Mary Ann Moon

Coronary artery bypass grafting produces better outcomes than drug-eluting coronary stents do in patients with multivessel disease, according to a database study.

Given recent reports of the danger of late stent thrombosis with the drug-eluting devices, it wasn't clear “whether the relative outcomes reported in earlier studies that compared coronary artery bypass grafting (CABG) with coronary stenting are reflective of current practice.” Most of those studies were done comparing CABG with bare metal stents.

So Dr. Edward L. Hannan of the State University of New York at Albany and his associates used public health databases to compare outcomes between 9,963 state residents who received multiple drug-eluting stents via percutaneous coronary intervention and 7,437 who underwent CABG between October 2003 and December 2004. They followed all subjects through the end of 2005 and presented their report in the Jan. 24 issue of the New England Journal of Medicine.

Patients who received stents had a lower survival rate at 18 months (93%) than did those who underwent CABG (94%), as well as lower rates of the combined end point of freedom from MI or death (88% vs. 92%, respectively).

Outcomes were superior with CABG regardless of whether patients had proximal left anterior descending artery disease. And there was a trend favoring CABG in three high-risk subgroups of patients: those with diabetes, those with left ventricular ejection fractions below 40%, and those aged 80 and older, Dr. Hannan and his associates said (N. Engl. J. Med. 2008;358:331–41).

In an accompanying editorial comment, Dr. Joseph P. Carrozza Jr. of Harvard Medical School, Boston, said, “The New York state registries are a sobering reality check for those who hoped the benefits of drug elution would level the playing field between CABG and stents.” Instead, the results “affirm that CABG remains the standard of care for patients who require multivessel coronary revascularization,” he said (New Engl. J. Med. 2008;358:405–7).

Coronary artery bypass grafting produces better outcomes than drug-eluting coronary stents do in patients with multivessel disease, according to a database study.

Given recent reports of the danger of late stent thrombosis with the drug-eluting devices, it wasn't clear “whether the relative outcomes reported in earlier studies that compared coronary artery bypass grafting (CABG) with coronary stenting are reflective of current practice.” Most of those studies were done comparing CABG with bare metal stents.

So Dr. Edward L. Hannan of the State University of New York at Albany and his associates used public health databases to compare outcomes between 9,963 state residents who received multiple drug-eluting stents via percutaneous coronary intervention and 7,437 who underwent CABG between October 2003 and December 2004. They followed all subjects through the end of 2005 and presented their report in the Jan. 24 issue of the New England Journal of Medicine.

Patients who received stents had a lower survival rate at 18 months (93%) than did those who underwent CABG (94%), as well as lower rates of the combined end point of freedom from MI or death (88% vs. 92%, respectively).

Outcomes were superior with CABG regardless of whether patients had proximal left anterior descending artery disease. And there was a trend favoring CABG in three high-risk subgroups of patients: those with diabetes, those with left ventricular ejection fractions below 40%, and those aged 80 and older, Dr. Hannan and his associates said (N. Engl. J. Med. 2008;358:331–41).

In an accompanying editorial comment, Dr. Joseph P. Carrozza Jr. of Harvard Medical School, Boston, said, “The New York state registries are a sobering reality check for those who hoped the benefits of drug elution would level the playing field between CABG and stents.” Instead, the results “affirm that CABG remains the standard of care for patients who require multivessel coronary revascularization,” he said (New Engl. J. Med. 2008;358:405–7).

Coronary artery bypass grafting produces better outcomes than drug-eluting coronary stents do in patients with multivessel disease, according to a database study.

Given recent reports of the danger of late stent thrombosis with the drug-eluting devices, it wasn't clear “whether the relative outcomes reported in earlier studies that compared coronary artery bypass grafting (CABG) with coronary stenting are reflective of current practice.” Most of those studies were done comparing CABG with bare metal stents.

So Dr. Edward L. Hannan of the State University of New York at Albany and his associates used public health databases to compare outcomes between 9,963 state residents who received multiple drug-eluting stents via percutaneous coronary intervention and 7,437 who underwent CABG between October 2003 and December 2004. They followed all subjects through the end of 2005 and presented their report in the Jan. 24 issue of the New England Journal of Medicine.

Patients who received stents had a lower survival rate at 18 months (93%) than did those who underwent CABG (94%), as well as lower rates of the combined end point of freedom from MI or death (88% vs. 92%, respectively).

Outcomes were superior with CABG regardless of whether patients had proximal left anterior descending artery disease. And there was a trend favoring CABG in three high-risk subgroups of patients: those with diabetes, those with left ventricular ejection fractions below 40%, and those aged 80 and older, Dr. Hannan and his associates said (N. Engl. J. Med. 2008;358:331–41).

In an accompanying editorial comment, Dr. Joseph P. Carrozza Jr. of Harvard Medical School, Boston, said, “The New York state registries are a sobering reality check for those who hoped the benefits of drug elution would level the playing field between CABG and stents.” Instead, the results “affirm that CABG remains the standard of care for patients who require multivessel coronary revascularization,” he said (New Engl. J. Med. 2008;358:405–7).

A citywide program that relies on patient referral by paramedics dramatically shortened door-to-balloon times and halved in-hospital mortality among patients with ST-segment elevation myocardial infarction.

Launched in May 2005 in Ottawa (population 800,000), the program allows specially trained paramedics to triage and transport STEMI patients directly to a percutaneous coronary intervention (PCI) center, bypassing the emergency department. The program was developed after researchers had shown that paramedics there could accurately interpret prehospital ECGs and identify STEMI, Dr. Michel R. Le May and his associates reported.

Paramedics with advanced training in cardiac life support perform and interpret 12-lead ECGs at the scene, then triage and transport patients with STEMI to the city's designated PCI center at the University of Ottawa Heart Institute, bypassing the city's four EDs. The paramedics also use a dedicated phone line to notify the cardiology team to anticipate the patient's arrival and assemble near the catheterization laboratory.

During the first year of the program, 135 STEMI patients were thus referred directly from the field by paramedics, said Dr. Le May of the heart institute and his associates (N. Engl. J. Med. 2008;358:231–40).

Another 209 STEMI patients went through the usual process of presenting to one of the four EDs either on their own or by ambulance not staffed by specially trained paramedics. These patients were triaged by an ED nurse, evaluated by an ED physician, and immediately transferred to the designated PCI center by ambulance. All the EDs were within a 10-minute ambulance ride of the PCI center. The median door-to-balloon time was significantly shorter for patients referred from the field (69 minutes) than for those transferred from EDs (123 minutes).

Door-to-balloon times of less than 90 minutes, as recommended in current guidelines, were achieved in 80% of patients referred from the field, compared with only 12% of those transferred from EDs, the investigators said.

“Before implementation of this approach, these patients (almost 40% of the entire cohort) would have been brought to the nearest hospital ED and considered for fibrinolysis. In this respect, the change in referral practice clearly benefited a substantial proportion of patients,” Dr. Le May and his associates noted.

In-hospital mortality was 3% for patients referred directly by paramedics, compared with 6% for those transferred from EDs. “Before we re-engineered our strategies, in-hospital mortality [for STEMI] was 10% for patients presenting to our city's EDs between 2002 and 2004,” they said.

A citywide program that relies on patient referral by paramedics dramatically shortened door-to-balloon times and halved in-hospital mortality among patients with ST-segment elevation myocardial infarction.

Launched in May 2005 in Ottawa (population 800,000), the program allows specially trained paramedics to triage and transport STEMI patients directly to a percutaneous coronary intervention (PCI) center, bypassing the emergency department. The program was developed after researchers had shown that paramedics there could accurately interpret prehospital ECGs and identify STEMI, Dr. Michel R. Le May and his associates reported.

Paramedics with advanced training in cardiac life support perform and interpret 12-lead ECGs at the scene, then triage and transport patients with STEMI to the city's designated PCI center at the University of Ottawa Heart Institute, bypassing the city's four EDs. The paramedics also use a dedicated phone line to notify the cardiology team to anticipate the patient's arrival and assemble near the catheterization laboratory.

