M. Alexander Otto

SEATTLE – Septic patients are more likely to respond to fluid therapy if their velocity time integral – a Doppler ultrasound measurement of blood flow across the left ventricular outflow tract – increases by 15% or more with a passive single-leg raise, according to a preliminary, observational study of 32 patients at New York Methodist Hospital.

A passive leg raise to 45 degrees simulates a 250- to 500-cc fluid bolus. "We have found that people who don’t respond with a VTI greater than 15% have higher repeat lactate levels. Instead of giving them 2 L [of fluid] and then reassessing, maybe they’re patients you want to start on pressors right away," Dr. Andrew Balk said at the annual meeting of the American College of Emergency Physicians.

Echocardiogram machines can automatically calculate VTI. The measurement, which Dr. Balk and his associates obtained from the apical five-chamber view, is a surrogate for, and can be used to calculate, cardiac output. Poor response to fluid challenge indicates that fluids are less likely to increase cardiac output and more likely to cause fluid overload, said Dr. Balk, associate director of the clinical ultrasound division at the hospital.

The patients’ mean age was 68 years, and those with valvular pathology and atrial fibrillation were excluded from the study.

The group’s mean baseline VTI was 22 cm (range, 15-29 cm), which leg raise elevated to a mean of 26 cm (18-34 cm), an increase of about 18% (4%-36%). A subsequent 2-L normal saline challenge increased VTI to a mean of 33 cm.

The mean baseline lactate level was 3.2 mmol/L (1.2-5.2 mmol/L), and 2 mmol/L (1-3 mmol/L) after the 2-L challenge. The percent change in VTI correlated significantly with the percent change in serum lactate levels. "Below-average responsiveness to the initial small fluid bolus was associated with a higher repeat lactate value ... which suggests an inverse relationship between a patient’s fluid responsiveness as observed by the change in VTI and the severity of sepsis," the researchers concluded.

The VTI/leg-raise approach looks promising as a possible quick bedside marker that identifies patients who need aggressive treatment, without the need for central line measurements, Dr. Balk said."The quickest initial fluid bolus you can get is a passive leg raise. You can watch for changes" in real time, and don’t have to move the probe from the point of maximum impact.

He reported having no disclosures.

aotto@frontlinemedcom.com

SEATTLE – Septic patients are more likely to respond to fluid therapy if their velocity time integral – a Doppler ultrasound measurement of blood flow across the left ventricular outflow tract – increases by 15% or more with a passive single-leg raise, according to a preliminary, observational study of 32 patients at New York Methodist Hospital.

A passive leg raise to 45 degrees simulates a 250- to 500-cc fluid bolus. "We have found that people who don’t respond with a VTI greater than 15% have higher repeat lactate levels. Instead of giving them 2 L [of fluid] and then reassessing, maybe they’re patients you want to start on pressors right away," Dr. Andrew Balk said at the annual meeting of the American College of Emergency Physicians.

Echocardiogram machines can automatically calculate VTI. The measurement, which Dr. Balk and his associates obtained from the apical five-chamber view, is a surrogate for, and can be used to calculate, cardiac output. Poor response to fluid challenge indicates that fluids are less likely to increase cardiac output and more likely to cause fluid overload, said Dr. Balk, associate director of the clinical ultrasound division at the hospital.

The patients’ mean age was 68 years, and those with valvular pathology and atrial fibrillation were excluded from the study.

The group’s mean baseline VTI was 22 cm (range, 15-29 cm), which leg raise elevated to a mean of 26 cm (18-34 cm), an increase of about 18% (4%-36%). A subsequent 2-L normal saline challenge increased VTI to a mean of 33 cm.

The mean baseline lactate level was 3.2 mmol/L (1.2-5.2 mmol/L), and 2 mmol/L (1-3 mmol/L) after the 2-L challenge. The percent change in VTI correlated significantly with the percent change in serum lactate levels. "Below-average responsiveness to the initial small fluid bolus was associated with a higher repeat lactate value ... which suggests an inverse relationship between a patient’s fluid responsiveness as observed by the change in VTI and the severity of sepsis," the researchers concluded.

The VTI/leg-raise approach looks promising as a possible quick bedside marker that identifies patients who need aggressive treatment, without the need for central line measurements, Dr. Balk said."The quickest initial fluid bolus you can get is a passive leg raise. You can watch for changes" in real time, and don’t have to move the probe from the point of maximum impact.

He reported having no disclosures.

aotto@frontlinemedcom.com

SEATTLE – Septic patients are more likely to respond to fluid therapy if their velocity time integral – a Doppler ultrasound measurement of blood flow across the left ventricular outflow tract – increases by 15% or more with a passive single-leg raise, according to a preliminary, observational study of 32 patients at New York Methodist Hospital.

A passive leg raise to 45 degrees simulates a 250- to 500-cc fluid bolus. "We have found that people who don’t respond with a VTI greater than 15% have higher repeat lactate levels. Instead of giving them 2 L [of fluid] and then reassessing, maybe they’re patients you want to start on pressors right away," Dr. Andrew Balk said at the annual meeting of the American College of Emergency Physicians.

Echocardiogram machines can automatically calculate VTI. The measurement, which Dr. Balk and his associates obtained from the apical five-chamber view, is a surrogate for, and can be used to calculate, cardiac output. Poor response to fluid challenge indicates that fluids are less likely to increase cardiac output and more likely to cause fluid overload, said Dr. Balk, associate director of the clinical ultrasound division at the hospital.

The patients’ mean age was 68 years, and those with valvular pathology and atrial fibrillation were excluded from the study.

The group’s mean baseline VTI was 22 cm (range, 15-29 cm), which leg raise elevated to a mean of 26 cm (18-34 cm), an increase of about 18% (4%-36%). A subsequent 2-L normal saline challenge increased VTI to a mean of 33 cm.

The mean baseline lactate level was 3.2 mmol/L (1.2-5.2 mmol/L), and 2 mmol/L (1-3 mmol/L) after the 2-L challenge. The percent change in VTI correlated significantly with the percent change in serum lactate levels. "Below-average responsiveness to the initial small fluid bolus was associated with a higher repeat lactate value ... which suggests an inverse relationship between a patient’s fluid responsiveness as observed by the change in VTI and the severity of sepsis," the researchers concluded.

The VTI/leg-raise approach looks promising as a possible quick bedside marker that identifies patients who need aggressive treatment, without the need for central line measurements, Dr. Balk said."The quickest initial fluid bolus you can get is a passive leg raise. You can watch for changes" in real time, and don’t have to move the probe from the point of maximum impact.

He reported having no disclosures.

aotto@frontlinemedcom.com

As C-reactive protein levels and erythrocyte sedimentation rates go up in patients with inflammatory bowel disease, the risk of colorectal cancer goes up, too, a finding that suggests a role for both as markers of colon cancer risk, Boston investigators reported in a prospective study published online Jan. 6 in Clinical Gastroenterology and Hepatology.

The team divided 3,145 IBD patients into quartiles based on median C-reactive protein (CRP) levels, and 4,008 others into quartiles based on median erythrocyte sedimentation rates (ESR), then followed them for a median of 6 years.

On multivariate analysis, there was a significant increase in the risk of colorectal cancer (CRC) across quartiles of CRP elevation (P for trend = .017). Higher median ESR was also independently associated with higher risk of CRC across quartiles (P for trend = .007) (Clin. Gastroenterol. Hepatol. 2014 Jan. 6 [doi: 10.1016/j.cgh.2013.12.030]).

"This association adds another clinical variable to help stratify patients into risk categories. There is an important need to identify high-risk subgroups that may benefit from continued intensive surveillance strategies while allowing for less frequent colonoscopies in patients at low risk of CRC. We believe that our findings ... suggest that an individual patient’s severity of inflammation may be helpful in further personalizing surveillance recommendations," and might even help monitor other outcomes, including treatment response, said the authors, led by Dr. Ashwin Ananthakrishnan, a gastroenterologist at Massachusetts General Hospital, Boston.

After adjustment for age, sex, race, IBD type, and other factors, the patients in the highest CRP quartile had more than double the risk of colorectal cancer compared with those in the lowest quartile (OR 2.72, 95% CI 0.95-7.76). The strength of association was similar in men and women, and in Crohn’s disease and ulcerative colitis.

Similarly, patients in the highest ESR quartile had double the risk compared with those in the lowest (OR 2.06, 95% CI 1.14-3.74). The correlation was strongest in ulcerative colitis patients and men.

The median CRP values in each of the quartiles were 0.8, 2.7, 7.5, and 32.8 mg/L. In the ESR group, the median quartile values were 7, 14, 25, and 50 mm/hr.

Overall, 33 patients in the CRP cohort and 102 patients in the ESR cohort developed colorectal cancer at a median age of 55 years. The median number of CRP measurements was three, and median number of ESR measurements six. More than half the subjects were women, most were white, and ulcerative colitis was slightly more common than was Crohn’s disease.

Adjusting for number of colonoscopies, intensity of health care utilization, use of corticosteroids, and other factors did not change results for either the CRP or ESR cohorts.

The National Institutes of Health funded the work. The investigators have no disclosures.

aotto@frontlinemedcom.com

As C-reactive protein levels and erythrocyte sedimentation rates go up in patients with inflammatory bowel disease, the risk of colorectal cancer goes up, too, a finding that suggests a role for both as markers of colon cancer risk, Boston investigators reported in a prospective study published online Jan. 6 in Clinical Gastroenterology and Hepatology.

The team divided 3,145 IBD patients into quartiles based on median C-reactive protein (CRP) levels, and 4,008 others into quartiles based on median erythrocyte sedimentation rates (ESR), then followed them for a median of 6 years.

On multivariate analysis, there was a significant increase in the risk of colorectal cancer (CRC) across quartiles of CRP elevation (P for trend = .017). Higher median ESR was also independently associated with higher risk of CRC across quartiles (P for trend = .007) (Clin. Gastroenterol. Hepatol. 2014 Jan. 6 [doi: 10.1016/j.cgh.2013.12.030]).

"This association adds another clinical variable to help stratify patients into risk categories. There is an important need to identify high-risk subgroups that may benefit from continued intensive surveillance strategies while allowing for less frequent colonoscopies in patients at low risk of CRC. We believe that our findings ... suggest that an individual patient’s severity of inflammation may be helpful in further personalizing surveillance recommendations," and might even help monitor other outcomes, including treatment response, said the authors, led by Dr. Ashwin Ananthakrishnan, a gastroenterologist at Massachusetts General Hospital, Boston.

