Mary Ann Moon

Two to three years of monthly subcutaneous injections of daclizumab HYP were more effective at reducing the relapse rate and the number of new or worsening brain lesions in patients with relapsing-remitting multiple sclerosis than were weekly intramuscular injections of interferon beta-1a in the phase III, randomized DECIDE trial.

However, the percentage of patients whose disability progressed after 12 weeks of treatment did not differ significantly between the group given daclizumab HYP and that given intramuscular interferon beta-1a (Avonex), and the rates of infection, cutaneous adverse effects, and liver-test abnormalities were higher with daclizumab HYP. “The enhanced efficacy was accompanied by an increased frequency of adverse events, such that the net clinical benefit will need to be carefully considered by patients and their providers,” wrote Dr. Ludwig Kappos of the Neurologic Clinic and Policlinic, departments of medicine, clinical research, and biomedicine and biomedical engineering, University Hospital Basel (Switzerland), and his associates.

Daclizumab HYP (high-yield process), a formulation of daclizumab developed for long-term subcutaneous administration, has less antibody-dependent cytotoxicity than do earlier formulations of the drug. The researchers compared the two therapies in 1,841 patients aged 18-55 years who were treated at 244 sites in 28 countries. These patients were randomly assigned in a double-blind fashion to receive either 150 mg daclizumab HYP every 4 weeks and intramuscular placebo once weekly (919 patients) or 30 mcg intramuscular interferon beta-1a once weekly and subcutaneous placebo every 4 weeks (922 patients) for 2-3 years. The median duration of treatment was 108.7 weeks for daclizumab HYP and 111.4 weeks for interferon beta-1a. Overall rates of treatment discontinuation and withdrawal from the study were similar between the two groups.

The primary endpoint of the study – the annualized relapse rate over 144 weeks – was significantly lower (by 45%) with daclizumab HYP (0.22) than with interferon beta-1a (0.39). This result was confirmed in two sensitivity analyses. In addition, the number of new or newly enlarged lesions on cranial MRI at week 96 was a significant 54% lower with daclizumab HYP than with interferon beta-1a, Dr. Kappos and his associates noted (N Engl J Med. 2015;373:1418-28. doi: 10.1056/NEJMoa1501481).

However, the percentage of patients whose disability progressed at 12 weeks, as measured by scores on the Expanded Disability Status Scale, was not significantly different between the daclizumab HYP group (16%) and the interferon beta-1a group (20%), nor was the percentage of patients free from relapse at week 144 (67% vs. 51%). The proportion of patients who reported clinically meaningful worsening of the physical impact of MS, as measured by the physical subscale score of the 29-item Multiple Sclerosis Impact Scale, also was not significantly different between the two study groups (19% vs. 23%).

The overall incidence of adverse events was 91% in both groups, and there was no between-group difference in the rate of clinically significant hematologic abnormalities. However, patients receiving daclizumab HYP were significantly more likely to report developing infections (65% vs. 57%); serious infections (4% vs. 2%); or cutaneous events such as rash, eczema, seborrheic dermatitis, acne, erythema, and pruritus (37% vs. 19%). More patients discontinued daclizumab HYP because of adverse events, excluding MS relapses (14% vs. 9%).

In addition, hepatobiliary disorders developed in 3% of patients given daclizumab HYP and 2% of those given interferon beta-1a. Liver enzyme elevations more than five times the upper limit of normal occurred in twice as many patients taking daclizumab HYP (6%) than in patients taking interferon beta-1a (3%).

“Long-term follow-up studies will continue to be important in assessing the treatment effects of MS therapies on disability progression, because studies of even 2-3 years’ duration capture only a small fraction of the lifelong treatment that most patients with MS will require,” Dr. Kappos and his associates added.

Two to three years of monthly subcutaneous injections of daclizumab HYP were more effective at reducing the relapse rate and the number of new or worsening brain lesions in patients with relapsing-remitting multiple sclerosis than were weekly intramuscular injections of interferon beta-1a in the phase III, randomized DECIDE trial.

However, the percentage of patients whose disability progressed after 12 weeks of treatment did not differ significantly between the group given daclizumab HYP and that given intramuscular interferon beta-1a (Avonex), and the rates of infection, cutaneous adverse effects, and liver-test abnormalities were higher with daclizumab HYP. “The enhanced efficacy was accompanied by an increased frequency of adverse events, such that the net clinical benefit will need to be carefully considered by patients and their providers,” wrote Dr. Ludwig Kappos of the Neurologic Clinic and Policlinic, departments of medicine, clinical research, and biomedicine and biomedical engineering, University Hospital Basel (Switzerland), and his associates.

Daclizumab HYP (high-yield process), a formulation of daclizumab developed for long-term subcutaneous administration, has less antibody-dependent cytotoxicity than do earlier formulations of the drug. The researchers compared the two therapies in 1,841 patients aged 18-55 years who were treated at 244 sites in 28 countries. These patients were randomly assigned in a double-blind fashion to receive either 150 mg daclizumab HYP every 4 weeks and intramuscular placebo once weekly (919 patients) or 30 mcg intramuscular interferon beta-1a once weekly and subcutaneous placebo every 4 weeks (922 patients) for 2-3 years. The median duration of treatment was 108.7 weeks for daclizumab HYP and 111.4 weeks for interferon beta-1a. Overall rates of treatment discontinuation and withdrawal from the study were similar between the two groups.

The primary endpoint of the study – the annualized relapse rate over 144 weeks – was significantly lower (by 45%) with daclizumab HYP (0.22) than with interferon beta-1a (0.39). This result was confirmed in two sensitivity analyses. In addition, the number of new or newly enlarged lesions on cranial MRI at week 96 was a significant 54% lower with daclizumab HYP than with interferon beta-1a, Dr. Kappos and his associates noted (N Engl J Med. 2015;373:1418-28. doi: 10.1056/NEJMoa1501481).

However, the percentage of patients whose disability progressed at 12 weeks, as measured by scores on the Expanded Disability Status Scale, was not significantly different between the daclizumab HYP group (16%) and the interferon beta-1a group (20%), nor was the percentage of patients free from relapse at week 144 (67% vs. 51%). The proportion of patients who reported clinically meaningful worsening of the physical impact of MS, as measured by the physical subscale score of the 29-item Multiple Sclerosis Impact Scale, also was not significantly different between the two study groups (19% vs. 23%).

