Sharon Worcester

Neither saxagliptin nor alogliptin was associated with increased – or decreased – rates of major adverse cardiovascular events in high-risk patients with type 2 diabetes mellitus in separate randomized, double-blind, placebo-controlled trials.

The findings with respect to these recently approved antidiabetic therapies – members of the same class of selective dipeptidyl peptidase–4 (DDP-4) inhibitors – provide clinicians with important information to help guide treatment decision-making for patients with type 2 diabetes and cardiovascular risk, the authors concluded.

Both studies were mandated by the Food and Drug Administration, which in 2008 began requiring all diabetes therapies to demonstrate cardiovascular safety after concerns were raised in 2007 about a link between rosiglitazone (Avandia) and an increased risk of myocardial infarction. The results were reported at the annual congress of the European Society of Cardiology, and were simultaneously published online Sept. 2 in the New England Journal of Medicine.

SAVOR-TIMI 53

SAVOR-TIMI 53 (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus–Thrombolysis in Myocardial Infarction 53) randomized 16,492 patients with type 2 diabetes and a history of established cardiovascular disease or multiple risk factors for vascular disease to either saxagliptin, doses ranging from 2.5 to 5 mg daily, or placebo.

The primary endpoint – a composite of cardiovascular death, myocardial infarction, or ischemic stroke – occurred at similar rates in 613 patients randomized to receive saxagliptin treatment and 609 patients randomized to receive placebo (7.3% and 7.2%, respectively) at a median follow-up of 2.1 years, Dr. Benjamin M. Scirica of Brigham and Women’s Hospital and Harvard Medical School, Boston, and his colleagues reported on behalf of the SAVOR-TIMI 53 Steering Committee and Investigators.

A major secondary endpoint – a composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or heart failure – also occurred at similar rates in the treatment and placebo groups (12.8% and 12.4%, respectively), they reported (N. Engl. J. Med. 2013 Sept. 2 [doi: 10.1056/NEJMoa1307684]).

However, more patients in the treatment group than in the placebo group were hospitalized for heart failure (3.5% vs. 2.8%), they noted, adding that this was an unexpected finding that merits further study.

The findings demonstrate that DPP-4 inhibition with saxagliptin neither increases nor decreases the rate of ischemic events over a median 2-year period, although longer duration of treatment may have different effects.

"Together with ongoing trials of other DPP-4 inhibitors and novel antihyperglycemic agents, these data will provide a more rigorous and robust evidence base than is currently available to guide the future care of patients with diabetes," they concluded.

EXAMINE

Similarly, the EXAMINE (Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care) trial showed that the primary endpoint – a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke – did not occur significantly more often at a median follow-up of 18 months in 2,679 patients randomized to receive treatment, compared with 2,701 patients randomized to receive placebo (11.3% vs. 11.8%, respectively), Dr. William B. White of the University of Connecticut School of Medicine, Farmington, and his colleagues reported on behalf of the EXAMINE investigators.

Patients included in this noninferiority study had type 2 diabetes and a recent acute myocardial infarction or unstable angina requiring hospitalization, who received standard-of-care treatment for diabetes and cardiovascular risk factors throughout the study period. Alogliptin doses ranged from 6.25 to 25 mg daily on the basis of the patients’ estimated glomerular filtration rate at baseline.

"The alogliptin and placebo groups did not differ significantly with respect to the incidence of serious adverse events (33.6% and 35.5%, respectively)," the investigators wrote (N. Engl. J. Med. 2013 Sept. 2 [doi: 10.1056/NEJMoa1305889]).

In this group of patients at very high cardiovascular event risk, alogliptin did not increase or decrease cardiovascular morbidity or mortality over a median 18-month period; the findings do not rule out longer-term risks with respect to cardiovascular endpoints, they noted.

"These data can be used to help guide clinicians in choosing among the many available antidiabetic agents when treating patients with type 2 diabetes and very high cardiovascular risk," they concluded.

The SAVOR-TIMI 53 trial was supported by AstraZeneca and Bristol-Myers Squibb. The EXAMINE trial was supported by Takeda Development Center Americas. Multiple authors for both studies reported disclosures. Details are provided with the full text of each article at NEJM.org.

Neither saxagliptin nor alogliptin was associated with increased – or decreased – rates of major adverse cardiovascular events in high-risk patients with type 2 diabetes mellitus in separate randomized, double-blind, placebo-controlled trials.

The findings with respect to these recently approved antidiabetic therapies – members of the same class of selective dipeptidyl peptidase–4 (DDP-4) inhibitors – provide clinicians with important information to help guide treatment decision-making for patients with type 2 diabetes and cardiovascular risk, the authors concluded.

Both studies were mandated by the Food and Drug Administration, which in 2008 began requiring all diabetes therapies to demonstrate cardiovascular safety after concerns were raised in 2007 about a link between rosiglitazone (Avandia) and an increased risk of myocardial infarction. The results were reported at the annual congress of the European Society of Cardiology, and were simultaneously published online Sept. 2 in the New England Journal of Medicine.

SAVOR-TIMI 53

SAVOR-TIMI 53 (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus–Thrombolysis in Myocardial Infarction 53) randomized 16,492 patients with type 2 diabetes and a history of established cardiovascular disease or multiple risk factors for vascular disease to either saxagliptin, doses ranging from 2.5 to 5 mg daily, or placebo.

The primary endpoint – a composite of cardiovascular death, myocardial infarction, or ischemic stroke – occurred at similar rates in 613 patients randomized to receive saxagliptin treatment and 609 patients randomized to receive placebo (7.3% and 7.2%, respectively) at a median follow-up of 2.1 years, Dr. Benjamin M. Scirica of Brigham and Women’s Hospital and Harvard Medical School, Boston, and his colleagues reported on behalf of the SAVOR-TIMI 53 Steering Committee and Investigators.

A major secondary endpoint – a composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or heart failure – also occurred at similar rates in the treatment and placebo groups (12.8% and 12.4%, respectively), they reported (N. Engl. J. Med. 2013 Sept. 2 [doi: 10.1056/NEJMoa1307684]).

However, more patients in the treatment group than in the placebo group were hospitalized for heart failure (3.5% vs. 2.8%), they noted, adding that this was an unexpected finding that merits further study.

The findings demonstrate that DPP-4 inhibition with saxagliptin neither increases nor decreases the rate of ischemic events over a median 2-year period, although longer duration of treatment may have different effects.

"Together with ongoing trials of other DPP-4 inhibitors and novel antihyperglycemic agents, these data will provide a more rigorous and robust evidence base than is currently available to guide the future care of patients with diabetes," they concluded.

EXAMINE

Similarly, the EXAMINE (Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care) trial showed that the primary endpoint – a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke – did not occur significantly more often at a median follow-up of 18 months in 2,679 patients randomized to receive treatment, compared with 2,701 patients randomized to receive placebo (11.3% vs. 11.8%, respectively), Dr. William B. White of the University of Connecticut School of Medicine, Farmington, and his colleagues reported on behalf of the EXAMINE investigators.

Patients included in this noninferiority study had type 2 diabetes and a recent acute myocardial infarction or unstable angina requiring hospitalization, who received standard-of-care treatment for diabetes and cardiovascular risk factors throughout the study period. Alogliptin doses ranged from 6.25 to 25 mg daily on the basis of the patients’ estimated glomerular filtration rate at baseline.

"The alogliptin and placebo groups did not differ significantly with respect to the incidence of serious adverse events (33.6% and 35.5%, respectively)," the investigators wrote (N. Engl. J. Med. 2013 Sept. 2 [doi: 10.1056/NEJMoa1305889]).

In this group of patients at very high cardiovascular event risk, alogliptin did not increase or decrease cardiovascular morbidity or mortality over a median 18-month period; the findings do not rule out longer-term risks with respect to cardiovascular endpoints, they noted.

"These data can be used to help guide clinicians in choosing among the many available antidiabetic agents when treating patients with type 2 diabetes and very high cardiovascular risk," they concluded.

The SAVOR-TIMI 53 trial was supported by AstraZeneca and Bristol-Myers Squibb. The EXAMINE trial was supported by Takeda Development Center Americas. Multiple authors for both studies reported disclosures. Details are provided with the full text of each article at NEJM.org.

Neither saxagliptin nor alogliptin was associated with increased – or decreased – rates of major adverse cardiovascular events in high-risk patients with type 2 diabetes mellitus in separate randomized, double-blind, placebo-controlled trials.

The findings with respect to these recently approved antidiabetic therapies – members of the same class of selective dipeptidyl peptidase–4 (DDP-4) inhibitors – provide clinicians with important information to help guide treatment decision-making for patients with type 2 diabetes and cardiovascular risk, the authors concluded.

Both studies were mandated by the Food and Drug Administration, which in 2008 began requiring all diabetes therapies to demonstrate cardiovascular safety after concerns were raised in 2007 about a link between rosiglitazone (Avandia) and an increased risk of myocardial infarction. The results were reported at the annual congress of the European Society of Cardiology, and were simultaneously published online Sept. 2 in the New England Journal of Medicine.

SAVOR-TIMI 53

SAVOR-TIMI 53 (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus–Thrombolysis in Myocardial Infarction 53) randomized 16,492 patients with type 2 diabetes and a history of established cardiovascular disease or multiple risk factors for vascular disease to either saxagliptin, doses ranging from 2.5 to 5 mg daily, or placebo.

The primary endpoint – a composite of cardiovascular death, myocardial infarction, or ischemic stroke – occurred at similar rates in 613 patients randomized to receive saxagliptin treatment and 609 patients randomized to receive placebo (7.3% and 7.2%, respectively) at a median follow-up of 2.1 years, Dr. Benjamin M. Scirica of Brigham and Women’s Hospital and Harvard Medical School, Boston, and his colleagues reported on behalf of the SAVOR-TIMI 53 Steering Committee and Investigators.

A major secondary endpoint – a composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or heart failure – also occurred at similar rates in the treatment and placebo groups (12.8% and 12.4%, respectively), they reported (N. Engl. J. Med. 2013 Sept. 2 [doi: 10.1056/NEJMoa1307684]).

However, more patients in the treatment group than in the placebo group were hospitalized for heart failure (3.5% vs. 2.8%), they noted, adding that this was an unexpected finding that merits further study.

The findings demonstrate that DPP-4 inhibition with saxagliptin neither increases nor decreases the rate of ischemic events over a median 2-year period, although longer duration of treatment may have different effects.

"Together with ongoing trials of other DPP-4 inhibitors and novel antihyperglycemic agents, these data will provide a more rigorous and robust evidence base than is currently available to guide the future care of patients with diabetes," they concluded.

EXAMINE

Similarly, the EXAMINE (Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care) trial showed that the primary endpoint – a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke – did not occur significantly more often at a median follow-up of 18 months in 2,679 patients randomized to receive treatment, compared with 2,701 patients randomized to receive placebo (11.3% vs. 11.8%, respectively), Dr. William B. White of the University of Connecticut School of Medicine, Farmington, and his colleagues reported on behalf of the EXAMINE investigators.

Patients included in this noninferiority study had type 2 diabetes and a recent acute myocardial infarction or unstable angina requiring hospitalization, who received standard-of-care treatment for diabetes and cardiovascular risk factors throughout the study period. Alogliptin doses ranged from 6.25 to 25 mg daily on the basis of the patients’ estimated glomerular filtration rate at baseline.

"The alogliptin and placebo groups did not differ significantly with respect to the incidence of serious adverse events (33.6% and 35.5%, respectively)," the investigators wrote (N. Engl. J. Med. 2013 Sept. 2 [doi: 10.1056/NEJMoa1305889]).

In this group of patients at very high cardiovascular event risk, alogliptin did not increase or decrease cardiovascular morbidity or mortality over a median 18-month period; the findings do not rule out longer-term risks with respect to cardiovascular endpoints, they noted.

"These data can be used to help guide clinicians in choosing among the many available antidiabetic agents when treating patients with type 2 diabetes and very high cardiovascular risk," they concluded.

The SAVOR-TIMI 53 trial was supported by AstraZeneca and Bristol-Myers Squibb. The EXAMINE trial was supported by Takeda Development Center Americas. Multiple authors for both studies reported disclosures. Details are provided with the full text of each article at NEJM.org.

Pretreatment with the P2Y₁₂ antagonist prasugrel in patients with non-ST–segment elevation acute coronary syndromes did not reduce the rate of major ischemic events, but did increase the rate of major bleeding complications within 30 days of coronary angiography in the randomized, controlled, phase III ACCOAST trial.

The incidence of the primary efficacy endpoint – a composite of death from cardiovascular causes, myocardial infarction, stroke, urgent revascularization, or glycoprotein IIb/IIIa inhibitor rescue therapy through day 7 – was similar in 2,037 patients who were randomized to receive prasugrel before and after angiography, and in 1,996 patients who were randomized to receive treatment only after angiography (10.0% and 9.8%; respectively; hazard ratio, 1.02), Dr. Gilles Montalescot of Institut de Cardiologie, Centre Hospitalier Universitaire Pitié-Salpêtrière, Paris, and colleagues found.

The findings were similar, with no significant differences noted between the pretreatment and control groups with respect to the primary efficacy endpoint, among the 2,770 patients managed by percutaneous coronary intervention (PCI), compared with the entire cohort ultimately managed by PCI, coronary artery bypass grafting (CABG), or medical treatment alone.