After adjustment for age, sex, race, IBD type, and other factors, the patients in the highest CRP quartile had more than double the risk of colorectal cancer compared with those in the lowest quartile (OR 2.72, 95% CI 0.95-7.76). The strength of association was similar in men and women, and in Crohn’s disease and ulcerative colitis.

Similarly, patients in the highest ESR quartile had double the risk compared with those in the lowest (OR 2.06, 95% CI 1.14-3.74). The correlation was strongest in ulcerative colitis patients and men.

The median CRP values in each of the quartiles were 0.8, 2.7, 7.5, and 32.8 mg/L. In the ESR group, the median quartile values were 7, 14, 25, and 50 mm/hr.

Overall, 33 patients in the CRP cohort and 102 patients in the ESR cohort developed colorectal cancer at a median age of 55 years. The median number of CRP measurements was three, and median number of ESR measurements six. More than half the subjects were women, most were white, and ulcerative colitis was slightly more common than was Crohn’s disease.

Adjusting for number of colonoscopies, intensity of health care utilization, use of corticosteroids, and other factors did not change results for either the CRP or ESR cohorts.

The National Institutes of Health funded the work. The investigators have no disclosures.

aotto@frontlinemedcom.com

As C-reactive protein levels and erythrocyte sedimentation rates go up in patients with inflammatory bowel disease, the risk of colorectal cancer goes up, too, a finding that suggests a role for both as markers of colon cancer risk, Boston investigators reported in a prospective study published online Jan. 6 in Clinical Gastroenterology and Hepatology.

The team divided 3,145 IBD patients into quartiles based on median C-reactive protein (CRP) levels, and 4,008 others into quartiles based on median erythrocyte sedimentation rates (ESR), then followed them for a median of 6 years.

On multivariate analysis, there was a significant increase in the risk of colorectal cancer (CRC) across quartiles of CRP elevation (P for trend = .017). Higher median ESR was also independently associated with higher risk of CRC across quartiles (P for trend = .007) (Clin. Gastroenterol. Hepatol. 2014 Jan. 6 [doi: 10.1016/j.cgh.2013.12.030]).

"This association adds another clinical variable to help stratify patients into risk categories. There is an important need to identify high-risk subgroups that may benefit from continued intensive surveillance strategies while allowing for less frequent colonoscopies in patients at low risk of CRC. We believe that our findings ... suggest that an individual patient’s severity of inflammation may be helpful in further personalizing surveillance recommendations," and might even help monitor other outcomes, including treatment response, said the authors, led by Dr. Ashwin Ananthakrishnan, a gastroenterologist at Massachusetts General Hospital, Boston.

After adjustment for age, sex, race, IBD type, and other factors, the patients in the highest CRP quartile had more than double the risk of colorectal cancer compared with those in the lowest quartile (OR 2.72, 95% CI 0.95-7.76). The strength of association was similar in men and women, and in Crohn’s disease and ulcerative colitis.

Similarly, patients in the highest ESR quartile had double the risk compared with those in the lowest (OR 2.06, 95% CI 1.14-3.74). The correlation was strongest in ulcerative colitis patients and men.

The median CRP values in each of the quartiles were 0.8, 2.7, 7.5, and 32.8 mg/L. In the ESR group, the median quartile values were 7, 14, 25, and 50 mm/hr.

Overall, 33 patients in the CRP cohort and 102 patients in the ESR cohort developed colorectal cancer at a median age of 55 years. The median number of CRP measurements was three, and median number of ESR measurements six. More than half the subjects were women, most were white, and ulcerative colitis was slightly more common than was Crohn’s disease.

Adjusting for number of colonoscopies, intensity of health care utilization, use of corticosteroids, and other factors did not change results for either the CRP or ESR cohorts.

The National Institutes of Health funded the work. The investigators have no disclosures.

aotto@frontlinemedcom.com

Methotrexate poses only a slight risk of pulmonary complications in rheumatoid arthritis patients, according to a meta-analysis of 22 double-blind, randomized trials comparing methotrexate to other drugs.

Physicians have worried for years that methotrexate might damage the already-frail lungs of RA patients, but the results suggest "the risk may be lower than previously believed," said the Irish investigators, led by Dr. Richard Conway, a senior research fellow in the department of rheumatology at Galway (Ireland) University Hospitals (Arthritis Rheum. 2013 Dec. 24 [doi: 10.1002/art.38322]).

Previous reports estimated that the incidence of methotrexate-induced lung disease was as high as 7.6% in RA patients, but the team found a modest increase in the risk of overall respiratory adverse events (relative risk, 1.10; 95% confidence interval, 1.02-1.19) and respiratory infections (RR, 1.11; 95% CI, 1.02-1.21), and no increase in noninfectious respiratory events (RR, 1.02; 95% CI, 0.65-1.60) and pulmonary deaths (RR, 1.53; 95% CI, 0.46-5.01).

The meta-analysis pooled trial results from as far back as 1990. Overall, 4,544 patients were treated with methotrexate, and 4,040 with active comparators. The studies ranged from 6 to 24 months in duration.

The findings matter because "the suspicion of methotrexate-induced lung injury frequently leads to the cessation of methotrexate in patients who may otherwise be benefiting from the treatment. It is ... of vital importance not to implicate methotrexate as a causative agent in adverse events with insufficient evidence, as the drug may save the patient’s life," the investigators wrote.

"In our experience, many cases of lung disease initially attributed to methotrexate are due to other causative factors including, but not limited to, rheumatoid interstitial lung disease and opportunistic infections, with some experiencing worsening lung disease following cessation of their methotrexate," they noted.

However, the team found that methotrexate users had an increased risk of pneumonitis in the studies that specifically reported pneumonitis rates (RR, 7.81; 95% CI, 1.76-34.72); one case was fatal.

But the finding "must be interpreted with caution due to the reduced number of patients in each group." Also, none of the 13 trials published after 2001 reported pneumonitis. Perhaps methotrexate complications were less well understood in the 1990s, so earlier trials included patients at higher risk for pulmonary problems. Also, investigators may have been more likely to pin pulmonary issues on methotrexate, the authors said.

The mean age in the studies that reported pneumonitis was 54.3 years, and 28% of the subjects were men, whereas the mean age in studies that did not report pneumonitis was 50.7 years and 22% of the patients were men.

"Historically, intramuscular gold and sulfasalazine, and more recently disease-modifying antirheumatic drugs such as leflunomide have [also] been linked to the development of interstitial lung disease. In recent times, a possible link has emerged with the use of a number of the biologic agents, initially anti-TNF-alpha agents and more recently rituximab and tocilizumab," the investigators wrote. All of those agents were among the comparators in the pooled trials.

"Rather than each single drug causing interstitial lung disease ... it is perhaps more likely that if a link is present, it involves the modification of the underlying pulmonary disease process in rheumatoid arthritis by the implicated agents," they suggested.

Dr. Conway and his colleagues had no external funding for the study, but he and three of the other four investigators reported grants and payments from almost 20 companies, including Roche, UCB, and Merck.

aotto@frontlinemedcom.com

Methotrexate poses only a slight risk of pulmonary complications in rheumatoid arthritis patients, according to a meta-analysis of 22 double-blind, randomized trials comparing methotrexate to other drugs.

Physicians have worried for years that methotrexate might damage the already-frail lungs of RA patients, but the results suggest "the risk may be lower than previously believed," said the Irish investigators, led by Dr. Richard Conway, a senior research fellow in the department of rheumatology at Galway (Ireland) University Hospitals (Arthritis Rheum. 2013 Dec. 24 [doi: 10.1002/art.38322]).

Previous reports estimated that the incidence of methotrexate-induced lung disease was as high as 7.6% in RA patients, but the team found a modest increase in the risk of overall respiratory adverse events (relative risk, 1.10; 95% confidence interval, 1.02-1.19) and respiratory infections (RR, 1.11; 95% CI, 1.02-1.21), and no increase in noninfectious respiratory events (RR, 1.02; 95% CI, 0.65-1.60) and pulmonary deaths (RR, 1.53; 95% CI, 0.46-5.01).

The meta-analysis pooled trial results from as far back as 1990. Overall, 4,544 patients were treated with methotrexate, and 4,040 with active comparators. The studies ranged from 6 to 24 months in duration.

The findings matter because "the suspicion of methotrexate-induced lung injury frequently leads to the cessation of methotrexate in patients who may otherwise be benefiting from the treatment. It is ... of vital importance not to implicate methotrexate as a causative agent in adverse events with insufficient evidence, as the drug may save the patient’s life," the investigators wrote.

"In our experience, many cases of lung disease initially attributed to methotrexate are due to other causative factors including, but not limited to, rheumatoid interstitial lung disease and opportunistic infections, with some experiencing worsening lung disease following cessation of their methotrexate," they noted.

However, the team found that methotrexate users had an increased risk of pneumonitis in the studies that specifically reported pneumonitis rates (RR, 7.81; 95% CI, 1.76-34.72); one case was fatal.

But the finding "must be interpreted with caution due to the reduced number of patients in each group." Also, none of the 13 trials published after 2001 reported pneumonitis. Perhaps methotrexate complications were less well understood in the 1990s, so earlier trials included patients at higher risk for pulmonary problems. Also, investigators may have been more likely to pin pulmonary issues on methotrexate, the authors said.

The mean age in the studies that reported pneumonitis was 54.3 years, and 28% of the subjects were men, whereas the mean age in studies that did not report pneumonitis was 50.7 years and 22% of the patients were men.

"Historically, intramuscular gold and sulfasalazine, and more recently disease-modifying antirheumatic drugs such as leflunomide have [also] been linked to the development of interstitial lung disease. In recent times, a possible link has emerged with the use of a number of the biologic agents, initially anti-TNF-alpha agents and more recently rituximab and tocilizumab," the investigators wrote. All of those agents were among the comparators in the pooled trials.

"Rather than each single drug causing interstitial lung disease ... it is perhaps more likely that if a link is present, it involves the modification of the underlying pulmonary disease process in rheumatoid arthritis by the implicated agents," they suggested.