The overall incidence of adverse events was 91% in both groups, and there was no between-group difference in the rate of clinically significant hematologic abnormalities. However, patients receiving daclizumab HYP were significantly more likely to report developing infections (65% vs. 57%); serious infections (4% vs. 2%); or cutaneous events such as rash, eczema, seborrheic dermatitis, acne, erythema, and pruritus (37% vs. 19%). More patients discontinued daclizumab HYP because of adverse events, excluding MS relapses (14% vs. 9%).

In addition, hepatobiliary disorders developed in 3% of patients given daclizumab HYP and 2% of those given interferon beta-1a. Liver enzyme elevations more than five times the upper limit of normal occurred in twice as many patients taking daclizumab HYP (6%) than in patients taking interferon beta-1a (3%).

“Long-term follow-up studies will continue to be important in assessing the treatment effects of MS therapies on disability progression, because studies of even 2-3 years’ duration capture only a small fraction of the lifelong treatment that most patients with MS will require,” Dr. Kappos and his associates added.

Two to three years of monthly subcutaneous injections of daclizumab HYP were more effective at reducing the relapse rate and the number of new or worsening brain lesions in patients with relapsing-remitting multiple sclerosis than were weekly intramuscular injections of interferon beta-1a in the phase III, randomized DECIDE trial.

However, the percentage of patients whose disability progressed after 12 weeks of treatment did not differ significantly between the group given daclizumab HYP and that given intramuscular interferon beta-1a (Avonex), and the rates of infection, cutaneous adverse effects, and liver-test abnormalities were higher with daclizumab HYP. “The enhanced efficacy was accompanied by an increased frequency of adverse events, such that the net clinical benefit will need to be carefully considered by patients and their providers,” wrote Dr. Ludwig Kappos of the Neurologic Clinic and Policlinic, departments of medicine, clinical research, and biomedicine and biomedical engineering, University Hospital Basel (Switzerland), and his associates.

Daclizumab HYP (high-yield process), a formulation of daclizumab developed for long-term subcutaneous administration, has less antibody-dependent cytotoxicity than do earlier formulations of the drug. The researchers compared the two therapies in 1,841 patients aged 18-55 years who were treated at 244 sites in 28 countries. These patients were randomly assigned in a double-blind fashion to receive either 150 mg daclizumab HYP every 4 weeks and intramuscular placebo once weekly (919 patients) or 30 mcg intramuscular interferon beta-1a once weekly and subcutaneous placebo every 4 weeks (922 patients) for 2-3 years. The median duration of treatment was 108.7 weeks for daclizumab HYP and 111.4 weeks for interferon beta-1a. Overall rates of treatment discontinuation and withdrawal from the study were similar between the two groups.

The primary endpoint of the study – the annualized relapse rate over 144 weeks – was significantly lower (by 45%) with daclizumab HYP (0.22) than with interferon beta-1a (0.39). This result was confirmed in two sensitivity analyses. In addition, the number of new or newly enlarged lesions on cranial MRI at week 96 was a significant 54% lower with daclizumab HYP than with interferon beta-1a, Dr. Kappos and his associates noted (N Engl J Med. 2015;373:1418-28. doi: 10.1056/NEJMoa1501481).

However, the percentage of patients whose disability progressed at 12 weeks, as measured by scores on the Expanded Disability Status Scale, was not significantly different between the daclizumab HYP group (16%) and the interferon beta-1a group (20%), nor was the percentage of patients free from relapse at week 144 (67% vs. 51%). The proportion of patients who reported clinically meaningful worsening of the physical impact of MS, as measured by the physical subscale score of the 29-item Multiple Sclerosis Impact Scale, also was not significantly different between the two study groups (19% vs. 23%).

The overall incidence of adverse events was 91% in both groups, and there was no between-group difference in the rate of clinically significant hematologic abnormalities. However, patients receiving daclizumab HYP were significantly more likely to report developing infections (65% vs. 57%); serious infections (4% vs. 2%); or cutaneous events such as rash, eczema, seborrheic dermatitis, acne, erythema, and pruritus (37% vs. 19%). More patients discontinued daclizumab HYP because of adverse events, excluding MS relapses (14% vs. 9%).

In addition, hepatobiliary disorders developed in 3% of patients given daclizumab HYP and 2% of those given interferon beta-1a. Liver enzyme elevations more than five times the upper limit of normal occurred in twice as many patients taking daclizumab HYP (6%) than in patients taking interferon beta-1a (3%).

“Long-term follow-up studies will continue to be important in assessing the treatment effects of MS therapies on disability progression, because studies of even 2-3 years’ duration capture only a small fraction of the lifelong treatment that most patients with MS will require,” Dr. Kappos and his associates added.

For the first time, an oral vaccine against Helicobacter pylori infection proved effective and safe in a phase III trial involving nearly 4,500 children in China, according to a report published in the Oct. 10 issue of the Lancet.

The vaccine’s efficacy waned somewhat after the first year but still significantly reduced H. pylori infection in approximately 1,000 of the recipients followed for the entire 3-year study period. This suggests that it could substantially reduce the rates of gastritis, peptic ulcer, gastric adenocarcinoma, and lymphoma associated with the infection, which currently affects more than half the world’s population, including more than 600 million in China, said Ming Zeng, Ph.D., of the Chinese National Institute for Food and Drug Control, Beijing, and associates.

©sgame/thinkstockphotos.com

Researchers at Third Military Medical University, Chongqing and Chongqing Kangwei Biotechnology, both in China, developed the new vaccine using DNA recombination technology to fuse urease B subunit proteins (gene derived from H. pylori) with heat-labile enterotoxin B subunit proteins (gene derived from E. coli). The vaccine was designed to be administered in three oral doses given 2 weeks apart, after study subjects fasted for at least 2 hours and then drank an 80-mL buffer solution containing sodium bicarbonate and sodium citrate.