However, the rate of a key safety endpoint – thrombolysis in myocardial infarction (TIMI) major bleeding episodes through day 7 – was increased in those in the pretreatment group, compared with the control group (2.6% vs. 1.4%; hazard ratio, 1.90), the investigators said, noting that the findings, which were reported at the annual congress of the European Society of Cardiology and simultaneously published online Sept. 1 in the New England Journal of Medicine, were confirmed at 30 days.

"There was an increase by a factor of 3 in all major bleeding not related to CABG and an increase by a factor of 6 in life-threatening bleeding not related to CABG. TIMI minor bleeding events were also increased with pretreatment compared with no pretreatment (hazard ratio, 2.50)," they wrote (N. Engl. J. Med. 2013 Sept. 1 [doi:10.1056/NEJM1308075]).

Patients in the trial were adults with a mean age of 63 years who had non-ST–segment elevation (NSTE) acute coronary syndromes and a positive troponin level. They were enrolled between Dec. 6, 2009, and Nov. 16, 2012. All were scheduled to undergo coronary angiography within 2-48 hours following randomization.

Those randomized to the pretreatment group received a 30-mg loading dose with prasugrel before angiography, and an additional 30 mg at the time of PCI. Those randomized to the control group received a placebo before the angiography, and 60 mg of prasugrel at the time of PCI.

In a pharmacodynamic substudy involving 23 patients, the investigators noted that "at the time of arterial access, a median of 4.8 hours after the first loading dose, there was greater platelet inhibition in the pretreatment group than in the control group, which may have contributed to the increased rate of bleeding complications in the pretreatment group."

Of note, the lack of protection afforded by prasugrel against ischemic events was demonstrated consistently across all prespecified subgroups, including high-risk groups such as the elderly, those with diabetes, and those with a Global Registry of Acute Coronary Events (GRACE) risk score of 140 or higher.

"This suggests that stronger [than clopidogrel] antiplatelet therapy does not prevent the occurrence of a myocardial infarction before catheterization or after PCI," the investigators wrote. Nonetheless, the lack of P2Y₁₂ inhibition in the control group did notresult in an excess of ischemic events in patients who underwent CABG or medical therapy. In fact, other studies have shown that currently, the risk of ischemic events is "extremely low" because of the short time between admission to the hospital and catheterization.

The benefit of adding clopidogrel to aspirin in patients with NSTE acute coronary syndromes was demonstrated in the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) study, in which a small subgroup of patients received the drug prior to undergoing PCI; the significant reduction in ischemic events set a precedent for clopidogrel treatment before catheterization, although subsequent studies have not supported the finding. The pretreatment use of clopidogrel and aspirin in patients with NSTE acute coronary syndrome to help reduce ischemic events following an invasive procedure is commonplace, and is included as a class I recommendation in guidelines from the American College of Cardiology Foundation–American Heart Association. This is despite a lack of rigorous studies supporting the practice, which has often been extended to new oral P2Y₁₂ antagonists like prasugrel as well, they explained.

However, prasugrel is more potent and has a more rapid onset of action than clopidogrel. "Our results support the administration of prasugrel when the coronary anatomy is known and after PCI is selected as the treatment strategy," they concluded.

This study was supported by Daiichi Sankyo and Eli Lilly. Multiple study authors, including Dr. Montalescot, reported having disclosures.

Pretreatment with the P2Y₁₂ antagonist prasugrel in patients with non-ST–segment elevation acute coronary syndromes did not reduce the rate of major ischemic events, but did increase the rate of major bleeding complications within 30 days of coronary angiography in the randomized, controlled, phase III ACCOAST trial.

The incidence of the primary efficacy endpoint – a composite of death from cardiovascular causes, myocardial infarction, stroke, urgent revascularization, or glycoprotein IIb/IIIa inhibitor rescue therapy through day 7 – was similar in 2,037 patients who were randomized to receive prasugrel before and after angiography, and in 1,996 patients who were randomized to receive treatment only after angiography (10.0% and 9.8%; respectively; hazard ratio, 1.02), Dr. Gilles Montalescot of Institut de Cardiologie, Centre Hospitalier Universitaire Pitié-Salpêtrière, Paris, and colleagues found.

The findings were similar, with no significant differences noted between the pretreatment and control groups with respect to the primary efficacy endpoint, among the 2,770 patients managed by percutaneous coronary intervention (PCI), compared with the entire cohort ultimately managed by PCI, coronary artery bypass grafting (CABG), or medical treatment alone.

However, the rate of a key safety endpoint – thrombolysis in myocardial infarction (TIMI) major bleeding episodes through day 7 – was increased in those in the pretreatment group, compared with the control group (2.6% vs. 1.4%; hazard ratio, 1.90), the investigators said, noting that the findings, which were reported at the annual congress of the European Society of Cardiology and simultaneously published online Sept. 1 in the New England Journal of Medicine, were confirmed at 30 days.

"There was an increase by a factor of 3 in all major bleeding not related to CABG and an increase by a factor of 6 in life-threatening bleeding not related to CABG. TIMI minor bleeding events were also increased with pretreatment compared with no pretreatment (hazard ratio, 2.50)," they wrote (N. Engl. J. Med. 2013 Sept. 1 [doi:10.1056/NEJM1308075]).

Patients in the trial were adults with a mean age of 63 years who had non-ST–segment elevation (NSTE) acute coronary syndromes and a positive troponin level. They were enrolled between Dec. 6, 2009, and Nov. 16, 2012. All were scheduled to undergo coronary angiography within 2-48 hours following randomization.

Those randomized to the pretreatment group received a 30-mg loading dose with prasugrel before angiography, and an additional 30 mg at the time of PCI. Those randomized to the control group received a placebo before the angiography, and 60 mg of prasugrel at the time of PCI.

In a pharmacodynamic substudy involving 23 patients, the investigators noted that "at the time of arterial access, a median of 4.8 hours after the first loading dose, there was greater platelet inhibition in the pretreatment group than in the control group, which may have contributed to the increased rate of bleeding complications in the pretreatment group."

Of note, the lack of protection afforded by prasugrel against ischemic events was demonstrated consistently across all prespecified subgroups, including high-risk groups such as the elderly, those with diabetes, and those with a Global Registry of Acute Coronary Events (GRACE) risk score of 140 or higher.

"This suggests that stronger [than clopidogrel] antiplatelet therapy does not prevent the occurrence of a myocardial infarction before catheterization or after PCI," the investigators wrote. Nonetheless, the lack of P2Y₁₂ inhibition in the control group did notresult in an excess of ischemic events in patients who underwent CABG or medical therapy. In fact, other studies have shown that currently, the risk of ischemic events is "extremely low" because of the short time between admission to the hospital and catheterization.

The benefit of adding clopidogrel to aspirin in patients with NSTE acute coronary syndromes was demonstrated in the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) study, in which a small subgroup of patients received the drug prior to undergoing PCI; the significant reduction in ischemic events set a precedent for clopidogrel treatment before catheterization, although subsequent studies have not supported the finding. The pretreatment use of clopidogrel and aspirin in patients with NSTE acute coronary syndrome to help reduce ischemic events following an invasive procedure is commonplace, and is included as a class I recommendation in guidelines from the American College of Cardiology Foundation–American Heart Association. This is despite a lack of rigorous studies supporting the practice, which has often been extended to new oral P2Y₁₂ antagonists like prasugrel as well, they explained.

However, prasugrel is more potent and has a more rapid onset of action than clopidogrel. "Our results support the administration of prasugrel when the coronary anatomy is known and after PCI is selected as the treatment strategy," they concluded.

This study was supported by Daiichi Sankyo and Eli Lilly. Multiple study authors, including Dr. Montalescot, reported having disclosures.

Pretreatment with the P2Y₁₂ antagonist prasugrel in patients with non-ST–segment elevation acute coronary syndromes did not reduce the rate of major ischemic events, but did increase the rate of major bleeding complications within 30 days of coronary angiography in the randomized, controlled, phase III ACCOAST trial.

The incidence of the primary efficacy endpoint – a composite of death from cardiovascular causes, myocardial infarction, stroke, urgent revascularization, or glycoprotein IIb/IIIa inhibitor rescue therapy through day 7 – was similar in 2,037 patients who were randomized to receive prasugrel before and after angiography, and in 1,996 patients who were randomized to receive treatment only after angiography (10.0% and 9.8%; respectively; hazard ratio, 1.02), Dr. Gilles Montalescot of Institut de Cardiologie, Centre Hospitalier Universitaire Pitié-Salpêtrière, Paris, and colleagues found.

The findings were similar, with no significant differences noted between the pretreatment and control groups with respect to the primary efficacy endpoint, among the 2,770 patients managed by percutaneous coronary intervention (PCI), compared with the entire cohort ultimately managed by PCI, coronary artery bypass grafting (CABG), or medical treatment alone.

However, the rate of a key safety endpoint – thrombolysis in myocardial infarction (TIMI) major bleeding episodes through day 7 – was increased in those in the pretreatment group, compared with the control group (2.6% vs. 1.4%; hazard ratio, 1.90), the investigators said, noting that the findings, which were reported at the annual congress of the European Society of Cardiology and simultaneously published online Sept. 1 in the New England Journal of Medicine, were confirmed at 30 days.

"There was an increase by a factor of 3 in all major bleeding not related to CABG and an increase by a factor of 6 in life-threatening bleeding not related to CABG. TIMI minor bleeding events were also increased with pretreatment compared with no pretreatment (hazard ratio, 2.50)," they wrote (N. Engl. J. Med. 2013 Sept. 1 [doi:10.1056/NEJM1308075]).

Patients in the trial were adults with a mean age of 63 years who had non-ST–segment elevation (NSTE) acute coronary syndromes and a positive troponin level. They were enrolled between Dec. 6, 2009, and Nov. 16, 2012. All were scheduled to undergo coronary angiography within 2-48 hours following randomization.

Those randomized to the pretreatment group received a 30-mg loading dose with prasugrel before angiography, and an additional 30 mg at the time of PCI. Those randomized to the control group received a placebo before the angiography, and 60 mg of prasugrel at the time of PCI.

In a pharmacodynamic substudy involving 23 patients, the investigators noted that "at the time of arterial access, a median of 4.8 hours after the first loading dose, there was greater platelet inhibition in the pretreatment group than in the control group, which may have contributed to the increased rate of bleeding complications in the pretreatment group."

Of note, the lack of protection afforded by prasugrel against ischemic events was demonstrated consistently across all prespecified subgroups, including high-risk groups such as the elderly, those with diabetes, and those with a Global Registry of Acute Coronary Events (GRACE) risk score of 140 or higher.

"This suggests that stronger [than clopidogrel] antiplatelet therapy does not prevent the occurrence of a myocardial infarction before catheterization or after PCI," the investigators wrote. Nonetheless, the lack of P2Y₁₂ inhibition in the control group did notresult in an excess of ischemic events in patients who underwent CABG or medical therapy. In fact, other studies have shown that currently, the risk of ischemic events is "extremely low" because of the short time between admission to the hospital and catheterization.

The benefit of adding clopidogrel to aspirin in patients with NSTE acute coronary syndromes was demonstrated in the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) study, in which a small subgroup of patients received the drug prior to undergoing PCI; the significant reduction in ischemic events set a precedent for clopidogrel treatment before catheterization, although subsequent studies have not supported the finding. The pretreatment use of clopidogrel and aspirin in patients with NSTE acute coronary syndrome to help reduce ischemic events following an invasive procedure is commonplace, and is included as a class I recommendation in guidelines from the American College of Cardiology Foundation–American Heart Association. This is despite a lack of rigorous studies supporting the practice, which has often been extended to new oral P2Y₁₂ antagonists like prasugrel as well, they explained.

However, prasugrel is more potent and has a more rapid onset of action than clopidogrel. "Our results support the administration of prasugrel when the coronary anatomy is known and after PCI is selected as the treatment strategy," they concluded.

This study was supported by Daiichi Sankyo and Eli Lilly. Multiple study authors, including Dr. Montalescot, reported having disclosures.

Carbonation produces a decrease in the neural processing of sweetness-related signals, particularly those from sucrose, a small functional neuroimaging study shows.

The findings, which suggest that the combination of CO₂ and sucrose might increase consumption of sucrose, could have implications for dietary interventions designed to regulate caloric intake, according to Dr. Francesco Di Salle of Salerno (Italy) University and his colleagues.

To assess the interference between CO₂ and perception of sweetness, as well as the differential effects of CO₂ on sucrose and aspartame-acesulfame, (As-Ac, an artificial sweetener combination commonly used in diet beverages), the investigators performed two functional magnetic resonance imaging (fMRI) experiments to evaluate changes in regional brain activity.

The first experiment, performed in nine volunteers, analyzed the effect of carbonation in four sweet Sprite-based solutions, including one carbonated and sweetened with sucrose, one noncarbonated and sweetened with sucrose, one carbonated and sweetened with As-Ac, and one noncarbonated and sweetened with As-Ac. The second experiment evaluated the spatial location of the strongest neural effects of sour taste and CO₂ within the insular cortex of eight subjects.

On fMRI, the presence of carbonation in sweet solutions "independently of the sweetening agent, reduced neural activity in the anterior insula (AI), orbitofrontal cortex (OFC), and posterior pons ... the effect of carbonation on sucrose was much higher than on perception of As-Ac," they noted, explaining that "at the perceptual level ... carbonation reduced the perception of sweetness and the differences between the sensory profiles of sucrose and As-Ac."