Dr. Conway and his colleagues had no external funding for the study, but he and three of the other four investigators reported grants and payments from almost 20 companies, including Roche, UCB, and Merck.

aotto@frontlinemedcom.com

Methotrexate poses only a slight risk of pulmonary complications in rheumatoid arthritis patients, according to a meta-analysis of 22 double-blind, randomized trials comparing methotrexate to other drugs.

Physicians have worried for years that methotrexate might damage the already-frail lungs of RA patients, but the results suggest "the risk may be lower than previously believed," said the Irish investigators, led by Dr. Richard Conway, a senior research fellow in the department of rheumatology at Galway (Ireland) University Hospitals (Arthritis Rheum. 2013 Dec. 24 [doi: 10.1002/art.38322]).

Previous reports estimated that the incidence of methotrexate-induced lung disease was as high as 7.6% in RA patients, but the team found a modest increase in the risk of overall respiratory adverse events (relative risk, 1.10; 95% confidence interval, 1.02-1.19) and respiratory infections (RR, 1.11; 95% CI, 1.02-1.21), and no increase in noninfectious respiratory events (RR, 1.02; 95% CI, 0.65-1.60) and pulmonary deaths (RR, 1.53; 95% CI, 0.46-5.01).

The meta-analysis pooled trial results from as far back as 1990. Overall, 4,544 patients were treated with methotrexate, and 4,040 with active comparators. The studies ranged from 6 to 24 months in duration.

The findings matter because "the suspicion of methotrexate-induced lung injury frequently leads to the cessation of methotrexate in patients who may otherwise be benefiting from the treatment. It is ... of vital importance not to implicate methotrexate as a causative agent in adverse events with insufficient evidence, as the drug may save the patient’s life," the investigators wrote.

"In our experience, many cases of lung disease initially attributed to methotrexate are due to other causative factors including, but not limited to, rheumatoid interstitial lung disease and opportunistic infections, with some experiencing worsening lung disease following cessation of their methotrexate," they noted.

However, the team found that methotrexate users had an increased risk of pneumonitis in the studies that specifically reported pneumonitis rates (RR, 7.81; 95% CI, 1.76-34.72); one case was fatal.

But the finding "must be interpreted with caution due to the reduced number of patients in each group." Also, none of the 13 trials published after 2001 reported pneumonitis. Perhaps methotrexate complications were less well understood in the 1990s, so earlier trials included patients at higher risk for pulmonary problems. Also, investigators may have been more likely to pin pulmonary issues on methotrexate, the authors said.

The mean age in the studies that reported pneumonitis was 54.3 years, and 28% of the subjects were men, whereas the mean age in studies that did not report pneumonitis was 50.7 years and 22% of the patients were men.

"Historically, intramuscular gold and sulfasalazine, and more recently disease-modifying antirheumatic drugs such as leflunomide have [also] been linked to the development of interstitial lung disease. In recent times, a possible link has emerged with the use of a number of the biologic agents, initially anti-TNF-alpha agents and more recently rituximab and tocilizumab," the investigators wrote. All of those agents were among the comparators in the pooled trials.

"Rather than each single drug causing interstitial lung disease ... it is perhaps more likely that if a link is present, it involves the modification of the underlying pulmonary disease process in rheumatoid arthritis by the implicated agents," they suggested.

Dr. Conway and his colleagues had no external funding for the study, but he and three of the other four investigators reported grants and payments from almost 20 companies, including Roche, UCB, and Merck.

aotto@frontlinemedcom.com

A skin patch vaccine designed to prevent traveler’s diarrhea was shown ineffective in a phase III trial published in Lancet Infectious Diseases.

The patch contained Escherichia coli heat-labile toxin. "Future vaccines against traveler’s diarrhea might need to include several antigens against various diarrheal pathogens, and might need to be able to generate mucosal and higher systemic immunity," concluded the investigators, led by Dr. Ronald Behrens of the Hospital for Tropical Diseases in London.

The subjects, healthy adults around 30 years old, were from Germany and the United Kingdom; 821 got a skin patch that contained 37.5 mcg heat-labile toxin and that they wore on their shoulder for 6 hours; 823 got a placebo patch. Both groups got a second patch on the opposite shoulder 2 weeks later (Lancet Infect. Dis. 2013 [doi:10.1016/S1473-3099(13)70297-4]).

Subjects then traveled to either Mexico or Guatemala for at least a week. They recorded their stool output in a diarrhea diary and provided samples for pathogen identification; 30 (3.7%; 95% confidence interval 2.5-5.2) in the heat-labile toxin-patch group and 46 (5.6%; 95% CI 4.1-7.4) in the placebo group were treated for moderate or severe enterotoxigenic E. coli (ETEC) diarrhea, passing four or more unformed stools in 24 hours.

Vaccine efficacy was 34.6%, (95% CI –2.2-58.9; P = .0621), with no statistical difference in the incidence of ETEC diarrhea between the two groups. "The vaccine did seem to provide a small amount of protection against heat-labile toxin-positive ETEC," but not against other forms of ETEC and diarrhea caused by other pathogens. Using a single antigen vaccine "might not be realistic," the investigators said.

The all-cause diarrhea incidence was 17.1% in the vaccine group and 15.2% in the placebo group. Even "a 100% effective ETEC vaccine would still have had only about 50% vaccine efficacy for moderate-to-severe all-cause diarrhea," they noted.

The vaccine was immunogenic; 84% of the treated subjects, but just 13% of placebo patients, converted to LT-specific serum immunoglobulin G; 41% (vs. 2% in the placebo group) seroconverted to anti-LT IgA, but "serum IgG and IgA titers were not associated with vaccine efficacy, suggesting that such titers cannot be used as a correlate of protection," the investigators said.

The number of ETEC cases was lower than expected, as well, which "might have reduced the precision of our findings," they said.

More than 90% of patients had local reactions to the LT patch, including redness, rash, pruritus, pain, edema, and hyperpigmentation. Vaccine-induced hyperpigmentation persisted at 6-month follow-up in about 20% of study subjects. About 56% of those given placebo had local patch reactions, but none had hyperpigmentation at 6 months.

"The LT component in the patch probably caused this vigorous dermal immune response in nearly all vaccine recipients," said the investigators, who also noted that other ETEC vaccines in development "have not yet shown clinically important benefits."

The study was funded by Intercell USA, makers of the vaccine. One of the 17 investigators is an Intercell employee, and study funding paid part of the other investigators’ salaries. Three investigators reported other financial relationships with Intercell, Salix Pharmaceuticals, or Norgine Pharmaceuticals.

aotto@frontlinemedcom.com

A skin patch vaccine designed to prevent traveler’s diarrhea was shown ineffective in a phase III trial published in Lancet Infectious Diseases.

The patch contained Escherichia coli heat-labile toxin. "Future vaccines against traveler’s diarrhea might need to include several antigens against various diarrheal pathogens, and might need to be able to generate mucosal and higher systemic immunity," concluded the investigators, led by Dr. Ronald Behrens of the Hospital for Tropical Diseases in London.

The subjects, healthy adults around 30 years old, were from Germany and the United Kingdom; 821 got a skin patch that contained 37.5 mcg heat-labile toxin and that they wore on their shoulder for 6 hours; 823 got a placebo patch. Both groups got a second patch on the opposite shoulder 2 weeks later (Lancet Infect. Dis. 2013 [doi:10.1016/S1473-3099(13)70297-4]).

Subjects then traveled to either Mexico or Guatemala for at least a week. They recorded their stool output in a diarrhea diary and provided samples for pathogen identification; 30 (3.7%; 95% confidence interval 2.5-5.2) in the heat-labile toxin-patch group and 46 (5.6%; 95% CI 4.1-7.4) in the placebo group were treated for moderate or severe enterotoxigenic E. coli (ETEC) diarrhea, passing four or more unformed stools in 24 hours.

Vaccine efficacy was 34.6%, (95% CI –2.2-58.9; P = .0621), with no statistical difference in the incidence of ETEC diarrhea between the two groups. "The vaccine did seem to provide a small amount of protection against heat-labile toxin-positive ETEC," but not against other forms of ETEC and diarrhea caused by other pathogens. Using a single antigen vaccine "might not be realistic," the investigators said.

The all-cause diarrhea incidence was 17.1% in the vaccine group and 15.2% in the placebo group. Even "a 100% effective ETEC vaccine would still have had only about 50% vaccine efficacy for moderate-to-severe all-cause diarrhea," they noted.

The vaccine was immunogenic; 84% of the treated subjects, but just 13% of placebo patients, converted to LT-specific serum immunoglobulin G; 41% (vs. 2% in the placebo group) seroconverted to anti-LT IgA, but "serum IgG and IgA titers were not associated with vaccine efficacy, suggesting that such titers cannot be used as a correlate of protection," the investigators said.

The number of ETEC cases was lower than expected, as well, which "might have reduced the precision of our findings," they said.

More than 90% of patients had local reactions to the LT patch, including redness, rash, pruritus, pain, edema, and hyperpigmentation. Vaccine-induced hyperpigmentation persisted at 6-month follow-up in about 20% of study subjects. About 56% of those given placebo had local patch reactions, but none had hyperpigmentation at 6 months.

"The LT component in the patch probably caused this vigorous dermal immune response in nearly all vaccine recipients," said the investigators, who also noted that other ETEC vaccines in development "have not yet shown clinically important benefits."

The study was funded by Intercell USA, makers of the vaccine. One of the 17 investigators is an Intercell employee, and study funding paid part of the other investigators’ salaries. Three investigators reported other financial relationships with Intercell, Salix Pharmaceuticals, or Norgine Pharmaceuticals.

aotto@frontlinemedcom.com

A skin patch vaccine designed to prevent traveler’s diarrhea was shown ineffective in a phase III trial published in Lancet Infectious Diseases.

The patch contained Escherichia coli heat-labile toxin. "Future vaccines against traveler’s diarrhea might need to include several antigens against various diarrheal pathogens, and might need to be able to generate mucosal and higher systemic immunity," concluded the investigators, led by Dr. Ronald Behrens of the Hospital for Tropical Diseases in London.

The subjects, healthy adults around 30 years old, were from Germany and the United Kingdom; 821 got a skin patch that contained 37.5 mcg heat-labile toxin and that they wore on their shoulder for 6 hours; 823 got a placebo patch. Both groups got a second patch on the opposite shoulder 2 weeks later (Lancet Infect. Dis. 2013 [doi:10.1016/S1473-3099(13)70297-4]).