During the first year of the program, 135 STEMI patients were thus referred directly from the field by paramedics, said Dr. Le May of the heart institute and his associates (N. Engl. J. Med. 2008;358:231–40).

Another 209 STEMI patients went through the usual process of presenting to one of the four EDs either on their own or by ambulance not staffed by specially trained paramedics. These patients were triaged by an ED nurse, evaluated by an ED physician, and immediately transferred to the designated PCI center by ambulance. All the EDs were within a 10-minute ambulance ride of the PCI center. The median door-to-balloon time was significantly shorter for patients referred from the field (69 minutes) than for those transferred from EDs (123 minutes).

Door-to-balloon times of less than 90 minutes, as recommended in current guidelines, were achieved in 80% of patients referred from the field, compared with only 12% of those transferred from EDs, the investigators said.

“Before implementation of this approach, these patients (almost 40% of the entire cohort) would have been brought to the nearest hospital ED and considered for fibrinolysis. In this respect, the change in referral practice clearly benefited a substantial proportion of patients,” Dr. Le May and his associates noted.

In-hospital mortality was 3% for patients referred directly by paramedics, compared with 6% for those transferred from EDs. “Before we re-engineered our strategies, in-hospital mortality [for STEMI] was 10% for patients presenting to our city's EDs between 2002 and 2004,” they said.

A citywide program that relies on patient referral by paramedics dramatically shortened door-to-balloon times and halved in-hospital mortality among patients with ST-segment elevation myocardial infarction.

Launched in May 2005 in Ottawa (population 800,000), the program allows specially trained paramedics to triage and transport STEMI patients directly to a percutaneous coronary intervention (PCI) center, bypassing the emergency department. The program was developed after researchers had shown that paramedics there could accurately interpret prehospital ECGs and identify STEMI, Dr. Michel R. Le May and his associates reported.

Paramedics with advanced training in cardiac life support perform and interpret 12-lead ECGs at the scene, then triage and transport patients with STEMI to the city's designated PCI center at the University of Ottawa Heart Institute, bypassing the city's four EDs. The paramedics also use a dedicated phone line to notify the cardiology team to anticipate the patient's arrival and assemble near the catheterization laboratory.

During the first year of the program, 135 STEMI patients were thus referred directly from the field by paramedics, said Dr. Le May of the heart institute and his associates (N. Engl. J. Med. 2008;358:231–40).

Another 209 STEMI patients went through the usual process of presenting to one of the four EDs either on their own or by ambulance not staffed by specially trained paramedics. These patients were triaged by an ED nurse, evaluated by an ED physician, and immediately transferred to the designated PCI center by ambulance. All the EDs were within a 10-minute ambulance ride of the PCI center. The median door-to-balloon time was significantly shorter for patients referred from the field (69 minutes) than for those transferred from EDs (123 minutes).

Door-to-balloon times of less than 90 minutes, as recommended in current guidelines, were achieved in 80% of patients referred from the field, compared with only 12% of those transferred from EDs, the investigators said.

“Before implementation of this approach, these patients (almost 40% of the entire cohort) would have been brought to the nearest hospital ED and considered for fibrinolysis. In this respect, the change in referral practice clearly benefited a substantial proportion of patients,” Dr. Le May and his associates noted.

In-hospital mortality was 3% for patients referred directly by paramedics, compared with 6% for those transferred from EDs. “Before we re-engineered our strategies, in-hospital mortality [for STEMI] was 10% for patients presenting to our city's EDs between 2002 and 2004,” they said.

The risk of myocardial infarction or death spikes during the 90 days after clopidogrel therapy is discontinued among patients treated for acute coronary syndromes, especially those treated medically.

Clustering of adverse coronary events has been reported after cessation of long-term aspirin and heparin therapy in acute coronary syndrome (ACS) patients. Dr. P. Michael Ho of the Denver Veterans Administration Medical Center and his associates assessed whether clopidogrel withdrawal was associated with a similar “rebound” effect.

The investigators analyzed data on all patients with acute MI or unstable angina who were discharged from any of 127 VA medical centers throughout the country between 2003 and 2005 with prescriptions for clopidogrel. A total of 1,568 of these patients who had been treated medically and 1,569 who had undergone PCI took the drug for a mean of 302 and 203 days, respectively, then discontinued the treatment.

In the medically treated patients, the combined end point of all-cause mortality or ACS occurred in 268 patients (17%) after they stopped taking clopidogrel. Significantly more (163) of those events occurred within 90 days of clopidogrel discontinuation than occurred at 91–180 days (57) or 181–270 days (26).

In PCI-treated patients, who took clopidogrel for an average of 278 days after their procedure, death or ACS occurred in 124 (8%) after discontinuation. As with the medically treated patients, significantly more of the primary end point events occurred within 90 days of cessation (73), compared with days 91–180 (29) and days 181–270 (8).

“We found a clustering of death or acute MI in the initial 90-day period after stopping treatment with clopidogrel, compared with later follow-up intervals,” the investigators said (JAMA 2008;299:532–9).

The incidence rate of adverse events was higher by far in the medically treated patients within 90 days of drug cessation, at 1.31 per 1,000 patient-days, than in those patients during days 91–180 (0.69) or in the PCI group during the same period (0.57).

This study was funded by the U.S. Department of Veterans Affairs. One of Dr. Ho's associates receives research support from Bristol-Myers Squibb and Sanofi-Aventis, both of which market clopidogrel.

The risk of myocardial infarction or death spikes during the 90 days after clopidogrel therapy is discontinued among patients treated for acute coronary syndromes, especially those treated medically.

Clustering of adverse coronary events has been reported after cessation of long-term aspirin and heparin therapy in acute coronary syndrome (ACS) patients. Dr. P. Michael Ho of the Denver Veterans Administration Medical Center and his associates assessed whether clopidogrel withdrawal was associated with a similar “rebound” effect.

The investigators analyzed data on all patients with acute MI or unstable angina who were discharged from any of 127 VA medical centers throughout the country between 2003 and 2005 with prescriptions for clopidogrel. A total of 1,568 of these patients who had been treated medically and 1,569 who had undergone PCI took the drug for a mean of 302 and 203 days, respectively, then discontinued the treatment.

In the medically treated patients, the combined end point of all-cause mortality or ACS occurred in 268 patients (17%) after they stopped taking clopidogrel. Significantly more (163) of those events occurred within 90 days of clopidogrel discontinuation than occurred at 91–180 days (57) or 181–270 days (26).

In PCI-treated patients, who took clopidogrel for an average of 278 days after their procedure, death or ACS occurred in 124 (8%) after discontinuation. As with the medically treated patients, significantly more of the primary end point events occurred within 90 days of cessation (73), compared with days 91–180 (29) and days 181–270 (8).

“We found a clustering of death or acute MI in the initial 90-day period after stopping treatment with clopidogrel, compared with later follow-up intervals,” the investigators said (JAMA 2008;299:532–9).

The incidence rate of adverse events was higher by far in the medically treated patients within 90 days of drug cessation, at 1.31 per 1,000 patient-days, than in those patients during days 91–180 (0.69) or in the PCI group during the same period (0.57).

This study was funded by the U.S. Department of Veterans Affairs. One of Dr. Ho's associates receives research support from Bristol-Myers Squibb and Sanofi-Aventis, both of which market clopidogrel.

The risk of myocardial infarction or death spikes during the 90 days after clopidogrel therapy is discontinued among patients treated for acute coronary syndromes, especially those treated medically.

Clustering of adverse coronary events has been reported after cessation of long-term aspirin and heparin therapy in acute coronary syndrome (ACS) patients. Dr. P. Michael Ho of the Denver Veterans Administration Medical Center and his associates assessed whether clopidogrel withdrawal was associated with a similar “rebound” effect.

The investigators analyzed data on all patients with acute MI or unstable angina who were discharged from any of 127 VA medical centers throughout the country between 2003 and 2005 with prescriptions for clopidogrel. A total of 1,568 of these patients who had been treated medically and 1,569 who had undergone PCI took the drug for a mean of 302 and 203 days, respectively, then discontinued the treatment.