This effect may increase sucrose intake, but is also favorable to diet beverage formulations being perceived as similar to regular beverage formulations, the investigators reported online May 28 ahead of print in Gastroenterology.

"It is also coherent with a process of prioritization among perceptual inputs (chemesthetic and gustatory information) deriving from the same body topography and converging to the same cortical regions (AI, OFC), they said (Gastroenterology 2013 [doi:10.1053/j.gastro.2013.05.041]).

To correlate neuroimaging with behavioral data, the ability of carbonation to modulate perception of sweetness was assessed in 14 subjects, who scored the level of perceived sweetness of the solutions on a visual analog scale ranging from 0 to 100 mm. The effect of 1,585 ppm of CO₂ added to a 10% glucose solution on the perception of sweetness was also tested in seven subjects.

CO₂ was able to significantly reduce sweet-induced taste perceptions as assessed by the volunteers’ visual analog scale recordings: The perception of Sprite-associated sweetness was significantly reduced by CO₂ (48 vs. 63 and 48 vs. 55 for As-Ac and sucrose, respectively).

"Similarly, in the presence of carbonation, sweet-induced perception of a 10% glucose solution was significantly reduced (36 vs. 53), the investigators said.

Given the widespread use of CO₂ in sweet beverages, the modulation of sweet perception by CO₂ is of interest, they noted.

The findings, which suggest that CO₂ modulates the perception of sweetness thereby reducing the global neural processing of sweetness, the processing of sucrose more than of As-Ac, and the processing difference between sweetening agents via modulation of the perception of sweetness, is "of utmost importance for designing carbonated beverages and is relevant to the regulation of caloric intake," they said.

"This effect is driven by the integration of information on gastric fullness and on nutrient depletion, conveyed to a brain network where the autonomic brainstem circuitry and tractus solitarius neurons play a critical role in homeostatic functions," they added.

It may be that taste and CO₂-related information influence food choices and intake through integration in the tractus solitarius with input from the gastrointestinal tract, they suggested, explaining that "the reduced discrimination between sucrose and As-Ac induced by CO₂ would promote the consumptions of low-calorie beverages and would converge with CO₂-induced gastric distention in limiting caloric intake."

This study was supported in part by the Coca-Cola Company. One author, Dr. Rosario Cuomo, was sponsored by the Coca-Cola Company. The remaining authors reported having no disclosures.

Carbonation produces a decrease in the neural processing of sweetness-related signals, particularly those from sucrose, a small functional neuroimaging study shows.

The findings, which suggest that the combination of CO₂ and sucrose might increase consumption of sucrose, could have implications for dietary interventions designed to regulate caloric intake, according to Dr. Francesco Di Salle of Salerno (Italy) University and his colleagues.

To assess the interference between CO₂ and perception of sweetness, as well as the differential effects of CO₂ on sucrose and aspartame-acesulfame, (As-Ac, an artificial sweetener combination commonly used in diet beverages), the investigators performed two functional magnetic resonance imaging (fMRI) experiments to evaluate changes in regional brain activity.

The first experiment, performed in nine volunteers, analyzed the effect of carbonation in four sweet Sprite-based solutions, including one carbonated and sweetened with sucrose, one noncarbonated and sweetened with sucrose, one carbonated and sweetened with As-Ac, and one noncarbonated and sweetened with As-Ac. The second experiment evaluated the spatial location of the strongest neural effects of sour taste and CO₂ within the insular cortex of eight subjects.

On fMRI, the presence of carbonation in sweet solutions "independently of the sweetening agent, reduced neural activity in the anterior insula (AI), orbitofrontal cortex (OFC), and posterior pons ... the effect of carbonation on sucrose was much higher than on perception of As-Ac," they noted, explaining that "at the perceptual level ... carbonation reduced the perception of sweetness and the differences between the sensory profiles of sucrose and As-Ac."

This effect may increase sucrose intake, but is also favorable to diet beverage formulations being perceived as similar to regular beverage formulations, the investigators reported online May 28 ahead of print in Gastroenterology.

"It is also coherent with a process of prioritization among perceptual inputs (chemesthetic and gustatory information) deriving from the same body topography and converging to the same cortical regions (AI, OFC), they said (Gastroenterology 2013 [doi:10.1053/j.gastro.2013.05.041]).

To correlate neuroimaging with behavioral data, the ability of carbonation to modulate perception of sweetness was assessed in 14 subjects, who scored the level of perceived sweetness of the solutions on a visual analog scale ranging from 0 to 100 mm. The effect of 1,585 ppm of CO₂ added to a 10% glucose solution on the perception of sweetness was also tested in seven subjects.

CO₂ was able to significantly reduce sweet-induced taste perceptions as assessed by the volunteers’ visual analog scale recordings: The perception of Sprite-associated sweetness was significantly reduced by CO₂ (48 vs. 63 and 48 vs. 55 for As-Ac and sucrose, respectively).

"Similarly, in the presence of carbonation, sweet-induced perception of a 10% glucose solution was significantly reduced (36 vs. 53), the investigators said.

Given the widespread use of CO₂ in sweet beverages, the modulation of sweet perception by CO₂ is of interest, they noted.

The findings, which suggest that CO₂ modulates the perception of sweetness thereby reducing the global neural processing of sweetness, the processing of sucrose more than of As-Ac, and the processing difference between sweetening agents via modulation of the perception of sweetness, is "of utmost importance for designing carbonated beverages and is relevant to the regulation of caloric intake," they said.

"This effect is driven by the integration of information on gastric fullness and on nutrient depletion, conveyed to a brain network where the autonomic brainstem circuitry and tractus solitarius neurons play a critical role in homeostatic functions," they added.

It may be that taste and CO₂-related information influence food choices and intake through integration in the tractus solitarius with input from the gastrointestinal tract, they suggested, explaining that "the reduced discrimination between sucrose and As-Ac induced by CO₂ would promote the consumptions of low-calorie beverages and would converge with CO₂-induced gastric distention in limiting caloric intake."

This study was supported in part by the Coca-Cola Company. One author, Dr. Rosario Cuomo, was sponsored by the Coca-Cola Company. The remaining authors reported having no disclosures.

Carbonation produces a decrease in the neural processing of sweetness-related signals, particularly those from sucrose, a small functional neuroimaging study shows.

The findings, which suggest that the combination of CO₂ and sucrose might increase consumption of sucrose, could have implications for dietary interventions designed to regulate caloric intake, according to Dr. Francesco Di Salle of Salerno (Italy) University and his colleagues.

To assess the interference between CO₂ and perception of sweetness, as well as the differential effects of CO₂ on sucrose and aspartame-acesulfame, (As-Ac, an artificial sweetener combination commonly used in diet beverages), the investigators performed two functional magnetic resonance imaging (fMRI) experiments to evaluate changes in regional brain activity.

The first experiment, performed in nine volunteers, analyzed the effect of carbonation in four sweet Sprite-based solutions, including one carbonated and sweetened with sucrose, one noncarbonated and sweetened with sucrose, one carbonated and sweetened with As-Ac, and one noncarbonated and sweetened with As-Ac. The second experiment evaluated the spatial location of the strongest neural effects of sour taste and CO₂ within the insular cortex of eight subjects.

On fMRI, the presence of carbonation in sweet solutions "independently of the sweetening agent, reduced neural activity in the anterior insula (AI), orbitofrontal cortex (OFC), and posterior pons ... the effect of carbonation on sucrose was much higher than on perception of As-Ac," they noted, explaining that "at the perceptual level ... carbonation reduced the perception of sweetness and the differences between the sensory profiles of sucrose and As-Ac."

This effect may increase sucrose intake, but is also favorable to diet beverage formulations being perceived as similar to regular beverage formulations, the investigators reported online May 28 ahead of print in Gastroenterology.

"It is also coherent with a process of prioritization among perceptual inputs (chemesthetic and gustatory information) deriving from the same body topography and converging to the same cortical regions (AI, OFC), they said (Gastroenterology 2013 [doi:10.1053/j.gastro.2013.05.041]).

To correlate neuroimaging with behavioral data, the ability of carbonation to modulate perception of sweetness was assessed in 14 subjects, who scored the level of perceived sweetness of the solutions on a visual analog scale ranging from 0 to 100 mm. The effect of 1,585 ppm of CO₂ added to a 10% glucose solution on the perception of sweetness was also tested in seven subjects.

CO₂ was able to significantly reduce sweet-induced taste perceptions as assessed by the volunteers’ visual analog scale recordings: The perception of Sprite-associated sweetness was significantly reduced by CO₂ (48 vs. 63 and 48 vs. 55 for As-Ac and sucrose, respectively).

"Similarly, in the presence of carbonation, sweet-induced perception of a 10% glucose solution was significantly reduced (36 vs. 53), the investigators said.

Given the widespread use of CO₂ in sweet beverages, the modulation of sweet perception by CO₂ is of interest, they noted.

The findings, which suggest that CO₂ modulates the perception of sweetness thereby reducing the global neural processing of sweetness, the processing of sucrose more than of As-Ac, and the processing difference between sweetening agents via modulation of the perception of sweetness, is "of utmost importance for designing carbonated beverages and is relevant to the regulation of caloric intake," they said.

"This effect is driven by the integration of information on gastric fullness and on nutrient depletion, conveyed to a brain network where the autonomic brainstem circuitry and tractus solitarius neurons play a critical role in homeostatic functions," they added.

It may be that taste and CO₂-related information influence food choices and intake through integration in the tractus solitarius with input from the gastrointestinal tract, they suggested, explaining that "the reduced discrimination between sucrose and As-Ac induced by CO₂ would promote the consumptions of low-calorie beverages and would converge with CO₂-induced gastric distention in limiting caloric intake."

This study was supported in part by the Coca-Cola Company. One author, Dr. Rosario Cuomo, was sponsored by the Coca-Cola Company. The remaining authors reported having no disclosures.

A hybrid colorectal cancer screening strategy that incorporates annual fecal immunological testing beginning at age 50 years and a single colonoscopy at age 66 years proved both clinically effective and cost-effective in a simulation model.

Using the Archimedes Model – a "large-scale integrated simulation of human physiology, diseases, and health care systems" – Tuan Dinh, Ph.D., of Archimedes Inc., San Francisco, and colleagues found that compared with no screening, the hybrid strategy with annual fecal immunological testing (FIT) reduced colorectal cancer incidence by 73%, gained 11,200 quality-adjusted life years (QALYs), and saved $126.8 million for every 100,000 people screened during a 30-year period.

Source: American Gastroenterological Association

Without screening, a cohort of 100,000 members of Kaiser Permanente Northern California who were included in the virtual study experienced 6,004 colorectal cancers and 1,837 colorectal cancer deaths. All methods of screening that were evaluated in the model – including annual FIT, colonoscopy at 10-year intervals, sigmoidoscopy at 5-year intervals, both FIT and sigmoidoscopy, and both FIT and colonoscopy – substantially reduced the colorectal cancer incidence, by 53%-76%, and added a significant number of QALYs, compared with no screening, the investigators reported online March 28 in Clinical Gastroenterology and Hepatology.

Colonoscopy as a single-modality screening strategy was most effective for colorectal cancer reduction (76%), and FIT alone was the least costly approach (with savings of $142.6 million per 100,000 persons, compared with no screening), but FIT plus colonoscopy came close: The hybrid strategy reduced colorectal cancer by 73%, and compared with FIT alone, gained 1,400 QALYs/100,000 at an incremental cost of $9,700 per QALY gained. Colonoscopy gained 500 QALY/100,000 more than the hybrid strategy at an incremental cost of $35,100 per QALY gained.

Furthermore, the hybrid strategy required 55% fewer FITs and 41% more colonoscopies than FIT alone, and required 2.1-2.3 fewer colonoscopies per person during 30 years than screening by colonoscopy alone, they reported (Clin. Gastroenterol. Hepatol. 2013 March 28 [doi: 10.1016/j.cgh.2013.03.013]).

On sensitivity analysis, a hybrid approach using biennial FIT was also cost-effective, compared with either FIT or colonoscopy alone.

The core of the Archimedes Model is "a set of equations that represent physiological pathways at the clinical level (i.e., at the level of detail of basic medical tests, clinical trials, and patient charts)." The colorectal cancer submodel, which was derived from public databases, published epidemiologic studies, and clinical trials, was developed in collaboration with the American Cancer Society, the authors explained.

The simulated population included a cross section of 2008 Kaiser Permanente members who were aged 50-75 years at the start of the virtual trial comparing the screening strategies.

The findings are important, given that colorectal cancer is the second-leading cause of cancer deaths among adults in the United States, and although colonoscopy is the recommended approach for primary screening in most U.S. guidelines, it is the most invasive, risky, and costly screening modality, the investigators noted.

Conversely, stool tests with follow-up colonoscopy for positive results are the least expensive. In the past, stool test strategies have been hampered by low sensitivity for adenomas and low specificity, but recent improvements in sensitivity and specificity of FIT has renewed interest in the use of stool tests, they said.

Though the hybrid FIT/colonoscopy strategy is limited by several factors – for example, the accuracy of any simulation model is dependent on assumptions about test performance and adherence, which may vary – the findings of this study suggest the hybrid strategy could improve outcomes while lowering costs.

"The simulation results indicated that [the hybrid strategy] required 37% fewer colonoscopies than [colonoscopy alone], while delivering only slightly inferior health benefits," the investigators said. These results demonstrate that "it is possible to design hybrid colorectal cancer screening strategies that can deliver health benefits and cost-effectiveness that are comparable to those of single-modality strategies, with a favorable impact on resource demand," they noted.