Subjects then traveled to either Mexico or Guatemala for at least a week. They recorded their stool output in a diarrhea diary and provided samples for pathogen identification; 30 (3.7%; 95% confidence interval 2.5-5.2) in the heat-labile toxin-patch group and 46 (5.6%; 95% CI 4.1-7.4) in the placebo group were treated for moderate or severe enterotoxigenic E. coli (ETEC) diarrhea, passing four or more unformed stools in 24 hours.

Vaccine efficacy was 34.6%, (95% CI –2.2-58.9; P = .0621), with no statistical difference in the incidence of ETEC diarrhea between the two groups. "The vaccine did seem to provide a small amount of protection against heat-labile toxin-positive ETEC," but not against other forms of ETEC and diarrhea caused by other pathogens. Using a single antigen vaccine "might not be realistic," the investigators said.

The all-cause diarrhea incidence was 17.1% in the vaccine group and 15.2% in the placebo group. Even "a 100% effective ETEC vaccine would still have had only about 50% vaccine efficacy for moderate-to-severe all-cause diarrhea," they noted.

The vaccine was immunogenic; 84% of the treated subjects, but just 13% of placebo patients, converted to LT-specific serum immunoglobulin G; 41% (vs. 2% in the placebo group) seroconverted to anti-LT IgA, but "serum IgG and IgA titers were not associated with vaccine efficacy, suggesting that such titers cannot be used as a correlate of protection," the investigators said.

The number of ETEC cases was lower than expected, as well, which "might have reduced the precision of our findings," they said.

More than 90% of patients had local reactions to the LT patch, including redness, rash, pruritus, pain, edema, and hyperpigmentation. Vaccine-induced hyperpigmentation persisted at 6-month follow-up in about 20% of study subjects. About 56% of those given placebo had local patch reactions, but none had hyperpigmentation at 6 months.

"The LT component in the patch probably caused this vigorous dermal immune response in nearly all vaccine recipients," said the investigators, who also noted that other ETEC vaccines in development "have not yet shown clinically important benefits."

The study was funded by Intercell USA, makers of the vaccine. One of the 17 investigators is an Intercell employee, and study funding paid part of the other investigators’ salaries. Three investigators reported other financial relationships with Intercell, Salix Pharmaceuticals, or Norgine Pharmaceuticals.

aotto@frontlinemedcom.com

VANCOUVER, B.C. – Ready to get started doing transradial percutaneous interventions? Begin under the guidance of an experienced practitioner, perform simple cases in lower-risk patients, and progress to more difficult cases as expertise builds, advised Dr. Asim Cheema, an interventional cardiologist at St. Michael’s Hospital in Toronto.

It’s best to start with a solid foundation in transfemoral PCI, and begin using the radial approach in stable patients who have single vessel disease and are presenting for angiography or some other elective procedure, he said.

"After about 40 patients, you can gradually start to become more comfortable doing multivessel PCI. Then, you can move on to an [acute coronary syndrome] setting, but still not STEMI [ST segment elevation myocardial infarction], and still predominately in larger males" because they have larger radial arteries. In the transition from transfemoral to transradial PCI, don’t hesitate to "switch to femoral [access] for unusual anatomy, technical difficulties," or other problems, Dr. Cheema said at the18th World Congress on Heart Disease.

At first, it’s best to avoid smaller and older patients. Transradial failure rates are greatest for those over age 75 years, in part because of subclavian tortuosity. Also, "if you are dealing with a small woman, she might have very small radial arteries that increase the chances of failure." Prior bypass grafting is a red flag for newer operators, too; among other problems, the grafts may be occluded. "Young patients and big patients and elective cases are where you want to start," he said.

Primary and complex PCI involving saphenous vein grafts or left main disease should not be attempted before doing more than 150 transradial procedures," recommended Dr. Cheema, who is a transradial PCI practitioner and researcher.

Familiarity with the technology is another important consideration, he said.

Hydrophilic sheaths, tapered and with a slippery coating, are important "because the radial artery is a small caliber vessel, [so] it’s more prone to spasm than the femoral artery. If you use a regular sheath, it causes spasm and you cannot maintain access," Dr. Cheema said.

"You want to use a 260-cm" exchange-length guide wire, as well, instead of the 180-cm wires used in femoral cases. "When you are doing radial [PCI], you have to be very careful about maintaining the wire position. You need a longer wire so it stays in place and your catheter can be exchanged," he said.

Dr. Cheema said he has no disclosures.

aotto@frontlinemedcom.com

VANCOUVER, B.C. – Ready to get started doing transradial percutaneous interventions? Begin under the guidance of an experienced practitioner, perform simple cases in lower-risk patients, and progress to more difficult cases as expertise builds, advised Dr. Asim Cheema, an interventional cardiologist at St. Michael’s Hospital in Toronto.

It’s best to start with a solid foundation in transfemoral PCI, and begin using the radial approach in stable patients who have single vessel disease and are presenting for angiography or some other elective procedure, he said.

"After about 40 patients, you can gradually start to become more comfortable doing multivessel PCI. Then, you can move on to an [acute coronary syndrome] setting, but still not STEMI [ST segment elevation myocardial infarction], and still predominately in larger males" because they have larger radial arteries. In the transition from transfemoral to transradial PCI, don’t hesitate to "switch to femoral [access] for unusual anatomy, technical difficulties," or other problems, Dr. Cheema said at the18th World Congress on Heart Disease.

At first, it’s best to avoid smaller and older patients. Transradial failure rates are greatest for those over age 75 years, in part because of subclavian tortuosity. Also, "if you are dealing with a small woman, she might have very small radial arteries that increase the chances of failure." Prior bypass grafting is a red flag for newer operators, too; among other problems, the grafts may be occluded. "Young patients and big patients and elective cases are where you want to start," he said.

Primary and complex PCI involving saphenous vein grafts or left main disease should not be attempted before doing more than 150 transradial procedures," recommended Dr. Cheema, who is a transradial PCI practitioner and researcher.

Familiarity with the technology is another important consideration, he said.

Hydrophilic sheaths, tapered and with a slippery coating, are important "because the radial artery is a small caliber vessel, [so] it’s more prone to spasm than the femoral artery. If you use a regular sheath, it causes spasm and you cannot maintain access," Dr. Cheema said.

"You want to use a 260-cm" exchange-length guide wire, as well, instead of the 180-cm wires used in femoral cases. "When you are doing radial [PCI], you have to be very careful about maintaining the wire position. You need a longer wire so it stays in place and your catheter can be exchanged," he said.

Dr. Cheema said he has no disclosures.

aotto@frontlinemedcom.com

VANCOUVER, B.C. – Ready to get started doing transradial percutaneous interventions? Begin under the guidance of an experienced practitioner, perform simple cases in lower-risk patients, and progress to more difficult cases as expertise builds, advised Dr. Asim Cheema, an interventional cardiologist at St. Michael’s Hospital in Toronto.

It’s best to start with a solid foundation in transfemoral PCI, and begin using the radial approach in stable patients who have single vessel disease and are presenting for angiography or some other elective procedure, he said.

"After about 40 patients, you can gradually start to become more comfortable doing multivessel PCI. Then, you can move on to an [acute coronary syndrome] setting, but still not STEMI [ST segment elevation myocardial infarction], and still predominately in larger males" because they have larger radial arteries. In the transition from transfemoral to transradial PCI, don’t hesitate to "switch to femoral [access] for unusual anatomy, technical difficulties," or other problems, Dr. Cheema said at the18th World Congress on Heart Disease.

At first, it’s best to avoid smaller and older patients. Transradial failure rates are greatest for those over age 75 years, in part because of subclavian tortuosity. Also, "if you are dealing with a small woman, she might have very small radial arteries that increase the chances of failure." Prior bypass grafting is a red flag for newer operators, too; among other problems, the grafts may be occluded. "Young patients and big patients and elective cases are where you want to start," he said.

Primary and complex PCI involving saphenous vein grafts or left main disease should not be attempted before doing more than 150 transradial procedures," recommended Dr. Cheema, who is a transradial PCI practitioner and researcher.

Familiarity with the technology is another important consideration, he said.

Hydrophilic sheaths, tapered and with a slippery coating, are important "because the radial artery is a small caliber vessel, [so] it’s more prone to spasm than the femoral artery. If you use a regular sheath, it causes spasm and you cannot maintain access," Dr. Cheema said.

"You want to use a 260-cm" exchange-length guide wire, as well, instead of the 180-cm wires used in femoral cases. "When you are doing radial [PCI], you have to be very careful about maintaining the wire position. You need a longer wire so it stays in place and your catheter can be exchanged," he said.

Dr. Cheema said he has no disclosures.

aotto@frontlinemedcom.com

Prolonged-exposure therapy – a standard treatment for posttraumatic stress disorder in adults – worked better than supportive counseling did to help adolescent girls to recover from sexual abuse, based on the results of a randomized trial comparing 3 months of weekly exposure therapy in 31 girls to supportive counseling in 30 others.

Further, the technique succeeded with master’s level mental health counselors who provided the exposure therapy after a 4-day training session, plus two follow-up sessions.

Those in the prolonged-exposure group improved from a baseline mean of 27.3 points to 6.7 points, an overall shift from moderately severe to below-threshold PTSD, on the clinician-assessed 51-point Child PTSD Symptom Scale–Interview. The supportive counseling group improved from a mean of 29.4 points to 16.1 points, going from an overall score of moderately severe to mild PTSD. The difference in outcomes was significant.

Prolonged-exposure therapy is rarely provided to adolescents because of concern that it may exacerbate PTSD symptoms or because of the belief that patients must master coping skills before exposure can safely be provided, noted study researcher Edna Foa, Ph.D., of the department of psychiatry at the University of Pennsylvania, Philadelphia, and her colleagues.

The findings imply that prolonged exposure therapy can be successfully administered by newly trained counselors at community mental health and rape crisis clinics. "This is important because the need for evidence-based treatment of PTSD far exceeds the availability of these services," the researchers wrote in a study published online Dec. 24 in JAMA.