In the medically treated patients, the combined end point of all-cause mortality or ACS occurred in 268 patients (17%) after they stopped taking clopidogrel. Significantly more (163) of those events occurred within 90 days of clopidogrel discontinuation than occurred at 91–180 days (57) or 181–270 days (26).

In PCI-treated patients, who took clopidogrel for an average of 278 days after their procedure, death or ACS occurred in 124 (8%) after discontinuation. As with the medically treated patients, significantly more of the primary end point events occurred within 90 days of cessation (73), compared with days 91–180 (29) and days 181–270 (8).

“We found a clustering of death or acute MI in the initial 90-day period after stopping treatment with clopidogrel, compared with later follow-up intervals,” the investigators said (JAMA 2008;299:532–9).

The incidence rate of adverse events was higher by far in the medically treated patients within 90 days of drug cessation, at 1.31 per 1,000 patient-days, than in those patients during days 91–180 (0.69) or in the PCI group during the same period (0.57).

This study was funded by the U.S. Department of Veterans Affairs. One of Dr. Ho's associates receives research support from Bristol-Myers Squibb and Sanofi-Aventis, both of which market clopidogrel.

The burden of depression is disproportionately higher among older women than older men because of their greater susceptibility to depression and—once depressed—their greater tendency to have persistent depression and their lower probability of death, suggest the results of a longitudinal study.

Clinically significant depressive symptoms affect 8%–20% of community-dwelling older people, and previous research has failed to explain the underlying gender differences, wrote Lisa C. Barry, Ph.D., of Yale University, New Haven, Conn., and her associates.

They assessed those differences in the onset and persistence of depression, as well as in overall mortality. They used data from a 1998 longitudinal study of 754 residents of New Haven aged 70 years and older at baseline. The subjects were followed using detailed in-home assessments every 18 months for up to 6 years (Arch. Gen. Psychiatry 2008;65:172–8).

At baseline, the subjects were a mean age of 78 years. Sixty-five percent of them were women, and 91% were non-Hispanic whites. On average, subjects had a high school education, had two chronic conditions, and were cognitively intact.

A total of 269 subjects (36%) had depressive symptoms at some time during the 6-year study. The prevalence of depressive symptoms was substantially higher in women than men at all time points.

Compared with men, women had a higher rate of making the transition from nondepressed to depressed status over time, a higher rate of remaining depressed over time, and a lower rate of making the transition to nondepressed status or to death over time.

“Older men generally have higher mortality rates than older women, irrespective of depression. [But] the mortality difference by sex was marked, with a nearly threefold difference in the odds ratios for thosewho were depressed, compared with those who were not,” they said, noting that previous studies may have been unable to detect these patterns because they did not account for fluctuations in depression over time.

“The consistency of our findings over four different time intervals provides strong evidence that depression is more likely to persist in older women than in men. [This] is somewhat surprising because women are more likely than men to receive pharmacologic and nonpharmacologic treatment for depression,” the researchers said.

“Whether women are treated less aggressively than men for late-life depression or are less likely to respond to conventional treatment is not known, but should be the focus of future research,” they said.

The study was supported by grants from the National Institute on Aging.

The researchers reported no disclosures.

The burden of depression is disproportionately higher among older women than older men because of their greater susceptibility to depression and—once depressed—their greater tendency to have persistent depression and their lower probability of death, suggest the results of a longitudinal study.

Clinically significant depressive symptoms affect 8%–20% of community-dwelling older people, and previous research has failed to explain the underlying gender differences, wrote Lisa C. Barry, Ph.D., of Yale University, New Haven, Conn., and her associates.

They assessed those differences in the onset and persistence of depression, as well as in overall mortality. They used data from a 1998 longitudinal study of 754 residents of New Haven aged 70 years and older at baseline. The subjects were followed using detailed in-home assessments every 18 months for up to 6 years (Arch. Gen. Psychiatry 2008;65:172–8).

At baseline, the subjects were a mean age of 78 years. Sixty-five percent of them were women, and 91% were non-Hispanic whites. On average, subjects had a high school education, had two chronic conditions, and were cognitively intact.

A total of 269 subjects (36%) had depressive symptoms at some time during the 6-year study. The prevalence of depressive symptoms was substantially higher in women than men at all time points.

Compared with men, women had a higher rate of making the transition from nondepressed to depressed status over time, a higher rate of remaining depressed over time, and a lower rate of making the transition to nondepressed status or to death over time.

“Older men generally have higher mortality rates than older women, irrespective of depression. [But] the mortality difference by sex was marked, with a nearly threefold difference in the odds ratios for thosewho were depressed, compared with those who were not,” they said, noting that previous studies may have been unable to detect these patterns because they did not account for fluctuations in depression over time.

“The consistency of our findings over four different time intervals provides strong evidence that depression is more likely to persist in older women than in men. [This] is somewhat surprising because women are more likely than men to receive pharmacologic and nonpharmacologic treatment for depression,” the researchers said.

“Whether women are treated less aggressively than men for late-life depression or are less likely to respond to conventional treatment is not known, but should be the focus of future research,” they said.

The study was supported by grants from the National Institute on Aging.

The researchers reported no disclosures.

The burden of depression is disproportionately higher among older women than older men because of their greater susceptibility to depression and—once depressed—their greater tendency to have persistent depression and their lower probability of death, suggest the results of a longitudinal study.

Clinically significant depressive symptoms affect 8%–20% of community-dwelling older people, and previous research has failed to explain the underlying gender differences, wrote Lisa C. Barry, Ph.D., of Yale University, New Haven, Conn., and her associates.

They assessed those differences in the onset and persistence of depression, as well as in overall mortality. They used data from a 1998 longitudinal study of 754 residents of New Haven aged 70 years and older at baseline. The subjects were followed using detailed in-home assessments every 18 months for up to 6 years (Arch. Gen. Psychiatry 2008;65:172–8).

At baseline, the subjects were a mean age of 78 years. Sixty-five percent of them were women, and 91% were non-Hispanic whites. On average, subjects had a high school education, had two chronic conditions, and were cognitively intact.

A total of 269 subjects (36%) had depressive symptoms at some time during the 6-year study. The prevalence of depressive symptoms was substantially higher in women than men at all time points.

Compared with men, women had a higher rate of making the transition from nondepressed to depressed status over time, a higher rate of remaining depressed over time, and a lower rate of making the transition to nondepressed status or to death over time.

“Older men generally have higher mortality rates than older women, irrespective of depression. [But] the mortality difference by sex was marked, with a nearly threefold difference in the odds ratios for thosewho were depressed, compared with those who were not,” they said, noting that previous studies may have been unable to detect these patterns because they did not account for fluctuations in depression over time.

“The consistency of our findings over four different time intervals provides strong evidence that depression is more likely to persist in older women than in men. [This] is somewhat surprising because women are more likely than men to receive pharmacologic and nonpharmacologic treatment for depression,” the researchers said.

“Whether women are treated less aggressively than men for late-life depression or are less likely to respond to conventional treatment is not known, but should be the focus of future research,” they said.

The study was supported by grants from the National Institute on Aging.

The researchers reported no disclosures.

Intensive intervention for type 2 diabetes, which addressed microalbuminuria, cholesterol, triglycerides, and blood pressure in addition to glucose control, reduced the risk of death by 20% over the course of 13 years in a Danish study.

Diabetes patients with persistent microalbuminuria who received about 8 years of intensive medical and behavioral therapy and were followed for an additional 5 years showed a 20% decline in absolute risk of death from any cause and a 13% decline in absolute risk of death from cardiovascular causes, compared with those receiving conventional care, said Dr. Peter Gaede of the Steno Diabetes Center, Copenhagen, and his associates.

They reported the 8-year results of their study previously; the current report reflects extended follow-up through 2006 of a cohort of 130 patients randomly assigned to receive either conventional diabetes treatment or therapy that targeted a glycated hemoglobin level of less than 6.5%, a fasting total cholesterol level of less than 175 mg/dL, a fasting serum triglyceride level of less than 150 mg/dL, a systolic blood pressure of less than 130 mm Hg, and a diastolic blood pressure of less than 80 mm Hg.