Future clinical studies should address whether hybrid strategies have the additional advantage of increasing screening adherence, they concluded.

This study was carried out by Archimedes under a contract with The Permanente Medical Group (TPMG). One author, Dr. Theodore R. Levin, is a TPMG shareholder, and another, Cindy Caldwell, is a TPMG employee. The authors reported having no other conflicts of interest.

A hybrid colorectal cancer screening strategy that incorporates annual fecal immunological testing beginning at age 50 years and a single colonoscopy at age 66 years proved both clinically effective and cost-effective in a simulation model.

Using the Archimedes Model – a "large-scale integrated simulation of human physiology, diseases, and health care systems" – Tuan Dinh, Ph.D., of Archimedes Inc., San Francisco, and colleagues found that compared with no screening, the hybrid strategy with annual fecal immunological testing (FIT) reduced colorectal cancer incidence by 73%, gained 11,200 quality-adjusted life years (QALYs), and saved $126.8 million for every 100,000 people screened during a 30-year period.

Source: American Gastroenterological Association

Without screening, a cohort of 100,000 members of Kaiser Permanente Northern California who were included in the virtual study experienced 6,004 colorectal cancers and 1,837 colorectal cancer deaths. All methods of screening that were evaluated in the model – including annual FIT, colonoscopy at 10-year intervals, sigmoidoscopy at 5-year intervals, both FIT and sigmoidoscopy, and both FIT and colonoscopy – substantially reduced the colorectal cancer incidence, by 53%-76%, and added a significant number of QALYs, compared with no screening, the investigators reported online March 28 in Clinical Gastroenterology and Hepatology.

Colonoscopy as a single-modality screening strategy was most effective for colorectal cancer reduction (76%), and FIT alone was the least costly approach (with savings of $142.6 million per 100,000 persons, compared with no screening), but FIT plus colonoscopy came close: The hybrid strategy reduced colorectal cancer by 73%, and compared with FIT alone, gained 1,400 QALYs/100,000 at an incremental cost of $9,700 per QALY gained. Colonoscopy gained 500 QALY/100,000 more than the hybrid strategy at an incremental cost of $35,100 per QALY gained.

Furthermore, the hybrid strategy required 55% fewer FITs and 41% more colonoscopies than FIT alone, and required 2.1-2.3 fewer colonoscopies per person during 30 years than screening by colonoscopy alone, they reported (Clin. Gastroenterol. Hepatol. 2013 March 28 [doi: 10.1016/j.cgh.2013.03.013]).

On sensitivity analysis, a hybrid approach using biennial FIT was also cost-effective, compared with either FIT or colonoscopy alone.

The core of the Archimedes Model is "a set of equations that represent physiological pathways at the clinical level (i.e., at the level of detail of basic medical tests, clinical trials, and patient charts)." The colorectal cancer submodel, which was derived from public databases, published epidemiologic studies, and clinical trials, was developed in collaboration with the American Cancer Society, the authors explained.

The simulated population included a cross section of 2008 Kaiser Permanente members who were aged 50-75 years at the start of the virtual trial comparing the screening strategies.

The findings are important, given that colorectal cancer is the second-leading cause of cancer deaths among adults in the United States, and although colonoscopy is the recommended approach for primary screening in most U.S. guidelines, it is the most invasive, risky, and costly screening modality, the investigators noted.

Conversely, stool tests with follow-up colonoscopy for positive results are the least expensive. In the past, stool test strategies have been hampered by low sensitivity for adenomas and low specificity, but recent improvements in sensitivity and specificity of FIT has renewed interest in the use of stool tests, they said.

Though the hybrid FIT/colonoscopy strategy is limited by several factors – for example, the accuracy of any simulation model is dependent on assumptions about test performance and adherence, which may vary – the findings of this study suggest the hybrid strategy could improve outcomes while lowering costs.

"The simulation results indicated that [the hybrid strategy] required 37% fewer colonoscopies than [colonoscopy alone], while delivering only slightly inferior health benefits," the investigators said. These results demonstrate that "it is possible to design hybrid colorectal cancer screening strategies that can deliver health benefits and cost-effectiveness that are comparable to those of single-modality strategies, with a favorable impact on resource demand," they noted.

Future clinical studies should address whether hybrid strategies have the additional advantage of increasing screening adherence, they concluded.

This study was carried out by Archimedes under a contract with The Permanente Medical Group (TPMG). One author, Dr. Theodore R. Levin, is a TPMG shareholder, and another, Cindy Caldwell, is a TPMG employee. The authors reported having no other conflicts of interest.

A hybrid colorectal cancer screening strategy that incorporates annual fecal immunological testing beginning at age 50 years and a single colonoscopy at age 66 years proved both clinically effective and cost-effective in a simulation model.

Using the Archimedes Model – a "large-scale integrated simulation of human physiology, diseases, and health care systems" – Tuan Dinh, Ph.D., of Archimedes Inc., San Francisco, and colleagues found that compared with no screening, the hybrid strategy with annual fecal immunological testing (FIT) reduced colorectal cancer incidence by 73%, gained 11,200 quality-adjusted life years (QALYs), and saved $126.8 million for every 100,000 people screened during a 30-year period.

Source: American Gastroenterological Association

Without screening, a cohort of 100,000 members of Kaiser Permanente Northern California who were included in the virtual study experienced 6,004 colorectal cancers and 1,837 colorectal cancer deaths. All methods of screening that were evaluated in the model – including annual FIT, colonoscopy at 10-year intervals, sigmoidoscopy at 5-year intervals, both FIT and sigmoidoscopy, and both FIT and colonoscopy – substantially reduced the colorectal cancer incidence, by 53%-76%, and added a significant number of QALYs, compared with no screening, the investigators reported online March 28 in Clinical Gastroenterology and Hepatology.

Colonoscopy as a single-modality screening strategy was most effective for colorectal cancer reduction (76%), and FIT alone was the least costly approach (with savings of $142.6 million per 100,000 persons, compared with no screening), but FIT plus colonoscopy came close: The hybrid strategy reduced colorectal cancer by 73%, and compared with FIT alone, gained 1,400 QALYs/100,000 at an incremental cost of $9,700 per QALY gained. Colonoscopy gained 500 QALY/100,000 more than the hybrid strategy at an incremental cost of $35,100 per QALY gained.

Furthermore, the hybrid strategy required 55% fewer FITs and 41% more colonoscopies than FIT alone, and required 2.1-2.3 fewer colonoscopies per person during 30 years than screening by colonoscopy alone, they reported (Clin. Gastroenterol. Hepatol. 2013 March 28 [doi: 10.1016/j.cgh.2013.03.013]).

On sensitivity analysis, a hybrid approach using biennial FIT was also cost-effective, compared with either FIT or colonoscopy alone.

The core of the Archimedes Model is "a set of equations that represent physiological pathways at the clinical level (i.e., at the level of detail of basic medical tests, clinical trials, and patient charts)." The colorectal cancer submodel, which was derived from public databases, published epidemiologic studies, and clinical trials, was developed in collaboration with the American Cancer Society, the authors explained.

The simulated population included a cross section of 2008 Kaiser Permanente members who were aged 50-75 years at the start of the virtual trial comparing the screening strategies.

The findings are important, given that colorectal cancer is the second-leading cause of cancer deaths among adults in the United States, and although colonoscopy is the recommended approach for primary screening in most U.S. guidelines, it is the most invasive, risky, and costly screening modality, the investigators noted.

Conversely, stool tests with follow-up colonoscopy for positive results are the least expensive. In the past, stool test strategies have been hampered by low sensitivity for adenomas and low specificity, but recent improvements in sensitivity and specificity of FIT has renewed interest in the use of stool tests, they said.

Though the hybrid FIT/colonoscopy strategy is limited by several factors – for example, the accuracy of any simulation model is dependent on assumptions about test performance and adherence, which may vary – the findings of this study suggest the hybrid strategy could improve outcomes while lowering costs.

"The simulation results indicated that [the hybrid strategy] required 37% fewer colonoscopies than [colonoscopy alone], while delivering only slightly inferior health benefits," the investigators said. These results demonstrate that "it is possible to design hybrid colorectal cancer screening strategies that can deliver health benefits and cost-effectiveness that are comparable to those of single-modality strategies, with a favorable impact on resource demand," they noted.

Future clinical studies should address whether hybrid strategies have the additional advantage of increasing screening adherence, they concluded.

This study was carried out by Archimedes under a contract with The Permanente Medical Group (TPMG). One author, Dr. Theodore R. Levin, is a TPMG shareholder, and another, Cindy Caldwell, is a TPMG employee. The authors reported having no other conflicts of interest.

Carbonation produces a decrease in the neural processing of sweetness-related signals, particularly those from sucrose, a small functional neuroimaging study shows.

The findings, which suggest that the combination of CO₂ and sucrose might increase consumption of sucrose, could have implications for dietary interventions designed to regulate caloric intake, according to Dr. Francesco Di Salle of Salerno (Italy) University and his colleagues.

To assess the interference between CO₂ and perception of sweetness, as well as the differential effects of CO₂ on sucrose and aspartame-acesulfame, (As-Ac, an artificial sweetener combination commonly used in diet beverages), the investigators performed two functional magnetic resonance imaging (fMRI) experiments to evaluate changes in regional brain activity.

© Irochka/Fotolia.com

The first experiment, performed in nine volunteers, analyzed the effect of carbonation in four sweet Sprite-based solutions, including one carbonated and sweetened with sucrose, one noncarbonated and sweetened with sucrose, one carbonated and sweetened with As-Ac, and one noncarbonated and sweetened with As-Ac. The second experiment evaluated the spatial location of the strongest neural effects of sour taste and CO₂ within the insular cortex of eight subjects.

On fMRI, the presence of carbonation in sweet solutions "independently of the sweetening agent, reduced neural activity in the anterior insula (AI), orbitofrontal cortex (OFC), and posterior pons ... the effect of carbonation on sucrose was much higher than on perception of As-Ac," they noted, explaining that "at the perceptual level ... carbonation reduced the perception of sweetness and the differences between the sensory profiles of sucrose and As-Ac."

This effect may increase sucrose intake, but is also favorable to diet beverage formulations being perceived as similar to regular beverage formulations, the investigators reported online May 28 ahead of print in Gastroenterology.

"It is also coherent with a process of prioritization among perceptual inputs (chemesthetic and gustatory information) deriving from the same body topography and converging to the same cortical regions (AI, OFC), they said (Gastroenterology 2013 [doi:10.1053/j.gastro.2013.05.041]).

To correlate neuroimaging with behavioral data, the ability of carbonation to modulate perception of sweetness was assessed in 14 subjects, who scored the level of perceived sweetness of the solutions on a visual analog scale ranging from 0 to 100 mm. The effect of 1,585 ppm of CO₂ added to a 10% glucose solution on the perception of sweetness was also tested in seven subjects.

CO₂ was able to significantly reduce sweet-induced taste perceptions as assessed by the volunteers’ visual analog scale recordings: The perception of Sprite-associated sweetness was significantly reduced by CO₂ (48 vs. 63 and 48 vs. 55 for As-Ac and sucrose, respectively).

"Similarly, in the presence of carbonation, sweet-induced perception of a 10% glucose solution was significantly reduced (36 vs. 53), the investigators said.

Given the widespread use of CO₂ in sweet beverages, the modulation of sweet perception by CO₂ is of interest, they noted.

The findings, which suggest that CO₂ modulates the perception of sweetness thereby reducing the global neural processing of sweetness, the processing of sucrose more than of As-Ac, and the processing difference between sweetening agents via modulation of the perception of sweetness, is "of utmost importance for designing carbonated beverages and is relevant to the regulation of caloric intake," they said.

"This effect is driven by the integration of information on gastric fullness and on nutrient depletion, conveyed to a brain network where the autonomic brainstem circuitry and tractus solitarius neurons play a critical role in homeostatic functions," they added.

It may be that taste and CO₂-related information influence food choices and intake through integration in the tractus solitarius with input from the gastrointestinal tract, they suggested, explaining that "the reduced discrimination between sucrose and As-Ac induced by CO₂ would promote the consumptions of low-calorie beverages and would converge with CO₂-induced gastric distention in limiting caloric intake."

This study was supported in part by the Coca-Cola Company. One author, Dr. Rosario Cuomo, was sponsored by the Coca-Cola Company. The remaining authors reported having no disclosures.

Carbonation produces a decrease in the neural processing of sweetness-related signals, particularly those from sucrose, a small functional neuroimaging study shows.

The findings, which suggest that the combination of CO₂ and sucrose might increase consumption of sucrose, could have implications for dietary interventions designed to regulate caloric intake, according to Dr. Francesco Di Salle of Salerno (Italy) University and his colleagues.

To assess the interference between CO₂ and perception of sweetness, as well as the differential effects of CO₂ on sucrose and aspartame-acesulfame, (As-Ac, an artificial sweetener combination commonly used in diet beverages), the investigators performed two functional magnetic resonance imaging (fMRI) experiments to evaluate changes in regional brain activity.

© Irochka/Fotolia.com

The first experiment, performed in nine volunteers, analyzed the effect of carbonation in four sweet Sprite-based solutions, including one carbonated and sweetened with sucrose, one noncarbonated and sweetened with sucrose, one carbonated and sweetened with As-Ac, and one noncarbonated and sweetened with As-Ac. The second experiment evaluated the spatial location of the strongest neural effects of sour taste and CO₂ within the insular cortex of eight subjects.