Dr. Zeng and associates compared the vaccine (2,232 participants) against an identical placebo (2,232 participants) in the single-center, double-blind, randomized trial, which involved children aged 6-15 years recruited from 12 schools in Ganyu County in eastern China. All the study participants were healthy and tested negative for past or present H. pylori infection at baseline.

The primary endpoint – the development of H. pylori infection within the first year after vaccination – occurred in 14 children who received the vaccine, which was significantly fewer than the 50 children who received placebo. This yielded a vaccine efficacy rate of 71.8% at 1 year. During extended follow-up of a subset of 3,014 participants at 2 years, 10 H. pylori infections developed in the vaccine group and 22 in the placebo group, for a vaccine efficacy of 55.0%. Similarly, at 3-year follow-up of 1,946 participants, vaccine efficacy was 55.8%, the investigators said (Lancet 2015 Oct 10;386:1457-64).

“The event rate of the placebo group varied from 2.4 to 1.4 per 100 person-years, whereas that of the vaccine group remained around 0.7/100 person-years” throughout the 3-year study period, they added.

The vaccine elicited a significantly greater immune response than did the placebo, as measured in serum IgG and salivary IgA. The geometric mean titer was 389.4 in vaccine recipients, compared with only 72.2 in the placebo group, and the seroconversion rate was 86.1% for the vaccine, compared with 4.6% for placebo. The “mild” waning trend in vaccine-elicited antibodies suggests that a booster dose may be necessary in later years, Dr. Zeng and associates wrote.

The incidence of adverse reactions to the vaccine was identical in the two study groups, at 7%. All adverse reactions were mild and resolved within 24 hours. The most frequent was vomiting, followed by fever and headache. No serious adverse events were considered to be related to the study drug. “However, the number of participants in this study might not be enough to identify rare vaccine-related adverse events. Longer-term follow-up is needed in much larger populations” and in more ethnically and demographically diverse groups to identify such rare reactions, they noted.

For the first time, an oral vaccine against Helicobacter pylori infection proved effective and safe in a phase III trial involving nearly 4,500 children in China, according to a report published in the Oct. 10 issue of the Lancet.

The vaccine’s efficacy waned somewhat after the first year but still significantly reduced H. pylori infection in approximately 1,000 of the recipients followed for the entire 3-year study period. This suggests that it could substantially reduce the rates of gastritis, peptic ulcer, gastric adenocarcinoma, and lymphoma associated with the infection, which currently affects more than half the world’s population, including more than 600 million in China, said Ming Zeng, Ph.D., of the Chinese National Institute for Food and Drug Control, Beijing, and associates.

©sgame/thinkstockphotos.com

Researchers at Third Military Medical University, Chongqing and Chongqing Kangwei Biotechnology, both in China, developed the new vaccine using DNA recombination technology to fuse urease B subunit proteins (gene derived from H. pylori) with heat-labile enterotoxin B subunit proteins (gene derived from E. coli). The vaccine was designed to be administered in three oral doses given 2 weeks apart, after study subjects fasted for at least 2 hours and then drank an 80-mL buffer solution containing sodium bicarbonate and sodium citrate.

Dr. Zeng and associates compared the vaccine (2,232 participants) against an identical placebo (2,232 participants) in the single-center, double-blind, randomized trial, which involved children aged 6-15 years recruited from 12 schools in Ganyu County in eastern China. All the study participants were healthy and tested negative for past or present H. pylori infection at baseline.

The primary endpoint – the development of H. pylori infection within the first year after vaccination – occurred in 14 children who received the vaccine, which was significantly fewer than the 50 children who received placebo. This yielded a vaccine efficacy rate of 71.8% at 1 year. During extended follow-up of a subset of 3,014 participants at 2 years, 10 H. pylori infections developed in the vaccine group and 22 in the placebo group, for a vaccine efficacy of 55.0%. Similarly, at 3-year follow-up of 1,946 participants, vaccine efficacy was 55.8%, the investigators said (Lancet 2015 Oct 10;386:1457-64).

“The event rate of the placebo group varied from 2.4 to 1.4 per 100 person-years, whereas that of the vaccine group remained around 0.7/100 person-years” throughout the 3-year study period, they added.

The vaccine elicited a significantly greater immune response than did the placebo, as measured in serum IgG and salivary IgA. The geometric mean titer was 389.4 in vaccine recipients, compared with only 72.2 in the placebo group, and the seroconversion rate was 86.1% for the vaccine, compared with 4.6% for placebo. The “mild” waning trend in vaccine-elicited antibodies suggests that a booster dose may be necessary in later years, Dr. Zeng and associates wrote.

The incidence of adverse reactions to the vaccine was identical in the two study groups, at 7%. All adverse reactions were mild and resolved within 24 hours. The most frequent was vomiting, followed by fever and headache. No serious adverse events were considered to be related to the study drug. “However, the number of participants in this study might not be enough to identify rare vaccine-related adverse events. Longer-term follow-up is needed in much larger populations” and in more ethnically and demographically diverse groups to identify such rare reactions, they noted.

For the first time, an oral vaccine against Helicobacter pylori infection proved effective and safe in a phase III trial involving nearly 4,500 children in China, according to a report published in the Oct. 10 issue of the Lancet.

The vaccine’s efficacy waned somewhat after the first year but still significantly reduced H. pylori infection in approximately 1,000 of the recipients followed for the entire 3-year study period. This suggests that it could substantially reduce the rates of gastritis, peptic ulcer, gastric adenocarcinoma, and lymphoma associated with the infection, which currently affects more than half the world’s population, including more than 600 million in China, said Ming Zeng, Ph.D., of the Chinese National Institute for Food and Drug Control, Beijing, and associates.

©sgame/thinkstockphotos.com

Researchers at Third Military Medical University, Chongqing and Chongqing Kangwei Biotechnology, both in China, developed the new vaccine using DNA recombination technology to fuse urease B subunit proteins (gene derived from H. pylori) with heat-labile enterotoxin B subunit proteins (gene derived from E. coli). The vaccine was designed to be administered in three oral doses given 2 weeks apart, after study subjects fasted for at least 2 hours and then drank an 80-mL buffer solution containing sodium bicarbonate and sodium citrate.