In addition to medications and lifestyle modifications to achieve those targets, those in the intensive-therapy group also received renin-angiotensin system blockers for microalbuminuria and low-dose aspirin. Overall mortality was 30% in the intensive-therapy group, compared with 50% in the conventional-care group. Nine of the patients (11%) in the intensive-therapy group died from cardiovascular causes, compared with 19 (24%) of the patients in the conventional-care group. There were 51 cardiovascular events in the intensive-care group and 158 in the conventional-care group. “The rate of death in the conventional-therapy group was 50%, a finding that underscores the poor prognosis for such patients in the absence of intensive treatment,” they said (N. Engl. J. Med. 2008;358:580–91).

Few serious effects were reported during regular follow-up interviews.

ELSEVIER GLOBAL MEDICAL NEWS

Intensive intervention for type 2 diabetes, which addressed microalbuminuria, cholesterol, triglycerides, and blood pressure in addition to glucose control, reduced the risk of death by 20% over the course of 13 years in a Danish study.

Diabetes patients with persistent microalbuminuria who received about 8 years of intensive medical and behavioral therapy and were followed for an additional 5 years showed a 20% decline in absolute risk of death from any cause and a 13% decline in absolute risk of death from cardiovascular causes, compared with those receiving conventional care, said Dr. Peter Gaede of the Steno Diabetes Center, Copenhagen, and his associates.

They reported the 8-year results of their study previously; the current report reflects extended follow-up through 2006 of a cohort of 130 patients randomly assigned to receive either conventional diabetes treatment or therapy that targeted a glycated hemoglobin level of less than 6.5%, a fasting total cholesterol level of less than 175 mg/dL, a fasting serum triglyceride level of less than 150 mg/dL, a systolic blood pressure of less than 130 mm Hg, and a diastolic blood pressure of less than 80 mm Hg.

In addition to medications and lifestyle modifications to achieve those targets, those in the intensive-therapy group also received renin-angiotensin system blockers for microalbuminuria and low-dose aspirin. Overall mortality was 30% in the intensive-therapy group, compared with 50% in the conventional-care group. Nine of the patients (11%) in the intensive-therapy group died from cardiovascular causes, compared with 19 (24%) of the patients in the conventional-care group. There were 51 cardiovascular events in the intensive-care group and 158 in the conventional-care group. “The rate of death in the conventional-therapy group was 50%, a finding that underscores the poor prognosis for such patients in the absence of intensive treatment,” they said (N. Engl. J. Med. 2008;358:580–91).

Few serious effects were reported during regular follow-up interviews.

ELSEVIER GLOBAL MEDICAL NEWS

Intensive intervention for type 2 diabetes, which addressed microalbuminuria, cholesterol, triglycerides, and blood pressure in addition to glucose control, reduced the risk of death by 20% over the course of 13 years in a Danish study.

Diabetes patients with persistent microalbuminuria who received about 8 years of intensive medical and behavioral therapy and were followed for an additional 5 years showed a 20% decline in absolute risk of death from any cause and a 13% decline in absolute risk of death from cardiovascular causes, compared with those receiving conventional care, said Dr. Peter Gaede of the Steno Diabetes Center, Copenhagen, and his associates.

They reported the 8-year results of their study previously; the current report reflects extended follow-up through 2006 of a cohort of 130 patients randomly assigned to receive either conventional diabetes treatment or therapy that targeted a glycated hemoglobin level of less than 6.5%, a fasting total cholesterol level of less than 175 mg/dL, a fasting serum triglyceride level of less than 150 mg/dL, a systolic blood pressure of less than 130 mm Hg, and a diastolic blood pressure of less than 80 mm Hg.

In addition to medications and lifestyle modifications to achieve those targets, those in the intensive-therapy group also received renin-angiotensin system blockers for microalbuminuria and low-dose aspirin. Overall mortality was 30% in the intensive-therapy group, compared with 50% in the conventional-care group. Nine of the patients (11%) in the intensive-therapy group died from cardiovascular causes, compared with 19 (24%) of the patients in the conventional-care group. There were 51 cardiovascular events in the intensive-care group and 158 in the conventional-care group. “The rate of death in the conventional-therapy group was 50%, a finding that underscores the poor prognosis for such patients in the absence of intensive treatment,” they said (N. Engl. J. Med. 2008;358:580–91).

Few serious effects were reported during regular follow-up interviews.

ELSEVIER GLOBAL MEDICAL NEWS

Laparoscopic adjustable gastric banding produced a 76% remission rate in the first randomized trial to compare the surgery against conventional treatment in obese patients with recent-onset type 2 diabetes.

“After 2 years, the surgical group displayed a 5 times higher remission rate and a 4 times greater reduction in [hemoglobin A_1c] values than the conventional-therapy group,” according to John B. Dixon, Ph.D., of Monash University, Melbourne, and his associates.

The surgical group also showed greater resolution of features of the metabolic syndrome and greater improvements in insulin sensitivity, lipid profiles, and hypertension, allowing for significant reduction in their use of medications for these conditions as well as their use of drugs for glycemic control.

The investigators attributed the procedure's benefits principally to its great effectiveness in inducing weight loss, rather than to other antidiabetes effects, such as those reported with the Roux-en-Y gastric bypass procedure.

In the study, patients diagnosed as having type 2 diabetes within the preceding 2 years and with a body mass index of 30–40 were randomly assigned to receive conventional medical and behavioral therapy either alone (26 subjects) or in addition to laparoscopic adjustable gastric banding via the pars flaccida technique (29 subjects). All subjects met with at least one member of a treatment team every 6 weeks during the 2-year follow-up.

The mean surgical time was 54 minutes; 80% of patients were discharged after 1 day of hospitalization.

The surgery group achieved a mean weight loss of 20.7%, compared with 1.4% for the conventional therapy group. Complete remission of diabetes occurred in 76% of the surgery group, compared with 15% of the controls, the authors said (JAMA 2008:299:316–23).

There were no surgical complications. The rate of postoperative wound infection was under 2%. Reoperation to enlarge the gastric pouch was needed in 5% of subjects.

In an editorial comment, Dr. David E. Cummings and Dr. David R. Flum of the University of Washington, Seattle, said the results should lead providers and professional societies to reconsider the role of surgery in treating diabetes.

“It may be time to view bariatric operations not as treatments for patients with BMI greater than a certain level, but rather as interventions about which all obese patients with diabetes should be informed and [to which they should be] given access,” they said (JAMA 2008;299:341–3).

EMILY BRANNAN, ILLUSTRATION

Laparoscopic adjustable gastric banding produced a 76% remission rate in the first randomized trial to compare the surgery against conventional treatment in obese patients with recent-onset type 2 diabetes.

“After 2 years, the surgical group displayed a 5 times higher remission rate and a 4 times greater reduction in [hemoglobin A_1c] values than the conventional-therapy group,” according to John B. Dixon, Ph.D., of Monash University, Melbourne, and his associates.

The surgical group also showed greater resolution of features of the metabolic syndrome and greater improvements in insulin sensitivity, lipid profiles, and hypertension, allowing for significant reduction in their use of medications for these conditions as well as their use of drugs for glycemic control.

The investigators attributed the procedure's benefits principally to its great effectiveness in inducing weight loss, rather than to other antidiabetes effects, such as those reported with the Roux-en-Y gastric bypass procedure.

In the study, patients diagnosed as having type 2 diabetes within the preceding 2 years and with a body mass index of 30–40 were randomly assigned to receive conventional medical and behavioral therapy either alone (26 subjects) or in addition to laparoscopic adjustable gastric banding via the pars flaccida technique (29 subjects). All subjects met with at least one member of a treatment team every 6 weeks during the 2-year follow-up.

The mean surgical time was 54 minutes; 80% of patients were discharged after 1 day of hospitalization.