The study subjects were recruited from Women Organized Against Rape, a rape crisis center in Philadelphia. They were 13-18 years old, with a mean age of about 15 years. More than half had at least one comorbid psychiatric diagnosis. Actively suicidal girls and those with uncontrolled bipolar disorder, schizophrenia, conduct disorder, or pervasive developmental disorder were excluded from the study, along with those who had started psychiatric drugs within 3 months.

Treatment included discussing the rationale for exposure, recounting the event, breathing exercises, and homework, plus a final project, such as making a booklet about the trauma and gains made in treatment. Counselors listened actively and with empathy during sessions, encouraged the girls to talk about their feelings, and told them they believed in their ability to cope. Not one of the girls in supportive counseling described their trauma during the sessions.

The exposure group completed a mean of 12 sessions; the supportive group, 11 sessions. Up to 14 sessions were available for both groups. More than 90% (28) of exposure subjects completed their sessions; 83.3% (25) of supportive counseling patients completed theirs.

Participants who received prolonged-exposure therapy had greater improvement in PTSD symptoms and were more likely to lose their PTSD diagnosis than were those who received supportive counseling. By the end of their sessions, about three-quarters (24) of the prolonged-exposure girls – but less than half (13) of the supportive counseling subjects – no longer met DSM-IV criteria for PTSD, also a significant difference.

The results of prolonged exposure also were superior to those of supportive counseling at 12-month follow-up, said Dr. Foa (JAMA 2013;310:2650-57 [doi:10.1001/jama.2013.282829]).

Those given exposure therapy also did significantly better on clinician- or subject-assessed measures of symptoms, depression, and function; the differences persisted through 12-months of follow-up.

The National Institutes of Health funded the work. The authors said they had no relevant commercial disclosures.

aotto@frontlinemedcom.com

Prolonged-exposure therapy – a standard treatment for posttraumatic stress disorder in adults – worked better than supportive counseling did to help adolescent girls to recover from sexual abuse, based on the results of a randomized trial comparing 3 months of weekly exposure therapy in 31 girls to supportive counseling in 30 others.

Further, the technique succeeded with master’s level mental health counselors who provided the exposure therapy after a 4-day training session, plus two follow-up sessions.

Those in the prolonged-exposure group improved from a baseline mean of 27.3 points to 6.7 points, an overall shift from moderately severe to below-threshold PTSD, on the clinician-assessed 51-point Child PTSD Symptom Scale–Interview. The supportive counseling group improved from a mean of 29.4 points to 16.1 points, going from an overall score of moderately severe to mild PTSD. The difference in outcomes was significant.

Prolonged-exposure therapy is rarely provided to adolescents because of concern that it may exacerbate PTSD symptoms or because of the belief that patients must master coping skills before exposure can safely be provided, noted study researcher Edna Foa, Ph.D., of the department of psychiatry at the University of Pennsylvania, Philadelphia, and her colleagues.

The findings imply that prolonged exposure therapy can be successfully administered by newly trained counselors at community mental health and rape crisis clinics. "This is important because the need for evidence-based treatment of PTSD far exceeds the availability of these services," the researchers wrote in a study published online Dec. 24 in JAMA.

The study subjects were recruited from Women Organized Against Rape, a rape crisis center in Philadelphia. They were 13-18 years old, with a mean age of about 15 years. More than half had at least one comorbid psychiatric diagnosis. Actively suicidal girls and those with uncontrolled bipolar disorder, schizophrenia, conduct disorder, or pervasive developmental disorder were excluded from the study, along with those who had started psychiatric drugs within 3 months.

Treatment included discussing the rationale for exposure, recounting the event, breathing exercises, and homework, plus a final project, such as making a booklet about the trauma and gains made in treatment. Counselors listened actively and with empathy during sessions, encouraged the girls to talk about their feelings, and told them they believed in their ability to cope. Not one of the girls in supportive counseling described their trauma during the sessions.

The exposure group completed a mean of 12 sessions; the supportive group, 11 sessions. Up to 14 sessions were available for both groups. More than 90% (28) of exposure subjects completed their sessions; 83.3% (25) of supportive counseling patients completed theirs.

Participants who received prolonged-exposure therapy had greater improvement in PTSD symptoms and were more likely to lose their PTSD diagnosis than were those who received supportive counseling. By the end of their sessions, about three-quarters (24) of the prolonged-exposure girls – but less than half (13) of the supportive counseling subjects – no longer met DSM-IV criteria for PTSD, also a significant difference.

The results of prolonged exposure also were superior to those of supportive counseling at 12-month follow-up, said Dr. Foa (JAMA 2013;310:2650-57 [doi:10.1001/jama.2013.282829]).

Those given exposure therapy also did significantly better on clinician- or subject-assessed measures of symptoms, depression, and function; the differences persisted through 12-months of follow-up.

The National Institutes of Health funded the work. The authors said they had no relevant commercial disclosures.

aotto@frontlinemedcom.com

Prolonged-exposure therapy – a standard treatment for posttraumatic stress disorder in adults – worked better than supportive counseling did to help adolescent girls to recover from sexual abuse, based on the results of a randomized trial comparing 3 months of weekly exposure therapy in 31 girls to supportive counseling in 30 others.

Further, the technique succeeded with master’s level mental health counselors who provided the exposure therapy after a 4-day training session, plus two follow-up sessions.

Those in the prolonged-exposure group improved from a baseline mean of 27.3 points to 6.7 points, an overall shift from moderately severe to below-threshold PTSD, on the clinician-assessed 51-point Child PTSD Symptom Scale–Interview. The supportive counseling group improved from a mean of 29.4 points to 16.1 points, going from an overall score of moderately severe to mild PTSD. The difference in outcomes was significant.

Prolonged-exposure therapy is rarely provided to adolescents because of concern that it may exacerbate PTSD symptoms or because of the belief that patients must master coping skills before exposure can safely be provided, noted study researcher Edna Foa, Ph.D., of the department of psychiatry at the University of Pennsylvania, Philadelphia, and her colleagues.

The findings imply that prolonged exposure therapy can be successfully administered by newly trained counselors at community mental health and rape crisis clinics. "This is important because the need for evidence-based treatment of PTSD far exceeds the availability of these services," the researchers wrote in a study published online Dec. 24 in JAMA.

The study subjects were recruited from Women Organized Against Rape, a rape crisis center in Philadelphia. They were 13-18 years old, with a mean age of about 15 years. More than half had at least one comorbid psychiatric diagnosis. Actively suicidal girls and those with uncontrolled bipolar disorder, schizophrenia, conduct disorder, or pervasive developmental disorder were excluded from the study, along with those who had started psychiatric drugs within 3 months.

Treatment included discussing the rationale for exposure, recounting the event, breathing exercises, and homework, plus a final project, such as making a booklet about the trauma and gains made in treatment. Counselors listened actively and with empathy during sessions, encouraged the girls to talk about their feelings, and told them they believed in their ability to cope. Not one of the girls in supportive counseling described their trauma during the sessions.

The exposure group completed a mean of 12 sessions; the supportive group, 11 sessions. Up to 14 sessions were available for both groups. More than 90% (28) of exposure subjects completed their sessions; 83.3% (25) of supportive counseling patients completed theirs.

Participants who received prolonged-exposure therapy had greater improvement in PTSD symptoms and were more likely to lose their PTSD diagnosis than were those who received supportive counseling. By the end of their sessions, about three-quarters (24) of the prolonged-exposure girls – but less than half (13) of the supportive counseling subjects – no longer met DSM-IV criteria for PTSD, also a significant difference.

The results of prolonged exposure also were superior to those of supportive counseling at 12-month follow-up, said Dr. Foa (JAMA 2013;310:2650-57 [doi:10.1001/jama.2013.282829]).

Those given exposure therapy also did significantly better on clinician- or subject-assessed measures of symptoms, depression, and function; the differences persisted through 12-months of follow-up.

The National Institutes of Health funded the work. The authors said they had no relevant commercial disclosures.

aotto@frontlinemedcom.com

Anti-carbamylated protein antibodies, a recently identified autoantibody system against carbamylated proteins, can be detected years before symptoms develop in rheumatoid arthritis, according to a retrospective study.

The finding suggests "another source of antibodies which can potentially contribute to RA pathogenesis. ... The moment of first appearance of anti-CarP [anti-carbamylated protein] antibodies is comparable with ACPA [anti-citrullinated protein antibodies] and earlier than IgM-RF [IgM-rheumatoid factor]," both now included in American College of Rheumatology/European League Against Rheumatism RA criteria, said senior author Dr. Leendert A. Trouw and lead author Jing Shi, Ph.D., of the department of rheumatology at Leiden (the Netherlands) University Medical Center and their colleagues.

Identifying people who could benefit most from early RA intervention "is a challenge, but the presence of autoantibodies could be a useful marker," the investigators said (Ann. Rheum. Dis. 2013 Dec. 13 [doi:10.1136/annrheumdis-2013-204154]).

Anti-CarP antibodies presented in both ACPA-positive and ACPA-negative patients; they "appear by and large [to be] two different autoantibody systems," the investigators said.

The authors tested years of blood samples from 79 donors in the Sanquin Blood Bank – the Dutch national blood bank – who were eventually diagnosed with RA, for the presence of anti-carbamylated-fetal calf serum (anti-Ca-FCS), anti-carbamylated-fibrinogen (anti-Ca-Fib), anticyclic citrullinated-peptide 2 (anti-CCP2) antibodies, and IgM-RF, all by enzyme-linked immunosorbent assay. Levels were considered elevated if they were two standard deviations above the mean of 141 age and sex-matched controls who did not develop RA. The subjects were white, with a median of five sequential sera obtained from blood samples 1-6 years apart. The future-RA group included 48 women; the mean age at diagnosis was 51 years.

Six years before diagnosis, more than half of the future-RA patients harbored one autoantibody, and at least 30% had all three autoantibody families within 4 years of diagnosis. Median levels of autoantibodies started to increase around 5-7 years before the diagnosis.

"IgM-RF, anti-Ca-FCS, anti-Ca-Fib and anti-CCP2 antibodies were [first] detectable [at] 10, 14, 14, and 14 years before diagnosis, respectively. These are the time points when the first samples of these donors were collected. The median of time points when anti-CCP2, anti-Ca-FCS, anti-Ca-Fib antibodies and IgM-RF were detectable were 6, 5, 7, and 2 years before the diagnosis," the investigators found.