Dr. Zeng and associates compared the vaccine (2,232 participants) against an identical placebo (2,232 participants) in the single-center, double-blind, randomized trial, which involved children aged 6-15 years recruited from 12 schools in Ganyu County in eastern China. All the study participants were healthy and tested negative for past or present H. pylori infection at baseline.

The primary endpoint – the development of H. pylori infection within the first year after vaccination – occurred in 14 children who received the vaccine, which was significantly fewer than the 50 children who received placebo. This yielded a vaccine efficacy rate of 71.8% at 1 year. During extended follow-up of a subset of 3,014 participants at 2 years, 10 H. pylori infections developed in the vaccine group and 22 in the placebo group, for a vaccine efficacy of 55.0%. Similarly, at 3-year follow-up of 1,946 participants, vaccine efficacy was 55.8%, the investigators said (Lancet 2015 Oct 10;386:1457-64).

“The event rate of the placebo group varied from 2.4 to 1.4 per 100 person-years, whereas that of the vaccine group remained around 0.7/100 person-years” throughout the 3-year study period, they added.

The vaccine elicited a significantly greater immune response than did the placebo, as measured in serum IgG and salivary IgA. The geometric mean titer was 389.4 in vaccine recipients, compared with only 72.2 in the placebo group, and the seroconversion rate was 86.1% for the vaccine, compared with 4.6% for placebo. The “mild” waning trend in vaccine-elicited antibodies suggests that a booster dose may be necessary in later years, Dr. Zeng and associates wrote.

The incidence of adverse reactions to the vaccine was identical in the two study groups, at 7%. All adverse reactions were mild and resolved within 24 hours. The most frequent was vomiting, followed by fever and headache. No serious adverse events were considered to be related to the study drug. “However, the number of participants in this study might not be enough to identify rare vaccine-related adverse events. Longer-term follow-up is needed in much larger populations” and in more ethnically and demographically diverse groups to identify such rare reactions, they noted.

For the first time, an oral vaccine against Helicobacter pylori infection proved effective and safe in a phase III trial involving nearly 4,500 children in China, according to a report published in the Oct. 10 issue of the Lancet.

The vaccine’s efficacy waned somewhat after the first year but still significantly reduced H. pylori infection in approximately 1,000 of the recipients followed for the entire 3-year study period. This suggests that it could substantially reduce the rates of gastritis, peptic ulcer, gastric adenocarcinoma, and lymphoma associated with the infection, which currently affects more than half the world’s population, including more than 600 million in China, said Ming Zeng, Ph.D., of the Chinese National Institute for Food and Drug Control, Beijing, and associates.

©sgame/thinkstockphotos.com

Researchers at Third Military Medical University, Chongqing and Chongqing Kangwei Biotechnology, both in China, developed the new vaccine using DNA recombination technology to fuse urease B subunit proteins (gene derived from H. pylori) with heat-labile enterotoxin B subunit proteins (gene derived from E. coli). The vaccine was designed to be administered in three oral doses given 2 weeks apart, after study subjects fasted for at least 2 hours and then drank an 80-mL buffer solution containing sodium bicarbonate and sodium citrate.

Dr. Zeng and associates compared the vaccine (2,232 participants) against an identical placebo (2,232 participants) in the single-center, double-blind, randomized trial, which involved children aged 6-15 years recruited from 12 schools in Ganyu County in eastern China. All the study participants were healthy and tested negative for past or present H. pylori infection at baseline.

The primary endpoint – the development of H. pylori infection within the first year after vaccination – occurred in 14 children who received the vaccine, which was significantly fewer than the 50 children who received placebo. This yielded a vaccine efficacy rate of 71.8% at 1 year. During extended follow-up of a subset of 3,014 participants at 2 years, 10 H. pylori infections developed in the vaccine group and 22 in the placebo group, for a vaccine efficacy of 55.0%. Similarly, at 3-year follow-up of 1,946 participants, vaccine efficacy was 55.8%, the investigators said (Lancet 2015 Oct 10;386:1457-64).

“The event rate of the placebo group varied from 2.4 to 1.4 per 100 person-years, whereas that of the vaccine group remained around 0.7/100 person-years” throughout the 3-year study period, they added.

The vaccine elicited a significantly greater immune response than did the placebo, as measured in serum IgG and salivary IgA. The geometric mean titer was 389.4 in vaccine recipients, compared with only 72.2 in the placebo group, and the seroconversion rate was 86.1% for the vaccine, compared with 4.6% for placebo. The “mild” waning trend in vaccine-elicited antibodies suggests that a booster dose may be necessary in later years, Dr. Zeng and associates wrote.

The incidence of adverse reactions to the vaccine was identical in the two study groups, at 7%. All adverse reactions were mild and resolved within 24 hours. The most frequent was vomiting, followed by fever and headache. No serious adverse events were considered to be related to the study drug. “However, the number of participants in this study might not be enough to identify rare vaccine-related adverse events. Longer-term follow-up is needed in much larger populations” and in more ethnically and demographically diverse groups to identify such rare reactions, they noted.

For the first time, an oral vaccine against Helicobacter pylori infection proved effective and safe in a phase III trial involving nearly 4,500 children in China, according to a report published in the Oct. 10 issue of the Lancet.

The vaccine’s efficacy waned somewhat after the first year but still significantly reduced H. pylori infection in approximately 1,000 of the recipients followed for the entire 3-year study period. This suggests that it could substantially reduce the rates of gastritis, peptic ulcer, gastric adenocarcinoma, and lymphoma associated with the infection, which currently affects more than half the world’s population, including more than 600 million in China, said Ming Zeng, Ph.D., of the Chinese National Institute for Food and Drug Control, Beijing, and associates.

©sgame/thinkstockphotos.com

Researchers at Third Military Medical University, Chongqing and Chongqing Kangwei Biotechnology, both in China, developed the new vaccine using DNA recombination technology to fuse urease B subunit proteins (gene derived from H. pylori) with heat-labile enterotoxin B subunit proteins (gene derived from E. coli). The vaccine was designed to be administered in three oral doses given 2 weeks apart, after study subjects fasted for at least 2 hours and then drank an 80-mL buffer solution containing sodium bicarbonate and sodium citrate.