The surgery group achieved a mean weight loss of 20.7%, compared with 1.4% for the conventional therapy group. Complete remission of diabetes occurred in 76% of the surgery group, compared with 15% of the controls, the authors said (JAMA 2008:299:316–23).

There were no surgical complications. The rate of postoperative wound infection was under 2%. Reoperation to enlarge the gastric pouch was needed in 5% of subjects.

In an editorial comment, Dr. David E. Cummings and Dr. David R. Flum of the University of Washington, Seattle, said the results should lead providers and professional societies to reconsider the role of surgery in treating diabetes.

“It may be time to view bariatric operations not as treatments for patients with BMI greater than a certain level, but rather as interventions about which all obese patients with diabetes should be informed and [to which they should be] given access,” they said (JAMA 2008;299:341–3).

EMILY BRANNAN, ILLUSTRATION

Laparoscopic adjustable gastric banding produced a 76% remission rate in the first randomized trial to compare the surgery against conventional treatment in obese patients with recent-onset type 2 diabetes.

“After 2 years, the surgical group displayed a 5 times higher remission rate and a 4 times greater reduction in [hemoglobin A_1c] values than the conventional-therapy group,” according to John B. Dixon, Ph.D., of Monash University, Melbourne, and his associates.

The surgical group also showed greater resolution of features of the metabolic syndrome and greater improvements in insulin sensitivity, lipid profiles, and hypertension, allowing for significant reduction in their use of medications for these conditions as well as their use of drugs for glycemic control.

The investigators attributed the procedure's benefits principally to its great effectiveness in inducing weight loss, rather than to other antidiabetes effects, such as those reported with the Roux-en-Y gastric bypass procedure.

In the study, patients diagnosed as having type 2 diabetes within the preceding 2 years and with a body mass index of 30–40 were randomly assigned to receive conventional medical and behavioral therapy either alone (26 subjects) or in addition to laparoscopic adjustable gastric banding via the pars flaccida technique (29 subjects). All subjects met with at least one member of a treatment team every 6 weeks during the 2-year follow-up.

The mean surgical time was 54 minutes; 80% of patients were discharged after 1 day of hospitalization.

The surgery group achieved a mean weight loss of 20.7%, compared with 1.4% for the conventional therapy group. Complete remission of diabetes occurred in 76% of the surgery group, compared with 15% of the controls, the authors said (JAMA 2008:299:316–23).

There were no surgical complications. The rate of postoperative wound infection was under 2%. Reoperation to enlarge the gastric pouch was needed in 5% of subjects.

In an editorial comment, Dr. David E. Cummings and Dr. David R. Flum of the University of Washington, Seattle, said the results should lead providers and professional societies to reconsider the role of surgery in treating diabetes.

“It may be time to view bariatric operations not as treatments for patients with BMI greater than a certain level, but rather as interventions about which all obese patients with diabetes should be informed and [to which they should be] given access,” they said (JAMA 2008;299:341–3).

EMILY BRANNAN, ILLUSTRATION

The risk of myocardial infarction or death spikes during the 90 days after clopidogrel therapy is discontinued among patients treated for acute coronary syndromes, especially those treated medically.

Clustering of adverse coronary events has been reported after cessation of long-term aspirin and heparin therapy in acute coronary syndrome (ACS) patients. Dr. P. Michael Ho of the Denver Veterans Administration Medical Center and his associates assessed whether clopidogrel withdrawal was associated with a similar “rebound” effect.

The investigators analyzed data on all patients with acute MI or unstable angina who were discharged from any of 127 VA medical centers throughout the country between 2003 and 2005 with prescriptions for clopidogrel. A total of 1,568 of these patients who had been treated medically and 1,569 who had undergone PCI took the drug for a mean of 302 and 203 days, respectively, then discontinued the treatment.

In the medically treated patients, the combined end point of all-cause mortality or ACS occurred in 268 patients (17%) after they stopped taking clopidogrel. Significantly more (163) of those events occurred within 90 days of clopidogrel discontinuation than occurred at 91–180 days (57) or 181–270 days (26).

In PCI-treated patients, who took clopidogrel for an average of 278 days after their procedure, death or ACS occurred in 124 (8%) after discontinuation. As with the medically treated patients, significantly more of the primary end point events occurred within 90 days of cessation (73), compared with days 91–180 (29) and days 181–270 (8). Of the PCI-treated patients, almost two-thirds received bare metal stents, while the rest got drug-eluting stents.

“We found a clustering of death or acute MI in the initial 90-day period after stopping treatment with clopidogrel, compared with later follow-up intervals. These findings were consistent among patient subgroups including those who took shorter vs. longer durations of clopidogrel therapy, among patients with and without diabetes, as well as among PCI-treated ACS patients,” the researchers said.

The rate of adverse events was nearly twice as high immediately after stopping clopidogrel than it was during later periods. The rate was higher by far in the medically treated patients within 90 days of drug cessation, at 1.31 per 1,000 patient-days, than in those patients during days 91–180 (0.69) or in the PCI group during the same period (0.57).

The findings support the hypothesis that there is a rebound hyperthrombotic period after stopping clopidogrel therapy. Additional studies are needed to confirm the findings and to identify the underlying mechanism so that strategies to prevent or attenuate this effect can be devised, they added (JAMA 2008;299:532–9).

Extended clopidogrel therapy might avoid the rebound effect, or other approaches—tapering clopidogrel, “bridging” the cessation of clopidogrel with another antithrombotic drug, or using alternative antiplatelet agents instead of clopidogrel—might attenuate it, they said.

This study was funded by the U.S. Department of Veterans Affairs. One of Dr. Ho's associates receives research support from Bristol-Myers Squibb and Sanofi-Aventis, both of which market clopidogrel.

The risk of myocardial infarction or death spikes during the 90 days after clopidogrel therapy is discontinued among patients treated for acute coronary syndromes, especially those treated medically.

Clustering of adverse coronary events has been reported after cessation of long-term aspirin and heparin therapy in acute coronary syndrome (ACS) patients. Dr. P. Michael Ho of the Denver Veterans Administration Medical Center and his associates assessed whether clopidogrel withdrawal was associated with a similar “rebound” effect.

The investigators analyzed data on all patients with acute MI or unstable angina who were discharged from any of 127 VA medical centers throughout the country between 2003 and 2005 with prescriptions for clopidogrel. A total of 1,568 of these patients who had been treated medically and 1,569 who had undergone PCI took the drug for a mean of 302 and 203 days, respectively, then discontinued the treatment.

In the medically treated patients, the combined end point of all-cause mortality or ACS occurred in 268 patients (17%) after they stopped taking clopidogrel. Significantly more (163) of those events occurred within 90 days of clopidogrel discontinuation than occurred at 91–180 days (57) or 181–270 days (26).

In PCI-treated patients, who took clopidogrel for an average of 278 days after their procedure, death or ACS occurred in 124 (8%) after discontinuation. As with the medically treated patients, significantly more of the primary end point events occurred within 90 days of cessation (73), compared with days 91–180 (29) and days 181–270 (8). Of the PCI-treated patients, almost two-thirds received bare metal stents, while the rest got drug-eluting stents.

“We found a clustering of death or acute MI in the initial 90-day period after stopping treatment with clopidogrel, compared with later follow-up intervals. These findings were consistent among patient subgroups including those who took shorter vs. longer durations of clopidogrel therapy, among patients with and without diabetes, as well as among PCI-treated ACS patients,” the researchers said.

The rate of adverse events was nearly twice as high immediately after stopping clopidogrel than it was during later periods. The rate was higher by far in the medically treated patients within 90 days of drug cessation, at 1.31 per 1,000 patient-days, than in those patients during days 91–180 (0.69) or in the PCI group during the same period (0.57).

The findings support the hypothesis that there is a rebound hyperthrombotic period after stopping clopidogrel therapy. Additional studies are needed to confirm the findings and to identify the underlying mechanism so that strategies to prevent or attenuate this effect can be devised, they added (JAMA 2008;299:532–9).