On fMRI, the presence of carbonation in sweet solutions "independently of the sweetening agent, reduced neural activity in the anterior insula (AI), orbitofrontal cortex (OFC), and posterior pons ... the effect of carbonation on sucrose was much higher than on perception of As-Ac," they noted, explaining that "at the perceptual level ... carbonation reduced the perception of sweetness and the differences between the sensory profiles of sucrose and As-Ac."

This effect may increase sucrose intake, but is also favorable to diet beverage formulations being perceived as similar to regular beverage formulations, the investigators reported online May 28 ahead of print in Gastroenterology.

"It is also coherent with a process of prioritization among perceptual inputs (chemesthetic and gustatory information) deriving from the same body topography and converging to the same cortical regions (AI, OFC), they said (Gastroenterology 2013 [doi:10.1053/j.gastro.2013.05.041]).

To correlate neuroimaging with behavioral data, the ability of carbonation to modulate perception of sweetness was assessed in 14 subjects, who scored the level of perceived sweetness of the solutions on a visual analog scale ranging from 0 to 100 mm. The effect of 1,585 ppm of CO₂ added to a 10% glucose solution on the perception of sweetness was also tested in seven subjects.

CO₂ was able to significantly reduce sweet-induced taste perceptions as assessed by the volunteers’ visual analog scale recordings: The perception of Sprite-associated sweetness was significantly reduced by CO₂ (48 vs. 63 and 48 vs. 55 for As-Ac and sucrose, respectively).

"Similarly, in the presence of carbonation, sweet-induced perception of a 10% glucose solution was significantly reduced (36 vs. 53), the investigators said.

Given the widespread use of CO₂ in sweet beverages, the modulation of sweet perception by CO₂ is of interest, they noted.

The findings, which suggest that CO₂ modulates the perception of sweetness thereby reducing the global neural processing of sweetness, the processing of sucrose more than of As-Ac, and the processing difference between sweetening agents via modulation of the perception of sweetness, is "of utmost importance for designing carbonated beverages and is relevant to the regulation of caloric intake," they said.

"This effect is driven by the integration of information on gastric fullness and on nutrient depletion, conveyed to a brain network where the autonomic brainstem circuitry and tractus solitarius neurons play a critical role in homeostatic functions," they added.

It may be that taste and CO₂-related information influence food choices and intake through integration in the tractus solitarius with input from the gastrointestinal tract, they suggested, explaining that "the reduced discrimination between sucrose and As-Ac induced by CO₂ would promote the consumptions of low-calorie beverages and would converge with CO₂-induced gastric distention in limiting caloric intake."

This study was supported in part by the Coca-Cola Company. One author, Dr. Rosario Cuomo, was sponsored by the Coca-Cola Company. The remaining authors reported having no disclosures.

Carbonation produces a decrease in the neural processing of sweetness-related signals, particularly those from sucrose, a small functional neuroimaging study shows.

The findings, which suggest that the combination of CO₂ and sucrose might increase consumption of sucrose, could have implications for dietary interventions designed to regulate caloric intake, according to Dr. Francesco Di Salle of Salerno (Italy) University and his colleagues.

To assess the interference between CO₂ and perception of sweetness, as well as the differential effects of CO₂ on sucrose and aspartame-acesulfame, (As-Ac, an artificial sweetener combination commonly used in diet beverages), the investigators performed two functional magnetic resonance imaging (fMRI) experiments to evaluate changes in regional brain activity.

© Irochka/Fotolia.com

The first experiment, performed in nine volunteers, analyzed the effect of carbonation in four sweet Sprite-based solutions, including one carbonated and sweetened with sucrose, one noncarbonated and sweetened with sucrose, one carbonated and sweetened with As-Ac, and one noncarbonated and sweetened with As-Ac. The second experiment evaluated the spatial location of the strongest neural effects of sour taste and CO₂ within the insular cortex of eight subjects.

On fMRI, the presence of carbonation in sweet solutions "independently of the sweetening agent, reduced neural activity in the anterior insula (AI), orbitofrontal cortex (OFC), and posterior pons ... the effect of carbonation on sucrose was much higher than on perception of As-Ac," they noted, explaining that "at the perceptual level ... carbonation reduced the perception of sweetness and the differences between the sensory profiles of sucrose and As-Ac."

This effect may increase sucrose intake, but is also favorable to diet beverage formulations being perceived as similar to regular beverage formulations, the investigators reported online May 28 ahead of print in Gastroenterology.

"It is also coherent with a process of prioritization among perceptual inputs (chemesthetic and gustatory information) deriving from the same body topography and converging to the same cortical regions (AI, OFC), they said (Gastroenterology 2013 [doi:10.1053/j.gastro.2013.05.041]).

To correlate neuroimaging with behavioral data, the ability of carbonation to modulate perception of sweetness was assessed in 14 subjects, who scored the level of perceived sweetness of the solutions on a visual analog scale ranging from 0 to 100 mm. The effect of 1,585 ppm of CO₂ added to a 10% glucose solution on the perception of sweetness was also tested in seven subjects.

CO₂ was able to significantly reduce sweet-induced taste perceptions as assessed by the volunteers’ visual analog scale recordings: The perception of Sprite-associated sweetness was significantly reduced by CO₂ (48 vs. 63 and 48 vs. 55 for As-Ac and sucrose, respectively).

"Similarly, in the presence of carbonation, sweet-induced perception of a 10% glucose solution was significantly reduced (36 vs. 53), the investigators said.

Given the widespread use of CO₂ in sweet beverages, the modulation of sweet perception by CO₂ is of interest, they noted.

The findings, which suggest that CO₂ modulates the perception of sweetness thereby reducing the global neural processing of sweetness, the processing of sucrose more than of As-Ac, and the processing difference between sweetening agents via modulation of the perception of sweetness, is "of utmost importance for designing carbonated beverages and is relevant to the regulation of caloric intake," they said.

"This effect is driven by the integration of information on gastric fullness and on nutrient depletion, conveyed to a brain network where the autonomic brainstem circuitry and tractus solitarius neurons play a critical role in homeostatic functions," they added.

It may be that taste and CO₂-related information influence food choices and intake through integration in the tractus solitarius with input from the gastrointestinal tract, they suggested, explaining that "the reduced discrimination between sucrose and As-Ac induced by CO₂ would promote the consumptions of low-calorie beverages and would converge with CO₂-induced gastric distention in limiting caloric intake."

This study was supported in part by the Coca-Cola Company. One author, Dr. Rosario Cuomo, was sponsored by the Coca-Cola Company. The remaining authors reported having no disclosures.

Endoscopic cystogastrostomy was as effective as surgical cystogastrostomy for pancreatic pseudocyst drainage in a randomized trial comparing the two approaches.

None of the 20 patients randomized to undergo endoscopic treatment, and 1 of 20 patients randomized to undergo surgery, experienced pseudocyst recurrence within 24 months of follow-up, Dr. Shyam Varadarajulu of the University of Alabama at Birmingham and his colleagues reported online May 31, ahead of print in Gastroenterology.

Source: American Gastroenterological Association

Moreover, those in the endoscopy group had a shorter hospital length of stay than did the patients in the surgery group (median of 2 vs. 6 days) and a lower mean cost of care ($7,011 vs. $15,052), the investigators reported (Gastroenterology 2013 May 31 [doi: 10.1053/j.gastro.2013.05.046]).

Patients included in the study were adults with intrapancreatic or extrapancreatic pseudocysts who were enrolled between Jan. 20 and Dec. 28, 2009, following evaluation by a gastroenterologist or surgeon in an outpatient clinic or inpatient setting.

The 20 patients in the endoscopy group underwent cystogastrostomy using endoscopic ultrasound guidance and fluoroscopy while they were under conscious sedation.

"Once the pseudocyst was identified, it was accessed using a 19-gauge needle, and the gastric wall was dilated up to 15 mm using a wire-guided balloon. Two plastic stents then were deployed to facilitate the drainage of pseudocyst contents into the stomach," the investigators explained, noting that endoscopy patients were discharged following the procedure.

No procedural complications occurred in any of the 20 patients. However, one patient presented to the hospital 13 days later with persistent abdominal pain; a computed tomography scan showed a residual 7-cm pseudocyst, which was successfully treated by deployment of additional stents. At 8-week follow-up, abdominal CT scans showed pseudocyst resolution in all 20 patients.

Endoscopic retrograde cholangiopancreatography (ERCP), which was performed in all of the endoscopy patients to assess and treat any pancreatic duct leaks, was successful in 18 of the 20 patients. Magnetic resonance cholangiopancreatography (MRCP), performed in those two patients, showed a normal pancreatic duct in one and a disconnected duct in the other, the investigators said.

The 20 patients in the surgery group were all treated by the same pancreatic surgeon, who used an endovascular stapler to create at least a 6-cm cystogastrostomy after obtaining entry to the pseudocyst.

"A nasogastric tube then was left in the stomach and passed into the pseudocyst cavity to allow for intermittent irrigation until postoperative day 1 ... the nasogastric tube was removed on postoperative day 1 and clear liquids were started on day 2," they said.

Patients were discharged once a soft diet was tolerated and pain adequately controlled.

One patient with ongoing alcohol consumption developed pseudocyst recurrence at 4 months and was managed by endoscopic cystogastrostomy.

Two surgery patients experienced complications, including a wound infection treated by local debridement and antibiotics in one patient, and a case of hematemesis in one patient who was on anticoagulation and who was readmitted 9 days after discharge. "At endoscopy, a visible clot was noted at the site of surgical anastomosis, and hemostasis was achieved by application of electrocautery," the investigators said.

Two other patients were not able to tolerate oral intake postoperatively; one of them was managed conservatively, and one required surgical placement of a temporary enteral feeding tube. In addition, one patient presented at 6 months with abdominal pain and was found on ERCP to have a stricture in the pancreatic tail that required management by distal pancreatectomy.

Overall, there were no differences in the rates of treatment success, treatment failure, complications, or reinterventions between the endoscopy and surgery groups.

However, in addition to the shorter hospital stay and lower costs in the endoscopy group, patients in that group had significantly greater improvement over time in physical and mental health component scores on the Medical Outcomes Study 36-Item Short-Form General Survey. Although the scores improved for both cohorts, they were 4.48 points and 4.41 points lower, respectively, in the surgery group than the endoscopy group, the investigators said.

The findings are of note because although endoscopic drainage of pancreatic pseudocysts is increasingly performed, surgical cystogastrostomy is still considered the gold standard for treatment, as randomized trials comparing the two approaches had not previously been performed.

"The clinical relevance of this study is substantial because it shows that endoscopically managed patients can be discharged home earlier with a better health-related quality of life, and treatment can be delivered at a lower cost," the investigators said.

The authors reported having no disclosures.

ginews@gastro.org

Endoscopic cystogastrostomy was as effective as surgical cystogastrostomy for pancreatic pseudocyst drainage in a randomized trial comparing the two approaches.

None of the 20 patients randomized to undergo endoscopic treatment, and 1 of 20 patients randomized to undergo surgery, experienced pseudocyst recurrence within 24 months of follow-up, Dr. Shyam Varadarajulu of the University of Alabama at Birmingham and his colleagues reported online May 31, ahead of print in Gastroenterology.

Source: American Gastroenterological Association

Moreover, those in the endoscopy group had a shorter hospital length of stay than did the patients in the surgery group (median of 2 vs. 6 days) and a lower mean cost of care ($7,011 vs. $15,052), the investigators reported (Gastroenterology 2013 May 31 [doi: 10.1053/j.gastro.2013.05.046]).

Patients included in the study were adults with intrapancreatic or extrapancreatic pseudocysts who were enrolled between Jan. 20 and Dec. 28, 2009, following evaluation by a gastroenterologist or surgeon in an outpatient clinic or inpatient setting.

The 20 patients in the endoscopy group underwent cystogastrostomy using endoscopic ultrasound guidance and fluoroscopy while they were under conscious sedation.

"Once the pseudocyst was identified, it was accessed using a 19-gauge needle, and the gastric wall was dilated up to 15 mm using a wire-guided balloon. Two plastic stents then were deployed to facilitate the drainage of pseudocyst contents into the stomach," the investigators explained, noting that endoscopy patients were discharged following the procedure.

No procedural complications occurred in any of the 20 patients. However, one patient presented to the hospital 13 days later with persistent abdominal pain; a computed tomography scan showed a residual 7-cm pseudocyst, which was successfully treated by deployment of additional stents. At 8-week follow-up, abdominal CT scans showed pseudocyst resolution in all 20 patients.

Endoscopic retrograde cholangiopancreatography (ERCP), which was performed in all of the endoscopy patients to assess and treat any pancreatic duct leaks, was successful in 18 of the 20 patients. Magnetic resonance cholangiopancreatography (MRCP), performed in those two patients, showed a normal pancreatic duct in one and a disconnected duct in the other, the investigators said.

The 20 patients in the surgery group were all treated by the same pancreatic surgeon, who used an endovascular stapler to create at least a 6-cm cystogastrostomy after obtaining entry to the pseudocyst.

"A nasogastric tube then was left in the stomach and passed into the pseudocyst cavity to allow for intermittent irrigation until postoperative day 1 ... the nasogastric tube was removed on postoperative day 1 and clear liquids were started on day 2," they said.

Patients were discharged once a soft diet was tolerated and pain adequately controlled.