Dr. Zeng and associates compared the vaccine (2,232 participants) against an identical placebo (2,232 participants) in the single-center, double-blind, randomized trial, which involved children aged 6-15 years recruited from 12 schools in Ganyu County in eastern China. All the study participants were healthy and tested negative for past or present H. pylori infection at baseline.

The primary endpoint – the development of H. pylori infection within the first year after vaccination – occurred in 14 children who received the vaccine, which was significantly fewer than the 50 children who received placebo. This yielded a vaccine efficacy rate of 71.8% at 1 year. During extended follow-up of a subset of 3,014 participants at 2 years, 10 H. pylori infections developed in the vaccine group and 22 in the placebo group, for a vaccine efficacy of 55.0%. Similarly, at 3-year follow-up of 1,946 participants, vaccine efficacy was 55.8%, the investigators said (Lancet 2015 Oct 10;386:1457-64).

“The event rate of the placebo group varied from 2.4 to 1.4 per 100 person-years, whereas that of the vaccine group remained around 0.7/100 person-years” throughout the 3-year study period, they added.

The vaccine elicited a significantly greater immune response than did the placebo, as measured in serum IgG and salivary IgA. The geometric mean titer was 389.4 in vaccine recipients, compared with only 72.2 in the placebo group, and the seroconversion rate was 86.1% for the vaccine, compared with 4.6% for placebo. The “mild” waning trend in vaccine-elicited antibodies suggests that a booster dose may be necessary in later years, Dr. Zeng and associates wrote.

The incidence of adverse reactions to the vaccine was identical in the two study groups, at 7%. All adverse reactions were mild and resolved within 24 hours. The most frequent was vomiting, followed by fever and headache. No serious adverse events were considered to be related to the study drug. “However, the number of participants in this study might not be enough to identify rare vaccine-related adverse events. Longer-term follow-up is needed in much larger populations” and in more ethnically and demographically diverse groups to identify such rare reactions, they noted.

For the first time, an oral vaccine against Helicobacter pylori infection proved effective and safe in a phase III trial involving nearly 4,500 children in China, according to a report published in the Oct. 10 issue of the Lancet.

The vaccine’s efficacy waned somewhat after the first year but still significantly reduced H. pylori infection in approximately 1,000 of the recipients followed for the entire 3-year study period. This suggests that it could substantially reduce the rates of gastritis, peptic ulcer, gastric adenocarcinoma, and lymphoma associated with the infection, which currently affects more than half the world’s population, including more than 600 million in China, said Ming Zeng, Ph.D., of the Chinese National Institute for Food and Drug Control, Beijing, and associates.

©sgame/thinkstockphotos.com

Researchers at Third Military Medical University, Chongqing and Chongqing Kangwei Biotechnology, both in China, developed the new vaccine using DNA recombination technology to fuse urease B subunit proteins (gene derived from H. pylori) with heat-labile enterotoxin B subunit proteins (gene derived from E. coli). The vaccine was designed to be administered in three oral doses given 2 weeks apart, after study subjects fasted for at least 2 hours and then drank an 80-mL buffer solution containing sodium bicarbonate and sodium citrate.

Dr. Zeng and associates compared the vaccine (2,232 participants) against an identical placebo (2,232 participants) in the single-center, double-blind, randomized trial, which involved children aged 6-15 years recruited from 12 schools in Ganyu County in eastern China. All the study participants were healthy and tested negative for past or present H. pylori infection at baseline.

The primary endpoint – the development of H. pylori infection within the first year after vaccination – occurred in 14 children who received the vaccine, which was significantly fewer than the 50 children who received placebo. This yielded a vaccine efficacy rate of 71.8% at 1 year. During extended follow-up of a subset of 3,014 participants at 2 years, 10 H. pylori infections developed in the vaccine group and 22 in the placebo group, for a vaccine efficacy of 55.0%. Similarly, at 3-year follow-up of 1,946 participants, vaccine efficacy was 55.8%, the investigators said (Lancet 2015 Oct 10;386:1457-64).

“The event rate of the placebo group varied from 2.4 to 1.4 per 100 person-years, whereas that of the vaccine group remained around 0.7/100 person-years” throughout the 3-year study period, they added.

The vaccine elicited a significantly greater immune response than did the placebo, as measured in serum IgG and salivary IgA. The geometric mean titer was 389.4 in vaccine recipients, compared with only 72.2 in the placebo group, and the seroconversion rate was 86.1% for the vaccine, compared with 4.6% for placebo. The “mild” waning trend in vaccine-elicited antibodies suggests that a booster dose may be necessary in later years, Dr. Zeng and associates wrote.

The incidence of adverse reactions to the vaccine was identical in the two study groups, at 7%. All adverse reactions were mild and resolved within 24 hours. The most frequent was vomiting, followed by fever and headache. No serious adverse events were considered to be related to the study drug. “However, the number of participants in this study might not be enough to identify rare vaccine-related adverse events. Longer-term follow-up is needed in much larger populations” and in more ethnically and demographically diverse groups to identify such rare reactions, they noted.

The severity of psoriasis appears to correlate with the degree of aortic vascular inflammation in patients who have psoriasis, according to a prospective observational study comparing patients with psoriasis with age- and sex-matched controls.

To better characterize the known relationship between psoriatic skin disease and atherosclerosis, they assessed vascular inflammation using 18F-fluorodeoxyglucose–positron emission tomography/computed tomography (FDG-PET/CT) of the aorta in 60 adults with moderate to severe psoriasis and 22 healthy control subjects (mean age, 44 years) during a 2-year period. FDG uptake in the blood vessel wall denotes activated endothelial cells and cellular infiltration in noncalcified atherosclerotic plaques and is a direct, reliable marker of vascular inflammation, said Dr. Haley B. Naik of the cardiovascular and pulmonary branch, National Heart, Lung, and Blood Institute in Bethesda Md., and her associates. The study was published online on Oct. 8 (Arterioscler Thromb Vasc Biol. 2015 Oct 8. doi: 10.1161/ATVBAHA.115.306460).