Extended clopidogrel therapy might avoid the rebound effect, or other approaches—tapering clopidogrel, “bridging” the cessation of clopidogrel with another antithrombotic drug, or using alternative antiplatelet agents instead of clopidogrel—might attenuate it, they said.

This study was funded by the U.S. Department of Veterans Affairs. One of Dr. Ho's associates receives research support from Bristol-Myers Squibb and Sanofi-Aventis, both of which market clopidogrel.

The risk of myocardial infarction or death spikes during the 90 days after clopidogrel therapy is discontinued among patients treated for acute coronary syndromes, especially those treated medically.

Clustering of adverse coronary events has been reported after cessation of long-term aspirin and heparin therapy in acute coronary syndrome (ACS) patients. Dr. P. Michael Ho of the Denver Veterans Administration Medical Center and his associates assessed whether clopidogrel withdrawal was associated with a similar “rebound” effect.

The investigators analyzed data on all patients with acute MI or unstable angina who were discharged from any of 127 VA medical centers throughout the country between 2003 and 2005 with prescriptions for clopidogrel. A total of 1,568 of these patients who had been treated medically and 1,569 who had undergone PCI took the drug for a mean of 302 and 203 days, respectively, then discontinued the treatment.

In the medically treated patients, the combined end point of all-cause mortality or ACS occurred in 268 patients (17%) after they stopped taking clopidogrel. Significantly more (163) of those events occurred within 90 days of clopidogrel discontinuation than occurred at 91–180 days (57) or 181–270 days (26).

In PCI-treated patients, who took clopidogrel for an average of 278 days after their procedure, death or ACS occurred in 124 (8%) after discontinuation. As with the medically treated patients, significantly more of the primary end point events occurred within 90 days of cessation (73), compared with days 91–180 (29) and days 181–270 (8). Of the PCI-treated patients, almost two-thirds received bare metal stents, while the rest got drug-eluting stents.

“We found a clustering of death or acute MI in the initial 90-day period after stopping treatment with clopidogrel, compared with later follow-up intervals. These findings were consistent among patient subgroups including those who took shorter vs. longer durations of clopidogrel therapy, among patients with and without diabetes, as well as among PCI-treated ACS patients,” the researchers said.

The rate of adverse events was nearly twice as high immediately after stopping clopidogrel than it was during later periods. The rate was higher by far in the medically treated patients within 90 days of drug cessation, at 1.31 per 1,000 patient-days, than in those patients during days 91–180 (0.69) or in the PCI group during the same period (0.57).

The findings support the hypothesis that there is a rebound hyperthrombotic period after stopping clopidogrel therapy. Additional studies are needed to confirm the findings and to identify the underlying mechanism so that strategies to prevent or attenuate this effect can be devised, they added (JAMA 2008;299:532–9).

Extended clopidogrel therapy might avoid the rebound effect, or other approaches—tapering clopidogrel, “bridging” the cessation of clopidogrel with another antithrombotic drug, or using alternative antiplatelet agents instead of clopidogrel—might attenuate it, they said.

This study was funded by the U.S. Department of Veterans Affairs. One of Dr. Ho's associates receives research support from Bristol-Myers Squibb and Sanofi-Aventis, both of which market clopidogrel.

Among teenagers and young adults who smoke marijuana, the minority who are not cigarette smokers have fewer problems personally, socially, and academically than do the majority who also smoke cigarettes, according to Swiss investigators.

The researchers analyzed data from a nationally representative survey of more than 7,000 Swiss students aged 16–20 years to examine the relationship among cannabis smoking, cigarette smoking, and overall functioning. They reported their findings in the Archives of Pediatric and Adolescent Medicine.

A total of 455 study subjects who smoked marijuana only, 1,703 who smoked both marijuana and cigarettes, and 3,105 who never smoked either substance completed anonymous questionnaires, reported Dr. Joan-Carles Suris of the University of Lausanne (Switzerland) and her associates.

The prevalence of youth who smoked pot but not cigarettes in the overall sample was 6%. Compared with the subjects who also smoked cigarettes, those who did not were less likely to feel depressed, to be sensation seeking, and to have been drunk. They were more likely to live in intact homes, to participate in sports, and to get good grades.

Compared with adolescents who abstained from both marijuana and cigarettes, the marijuana-only smokers were less likely to have a good relationship with their parents and more likely to skip classes. However, they still achieved the same good grades as the abstainers.

Interestingly, those people in the marijuana-only group were more likely to participate in sports and had better relationships with their peers than did the abstainers. This may be because marijuana “is largely used by adolescents for socializing purposes,” Dr. Suris and her associates said (Arch. Pediatr. Adolesc. Med. 2007;161:1042–7).

The findings support those of many previous studies, showing that adolescents who smoke both marijuana and cigarettes are more likely to be heavy pot users, to have started smoking pot before the age of 15, and to have abused alcohol.

They also confirm that early initiation of marijuana use is associated with problematic polydrug use and alcohol abuse, the investigators said.

Among teenagers and young adults who smoke marijuana, the minority who are not cigarette smokers have fewer problems personally, socially, and academically than do the majority who also smoke cigarettes, according to Swiss investigators.

The researchers analyzed data from a nationally representative survey of more than 7,000 Swiss students aged 16–20 years to examine the relationship among cannabis smoking, cigarette smoking, and overall functioning. They reported their findings in the Archives of Pediatric and Adolescent Medicine.

A total of 455 study subjects who smoked marijuana only, 1,703 who smoked both marijuana and cigarettes, and 3,105 who never smoked either substance completed anonymous questionnaires, reported Dr. Joan-Carles Suris of the University of Lausanne (Switzerland) and her associates.

The prevalence of youth who smoked pot but not cigarettes in the overall sample was 6%. Compared with the subjects who also smoked cigarettes, those who did not were less likely to feel depressed, to be sensation seeking, and to have been drunk. They were more likely to live in intact homes, to participate in sports, and to get good grades.

Compared with adolescents who abstained from both marijuana and cigarettes, the marijuana-only smokers were less likely to have a good relationship with their parents and more likely to skip classes. However, they still achieved the same good grades as the abstainers.

Interestingly, those people in the marijuana-only group were more likely to participate in sports and had better relationships with their peers than did the abstainers. This may be because marijuana “is largely used by adolescents for socializing purposes,” Dr. Suris and her associates said (Arch. Pediatr. Adolesc. Med. 2007;161:1042–7).

The findings support those of many previous studies, showing that adolescents who smoke both marijuana and cigarettes are more likely to be heavy pot users, to have started smoking pot before the age of 15, and to have abused alcohol.

They also confirm that early initiation of marijuana use is associated with problematic polydrug use and alcohol abuse, the investigators said.

Among teenagers and young adults who smoke marijuana, the minority who are not cigarette smokers have fewer problems personally, socially, and academically than do the majority who also smoke cigarettes, according to Swiss investigators.

The researchers analyzed data from a nationally representative survey of more than 7,000 Swiss students aged 16–20 years to examine the relationship among cannabis smoking, cigarette smoking, and overall functioning. They reported their findings in the Archives of Pediatric and Adolescent Medicine.

A total of 455 study subjects who smoked marijuana only, 1,703 who smoked both marijuana and cigarettes, and 3,105 who never smoked either substance completed anonymous questionnaires, reported Dr. Joan-Carles Suris of the University of Lausanne (Switzerland) and her associates.

The prevalence of youth who smoked pot but not cigarettes in the overall sample was 6%. Compared with the subjects who also smoked cigarettes, those who did not were less likely to feel depressed, to be sensation seeking, and to have been drunk. They were more likely to live in intact homes, to participate in sports, and to get good grades.

Compared with adolescents who abstained from both marijuana and cigarettes, the marijuana-only smokers were less likely to have a good relationship with their parents and more likely to skip classes. However, they still achieved the same good grades as the abstainers.

Interestingly, those people in the marijuana-only group were more likely to participate in sports and had better relationships with their peers than did the abstainers. This may be because marijuana “is largely used by adolescents for socializing purposes,” Dr. Suris and her associates said (Arch. Pediatr. Adolesc. Med. 2007;161:1042–7).