Anti-Ca-FCS antibodies were present in 27% and anti-Ca-Fib antibodies in 38% of patients at their last blood draw, which came at a mean of 1.4 years before diagnosis.

Although "anti-CCP antibodies or IgM-RF can be found in both patients and their healthy first-degree relatives, the combination of both anti-CCP and RF is predominantly found in the RA patients. This supports the notion that ACPA and anti-CarP antibodies may initiate the primary target recognition but that amplification of IgM-RF is important for progression towards clinical RA, for example, by enhancing complement activation," they wrote.

The study was funded by the Dutch Arthritis Foundation, the Netherlands Organisation for Scientific Research, Masterswitch project FP7, the Innovative Medicines Initiative Joint Undertaking funded project BeTheCure (through a Pfizer contract), and the Netherlands Proteomics Center and the Center for Medical Systems Biology (as part of the Netherlands Genomics Initiative). Dr. Trouw is supported by a Janssen Biologics fellowship.

aotto@frontlinemedcom.com

Anti-carbamylated protein antibodies, a recently identified autoantibody system against carbamylated proteins, can be detected years before symptoms develop in rheumatoid arthritis, according to a retrospective study.

The finding suggests "another source of antibodies which can potentially contribute to RA pathogenesis. ... The moment of first appearance of anti-CarP [anti-carbamylated protein] antibodies is comparable with ACPA [anti-citrullinated protein antibodies] and earlier than IgM-RF [IgM-rheumatoid factor]," both now included in American College of Rheumatology/European League Against Rheumatism RA criteria, said senior author Dr. Leendert A. Trouw and lead author Jing Shi, Ph.D., of the department of rheumatology at Leiden (the Netherlands) University Medical Center and their colleagues.

Identifying people who could benefit most from early RA intervention "is a challenge, but the presence of autoantibodies could be a useful marker," the investigators said (Ann. Rheum. Dis. 2013 Dec. 13 [doi:10.1136/annrheumdis-2013-204154]).

Anti-CarP antibodies presented in both ACPA-positive and ACPA-negative patients; they "appear by and large [to be] two different autoantibody systems," the investigators said.

The authors tested years of blood samples from 79 donors in the Sanquin Blood Bank – the Dutch national blood bank – who were eventually diagnosed with RA, for the presence of anti-carbamylated-fetal calf serum (anti-Ca-FCS), anti-carbamylated-fibrinogen (anti-Ca-Fib), anticyclic citrullinated-peptide 2 (anti-CCP2) antibodies, and IgM-RF, all by enzyme-linked immunosorbent assay. Levels were considered elevated if they were two standard deviations above the mean of 141 age and sex-matched controls who did not develop RA. The subjects were white, with a median of five sequential sera obtained from blood samples 1-6 years apart. The future-RA group included 48 women; the mean age at diagnosis was 51 years.

Six years before diagnosis, more than half of the future-RA patients harbored one autoantibody, and at least 30% had all three autoantibody families within 4 years of diagnosis. Median levels of autoantibodies started to increase around 5-7 years before the diagnosis.

"IgM-RF, anti-Ca-FCS, anti-Ca-Fib and anti-CCP2 antibodies were [first] detectable [at] 10, 14, 14, and 14 years before diagnosis, respectively. These are the time points when the first samples of these donors were collected. The median of time points when anti-CCP2, anti-Ca-FCS, anti-Ca-Fib antibodies and IgM-RF were detectable were 6, 5, 7, and 2 years before the diagnosis," the investigators found.

Anti-Ca-FCS antibodies were present in 27% and anti-Ca-Fib antibodies in 38% of patients at their last blood draw, which came at a mean of 1.4 years before diagnosis.

Although "anti-CCP antibodies or IgM-RF can be found in both patients and their healthy first-degree relatives, the combination of both anti-CCP and RF is predominantly found in the RA patients. This supports the notion that ACPA and anti-CarP antibodies may initiate the primary target recognition but that amplification of IgM-RF is important for progression towards clinical RA, for example, by enhancing complement activation," they wrote.

The study was funded by the Dutch Arthritis Foundation, the Netherlands Organisation for Scientific Research, Masterswitch project FP7, the Innovative Medicines Initiative Joint Undertaking funded project BeTheCure (through a Pfizer contract), and the Netherlands Proteomics Center and the Center for Medical Systems Biology (as part of the Netherlands Genomics Initiative). Dr. Trouw is supported by a Janssen Biologics fellowship.

aotto@frontlinemedcom.com

Anti-carbamylated protein antibodies, a recently identified autoantibody system against carbamylated proteins, can be detected years before symptoms develop in rheumatoid arthritis, according to a retrospective study.

The finding suggests "another source of antibodies which can potentially contribute to RA pathogenesis. ... The moment of first appearance of anti-CarP [anti-carbamylated protein] antibodies is comparable with ACPA [anti-citrullinated protein antibodies] and earlier than IgM-RF [IgM-rheumatoid factor]," both now included in American College of Rheumatology/European League Against Rheumatism RA criteria, said senior author Dr. Leendert A. Trouw and lead author Jing Shi, Ph.D., of the department of rheumatology at Leiden (the Netherlands) University Medical Center and their colleagues.

Identifying people who could benefit most from early RA intervention "is a challenge, but the presence of autoantibodies could be a useful marker," the investigators said (Ann. Rheum. Dis. 2013 Dec. 13 [doi:10.1136/annrheumdis-2013-204154]).

Anti-CarP antibodies presented in both ACPA-positive and ACPA-negative patients; they "appear by and large [to be] two different autoantibody systems," the investigators said.

The authors tested years of blood samples from 79 donors in the Sanquin Blood Bank – the Dutch national blood bank – who were eventually diagnosed with RA, for the presence of anti-carbamylated-fetal calf serum (anti-Ca-FCS), anti-carbamylated-fibrinogen (anti-Ca-Fib), anticyclic citrullinated-peptide 2 (anti-CCP2) antibodies, and IgM-RF, all by enzyme-linked immunosorbent assay. Levels were considered elevated if they were two standard deviations above the mean of 141 age and sex-matched controls who did not develop RA. The subjects were white, with a median of five sequential sera obtained from blood samples 1-6 years apart. The future-RA group included 48 women; the mean age at diagnosis was 51 years.

Six years before diagnosis, more than half of the future-RA patients harbored one autoantibody, and at least 30% had all three autoantibody families within 4 years of diagnosis. Median levels of autoantibodies started to increase around 5-7 years before the diagnosis.

"IgM-RF, anti-Ca-FCS, anti-Ca-Fib and anti-CCP2 antibodies were [first] detectable [at] 10, 14, 14, and 14 years before diagnosis, respectively. These are the time points when the first samples of these donors were collected. The median of time points when anti-CCP2, anti-Ca-FCS, anti-Ca-Fib antibodies and IgM-RF were detectable were 6, 5, 7, and 2 years before the diagnosis," the investigators found.

Anti-Ca-FCS antibodies were present in 27% and anti-Ca-Fib antibodies in 38% of patients at their last blood draw, which came at a mean of 1.4 years before diagnosis.

Although "anti-CCP antibodies or IgM-RF can be found in both patients and their healthy first-degree relatives, the combination of both anti-CCP and RF is predominantly found in the RA patients. This supports the notion that ACPA and anti-CarP antibodies may initiate the primary target recognition but that amplification of IgM-RF is important for progression towards clinical RA, for example, by enhancing complement activation," they wrote.

The study was funded by the Dutch Arthritis Foundation, the Netherlands Organisation for Scientific Research, Masterswitch project FP7, the Innovative Medicines Initiative Joint Undertaking funded project BeTheCure (through a Pfizer contract), and the Netherlands Proteomics Center and the Center for Medical Systems Biology (as part of the Netherlands Genomics Initiative). Dr. Trouw is supported by a Janssen Biologics fellowship.

aotto@frontlinemedcom.com

The Food and Drug Administration on Dec. 18 approved Anoro Ellipta (umeclidinium 62.5 mcg/vilanterol 25 mcg), an anticholinergic/beta2-agonist, once-daily combination inhaler for long-term maintenance treatment of airflow obstruction in chronic obstructive pulmonary disease.

Manufacturer GlaxoSmithKline plans to launch the product during the first quarter of 2014, the company said in a statement.

FDA’s review panel unanimously agreed that the inhaler provided clinically meaningful benefits, based on Glaxo’s clinical trials, but panelists were concerned about its safety in patients with severe heart disease. There were numerical imbalances in ischemia-related events in primary efficacy trials that were not seen in a long-term safety study. Generalizability of the cardiac safety data was also a concern because trial exclusion criteria may have eliminated patients with more severe heart disease.

Glaxo noted in its statement that the drug "should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. ... Beta2-agonists, such as vilanterol, should be administered with extreme caution to patients being treated with drugs known to prolong the QTc interval or within 2 weeks of discontinuation of such agents."

Caution also was advised when Anoro Ellipta is considered for coadministration "with long-term ketoconazole and other known strong cytochrome P450 3A4 inhibitors because increased cardiovascular adverse effects may occur," the company said.

The FDA also noted cardiovascular effects among "serious side effects," as well as paradoxical bronchospasm, narrow-angle glaucoma, and worsening of urinary retention.

More common side effects include pharyngitis, sinusitis, lower respiratory tract infection, constipation, diarrhea, extremity pain, muscle spasms, neck pain, and chest pain.

The product will come with a patient medication guide and carry a boxed warning that long-acting beta2-adrenergic agonists like vilanterol increase the risk of asthma-related death. Umeclidinium, the other drug in the combination inhaler, is an anticholinergic.

"Anoro Ellipta should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of COPD, or as rescue therapy for the treatment of acute episodes of bronchospasm, which should be treated with an inhaled, short-acting beta2-agonist," Glaxo noted.

Frontline Medical News reporter Elizabeth Mechcatie contributed to this report.

aotto@frontlinemedcom.com

The Food and Drug Administration on Dec. 18 approved Anoro Ellipta (umeclidinium 62.5 mcg/vilanterol 25 mcg), an anticholinergic/beta2-agonist, once-daily combination inhaler for long-term maintenance treatment of airflow obstruction in chronic obstructive pulmonary disease.

Manufacturer GlaxoSmithKline plans to launch the product during the first quarter of 2014, the company said in a statement.