As the severity of psoriasis increased, as measured by scores on the Psoriasis Area Severity Index (PASI), the degree of vascular inflammation also increased. This association was stronger than would be expected, given the psoriasis patients’ already increased cardiovascular risk based on traditional risk factors (their higher incidence of obesity, dyslipidemia, hypertension, diabetes, and smoking) and their elevated Framingham risk scores and higher levels of C-reactive protein. This suggests that “psoriasis plaques are biologically active in promoting inflammation at remote sites,” the investigators concluded.

In addition, they found that the absolute neutrophil count in the circulation was significantly elevated in psoriasis patients, compared with control subjects (mean, 3.7 vs. 2.9). Immunophenotyping by flow cytometry identified a significant increase in neutrophil frequencies in whole blood (mean, 65.2 vs. 56.3). Protein markers of neutrophil activation also were significantly elevated. Levels of these markers correlated with both psoriasis severity and vascular inflammation, suggesting that the two disorders may share the same immune-mediated mechanism.

“Our observation that the psoriatic atherosclerotic milieu is upregulated in concert with markers of neutrophil activation underscores the concept that atherosclerosis may involve complex neutrophil biology, which future studies should focus on elucidating, especially after intervention,” Dr. Naik and her associates added.

The severity of psoriasis appears to correlate with the degree of aortic vascular inflammation in patients who have psoriasis, according to a prospective observational study comparing patients with psoriasis with age- and sex-matched controls.

To better characterize the known relationship between psoriatic skin disease and atherosclerosis, they assessed vascular inflammation using 18F-fluorodeoxyglucose–positron emission tomography/computed tomography (FDG-PET/CT) of the aorta in 60 adults with moderate to severe psoriasis and 22 healthy control subjects (mean age, 44 years) during a 2-year period. FDG uptake in the blood vessel wall denotes activated endothelial cells and cellular infiltration in noncalcified atherosclerotic plaques and is a direct, reliable marker of vascular inflammation, said Dr. Haley B. Naik of the cardiovascular and pulmonary branch, National Heart, Lung, and Blood Institute in Bethesda Md., and her associates. The study was published online on Oct. 8 (Arterioscler Thromb Vasc Biol. 2015 Oct 8. doi: 10.1161/ATVBAHA.115.306460).

As the severity of psoriasis increased, as measured by scores on the Psoriasis Area Severity Index (PASI), the degree of vascular inflammation also increased. This association was stronger than would be expected, given the psoriasis patients’ already increased cardiovascular risk based on traditional risk factors (their higher incidence of obesity, dyslipidemia, hypertension, diabetes, and smoking) and their elevated Framingham risk scores and higher levels of C-reactive protein. This suggests that “psoriasis plaques are biologically active in promoting inflammation at remote sites,” the investigators concluded.

In addition, they found that the absolute neutrophil count in the circulation was significantly elevated in psoriasis patients, compared with control subjects (mean, 3.7 vs. 2.9). Immunophenotyping by flow cytometry identified a significant increase in neutrophil frequencies in whole blood (mean, 65.2 vs. 56.3). Protein markers of neutrophil activation also were significantly elevated. Levels of these markers correlated with both psoriasis severity and vascular inflammation, suggesting that the two disorders may share the same immune-mediated mechanism.

“Our observation that the psoriatic atherosclerotic milieu is upregulated in concert with markers of neutrophil activation underscores the concept that atherosclerosis may involve complex neutrophil biology, which future studies should focus on elucidating, especially after intervention,” Dr. Naik and her associates added.

The severity of psoriasis appears to correlate with the degree of aortic vascular inflammation in patients who have psoriasis, according to a prospective observational study comparing patients with psoriasis with age- and sex-matched controls.

To better characterize the known relationship between psoriatic skin disease and atherosclerosis, they assessed vascular inflammation using 18F-fluorodeoxyglucose–positron emission tomography/computed tomography (FDG-PET/CT) of the aorta in 60 adults with moderate to severe psoriasis and 22 healthy control subjects (mean age, 44 years) during a 2-year period. FDG uptake in the blood vessel wall denotes activated endothelial cells and cellular infiltration in noncalcified atherosclerotic plaques and is a direct, reliable marker of vascular inflammation, said Dr. Haley B. Naik of the cardiovascular and pulmonary branch, National Heart, Lung, and Blood Institute in Bethesda Md., and her associates. The study was published online on Oct. 8 (Arterioscler Thromb Vasc Biol. 2015 Oct 8. doi: 10.1161/ATVBAHA.115.306460).

As the severity of psoriasis increased, as measured by scores on the Psoriasis Area Severity Index (PASI), the degree of vascular inflammation also increased. This association was stronger than would be expected, given the psoriasis patients’ already increased cardiovascular risk based on traditional risk factors (their higher incidence of obesity, dyslipidemia, hypertension, diabetes, and smoking) and their elevated Framingham risk scores and higher levels of C-reactive protein. This suggests that “psoriasis plaques are biologically active in promoting inflammation at remote sites,” the investigators concluded.

In addition, they found that the absolute neutrophil count in the circulation was significantly elevated in psoriasis patients, compared with control subjects (mean, 3.7 vs. 2.9). Immunophenotyping by flow cytometry identified a significant increase in neutrophil frequencies in whole blood (mean, 65.2 vs. 56.3). Protein markers of neutrophil activation also were significantly elevated. Levels of these markers correlated with both psoriasis severity and vascular inflammation, suggesting that the two disorders may share the same immune-mediated mechanism.

“Our observation that the psoriatic atherosclerotic milieu is upregulated in concert with markers of neutrophil activation underscores the concept that atherosclerosis may involve complex neutrophil biology, which future studies should focus on elucidating, especially after intervention,” Dr. Naik and her associates added.

The number of self-harm emergencies increases by 50% after bariatric surgery, according to a report published online Oct. 7 in JAMA Surgery.

Mental health problems are common among both morbidly obese adults and patients undergoing bariatric surgery, and a recent meta-analysis of 30 studies found that suicide risk was four times higher among patients undergoing bariatric surgery than in the general population. To examine this association, researchers performed a population-based longitudinal cohort study comparing self-harm behaviors during the 3 years before bariatric surgery with those during the 3 years after bariatric surgery in all 8,815 adults who underwent gastric bypass, intestinal bypass, and sleeve gastrectomy in Ontario during a 5-year period.