One patient with ongoing alcohol consumption developed pseudocyst recurrence at 4 months and was managed by endoscopic cystogastrostomy.

Two surgery patients experienced complications, including a wound infection treated by local debridement and antibiotics in one patient, and a case of hematemesis in one patient who was on anticoagulation and who was readmitted 9 days after discharge. "At endoscopy, a visible clot was noted at the site of surgical anastomosis, and hemostasis was achieved by application of electrocautery," the investigators said.

Two other patients were not able to tolerate oral intake postoperatively; one of them was managed conservatively, and one required surgical placement of a temporary enteral feeding tube. In addition, one patient presented at 6 months with abdominal pain and was found on ERCP to have a stricture in the pancreatic tail that required management by distal pancreatectomy.

Overall, there were no differences in the rates of treatment success, treatment failure, complications, or reinterventions between the endoscopy and surgery groups.

However, in addition to the shorter hospital stay and lower costs in the endoscopy group, patients in that group had significantly greater improvement over time in physical and mental health component scores on the Medical Outcomes Study 36-Item Short-Form General Survey. Although the scores improved for both cohorts, they were 4.48 points and 4.41 points lower, respectively, in the surgery group than the endoscopy group, the investigators said.

The findings are of note because although endoscopic drainage of pancreatic pseudocysts is increasingly performed, surgical cystogastrostomy is still considered the gold standard for treatment, as randomized trials comparing the two approaches had not previously been performed.

"The clinical relevance of this study is substantial because it shows that endoscopically managed patients can be discharged home earlier with a better health-related quality of life, and treatment can be delivered at a lower cost," the investigators said.

The authors reported having no disclosures.

ginews@gastro.org

Endoscopic cystogastrostomy was as effective as surgical cystogastrostomy for pancreatic pseudocyst drainage in a randomized trial comparing the two approaches.

None of the 20 patients randomized to undergo endoscopic treatment, and 1 of 20 patients randomized to undergo surgery, experienced pseudocyst recurrence within 24 months of follow-up, Dr. Shyam Varadarajulu of the University of Alabama at Birmingham and his colleagues reported online May 31, ahead of print in Gastroenterology.

Source: American Gastroenterological Association

Moreover, those in the endoscopy group had a shorter hospital length of stay than did the patients in the surgery group (median of 2 vs. 6 days) and a lower mean cost of care ($7,011 vs. $15,052), the investigators reported (Gastroenterology 2013 May 31 [doi: 10.1053/j.gastro.2013.05.046]).

Patients included in the study were adults with intrapancreatic or extrapancreatic pseudocysts who were enrolled between Jan. 20 and Dec. 28, 2009, following evaluation by a gastroenterologist or surgeon in an outpatient clinic or inpatient setting.

The 20 patients in the endoscopy group underwent cystogastrostomy using endoscopic ultrasound guidance and fluoroscopy while they were under conscious sedation.

"Once the pseudocyst was identified, it was accessed using a 19-gauge needle, and the gastric wall was dilated up to 15 mm using a wire-guided balloon. Two plastic stents then were deployed to facilitate the drainage of pseudocyst contents into the stomach," the investigators explained, noting that endoscopy patients were discharged following the procedure.

No procedural complications occurred in any of the 20 patients. However, one patient presented to the hospital 13 days later with persistent abdominal pain; a computed tomography scan showed a residual 7-cm pseudocyst, which was successfully treated by deployment of additional stents. At 8-week follow-up, abdominal CT scans showed pseudocyst resolution in all 20 patients.

Endoscopic retrograde cholangiopancreatography (ERCP), which was performed in all of the endoscopy patients to assess and treat any pancreatic duct leaks, was successful in 18 of the 20 patients. Magnetic resonance cholangiopancreatography (MRCP), performed in those two patients, showed a normal pancreatic duct in one and a disconnected duct in the other, the investigators said.

The 20 patients in the surgery group were all treated by the same pancreatic surgeon, who used an endovascular stapler to create at least a 6-cm cystogastrostomy after obtaining entry to the pseudocyst.

"A nasogastric tube then was left in the stomach and passed into the pseudocyst cavity to allow for intermittent irrigation until postoperative day 1 ... the nasogastric tube was removed on postoperative day 1 and clear liquids were started on day 2," they said.

Patients were discharged once a soft diet was tolerated and pain adequately controlled.

One patient with ongoing alcohol consumption developed pseudocyst recurrence at 4 months and was managed by endoscopic cystogastrostomy.

Two surgery patients experienced complications, including a wound infection treated by local debridement and antibiotics in one patient, and a case of hematemesis in one patient who was on anticoagulation and who was readmitted 9 days after discharge. "At endoscopy, a visible clot was noted at the site of surgical anastomosis, and hemostasis was achieved by application of electrocautery," the investigators said.

Two other patients were not able to tolerate oral intake postoperatively; one of them was managed conservatively, and one required surgical placement of a temporary enteral feeding tube. In addition, one patient presented at 6 months with abdominal pain and was found on ERCP to have a stricture in the pancreatic tail that required management by distal pancreatectomy.

Overall, there were no differences in the rates of treatment success, treatment failure, complications, or reinterventions between the endoscopy and surgery groups.

However, in addition to the shorter hospital stay and lower costs in the endoscopy group, patients in that group had significantly greater improvement over time in physical and mental health component scores on the Medical Outcomes Study 36-Item Short-Form General Survey. Although the scores improved for both cohorts, they were 4.48 points and 4.41 points lower, respectively, in the surgery group than the endoscopy group, the investigators said.

The findings are of note because although endoscopic drainage of pancreatic pseudocysts is increasingly performed, surgical cystogastrostomy is still considered the gold standard for treatment, as randomized trials comparing the two approaches had not previously been performed.

"The clinical relevance of this study is substantial because it shows that endoscopically managed patients can be discharged home earlier with a better health-related quality of life, and treatment can be delivered at a lower cost," the investigators said.

The authors reported having no disclosures.

ginews@gastro.org

Left ventricular late gadolinium enhancement – a marker of myocardial fibrosis – occurs commonly and may predict mortality in patients with atrial fibrillation, a prospective observational study has shown.

Of 664 consecutive patients with atrial fibrillation and no known prior myocardial infarction who were referred for radiofrequency ablation of the pulmonary veins between September 2006 and June 2011, 88 (13%) had unanticipated left ventricular late gadolinium enhancement (LV LGE) identified via cardiac magnetic resonance imaging, and 68 died over a median follow-up of 42 months. The mortality rate was 8.1% among those with LV LGE, compared with 2.3% among those without LV LGE, Dr. Thomas G. Neilan of Brigham and Women’s Hospital and Massachusetts General Hospital, Boston, and his colleagues reported online Aug. 28 in the Journal of the American College of Cardiology.

After adjustment for key variables, including sex, diabetes, and heart failure, the presence of LV LGE was significantly linked with mortality. Age and the extent of LGE were the strongest independent predictors of mortality (hazard ratios, 1.05 and 1.15, respectively), the investigators said (J. Am. Coll. Cardiol. 2013 Aug. 28 [doi.org/10.1016/j.jacc.2013.07.067 ]).

The presence of LV LGE provided strong prognostic information, they said, noting that each 1% increase in LGE was associated with a 15% increased risk of death.

The findings were similar when an additional 56 patients with a history of myocardial infarction were included in the analysis, they noted.

Patients in the study had an average age of 56 years. Most (73%) were men.

The pattern of LV LGE was ischemic in 59% and nonischemic in 41%; among those with no history of myocardial infarction, the pattern was ischemic in 50% and nonischemic in 50%.

The findings provide needed information about the presence, pattern, and prognostic significance of left ventricular myocardial fibrosis in patients with atrial fibrillation.

The presence of LV LGE provides "strong and complementary" prognostic information in patients with several conditions, such as congenital heart disease, myocardial infarction, and myocarditis to name a few, but limited data are available regarding the presence and prognostic significance of LV LGE in patients with atrial fibrillation, the investigators said.

The current findings highlight the frequency of LV LGE in this population and its strong association with mortality, and support "the robust and additive prognostic information" provided by cardiac magnetic resonance imaging in patients being referred for pulmonary vein isolation, they concluded, adding that the findings also may support further study in this high-risk cohort.

Left ventricular late gadolinium enhancement – a marker of myocardial fibrosis – occurs commonly and may predict mortality in patients with atrial fibrillation, a prospective observational study has shown.

Of 664 consecutive patients with atrial fibrillation and no known prior myocardial infarction who were referred for radiofrequency ablation of the pulmonary veins between September 2006 and June 2011, 88 (13%) had unanticipated left ventricular late gadolinium enhancement (LV LGE) identified via cardiac magnetic resonance imaging, and 68 died over a median follow-up of 42 months. The mortality rate was 8.1% among those with LV LGE, compared with 2.3% among those without LV LGE, Dr. Thomas G. Neilan of Brigham and Women’s Hospital and Massachusetts General Hospital, Boston, and his colleagues reported online Aug. 28 in the Journal of the American College of Cardiology.

After adjustment for key variables, including sex, diabetes, and heart failure, the presence of LV LGE was significantly linked with mortality. Age and the extent of LGE were the strongest independent predictors of mortality (hazard ratios, 1.05 and 1.15, respectively), the investigators said (J. Am. Coll. Cardiol. 2013 Aug. 28 [doi.org/10.1016/j.jacc.2013.07.067 ]).

The presence of LV LGE provided strong prognostic information, they said, noting that each 1% increase in LGE was associated with a 15% increased risk of death.

The findings were similar when an additional 56 patients with a history of myocardial infarction were included in the analysis, they noted.

Patients in the study had an average age of 56 years. Most (73%) were men.

The pattern of LV LGE was ischemic in 59% and nonischemic in 41%; among those with no history of myocardial infarction, the pattern was ischemic in 50% and nonischemic in 50%.

The findings provide needed information about the presence, pattern, and prognostic significance of left ventricular myocardial fibrosis in patients with atrial fibrillation.

The presence of LV LGE provides "strong and complementary" prognostic information in patients with several conditions, such as congenital heart disease, myocardial infarction, and myocarditis to name a few, but limited data are available regarding the presence and prognostic significance of LV LGE in patients with atrial fibrillation, the investigators said.

The current findings highlight the frequency of LV LGE in this population and its strong association with mortality, and support "the robust and additive prognostic information" provided by cardiac magnetic resonance imaging in patients being referred for pulmonary vein isolation, they concluded, adding that the findings also may support further study in this high-risk cohort.

Left ventricular late gadolinium enhancement – a marker of myocardial fibrosis – occurs commonly and may predict mortality in patients with atrial fibrillation, a prospective observational study has shown.

Of 664 consecutive patients with atrial fibrillation and no known prior myocardial infarction who were referred for radiofrequency ablation of the pulmonary veins between September 2006 and June 2011, 88 (13%) had unanticipated left ventricular late gadolinium enhancement (LV LGE) identified via cardiac magnetic resonance imaging, and 68 died over a median follow-up of 42 months. The mortality rate was 8.1% among those with LV LGE, compared with 2.3% among those without LV LGE, Dr. Thomas G. Neilan of Brigham and Women’s Hospital and Massachusetts General Hospital, Boston, and his colleagues reported online Aug. 28 in the Journal of the American College of Cardiology.

After adjustment for key variables, including sex, diabetes, and heart failure, the presence of LV LGE was significantly linked with mortality. Age and the extent of LGE were the strongest independent predictors of mortality (hazard ratios, 1.05 and 1.15, respectively), the investigators said (J. Am. Coll. Cardiol. 2013 Aug. 28 [doi.org/10.1016/j.jacc.2013.07.067 ]).

The presence of LV LGE provided strong prognostic information, they said, noting that each 1% increase in LGE was associated with a 15% increased risk of death.

The findings were similar when an additional 56 patients with a history of myocardial infarction were included in the analysis, they noted.

Patients in the study had an average age of 56 years. Most (73%) were men.

The pattern of LV LGE was ischemic in 59% and nonischemic in 41%; among those with no history of myocardial infarction, the pattern was ischemic in 50% and nonischemic in 50%.

The findings provide needed information about the presence, pattern, and prognostic significance of left ventricular myocardial fibrosis in patients with atrial fibrillation.

The presence of LV LGE provides "strong and complementary" prognostic information in patients with several conditions, such as congenital heart disease, myocardial infarction, and myocarditis to name a few, but limited data are available regarding the presence and prognostic significance of LV LGE in patients with atrial fibrillation, the investigators said.

The current findings highlight the frequency of LV LGE in this population and its strong association with mortality, and support "the robust and additive prognostic information" provided by cardiac magnetic resonance imaging in patients being referred for pulmonary vein isolation, they concluded, adding that the findings also may support further study in this high-risk cohort.

Ascorbic acid may protect against contrast-induced-acute kidney injury in patients undergoing coronary angiography, a meta-analysis of nine randomized controlled trials has shown.

The overall incidence of contrast-induced acute kidney injury (CI-AKI) among 740 patients who received ascorbic acid and who were included in the final analysis was 9.6%, compared with 16.8% in 796 patients who received placebo or an alternative pharmacologic treatment, Dr. Umar Sadat of Cambridge (England) University Hospitals NHS Foundation Trust, and colleagues reported.

"In the pooled analysis using random effects model, patients receiving ascorbic acid had 33% less risk of CI-AKI compared to the control group (risk ratio, 0.672)," a statistically significant difference, the investigators wrote.

The findings were published online Aug. 28 in the Journal of the American College of Cardiology.