FDA’s review panel unanimously agreed that the inhaler provided clinically meaningful benefits, based on Glaxo’s clinical trials, but panelists were concerned about its safety in patients with severe heart disease. There were numerical imbalances in ischemia-related events in primary efficacy trials that were not seen in a long-term safety study. Generalizability of the cardiac safety data was also a concern because trial exclusion criteria may have eliminated patients with more severe heart disease.

Glaxo noted in its statement that the drug "should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. ... Beta2-agonists, such as vilanterol, should be administered with extreme caution to patients being treated with drugs known to prolong the QTc interval or within 2 weeks of discontinuation of such agents."

Caution also was advised when Anoro Ellipta is considered for coadministration "with long-term ketoconazole and other known strong cytochrome P450 3A4 inhibitors because increased cardiovascular adverse effects may occur," the company said.

The FDA also noted cardiovascular effects among "serious side effects," as well as paradoxical bronchospasm, narrow-angle glaucoma, and worsening of urinary retention.

More common side effects include pharyngitis, sinusitis, lower respiratory tract infection, constipation, diarrhea, extremity pain, muscle spasms, neck pain, and chest pain.

The product will come with a patient medication guide and carry a boxed warning that long-acting beta2-adrenergic agonists like vilanterol increase the risk of asthma-related death. Umeclidinium, the other drug in the combination inhaler, is an anticholinergic.

"Anoro Ellipta should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of COPD, or as rescue therapy for the treatment of acute episodes of bronchospasm, which should be treated with an inhaled, short-acting beta2-agonist," Glaxo noted.

Frontline Medical News reporter Elizabeth Mechcatie contributed to this report.

aotto@frontlinemedcom.com

The Food and Drug Administration on Dec. 18 approved Anoro Ellipta (umeclidinium 62.5 mcg/vilanterol 25 mcg), an anticholinergic/beta2-agonist, once-daily combination inhaler for long-term maintenance treatment of airflow obstruction in chronic obstructive pulmonary disease.

Manufacturer GlaxoSmithKline plans to launch the product during the first quarter of 2014, the company said in a statement.

FDA’s review panel unanimously agreed that the inhaler provided clinically meaningful benefits, based on Glaxo’s clinical trials, but panelists were concerned about its safety in patients with severe heart disease. There were numerical imbalances in ischemia-related events in primary efficacy trials that were not seen in a long-term safety study. Generalizability of the cardiac safety data was also a concern because trial exclusion criteria may have eliminated patients with more severe heart disease.

Glaxo noted in its statement that the drug "should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. ... Beta2-agonists, such as vilanterol, should be administered with extreme caution to patients being treated with drugs known to prolong the QTc interval or within 2 weeks of discontinuation of such agents."

Caution also was advised when Anoro Ellipta is considered for coadministration "with long-term ketoconazole and other known strong cytochrome P450 3A4 inhibitors because increased cardiovascular adverse effects may occur," the company said.

The FDA also noted cardiovascular effects among "serious side effects," as well as paradoxical bronchospasm, narrow-angle glaucoma, and worsening of urinary retention.

More common side effects include pharyngitis, sinusitis, lower respiratory tract infection, constipation, diarrhea, extremity pain, muscle spasms, neck pain, and chest pain.

The product will come with a patient medication guide and carry a boxed warning that long-acting beta2-adrenergic agonists like vilanterol increase the risk of asthma-related death. Umeclidinium, the other drug in the combination inhaler, is an anticholinergic.

"Anoro Ellipta should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of COPD, or as rescue therapy for the treatment of acute episodes of bronchospasm, which should be treated with an inhaled, short-acting beta2-agonist," Glaxo noted.

Frontline Medical News reporter Elizabeth Mechcatie contributed to this report.

aotto@frontlinemedcom.com

SEATTLE – In almost all cases, it’s best to stay on the scene to work a cardiac arrest resuscitation until the return of spontaneous circulation or efforts are stopped because of futility, according to Dr. Brent Myers, director of emergency medical services in Raleigh/Wake County, N.C.

The probability of neurologically intact survival is at least 10-fold higher, and by some estimates up to 35-fold higher, when resuscitation is achieved in the field, instead of en route to the emergency department, Dr. Myers said at the annual meeting of the American College of Emergency Physicians. Neurologically intact survival quadrupled to 11.5% for patients in ventricular fibrillation and to 40.8% for those with ventricular tachycardia after the approach was adopted in Wake County, he reported. (Ann. Emerg. Med. 2010;56:348-57).

"Load-and-go is not the appropriate approach; resuscitation is a prehospital exercise," Dr. Myers said. "In the vast majority of cases, if we interrupt compressions to move patients" – which is unavoidable with even the most careful transport – "we have sealed their fate."

An ever-increasing number of emergency medicine experts agree, but some EMS systems still have forced moves at, for example, 20 minutes. That standard probably accounts for much of the considerable regional variations in survival of cardiac arrest patients. "The variability, in large portion, can be explained simply by who’s on the chest and who’s not. As you stay on the chest above 80% of the time, your odds of survival triple," he said (for example, Circulation 2010;122:S685-705; JAMA 2008;300:1423-31).

"How long we should stay on the scene still needs further research, [but] the old rule that says you shouldn’t go beyond 30 minutes is clearly not true. We just don’t know what the new time is; it’s somewhere north of 30 minutes," he said.

In general, Wake County crews keep at resuscitation until asystole or disorganized pulseless electrical activity (PEA). "We don’t ever terminate [a patient with ventricular fibrillation] or good-looking PEA, which has resulted in prolonged resuscitation times" of sometimes 50 minutes or more. "They are very unlikely to survive after 40 minutes; but if they do, they are just as likely to be neurologically intact. We are not creating persistently vegetative states," Dr. Myers said.

In-home termination – which happens in almost half of Wake County cases – goes hand in hand with the approach. "The systems with the highest resuscitation rates also have the highest field termination rates. I don’t think that’s an accident; it’s a marker that [they] are focusing resuscitations on the scene," he said.

"You have to have the capacity to terminate, [and] be ready to [help] families" with grief. "Every published paper indicates that family members want to be present for the resuscitation." Among the most important things for them are knowing their loved one is not in pain and being able to touch the body; the cleanliness of the body is also important (Ann. Emerg. Med. 2002;40:521-3).

There may be a small number of patients who benefit from intra-arrest transport, but "we do not have sufficient data" to identify them. One group might be young, otherwise-healthy people in VF who can be whisked straight into a cath lab. "It sounds good, but we haven’t proven it yet," Dr. Myers said.

Rearrest is most likely within 10 minutes of a successful resuscitation, so, just in case, Dr. Myers’ crews stay put with patients for 10 minutes after they come around, before transport. If they re-arrest en route to the ED, in most cases crews "pull over and work the arrest right there in the ambulance," he said.

Dr. Myers reported having no disclosures.

aotto@frontlinemedcom.com

SEATTLE – In almost all cases, it’s best to stay on the scene to work a cardiac arrest resuscitation until the return of spontaneous circulation or efforts are stopped because of futility, according to Dr. Brent Myers, director of emergency medical services in Raleigh/Wake County, N.C.

The probability of neurologically intact survival is at least 10-fold higher, and by some estimates up to 35-fold higher, when resuscitation is achieved in the field, instead of en route to the emergency department, Dr. Myers said at the annual meeting of the American College of Emergency Physicians. Neurologically intact survival quadrupled to 11.5% for patients in ventricular fibrillation and to 40.8% for those with ventricular tachycardia after the approach was adopted in Wake County, he reported. (Ann. Emerg. Med. 2010;56:348-57).

"Load-and-go is not the appropriate approach; resuscitation is a prehospital exercise," Dr. Myers said. "In the vast majority of cases, if we interrupt compressions to move patients" – which is unavoidable with even the most careful transport – "we have sealed their fate."

An ever-increasing number of emergency medicine experts agree, but some EMS systems still have forced moves at, for example, 20 minutes. That standard probably accounts for much of the considerable regional variations in survival of cardiac arrest patients. "The variability, in large portion, can be explained simply by who’s on the chest and who’s not. As you stay on the chest above 80% of the time, your odds of survival triple," he said (for example, Circulation 2010;122:S685-705; JAMA 2008;300:1423-31).

"How long we should stay on the scene still needs further research, [but] the old rule that says you shouldn’t go beyond 30 minutes is clearly not true. We just don’t know what the new time is; it’s somewhere north of 30 minutes," he said.

In general, Wake County crews keep at resuscitation until asystole or disorganized pulseless electrical activity (PEA). "We don’t ever terminate [a patient with ventricular fibrillation] or good-looking PEA, which has resulted in prolonged resuscitation times" of sometimes 50 minutes or more. "They are very unlikely to survive after 40 minutes; but if they do, they are just as likely to be neurologically intact. We are not creating persistently vegetative states," Dr. Myers said.

In-home termination – which happens in almost half of Wake County cases – goes hand in hand with the approach. "The systems with the highest resuscitation rates also have the highest field termination rates. I don’t think that’s an accident; it’s a marker that [they] are focusing resuscitations on the scene," he said.

"You have to have the capacity to terminate, [and] be ready to [help] families" with grief. "Every published paper indicates that family members want to be present for the resuscitation." Among the most important things for them are knowing their loved one is not in pain and being able to touch the body; the cleanliness of the body is also important (Ann. Emerg. Med. 2002;40:521-3).

There may be a small number of patients who benefit from intra-arrest transport, but "we do not have sufficient data" to identify them. One group might be young, otherwise-healthy people in VF who can be whisked straight into a cath lab. "It sounds good, but we haven’t proven it yet," Dr. Myers said.

Rearrest is most likely within 10 minutes of a successful resuscitation, so, just in case, Dr. Myers’ crews stay put with patients for 10 minutes after they come around, before transport. If they re-arrest en route to the ED, in most cases crews "pull over and work the arrest right there in the ambulance," he said.

Dr. Myers reported having no disclosures.

aotto@frontlinemedcom.com

SEATTLE – In almost all cases, it’s best to stay on the scene to work a cardiac arrest resuscitation until the return of spontaneous circulation or efforts are stopped because of futility, according to Dr. Brent Myers, director of emergency medical services in Raleigh/Wake County, N.C.