KatarzynaBialasiewicz/Thinkstock.com

This cohort reflects the practice of approximately 200 surgeons. Self-harm behaviors were categorized as medication overdose, alcohol-related, poisoning by toxic chemicals, or physical trauma. Approximately 64% of the study population had a history of anxiety disorders, 7.8% had general mental health disorders, and 0.6% reported alcohol misuse before undergoing bariatric surgery, wrote Junaid A. Bhatti, Ph.D., of the department of evaluative clinical sciences, Sunnybrook Research Institute, Toronto, and the department of surgery, University of Toronto.

There were 62 self-harm events during the preoperative interval and 96 during the postoperative interval. The mean incidence of self harm was 2.33 events per 1,000 patients during the 3 years before surgery and 3.63 per 1,000 during the 3 years after surgery, for a rate ratio of 1.54. This represents an increase of approximately 50% after bariatric surgery. The postoperative self-harm rate also was three times as high as that in the general Ontario population (1.2 per 1,000 people) during the same period.

Most of these incidents (73%) were medication overdoses. These were considered serious suicide attempts posing significant risk to the patients; they required ambulance transport and hospital admission. Physical trauma such as self-hanging accounted for another 21%. Almost all of the patients with postoperative self-harm behaviors had a known history of mental health problems, chiefly major depression. These findings suggest the need for increased screening and monitoring for excessive drug or alcohol use, as well as activating a reliable support network to mitigate the stress that follows profound changes in diet and lifestyle, Dr. Bhatti and his associates said (JAMA Surg. 2015 Oct 7. doi: 10.1001/jamasurg.2015.3414).

The reason for this rise in self-harm behaviors is not yet known. Some experts contend that changes in alcohol metabolism following bariatric surgery raise the likelihood of intoxication or alcohol-related disinhibition, both of which can escalate impulsivity. Others argue that morbid obesity arises from a food addiction, and after the procedure patients may turn from overeating to alcohol/substance abuse. Most agree that the surgery and the lifestyle changes it requires increase the patient’s stress and anxiety, which can exacerbate preexisting mental health problems. Finally, bariatric surgery itself alters neurohormone levels, which could in turn predispose patients to depression or suicidal behaviors, the investigators said.

This study was limited in that the data didn’t allow the researchers to account for some important surgery-related factors, including patients’ failure to lose a significant amount of weight. In addition, the study focused on self-harm behaviors that led to emergency-department visits; since completed suicides generally don’t include ED visits, some cases of self-harm that ended in death could not be included.

The Canadian Institutes of Health Research, the Canada Research Chair in Medical Decision Sciences, and the Da Souza Chair in Trauma Research funded the study. Dr. Bhatti and his associates reported having no relevant financial disclosures.

The number of self-harm emergencies increases by 50% after bariatric surgery, according to a report published online Oct. 7 in JAMA Surgery.

Mental health problems are common among both morbidly obese adults and patients undergoing bariatric surgery, and a recent meta-analysis of 30 studies found that suicide risk was four times higher among patients undergoing bariatric surgery than in the general population. To examine this association, researchers performed a population-based longitudinal cohort study comparing self-harm behaviors during the 3 years before bariatric surgery with those during the 3 years after bariatric surgery in all 8,815 adults who underwent gastric bypass, intestinal bypass, and sleeve gastrectomy in Ontario during a 5-year period.

KatarzynaBialasiewicz/Thinkstock.com

This cohort reflects the practice of approximately 200 surgeons. Self-harm behaviors were categorized as medication overdose, alcohol-related, poisoning by toxic chemicals, or physical trauma. Approximately 64% of the study population had a history of anxiety disorders, 7.8% had general mental health disorders, and 0.6% reported alcohol misuse before undergoing bariatric surgery, wrote Junaid A. Bhatti, Ph.D., of the department of evaluative clinical sciences, Sunnybrook Research Institute, Toronto, and the department of surgery, University of Toronto.

There were 62 self-harm events during the preoperative interval and 96 during the postoperative interval. The mean incidence of self harm was 2.33 events per 1,000 patients during the 3 years before surgery and 3.63 per 1,000 during the 3 years after surgery, for a rate ratio of 1.54. This represents an increase of approximately 50% after bariatric surgery. The postoperative self-harm rate also was three times as high as that in the general Ontario population (1.2 per 1,000 people) during the same period.

Most of these incidents (73%) were medication overdoses. These were considered serious suicide attempts posing significant risk to the patients; they required ambulance transport and hospital admission. Physical trauma such as self-hanging accounted for another 21%. Almost all of the patients with postoperative self-harm behaviors had a known history of mental health problems, chiefly major depression. These findings suggest the need for increased screening and monitoring for excessive drug or alcohol use, as well as activating a reliable support network to mitigate the stress that follows profound changes in diet and lifestyle, Dr. Bhatti and his associates said (JAMA Surg. 2015 Oct 7. doi: 10.1001/jamasurg.2015.3414).

The reason for this rise in self-harm behaviors is not yet known. Some experts contend that changes in alcohol metabolism following bariatric surgery raise the likelihood of intoxication or alcohol-related disinhibition, both of which can escalate impulsivity. Others argue that morbid obesity arises from a food addiction, and after the procedure patients may turn from overeating to alcohol/substance abuse. Most agree that the surgery and the lifestyle changes it requires increase the patient’s stress and anxiety, which can exacerbate preexisting mental health problems. Finally, bariatric surgery itself alters neurohormone levels, which could in turn predispose patients to depression or suicidal behaviors, the investigators said.

This study was limited in that the data didn’t allow the researchers to account for some important surgery-related factors, including patients’ failure to lose a significant amount of weight. In addition, the study focused on self-harm behaviors that led to emergency-department visits; since completed suicides generally don’t include ED visits, some cases of self-harm that ended in death could not be included.

The Canadian Institutes of Health Research, the Canada Research Chair in Medical Decision Sciences, and the Da Souza Chair in Trauma Research funded the study. Dr. Bhatti and his associates reported having no relevant financial disclosures.