The findings support those of many previous studies, showing that adolescents who smoke both marijuana and cigarettes are more likely to be heavy pot users, to have started smoking pot before the age of 15, and to have abused alcohol.

They also confirm that early initiation of marijuana use is associated with problematic polydrug use and alcohol abuse, the investigators said.

A newly discovered gene sequence variant is strongly associated with periodic limb movements in sleep, a component of restless legs syndrome, reported Dr. Hreinn Stefansson of deCODE Genetics, Reykjavik, Iceland, and associates.

Even though the authenticity of restless legs syndrome (RLS) has been called into question, “our study provides evidence that periodic limb movements in sleep is a genuine syndrome with an ascertainable phenotype and a genetic basis,” the researchers said.

Restless legs syndrome is characterized by uncomfortable and distressing sensory urges to move the legs during rest or inactivity. The condition often but not always involves involuntary, highly stereotypical, regularly occurring foot and leg movements in sleep.

The pathogenesis of the disorder is unclear, but it has been linked to low iron levels and has “a substantial” genetic component, according to the researchers.

Dr. Stefansson and associates genotyped 306 case subjects who had periodic limb movements in sleep, most of whom also had restless legs syndrome, as well as 15,664 control subjects from the general Icelandic population.

Overall, the researchers were able to assess more than 300,000 single nucleotide polymorphism (SNP) markers distributed across the human genome.

The researchers found a strong link between the disorder and allele A of rs3923809 on chromosome 6p.

To validate these results, they then conducted replication studies in an additional Icelandic cohort that included 123 case subjects and 1,233 control subjects, and in a U.S. cohort of 188 case subjects recruited from a sleep disorders center and 662 control subjects.

The association was evident in each study population, and it was highly significant when all three of the samples were combined, the investigators said (N. Engl. J. Med. 2007;357:639–47).

Subjects who carried the gene sequence variant also had higher ferritin indexes, a measure inversely related to bodily iron stores, as well as decreased serum ferritin levels. This correlation “is consistent with the suspected involvement of iron depletion in the pathogenesis” of RLS, Dr. Stefansson and his associates added.

In an editorial accompanying the study, Dr. John W. Winkelman of, Brigham and Women's Hospital and Harvard Medical School, Boston, said the results offer “hope to patients with periodic limb movements in sleep and RLS that the syndrome's pathophysiology will be understood, and that such knowledge will lead to additional effective and durable treatments” (N. Engl. J. Med. 2007;357:703–5).

A newly discovered gene sequence variant is strongly associated with periodic limb movements in sleep, a component of restless legs syndrome, reported Dr. Hreinn Stefansson of deCODE Genetics, Reykjavik, Iceland, and associates.

Even though the authenticity of restless legs syndrome (RLS) has been called into question, “our study provides evidence that periodic limb movements in sleep is a genuine syndrome with an ascertainable phenotype and a genetic basis,” the researchers said.

Restless legs syndrome is characterized by uncomfortable and distressing sensory urges to move the legs during rest or inactivity. The condition often but not always involves involuntary, highly stereotypical, regularly occurring foot and leg movements in sleep.

The pathogenesis of the disorder is unclear, but it has been linked to low iron levels and has “a substantial” genetic component, according to the researchers.

Dr. Stefansson and associates genotyped 306 case subjects who had periodic limb movements in sleep, most of whom also had restless legs syndrome, as well as 15,664 control subjects from the general Icelandic population.

Overall, the researchers were able to assess more than 300,000 single nucleotide polymorphism (SNP) markers distributed across the human genome.

The researchers found a strong link between the disorder and allele A of rs3923809 on chromosome 6p.

To validate these results, they then conducted replication studies in an additional Icelandic cohort that included 123 case subjects and 1,233 control subjects, and in a U.S. cohort of 188 case subjects recruited from a sleep disorders center and 662 control subjects.

The association was evident in each study population, and it was highly significant when all three of the samples were combined, the investigators said (N. Engl. J. Med. 2007;357:639–47).

Subjects who carried the gene sequence variant also had higher ferritin indexes, a measure inversely related to bodily iron stores, as well as decreased serum ferritin levels. This correlation “is consistent with the suspected involvement of iron depletion in the pathogenesis” of RLS, Dr. Stefansson and his associates added.

In an editorial accompanying the study, Dr. John W. Winkelman of, Brigham and Women's Hospital and Harvard Medical School, Boston, said the results offer “hope to patients with periodic limb movements in sleep and RLS that the syndrome's pathophysiology will be understood, and that such knowledge will lead to additional effective and durable treatments” (N. Engl. J. Med. 2007;357:703–5).

A newly discovered gene sequence variant is strongly associated with periodic limb movements in sleep, a component of restless legs syndrome, reported Dr. Hreinn Stefansson of deCODE Genetics, Reykjavik, Iceland, and associates.

Even though the authenticity of restless legs syndrome (RLS) has been called into question, “our study provides evidence that periodic limb movements in sleep is a genuine syndrome with an ascertainable phenotype and a genetic basis,” the researchers said.

Restless legs syndrome is characterized by uncomfortable and distressing sensory urges to move the legs during rest or inactivity. The condition often but not always involves involuntary, highly stereotypical, regularly occurring foot and leg movements in sleep.

The pathogenesis of the disorder is unclear, but it has been linked to low iron levels and has “a substantial” genetic component, according to the researchers.

Dr. Stefansson and associates genotyped 306 case subjects who had periodic limb movements in sleep, most of whom also had restless legs syndrome, as well as 15,664 control subjects from the general Icelandic population.

Overall, the researchers were able to assess more than 300,000 single nucleotide polymorphism (SNP) markers distributed across the human genome.

The researchers found a strong link between the disorder and allele A of rs3923809 on chromosome 6p.

To validate these results, they then conducted replication studies in an additional Icelandic cohort that included 123 case subjects and 1,233 control subjects, and in a U.S. cohort of 188 case subjects recruited from a sleep disorders center and 662 control subjects.

The association was evident in each study population, and it was highly significant when all three of the samples were combined, the investigators said (N. Engl. J. Med. 2007;357:639–47).

Subjects who carried the gene sequence variant also had higher ferritin indexes, a measure inversely related to bodily iron stores, as well as decreased serum ferritin levels. This correlation “is consistent with the suspected involvement of iron depletion in the pathogenesis” of RLS, Dr. Stefansson and his associates added.

In an editorial accompanying the study, Dr. John W. Winkelman of, Brigham and Women's Hospital and Harvard Medical School, Boston, said the results offer “hope to patients with periodic limb movements in sleep and RLS that the syndrome's pathophysiology will be understood, and that such knowledge will lead to additional effective and durable treatments” (N. Engl. J. Med. 2007;357:703–5).

The prevalence of unnecessary activation of a cardiac catheterization laboratory for suspected ST-segment elevation myocardial infarction ranged from 9.5% to 14% in one Midwestern coronary intervention network, depending on the diagnostic criteria used, researchers reported.

“Upstream” activation of a coronary catheterization lab by the emergency department physician is a key strategy to reducing door-to-reperfusion times in cases of suspected MI.

However, in the press to speed this process, the medical community may have overlooked one adverse conse-quence: false-positive referrals to percutaneous coronary intervention (PCI) centers, according to Dr. David M. Larson of the Minneapolis Heart Institute, Abbott Northwestern Hospital, and his associates.

This is “a significant concern” because unnecessary coronary angiography is a risk to the patient and “may impose a burden on limited human and physical catheterization laboratory resources,” they noted.

The investigators assessed such false-positives in a study of 1,345 consecutive patients suspected of having ST-segment elevation MI (STEMI) and referred to their regional catheterization lab between 2003 and 2006. The lab covers a network of about 30 medical centers within a 200-mile area, “representing a wide range of hospital sizes and emergency department volumes” in a real-life setting.

The rate of false-positive cath lab activations was 14% in patients who showed no clear “culprit” artery on angiography. Review of their initial ECGs showed that 24 of these patients (1.8%) did not have ST-segment elevation but instead had ST-segment depression, T-wave inversion, or nonspecific ST changes.