The probability of neurologically intact survival is at least 10-fold higher, and by some estimates up to 35-fold higher, when resuscitation is achieved in the field, instead of en route to the emergency department, Dr. Myers said at the annual meeting of the American College of Emergency Physicians. Neurologically intact survival quadrupled to 11.5% for patients in ventricular fibrillation and to 40.8% for those with ventricular tachycardia after the approach was adopted in Wake County, he reported. (Ann. Emerg. Med. 2010;56:348-57).

"Load-and-go is not the appropriate approach; resuscitation is a prehospital exercise," Dr. Myers said. "In the vast majority of cases, if we interrupt compressions to move patients" – which is unavoidable with even the most careful transport – "we have sealed their fate."

An ever-increasing number of emergency medicine experts agree, but some EMS systems still have forced moves at, for example, 20 minutes. That standard probably accounts for much of the considerable regional variations in survival of cardiac arrest patients. "The variability, in large portion, can be explained simply by who’s on the chest and who’s not. As you stay on the chest above 80% of the time, your odds of survival triple," he said (for example, Circulation 2010;122:S685-705; JAMA 2008;300:1423-31).

"How long we should stay on the scene still needs further research, [but] the old rule that says you shouldn’t go beyond 30 minutes is clearly not true. We just don’t know what the new time is; it’s somewhere north of 30 minutes," he said.

In general, Wake County crews keep at resuscitation until asystole or disorganized pulseless electrical activity (PEA). "We don’t ever terminate [a patient with ventricular fibrillation] or good-looking PEA, which has resulted in prolonged resuscitation times" of sometimes 50 minutes or more. "They are very unlikely to survive after 40 minutes; but if they do, they are just as likely to be neurologically intact. We are not creating persistently vegetative states," Dr. Myers said.

In-home termination – which happens in almost half of Wake County cases – goes hand in hand with the approach. "The systems with the highest resuscitation rates also have the highest field termination rates. I don’t think that’s an accident; it’s a marker that [they] are focusing resuscitations on the scene," he said.

"You have to have the capacity to terminate, [and] be ready to [help] families" with grief. "Every published paper indicates that family members want to be present for the resuscitation." Among the most important things for them are knowing their loved one is not in pain and being able to touch the body; the cleanliness of the body is also important (Ann. Emerg. Med. 2002;40:521-3).

There may be a small number of patients who benefit from intra-arrest transport, but "we do not have sufficient data" to identify them. One group might be young, otherwise-healthy people in VF who can be whisked straight into a cath lab. "It sounds good, but we haven’t proven it yet," Dr. Myers said.

Rearrest is most likely within 10 minutes of a successful resuscitation, so, just in case, Dr. Myers’ crews stay put with patients for 10 minutes after they come around, before transport. If they re-arrest en route to the ED, in most cases crews "pull over and work the arrest right there in the ambulance," he said.

Dr. Myers reported having no disclosures.

aotto@frontlinemedcom.com

Daily multivitamins didn’t slow age-related cognitive decline, according to a multiyear, placebo-controlled study of almost 6,000 elderly male physicians.

"We saw no benefit of a daily multivitamin in slowing cognitive decline after more than a decade of treatment and follow-up. Long-term use of a daily multivitamin did not provide cognitive benefits," concluded investigators led by Francine Grodstein, Sc.D., and Jacqueline O’Brien, Sc.D., both of Brigham and Women’s Hospital, Boston, in an article published Dec. 16 in Annals of Internal Medicine.

As part of the Physicians’ Health Study II, 2,980 male physicians at least 65 years old were randomized to daily Centrum Silver (Pfizer) and 2,967 others to placebo. The groups had no significant differences in alcohol use, smoking, cardiovascular disease, diabetes, hypertension, hypercholesterolemia, exercise, or depression. The mean age at enrollment in both groups was about 72 years.

©Graça Victoria/iStockphoto.com

The men then took the East Boston Memory Test, the Telephone Interview for Cognitive Status (TICS), and other validated tests from which global composite and verbal memory scores were calculated. Testing was repeated three more times over an average duration of 8.5 years.

The researchers found no significant differences between the two groups over time in cognitive function change. During the follow-up period, the average difference in change between the multivitamin and placebo groups was –0.01 standard unit (confidence interval, –0.04 to 0.02) for the global composite score and –0.005 SU (CI, –0.04 to 0.03) for the verbal memory score. "At each follow-up assessment, there were no differences between the mean global composite" and verbal memory scores, the investigators said.

Likewise, multivitamins had no protective effect in subanalyses based on smoking, alcohol intake, body mass index, diabetes, hypertension, hypercholesterolemia, diet, depression, or folate use.

About 84% of patients in both groups reported taking at least two-thirds of their study pills. Overall, there was a mean yearly drop of 0.16 points on the 50-point TICS scale.

"A limitation of this study is that our population of male physician participants may have been too well nourished to observe benefits of supplementation," the investigators said. "This population is also unique in that the participants are all highly educated men, so it is possible that effects of multivitamins could have been different in a study population with varying levels of educational attainment."

Previous randomized, controlled studies of multivitamins and cognition have not shown benefits in patients who are well nourished, the researchers noted. "Trials testing high doses of individual vitamin supplements have generally had null results for cognition as well, including large-scale trials of antioxidant supplements and B vitamins," they added.

Two of the 11 investigators reported grants from BASF. The study was funded by the National Institutes of Health, BASF, Pfizer, and DSM Nutritional Products.

aotto@frontlinemedcom.com

Daily multivitamins didn’t slow age-related cognitive decline, according to a multiyear, placebo-controlled study of almost 6,000 elderly male physicians.

"We saw no benefit of a daily multivitamin in slowing cognitive decline after more than a decade of treatment and follow-up. Long-term use of a daily multivitamin did not provide cognitive benefits," concluded investigators led by Francine Grodstein, Sc.D., and Jacqueline O’Brien, Sc.D., both of Brigham and Women’s Hospital, Boston, in an article published Dec. 16 in Annals of Internal Medicine.

As part of the Physicians’ Health Study II, 2,980 male physicians at least 65 years old were randomized to daily Centrum Silver (Pfizer) and 2,967 others to placebo. The groups had no significant differences in alcohol use, smoking, cardiovascular disease, diabetes, hypertension, hypercholesterolemia, exercise, or depression. The mean age at enrollment in both groups was about 72 years.

©Graça Victoria/iStockphoto.com

The men then took the East Boston Memory Test, the Telephone Interview for Cognitive Status (TICS), and other validated tests from which global composite and verbal memory scores were calculated. Testing was repeated three more times over an average duration of 8.5 years.

The researchers found no significant differences between the two groups over time in cognitive function change. During the follow-up period, the average difference in change between the multivitamin and placebo groups was –0.01 standard unit (confidence interval, –0.04 to 0.02) for the global composite score and –0.005 SU (CI, –0.04 to 0.03) for the verbal memory score. "At each follow-up assessment, there were no differences between the mean global composite" and verbal memory scores, the investigators said.

Likewise, multivitamins had no protective effect in subanalyses based on smoking, alcohol intake, body mass index, diabetes, hypertension, hypercholesterolemia, diet, depression, or folate use.

About 84% of patients in both groups reported taking at least two-thirds of their study pills. Overall, there was a mean yearly drop of 0.16 points on the 50-point TICS scale.

"A limitation of this study is that our population of male physician participants may have been too well nourished to observe benefits of supplementation," the investigators said. "This population is also unique in that the participants are all highly educated men, so it is possible that effects of multivitamins could have been different in a study population with varying levels of educational attainment."

Previous randomized, controlled studies of multivitamins and cognition have not shown benefits in patients who are well nourished, the researchers noted. "Trials testing high doses of individual vitamin supplements have generally had null results for cognition as well, including large-scale trials of antioxidant supplements and B vitamins," they added.

Two of the 11 investigators reported grants from BASF. The study was funded by the National Institutes of Health, BASF, Pfizer, and DSM Nutritional Products.

aotto@frontlinemedcom.com

Daily multivitamins didn’t slow age-related cognitive decline, according to a multiyear, placebo-controlled study of almost 6,000 elderly male physicians.

"We saw no benefit of a daily multivitamin in slowing cognitive decline after more than a decade of treatment and follow-up. Long-term use of a daily multivitamin did not provide cognitive benefits," concluded investigators led by Francine Grodstein, Sc.D., and Jacqueline O’Brien, Sc.D., both of Brigham and Women’s Hospital, Boston, in an article published Dec. 16 in Annals of Internal Medicine.

As part of the Physicians’ Health Study II, 2,980 male physicians at least 65 years old were randomized to daily Centrum Silver (Pfizer) and 2,967 others to placebo. The groups had no significant differences in alcohol use, smoking, cardiovascular disease, diabetes, hypertension, hypercholesterolemia, exercise, or depression. The mean age at enrollment in both groups was about 72 years.

©Graça Victoria/iStockphoto.com

The men then took the East Boston Memory Test, the Telephone Interview for Cognitive Status (TICS), and other validated tests from which global composite and verbal memory scores were calculated. Testing was repeated three more times over an average duration of 8.5 years.

The researchers found no significant differences between the two groups over time in cognitive function change. During the follow-up period, the average difference in change between the multivitamin and placebo groups was –0.01 standard unit (confidence interval, –0.04 to 0.02) for the global composite score and –0.005 SU (CI, –0.04 to 0.03) for the verbal memory score. "At each follow-up assessment, there were no differences between the mean global composite" and verbal memory scores, the investigators said.

Likewise, multivitamins had no protective effect in subanalyses based on smoking, alcohol intake, body mass index, diabetes, hypertension, hypercholesterolemia, diet, depression, or folate use.

About 84% of patients in both groups reported taking at least two-thirds of their study pills. Overall, there was a mean yearly drop of 0.16 points on the 50-point TICS scale.

"A limitation of this study is that our population of male physician participants may have been too well nourished to observe benefits of supplementation," the investigators said. "This population is also unique in that the participants are all highly educated men, so it is possible that effects of multivitamins could have been different in a study population with varying levels of educational attainment."

Previous randomized, controlled studies of multivitamins and cognition have not shown benefits in patients who are well nourished, the researchers noted. "Trials testing high doses of individual vitamin supplements have generally had null results for cognition as well, including large-scale trials of antioxidant supplements and B vitamins," they added.

Two of the 11 investigators reported grants from BASF. The study was funded by the National Institutes of Health, BASF, Pfizer, and DSM Nutritional Products.

aotto@frontlinemedcom.com