The investigators systematically reviewed Medline, Embase, and Cochrane central databases for studies published from inception to May 2013 on the incidence of CI-AKI in patients undergoing coronary angiography. Studies that were included in the meta-analysis had at least one arm that involved treatment with ascorbic acid alone or in combination with saline hydration. Ultimately, nine studies involving a total of 1,536 patients with baseline renal impairment were included (J. Am. Coll. Cardiol. 2013 Aug. 28).

The findings, which provide "robust evidence that ascorbic acid reduces the risk of CI-AKI, albeit by a small magnitude," suggest that ascorbic acid has nephroprotective qualities and could form a part of effective prophylactic pharmacologic regimens to protect patients undergoing coronary angiography against CI-AKI.

It makes sense that ascorbic acid – a form of vitamin C – could provide nephroprotection, because strong evidence suggests it acts as a potent antioxidant by scavenging physiologically relevant reactive oxygen species (ROS), they explained, noting that ROS-induced oxidative stress and renal vasoconstriction have been implicated in the etiology of CI-AKI.

The findings are important, because the incidence of CI-AKI is rising in tandem with the increasing number of contrast media–enhanced radiologic procedures and with a rise in the octogenarian population with comorbidities such as hypertension, diabetes, and renovascular disease that predispose patients to renal impairment, the investigators said.

However, further investigation regarding the optimal dosage and route of administration of ascorbic acid in order to assess its full potential as a nephroprotective agent is warranted, they concluded.

Ascorbic acid may protect against contrast-induced-acute kidney injury in patients undergoing coronary angiography, a meta-analysis of nine randomized controlled trials has shown.

The overall incidence of contrast-induced acute kidney injury (CI-AKI) among 740 patients who received ascorbic acid and who were included in the final analysis was 9.6%, compared with 16.8% in 796 patients who received placebo or an alternative pharmacologic treatment, Dr. Umar Sadat of Cambridge (England) University Hospitals NHS Foundation Trust, and colleagues reported.

"In the pooled analysis using random effects model, patients receiving ascorbic acid had 33% less risk of CI-AKI compared to the control group (risk ratio, 0.672)," a statistically significant difference, the investigators wrote.

The findings were published online Aug. 28 in the Journal of the American College of Cardiology.

The investigators systematically reviewed Medline, Embase, and Cochrane central databases for studies published from inception to May 2013 on the incidence of CI-AKI in patients undergoing coronary angiography. Studies that were included in the meta-analysis had at least one arm that involved treatment with ascorbic acid alone or in combination with saline hydration. Ultimately, nine studies involving a total of 1,536 patients with baseline renal impairment were included (J. Am. Coll. Cardiol. 2013 Aug. 28).

The findings, which provide "robust evidence that ascorbic acid reduces the risk of CI-AKI, albeit by a small magnitude," suggest that ascorbic acid has nephroprotective qualities and could form a part of effective prophylactic pharmacologic regimens to protect patients undergoing coronary angiography against CI-AKI.

It makes sense that ascorbic acid – a form of vitamin C – could provide nephroprotection, because strong evidence suggests it acts as a potent antioxidant by scavenging physiologically relevant reactive oxygen species (ROS), they explained, noting that ROS-induced oxidative stress and renal vasoconstriction have been implicated in the etiology of CI-AKI.

The findings are important, because the incidence of CI-AKI is rising in tandem with the increasing number of contrast media–enhanced radiologic procedures and with a rise in the octogenarian population with comorbidities such as hypertension, diabetes, and renovascular disease that predispose patients to renal impairment, the investigators said.

However, further investigation regarding the optimal dosage and route of administration of ascorbic acid in order to assess its full potential as a nephroprotective agent is warranted, they concluded.

Ascorbic acid may protect against contrast-induced-acute kidney injury in patients undergoing coronary angiography, a meta-analysis of nine randomized controlled trials has shown.

The overall incidence of contrast-induced acute kidney injury (CI-AKI) among 740 patients who received ascorbic acid and who were included in the final analysis was 9.6%, compared with 16.8% in 796 patients who received placebo or an alternative pharmacologic treatment, Dr. Umar Sadat of Cambridge (England) University Hospitals NHS Foundation Trust, and colleagues reported.

"In the pooled analysis using random effects model, patients receiving ascorbic acid had 33% less risk of CI-AKI compared to the control group (risk ratio, 0.672)," a statistically significant difference, the investigators wrote.

The findings were published online Aug. 28 in the Journal of the American College of Cardiology.

The investigators systematically reviewed Medline, Embase, and Cochrane central databases for studies published from inception to May 2013 on the incidence of CI-AKI in patients undergoing coronary angiography. Studies that were included in the meta-analysis had at least one arm that involved treatment with ascorbic acid alone or in combination with saline hydration. Ultimately, nine studies involving a total of 1,536 patients with baseline renal impairment were included (J. Am. Coll. Cardiol. 2013 Aug. 28).

The findings, which provide "robust evidence that ascorbic acid reduces the risk of CI-AKI, albeit by a small magnitude," suggest that ascorbic acid has nephroprotective qualities and could form a part of effective prophylactic pharmacologic regimens to protect patients undergoing coronary angiography against CI-AKI.

It makes sense that ascorbic acid – a form of vitamin C – could provide nephroprotection, because strong evidence suggests it acts as a potent antioxidant by scavenging physiologically relevant reactive oxygen species (ROS), they explained, noting that ROS-induced oxidative stress and renal vasoconstriction have been implicated in the etiology of CI-AKI.

The findings are important, because the incidence of CI-AKI is rising in tandem with the increasing number of contrast media–enhanced radiologic procedures and with a rise in the octogenarian population with comorbidities such as hypertension, diabetes, and renovascular disease that predispose patients to renal impairment, the investigators said.

However, further investigation regarding the optimal dosage and route of administration of ascorbic acid in order to assess its full potential as a nephroprotective agent is warranted, they concluded.

Consistent dietary intake of long-chain n-3 polyunsaturated fatty acids typically found in fish was associated with a reduced risk of rheumatoid arthritis in a prospective cohort study of Swedish women.

The study of 32,232 middle-aged and older Swedish women included 205 who developed rheumatoid arthritis (RA) during a mean follow-up of 7.5 years. Those who reported intake of more than 0.21 g/day of dietary long-chain n-3 polyunsaturated fatty acids (PUFAs), also called omega-3 fatty acids, at the time of an assessment in 1997 had a 35% reduction in the risk of developing RA, compared with women who reported lower intake (adjusted relative risk, 0.65), reported Dr. Daniela Di Giuseppe of the Karolinska Institute, Stockholm, and her colleagues.

© Suprijono Suharjoto/Fotolia.com

"The population prevented fraction, the equivalent of the population attributable risk when analyzing a protective factor, was 0.28. This indicates that 28% of the hypothetical total load of disease could be prevented by exposure to greater than 0.21 g/day of dietary long-chain n-3 PUFAs," the investigators wrote.

Consistent long-term intake of more than 0.21 g/day was associated with even greater risk reduction. Women who reported intake at that level at assessments in both 1987 and 1997 had a 52% reduction in risk, compared with those with lower intake (adjusted RR, 0.48), they said.

Those who reported consistent long-term consumption of at least one serving of fish weekly had a 29% reduction in risk, compared with those who had less than one serving weekly (adjusted RR, 0.71), they noted (Ann. Rheum. Dis. 2013 Aug. 12 [doi: 10.1136/annrheumdis-2013-203338]).

"The inverse association between fish consumption and RA can be attributed mainly to its content of long-chain n-3 PUFAs," they wrote.

Of note, the use of fish oil supplementation was not associated with the development of RA in this study (relative risk, 1.32 for ever vs. never users). However, there were only 17 users, and information about dose and duration of use was lacking.

Study subjects were participants in the population-based Swedish Mammography Cohort. The women, who were aged 54-89 years at follow-up, completed detailed food-frequency questionnaires at the 1987 and 1997 assessments.

The multivariable relative risks for dietary long-chain n-3 PUFAs were adjusted for cigarette smoking, alcohol intake, aspirin use, and energy intake. The multivariable relative risks for long-term fish consumption were also adjusted for quartiles of red meat and dairy food consumption.

The findings have implications for dietary guidelines with respect to fish consumption, the investigators said.

RA is known to be influenced by both genetic and environmental factors, but little is known about important modifiable risk factors other than smoking and alcohol consumption, they said, noting that the evidence regarding a role for dietary long-chain n-3 PUFAs has been limited, and study results have been conflicting.

However, the current study suggests that intake of at least 0.21 g/day is indeed of benefit. That intake is about the equivalent of at least one serving of fatty fish, such as salmon, or four servings of lean fish, such as cod, each week, the investigators explained. They suggested that dietary long-chain n-3 PUFAs may protect against RA through their anti-inflammatory properties, particularly through the synthesis of eicosanoids.

These intake levels are in line with recommendations from the American Dietary Guideline Advisory Committee, which advised eating fish twice weekly.

"In conclusion, the study indicates a potentially important role for dietary long-chain n-3 PUFAs in the etiology of RA, and that adherence to existing dietary guidelines regarding fish consumption may also be beneficial in terms of RA risk," they wrote.

The study was supported by research grants from the Swedish Research Council/Committee for Research Infrastructure for Maintenance of the Swedish Mammography Cohort, and from the Karolinska Institute’s Award for Ph.D. Students. The authors reported having no disclosures.

Consistent dietary intake of long-chain n-3 polyunsaturated fatty acids typically found in fish was associated with a reduced risk of rheumatoid arthritis in a prospective cohort study of Swedish women.

The study of 32,232 middle-aged and older Swedish women included 205 who developed rheumatoid arthritis (RA) during a mean follow-up of 7.5 years. Those who reported intake of more than 0.21 g/day of dietary long-chain n-3 polyunsaturated fatty acids (PUFAs), also called omega-3 fatty acids, at the time of an assessment in 1997 had a 35% reduction in the risk of developing RA, compared with women who reported lower intake (adjusted relative risk, 0.65), reported Dr. Daniela Di Giuseppe of the Karolinska Institute, Stockholm, and her colleagues.

© Suprijono Suharjoto/Fotolia.com

"The population prevented fraction, the equivalent of the population attributable risk when analyzing a protective factor, was 0.28. This indicates that 28% of the hypothetical total load of disease could be prevented by exposure to greater than 0.21 g/day of dietary long-chain n-3 PUFAs," the investigators wrote.

Consistent long-term intake of more than 0.21 g/day was associated with even greater risk reduction. Women who reported intake at that level at assessments in both 1987 and 1997 had a 52% reduction in risk, compared with those with lower intake (adjusted RR, 0.48), they said.

Those who reported consistent long-term consumption of at least one serving of fish weekly had a 29% reduction in risk, compared with those who had less than one serving weekly (adjusted RR, 0.71), they noted (Ann. Rheum. Dis. 2013 Aug. 12 [doi: 10.1136/annrheumdis-2013-203338]).

"The inverse association between fish consumption and RA can be attributed mainly to its content of long-chain n-3 PUFAs," they wrote.

Of note, the use of fish oil supplementation was not associated with the development of RA in this study (relative risk, 1.32 for ever vs. never users). However, there were only 17 users, and information about dose and duration of use was lacking.

Study subjects were participants in the population-based Swedish Mammography Cohort. The women, who were aged 54-89 years at follow-up, completed detailed food-frequency questionnaires at the 1987 and 1997 assessments.

The multivariable relative risks for dietary long-chain n-3 PUFAs were adjusted for cigarette smoking, alcohol intake, aspirin use, and energy intake. The multivariable relative risks for long-term fish consumption were also adjusted for quartiles of red meat and dairy food consumption.

The findings have implications for dietary guidelines with respect to fish consumption, the investigators said.

RA is known to be influenced by both genetic and environmental factors, but little is known about important modifiable risk factors other than smoking and alcohol consumption, they said, noting that the evidence regarding a role for dietary long-chain n-3 PUFAs has been limited, and study results have been conflicting.

However, the current study suggests that intake of at least 0.21 g/day is indeed of benefit. That intake is about the equivalent of at least one serving of fatty fish, such as salmon, or four servings of lean fish, such as cod, each week, the investigators explained. They suggested that dietary long-chain n-3 PUFAs may protect against RA through their anti-inflammatory properties, particularly through the synthesis of eicosanoids.

These intake levels are in line with recommendations from the American Dietary Guideline Advisory Committee, which advised eating fish twice weekly.

"In conclusion, the study indicates a potentially important role for dietary long-chain n-3 PUFAs in the etiology of RA, and that adherence to existing dietary guidelines regarding fish consumption may also be beneficial in terms of RA risk," they wrote.

The study was supported by research grants from the Swedish Research Council/Committee for Research Infrastructure for Maintenance of the Swedish Mammography Cohort, and from the Karolinska Institute’s Award for Ph.D. Students. The authors reported having no disclosures.

Consistent dietary intake of long-chain n-3 polyunsaturated fatty acids typically found in fish was associated with a reduced risk of rheumatoid arthritis in a prospective cohort study of Swedish women.

The study of 32,232 middle-aged and older Swedish women included 205 who developed rheumatoid arthritis (RA) during a mean follow-up of 7.5 years. Those who reported intake of more than 0.21 g/day of dietary long-chain n-3 polyunsaturated fatty acids (PUFAs), also called omega-3 fatty acids, at the time of an assessment in 1997 had a 35% reduction in the risk of developing RA, compared with women who reported lower intake (adjusted relative risk, 0.65), reported Dr. Daniela Di Giuseppe of the Karolinska Institute, Stockholm, and her colleagues.

