold increase in risk of progression to dementia for participants with MCI who drank heavily, we saw that even lesser amounts of alcohol were associated with greater declines in a measure of overall cognition over the 6-year study,” she said.

The protective mechanism of mild drinking remains a mystery, she said.

“We don't fully understand how alcohol may be protective against dementia,” said Dr. Sink. However, since for many people, MCI is a transition state between normal cognition and dementia, it may be that any protective benefits from moderate alcohol intake are too late once the process of cognitive impairment begins. Alternatively, the results could be consistent with the cognitive reserve hypothesis, in that those who are already declining aren't as resilient to neurotoxic effects of heavy alcohol use as cognitively normal older adults might be.”

Dr. Sink said she had no conflicts of interest with regard to the study.

'The results of our study apply only to older adults who reported drinking alcohol at the start of the study.'

Source DR. SINK

VIENNA – A drink or two a day seems to protect against the development of dementia in cognitively normal elderly adults, a study suggests.

But moderate alcohol consumption doesn't improve thinking processes in those who already have mild cognitive impairment (MCI), and heavy drinking can tip the scales from mild impairment to dementia, Dr. Kaycee M. Sink said at the International Conference on Alzheimer's Disease.

“Our findings support current recommendations for alcohol consumption [of one drink per day for women and two for men], at least for older adults with normal cognition,” Dr. Sink said in an interview.

However, she warned, alcohol's brain benefit can't be used as an excuse to take up drinking at an advanced age. “The results of our study apply only to older adults who reported drinking alcohol at the start of the study. They can't be extrapolated to those who do not currently drink–that is, we cannot recommend that someone in his 70s or 80s start drinking alcohol to try to prevent dementia,” said Dr. Sink of Wake Forest University, Winston-Salem, N.C.

Dr. Sink and her colleagues based their study on data extracted from the Ginkgo Evaluation of Memory (GEM) study, which enrolled 3,069 participants aged 75 or older with normal cognition or mild cognitive impairment. They were randomized to twice-daily doses of either placebo or 120 mg of ginkgo extract. Although the extract was safe, it was not associated with any significant cognitive improvement (JAMA 2008;300:2253-62).

At baseline, the subjects' average age was 78 years; 2,587 were cognitively normal, and 482 had MCI. MCI was present in 20% of the alcohol abstainers and 12% of the consumers.

Subjects self-reported daily alcohol consumption as abstinent, light (1-7 drinks a week), moderate (8-14 drinks), or heavy (more than 14 drinks). Abstinence was reported by 43%, light drinking by 38%, moderate drinking by 9%, and heavy drinking by 10%.

There were 523 new cases of dementia during the 6-year follow-up period. After adjustment for demographics, smoking, medical comorbidities, depression, social activity, and baseline cognition, moderate alcohol consumption conferred a 37% reduction in the risk of dementia in those who were cognitively normal at baseline. But moderate drinking did not reduce the dementia risk for those who already had MCI at baseline.

Heavy drinking conferred a nonsignificant 18% risk reduction for cognitively normal subjects. But in those who already had MCI, heavy drinking significantly increased by 92% the risk of progression to dementia. “Heavy alcohol use is associated long-term toxic effects in the brain. In addition to the almost twofold increase in risk of progression to dementia for participants with MCI who drank heavily, we saw that even lesser amounts of alcohol were associated with greater declines in a measure of overall cognition over the 6-year study,” she said.

The protective mechanism of mild drinking remains a mystery, she said.

“We don't fully understand how alcohol may be protective against dementia,” said Dr. Sink. However, since for many people, MCI is a transition state between normal cognition and dementia, it may be that any protective benefits from moderate alcohol intake are too late once the process of cognitive impairment begins. Alternatively, the results could be consistent with the cognitive reserve hypothesis, in that those who are already declining aren't as resilient to neurotoxic effects of heavy alcohol use as cognitively normal older adults might be.”

Dr. Sink said she had no conflicts of interest with regard to the study.

'The results of our study apply only to older adults who reported drinking alcohol at the start of the study.'

Source DR. SINK