A total of 127 patients with no clear culprit artery also had negative results on tests of cardiac biomarkers and were therefore considered to be free of significant coronary artery disease, for a false-positive rate of 9.5%.

However, 64 patients with no clear culprit artery proved to have positive biomarker tests and were found to have MI due to emboli or spasm, myocarditis, stress cardiomyopathy, or STEMI with no angiographic lesion.

The rate of false-positive cath lab activations was 11.2% in patients who had negative biomarker results. However, 26 of these patients (17%) showed a clear culprit artery on angiography and were diagnosed as having either aborted STEMI or unstable angina.

“Our results indicate that a wide spectrum of etiologies may lead to false-positive catheterization laboratory activation. Many of these include high-risk patients who may benefit” from angiography even if they don't proceed to PCI, Dr. Larson and his associates said (JAMA 2007;298:2754–60).

In an editorial comment accompanying this report, Dr. Frederick A. Masoudi of the Denver Health Medical Center said that prior to this “important” study, little had been known about false-positives in PCI systems, and they were assumed to be “relatively rare.”

According to any of the diagnostic criteria in this study, “no fewer than 1 in 11 referrals were considered false positives,” a proportion that certainly is not trivial, he said (JAMA 2007;298:2790–1).

In some of the cases in this study, such as those for whom the electrocardiogram was seemingly misinterpreted, the risks of unnecessary angiography clearly outweighed any potential benefits.

However, in others, “such as those ultimately diagnosed with stress cardiomyopathy or coronary artery spasm, coronary angiography was likely an appropriate diagnostic test even though PCI was ultimately not performed,” Dr. Masoudi noted.

“False-positive catheterization laboratory activation may be another quality metric to monitor for a STEMI program.” the study investigators concluded.

The prevalence of unnecessary activation of a cardiac catheterization laboratory for suspected ST-segment elevation myocardial infarction ranged from 9.5% to 14% in one Midwestern coronary intervention network, depending on the diagnostic criteria used, researchers reported.

“Upstream” activation of a coronary catheterization lab by the emergency department physician is a key strategy to reducing door-to-reperfusion times in cases of suspected MI.

However, in the press to speed this process, the medical community may have overlooked one adverse conse-quence: false-positive referrals to percutaneous coronary intervention (PCI) centers, according to Dr. David M. Larson of the Minneapolis Heart Institute, Abbott Northwestern Hospital, and his associates.

This is “a significant concern” because unnecessary coronary angiography is a risk to the patient and “may impose a burden on limited human and physical catheterization laboratory resources,” they noted.

The investigators assessed such false-positives in a study of 1,345 consecutive patients suspected of having ST-segment elevation MI (STEMI) and referred to their regional catheterization lab between 2003 and 2006. The lab covers a network of about 30 medical centers within a 200-mile area, “representing a wide range of hospital sizes and emergency department volumes” in a real-life setting.

The rate of false-positive cath lab activations was 14% in patients who showed no clear “culprit” artery on angiography. Review of their initial ECGs showed that 24 of these patients (1.8%) did not have ST-segment elevation but instead had ST-segment depression, T-wave inversion, or nonspecific ST changes.

A total of 127 patients with no clear culprit artery also had negative results on tests of cardiac biomarkers and were therefore considered to be free of significant coronary artery disease, for a false-positive rate of 9.5%.

However, 64 patients with no clear culprit artery proved to have positive biomarker tests and were found to have MI due to emboli or spasm, myocarditis, stress cardiomyopathy, or STEMI with no angiographic lesion.

The rate of false-positive cath lab activations was 11.2% in patients who had negative biomarker results. However, 26 of these patients (17%) showed a clear culprit artery on angiography and were diagnosed as having either aborted STEMI or unstable angina.

“Our results indicate that a wide spectrum of etiologies may lead to false-positive catheterization laboratory activation. Many of these include high-risk patients who may benefit” from angiography even if they don't proceed to PCI, Dr. Larson and his associates said (JAMA 2007;298:2754–60).

In an editorial comment accompanying this report, Dr. Frederick A. Masoudi of the Denver Health Medical Center said that prior to this “important” study, little had been known about false-positives in PCI systems, and they were assumed to be “relatively rare.”

According to any of the diagnostic criteria in this study, “no fewer than 1 in 11 referrals were considered false positives,” a proportion that certainly is not trivial, he said (JAMA 2007;298:2790–1).

In some of the cases in this study, such as those for whom the electrocardiogram was seemingly misinterpreted, the risks of unnecessary angiography clearly outweighed any potential benefits.

However, in others, “such as those ultimately diagnosed with stress cardiomyopathy or coronary artery spasm, coronary angiography was likely an appropriate diagnostic test even though PCI was ultimately not performed,” Dr. Masoudi noted.

“False-positive catheterization laboratory activation may be another quality metric to monitor for a STEMI program.” the study investigators concluded.

The prevalence of unnecessary activation of a cardiac catheterization laboratory for suspected ST-segment elevation myocardial infarction ranged from 9.5% to 14% in one Midwestern coronary intervention network, depending on the diagnostic criteria used, researchers reported.

“Upstream” activation of a coronary catheterization lab by the emergency department physician is a key strategy to reducing door-to-reperfusion times in cases of suspected MI.

However, in the press to speed this process, the medical community may have overlooked one adverse conse-quence: false-positive referrals to percutaneous coronary intervention (PCI) centers, according to Dr. David M. Larson of the Minneapolis Heart Institute, Abbott Northwestern Hospital, and his associates.

This is “a significant concern” because unnecessary coronary angiography is a risk to the patient and “may impose a burden on limited human and physical catheterization laboratory resources,” they noted.

The investigators assessed such false-positives in a study of 1,345 consecutive patients suspected of having ST-segment elevation MI (STEMI) and referred to their regional catheterization lab between 2003 and 2006. The lab covers a network of about 30 medical centers within a 200-mile area, “representing a wide range of hospital sizes and emergency department volumes” in a real-life setting.

The rate of false-positive cath lab activations was 14% in patients who showed no clear “culprit” artery on angiography. Review of their initial ECGs showed that 24 of these patients (1.8%) did not have ST-segment elevation but instead had ST-segment depression, T-wave inversion, or nonspecific ST changes.

A total of 127 patients with no clear culprit artery also had negative results on tests of cardiac biomarkers and were therefore considered to be free of significant coronary artery disease, for a false-positive rate of 9.5%.

However, 64 patients with no clear culprit artery proved to have positive biomarker tests and were found to have MI due to emboli or spasm, myocarditis, stress cardiomyopathy, or STEMI with no angiographic lesion.

The rate of false-positive cath lab activations was 11.2% in patients who had negative biomarker results. However, 26 of these patients (17%) showed a clear culprit artery on angiography and were diagnosed as having either aborted STEMI or unstable angina.

“Our results indicate that a wide spectrum of etiologies may lead to false-positive catheterization laboratory activation. Many of these include high-risk patients who may benefit” from angiography even if they don't proceed to PCI, Dr. Larson and his associates said (JAMA 2007;298:2754–60).

In an editorial comment accompanying this report, Dr. Frederick A. Masoudi of the Denver Health Medical Center said that prior to this “important” study, little had been known about false-positives in PCI systems, and they were assumed to be “relatively rare.”

According to any of the diagnostic criteria in this study, “no fewer than 1 in 11 referrals were considered false positives,” a proportion that certainly is not trivial, he said (JAMA 2007;298:2790–1).

In some of the cases in this study, such as those for whom the electrocardiogram was seemingly misinterpreted, the risks of unnecessary angiography clearly outweighed any potential benefits.

However, in others, “such as those ultimately diagnosed with stress cardiomyopathy or coronary artery spasm, coronary angiography was likely an appropriate diagnostic test even though PCI was ultimately not performed,” Dr. Masoudi noted.

“False-positive catheterization laboratory activation may be another quality metric to monitor for a STEMI program.” the study investigators concluded.