© Suprijono Suharjoto/Fotolia.com

"The population prevented fraction, the equivalent of the population attributable risk when analyzing a protective factor, was 0.28. This indicates that 28% of the hypothetical total load of disease could be prevented by exposure to greater than 0.21 g/day of dietary long-chain n-3 PUFAs," the investigators wrote.

Consistent long-term intake of more than 0.21 g/day was associated with even greater risk reduction. Women who reported intake at that level at assessments in both 1987 and 1997 had a 52% reduction in risk, compared with those with lower intake (adjusted RR, 0.48), they said.

Those who reported consistent long-term consumption of at least one serving of fish weekly had a 29% reduction in risk, compared with those who had less than one serving weekly (adjusted RR, 0.71), they noted (Ann. Rheum. Dis. 2013 Aug. 12 [doi: 10.1136/annrheumdis-2013-203338]).

"The inverse association between fish consumption and RA can be attributed mainly to its content of long-chain n-3 PUFAs," they wrote.

Of note, the use of fish oil supplementation was not associated with the development of RA in this study (relative risk, 1.32 for ever vs. never users). However, there were only 17 users, and information about dose and duration of use was lacking.

Study subjects were participants in the population-based Swedish Mammography Cohort. The women, who were aged 54-89 years at follow-up, completed detailed food-frequency questionnaires at the 1987 and 1997 assessments.

The multivariable relative risks for dietary long-chain n-3 PUFAs were adjusted for cigarette smoking, alcohol intake, aspirin use, and energy intake. The multivariable relative risks for long-term fish consumption were also adjusted for quartiles of red meat and dairy food consumption.

The findings have implications for dietary guidelines with respect to fish consumption, the investigators said.

RA is known to be influenced by both genetic and environmental factors, but little is known about important modifiable risk factors other than smoking and alcohol consumption, they said, noting that the evidence regarding a role for dietary long-chain n-3 PUFAs has been limited, and study results have been conflicting.

However, the current study suggests that intake of at least 0.21 g/day is indeed of benefit. That intake is about the equivalent of at least one serving of fatty fish, such as salmon, or four servings of lean fish, such as cod, each week, the investigators explained. They suggested that dietary long-chain n-3 PUFAs may protect against RA through their anti-inflammatory properties, particularly through the synthesis of eicosanoids.

These intake levels are in line with recommendations from the American Dietary Guideline Advisory Committee, which advised eating fish twice weekly.

"In conclusion, the study indicates a potentially important role for dietary long-chain n-3 PUFAs in the etiology of RA, and that adherence to existing dietary guidelines regarding fish consumption may also be beneficial in terms of RA risk," they wrote.

The study was supported by research grants from the Swedish Research Council/Committee for Research Infrastructure for Maintenance of the Swedish Mammography Cohort, and from the Karolinska Institute’s Award for Ph.D. Students. The authors reported having no disclosures.

Smokers who are heavily addicted to nicotine are significantly more likely to gain weight when they try to quit, researchers report.

Investigators studying 186 patients who successfully quit smoking after receiving nicotine replacement therapy at an outpatient clinic found that mean body mass index increased significantly from 23.5 kg/m² at an initial consultation to 23.9 kg/m² at 3 months after the start of therapy. A high Fagerstrom Test for Nicotine Dependence (FTND) score, indicating severe dependency, was found on multivariate analysis to be the strongest predictor of increase (using a gender-adjusted standardized coefficient).

Dr. Maki Komiyama of Kyoto (Japan) Medical Center and colleagues reported their findings online Aug. 21 in the open access journal PLoS One (PLoS One 2013 Aug. 21 [doi:10.1371/journal.pone.0072010]).

The findings are important because, while smoking cessation is known to reduce cardiovascular and cancer risk and to reduce all-cause mortality, associated weight gain is linked with greater risk of glucose intolerance and a reduction in the beneficial effects that quitting has on pulmonary function. Concerns about weight gain also can lead to a failure to quit smoking, they said.

"Even if one is expected to experience post-cessation weight gain, quitting smoking still leads to a reduced cardiovascular risk. However, there is also a possibility that if one can prevent post-cessation weight gain, then this will further reduce the cardiovascular risk due to having ceased smoking," they wrote.

"Even if one is expected to experience post-cessation weight gain, quitting smoking still leads to a reduced cardiovascular risk"

Thus, they continued, the ability to predict which patients are likely to gain weight during smoking cessation therapy – and performing weight control accordingly at the outset – could lead to improved outcomes, and the findings of this study may be useful for discriminating such patient groups.

Study participants were 132 men and 54 women with a mean age of 59.6 years who visited the smoking cessation clinic at the National Hospital Organization Kyoto Medical Center between July 2007 and November 2011 and successfully quit smoking.

Other factors found on univariate analysis to be significantly associated with BMI increase included triglyceride level, high-density lipoprotein cholesterol, and daily cigarette consumption. "To further investigate ... we performed multivariate analysis. The results demonstrated that the triglyceride level and FTND score were factors determining the post-cessation BMI increase, and that the FTND score was the strongest one," the investigators wrote.

An FTND score of 8 or more (on a scale of 1-10) was associated with larger postcessation BMI increase, and the increase was statistically significant when compared with the level of BMI increase in those with a score of 7 or less, they noted.

"The result that a high FTND score was the most important determinant of a BMI increase supports the hypothesis that post-cessation weight gain is one of the nicotine withdrawal symptoms," they said.

As for the association between triglyceride elevation and weight gain, the mechanism is not clearly understood and requires further study, they noted.

With the exception of two patients who did not receive medical treatment, study participants were treated with either oral varenicline (95 patients) or nicotine patch (89 patients). No difference was seen between the varenicline and nicotine patch groups with respect to BMI increase, but the varenicline group had higher nicotine dependency.

They also noted that, in their study, "although a significant increase in BMI was confirmed after smoking-cessation therapy, the BMI increase was only 0.4 kg/m² (1.1 kg), which is much smaller than reported in previous studies for people who quit smoking on their own initiative (2.8-3.8 kg)."

Additional study is needed to determine the appropriate timing for initiating interventions against post–smoking cessation weight gain, they noted.

This study was supported by a grant-in-aid for clinical research from the National Hospital Organization and the Pfizer Health Research Foundation. The authors reported that one study drug (varenicline) is manufactured by Pfizer but confirmed "that this does not alter their adherence to all the PLoS One policies on sharing data and materials."

Smokers who are heavily addicted to nicotine are significantly more likely to gain weight when they try to quit, researchers report.

Investigators studying 186 patients who successfully quit smoking after receiving nicotine replacement therapy at an outpatient clinic found that mean body mass index increased significantly from 23.5 kg/m² at an initial consultation to 23.9 kg/m² at 3 months after the start of therapy. A high Fagerstrom Test for Nicotine Dependence (FTND) score, indicating severe dependency, was found on multivariate analysis to be the strongest predictor of increase (using a gender-adjusted standardized coefficient).

Dr. Maki Komiyama of Kyoto (Japan) Medical Center and colleagues reported their findings online Aug. 21 in the open access journal PLoS One (PLoS One 2013 Aug. 21 [doi:10.1371/journal.pone.0072010]).

The findings are important because, while smoking cessation is known to reduce cardiovascular and cancer risk and to reduce all-cause mortality, associated weight gain is linked with greater risk of glucose intolerance and a reduction in the beneficial effects that quitting has on pulmonary function. Concerns about weight gain also can lead to a failure to quit smoking, they said.

"Even if one is expected to experience post-cessation weight gain, quitting smoking still leads to a reduced cardiovascular risk. However, there is also a possibility that if one can prevent post-cessation weight gain, then this will further reduce the cardiovascular risk due to having ceased smoking," they wrote.

"Even if one is expected to experience post-cessation weight gain, quitting smoking still leads to a reduced cardiovascular risk"

Thus, they continued, the ability to predict which patients are likely to gain weight during smoking cessation therapy – and performing weight control accordingly at the outset – could lead to improved outcomes, and the findings of this study may be useful for discriminating such patient groups.

Study participants were 132 men and 54 women with a mean age of 59.6 years who visited the smoking cessation clinic at the National Hospital Organization Kyoto Medical Center between July 2007 and November 2011 and successfully quit smoking.

Other factors found on univariate analysis to be significantly associated with BMI increase included triglyceride level, high-density lipoprotein cholesterol, and daily cigarette consumption. "To further investigate ... we performed multivariate analysis. The results demonstrated that the triglyceride level and FTND score were factors determining the post-cessation BMI increase, and that the FTND score was the strongest one," the investigators wrote.

An FTND score of 8 or more (on a scale of 1-10) was associated with larger postcessation BMI increase, and the increase was statistically significant when compared with the level of BMI increase in those with a score of 7 or less, they noted.

"The result that a high FTND score was the most important determinant of a BMI increase supports the hypothesis that post-cessation weight gain is one of the nicotine withdrawal symptoms," they said.

As for the association between triglyceride elevation and weight gain, the mechanism is not clearly understood and requires further study, they noted.

With the exception of two patients who did not receive medical treatment, study participants were treated with either oral varenicline (95 patients) or nicotine patch (89 patients). No difference was seen between the varenicline and nicotine patch groups with respect to BMI increase, but the varenicline group had higher nicotine dependency.

They also noted that, in their study, "although a significant increase in BMI was confirmed after smoking-cessation therapy, the BMI increase was only 0.4 kg/m² (1.1 kg), which is much smaller than reported in previous studies for people who quit smoking on their own initiative (2.8-3.8 kg)."

Additional study is needed to determine the appropriate timing for initiating interventions against post–smoking cessation weight gain, they noted.

This study was supported by a grant-in-aid for clinical research from the National Hospital Organization and the Pfizer Health Research Foundation. The authors reported that one study drug (varenicline) is manufactured by Pfizer but confirmed "that this does not alter their adherence to all the PLoS One policies on sharing data and materials."

Smokers who are heavily addicted to nicotine are significantly more likely to gain weight when they try to quit, researchers report.

Investigators studying 186 patients who successfully quit smoking after receiving nicotine replacement therapy at an outpatient clinic found that mean body mass index increased significantly from 23.5 kg/m² at an initial consultation to 23.9 kg/m² at 3 months after the start of therapy. A high Fagerstrom Test for Nicotine Dependence (FTND) score, indicating severe dependency, was found on multivariate analysis to be the strongest predictor of increase (using a gender-adjusted standardized coefficient).

Dr. Maki Komiyama of Kyoto (Japan) Medical Center and colleagues reported their findings online Aug. 21 in the open access journal PLoS One (PLoS One 2013 Aug. 21 [doi:10.1371/journal.pone.0072010]).

The findings are important because, while smoking cessation is known to reduce cardiovascular and cancer risk and to reduce all-cause mortality, associated weight gain is linked with greater risk of glucose intolerance and a reduction in the beneficial effects that quitting has on pulmonary function. Concerns about weight gain also can lead to a failure to quit smoking, they said.

"Even if one is expected to experience post-cessation weight gain, quitting smoking still leads to a reduced cardiovascular risk. However, there is also a possibility that if one can prevent post-cessation weight gain, then this will further reduce the cardiovascular risk due to having ceased smoking," they wrote.

"Even if one is expected to experience post-cessation weight gain, quitting smoking still leads to a reduced cardiovascular risk"

Thus, they continued, the ability to predict which patients are likely to gain weight during smoking cessation therapy – and performing weight control accordingly at the outset – could lead to improved outcomes, and the findings of this study may be useful for discriminating such patient groups.

Study participants were 132 men and 54 women with a mean age of 59.6 years who visited the smoking cessation clinic at the National Hospital Organization Kyoto Medical Center between July 2007 and November 2011 and successfully quit smoking.

Other factors found on univariate analysis to be significantly associated with BMI increase included triglyceride level, high-density lipoprotein cholesterol, and daily cigarette consumption. "To further investigate ... we performed multivariate analysis. The results demonstrated that the triglyceride level and FTND score were factors determining the post-cessation BMI increase, and that the FTND score was the strongest one," the investigators wrote.

An FTND score of 8 or more (on a scale of 1-10) was associated with larger postcessation BMI increase, and the increase was statistically significant when compared with the level of BMI increase in those with a score of 7 or less, they noted.

"The result that a high FTND score was the most important determinant of a BMI increase supports the hypothesis that post-cessation weight gain is one of the nicotine withdrawal symptoms," they said.

As for the association between triglyceride elevation and weight gain, the mechanism is not clearly understood and requires further study, they noted.

With the exception of two patients who did not receive medical treatment, study participants were treated with either oral varenicline (95 patients) or nicotine patch (89 patients). No difference was seen between the varenicline and nicotine patch groups with respect to BMI increase, but the varenicline group had higher nicotine dependency.

They also noted that, in their study, "although a significant increase in BMI was confirmed after smoking-cessation therapy, the BMI increase was only 0.4 kg/m² (1.1 kg), which is much smaller than reported in previous studies for people who quit smoking on their own initiative (2.8-3.8 kg)."

Additional study is needed to determine the appropriate timing for initiating interventions against post–smoking cessation weight gain, they noted.

This study was supported by a grant-in-aid for clinical research from the National Hospital Organization and the Pfizer Health Research Foundation. The authors reported that one study drug (varenicline) is manufactured by Pfizer but confirmed "that this does not alter their adherence to all the PLoS One policies on sharing data and materials."