The number of self-harm emergencies increases by 50% after bariatric surgery, according to a report published online Oct. 7 in JAMA Surgery.

Mental health problems are common among both morbidly obese adults and patients undergoing bariatric surgery, and a recent meta-analysis of 30 studies found that suicide risk was four times higher among patients undergoing bariatric surgery than in the general population. To examine this association, researchers performed a population-based longitudinal cohort study comparing self-harm behaviors during the 3 years before bariatric surgery with those during the 3 years after bariatric surgery in all 8,815 adults who underwent gastric bypass, intestinal bypass, and sleeve gastrectomy in Ontario during a 5-year period.

KatarzynaBialasiewicz/Thinkstock.com

This cohort reflects the practice of approximately 200 surgeons. Self-harm behaviors were categorized as medication overdose, alcohol-related, poisoning by toxic chemicals, or physical trauma. Approximately 64% of the study population had a history of anxiety disorders, 7.8% had general mental health disorders, and 0.6% reported alcohol misuse before undergoing bariatric surgery, wrote Junaid A. Bhatti, Ph.D., of the department of evaluative clinical sciences, Sunnybrook Research Institute, Toronto, and the department of surgery, University of Toronto.

There were 62 self-harm events during the preoperative interval and 96 during the postoperative interval. The mean incidence of self harm was 2.33 events per 1,000 patients during the 3 years before surgery and 3.63 per 1,000 during the 3 years after surgery, for a rate ratio of 1.54. This represents an increase of approximately 50% after bariatric surgery. The postoperative self-harm rate also was three times as high as that in the general Ontario population (1.2 per 1,000 people) during the same period.

Most of these incidents (73%) were medication overdoses. These were considered serious suicide attempts posing significant risk to the patients; they required ambulance transport and hospital admission. Physical trauma such as self-hanging accounted for another 21%. Almost all of the patients with postoperative self-harm behaviors had a known history of mental health problems, chiefly major depression. These findings suggest the need for increased screening and monitoring for excessive drug or alcohol use, as well as activating a reliable support network to mitigate the stress that follows profound changes in diet and lifestyle, Dr. Bhatti and his associates said (JAMA Surg. 2015 Oct 7. doi: 10.1001/jamasurg.2015.3414).

The reason for this rise in self-harm behaviors is not yet known. Some experts contend that changes in alcohol metabolism following bariatric surgery raise the likelihood of intoxication or alcohol-related disinhibition, both of which can escalate impulsivity. Others argue that morbid obesity arises from a food addiction, and after the procedure patients may turn from overeating to alcohol/substance abuse. Most agree that the surgery and the lifestyle changes it requires increase the patient’s stress and anxiety, which can exacerbate preexisting mental health problems. Finally, bariatric surgery itself alters neurohormone levels, which could in turn predispose patients to depression or suicidal behaviors, the investigators said.

This study was limited in that the data didn’t allow the researchers to account for some important surgery-related factors, including patients’ failure to lose a significant amount of weight. In addition, the study focused on self-harm behaviors that led to emergency-department visits; since completed suicides generally don’t include ED visits, some cases of self-harm that ended in death could not be included.

The Canadian Institutes of Health Research, the Canada Research Chair in Medical Decision Sciences, and the Da Souza Chair in Trauma Research funded the study. Dr. Bhatti and his associates reported having no relevant financial disclosures.

The cumulative rates of anal, colorectal, and liver cancers are increasing among HIV-positive patients, mainly because in the antiretroviral era they are living long enough for these malignancies to develop, according to a report published online Oct. 5 in Annals of Internal Medicine.

Certain cancers are known to be more common among HIV-infected than among noninfected adults, but it has been uncertain whether this is because of a true increase in incidence or simply to these patients’ greater longevity in recent years, said Michael J. Silverberg, Ph.D., a research scientist at Kaiser Permanente Division of Research, Oakland Calif., and his associates.

The investigators analyzed data from 16 U.S. and Canadian cohorts participating in the North American Cohort Collaboration on Research and Design to compare time trends in cancer incidence between 86,620 adults with HIV and 196,987 demographically similar control subjects without HIV. These study participants were followed from 1996 to 2009 for the development of nine cancers: Kaposi’s sarcoma, non-Hodgkin’s lymphoma, lung cancer, anal cancer, colorectal cancer, liver cancer, oral cavity/pharyngeal cancer, Hodgkin’s lymphoma, and melanoma. As expected, the incidences of all of these malignancies were higher among patients with HIV than among control subjects.

The cumulative incidence of anal, colorectal, and liver cancer increased over time among HIV-positive but not among HIV-negative adults. This was attributed primarily to the declining death rate among HIV-positive patients, which “presumably allowed more persons to survive long enough to have long-term exposure to human papillomavirus infection” in the case of anal cancer and to hepatitis B and C virus infection in the case of liver cancer. In the case of colorectal cancer, rates steadily declined in the control subjects as they have in the general population due to increased screening and earlier detection of lesions with malignant potential. “We hypothesize that this disparity in colorectal cancer trends may be because persons with HIV lag behind” in getting screened for colorectal cancer, Dr. Silverberg and his associates said (Ann Intern Med. 2015 Oct 5. doi: 10.7326/M14-2768).

Kaposi’s sarcoma, non-Hodgkin’s lymphoma, and lung cancer “remain of great concern” among HIV-positive adults, and the investigators calculated that each of these malignancies carry high lifetime (to age 75 years) risks of 1 in 25 in this patient population. “Efforts need to be intensified to promote early, sustained [antiretroviral therapy], the only known approach to prevention of these and possibly other cancer types linked to immunosuppression or inflammation,” they noted.

Time trends in the rates of oral/pharyngeal cancer, Hodgkin’s lymphoma, and melanoma did not differ significantly between patients with HIV and control subjects.

This study was supported by the National Institutes of Health, the Centers for Disease Control and Prevention, the Agency for Healthcare Research and Quality, the Health Resources and Services Administration, the Canadian Institutes of Health Research, the Ontario ministry of Health and Long-Term Care, the government of Alberta, and the National Cancer Institute. Dr. Silverberg reported receiving grants from Pfizer and Merck; his associates reported ties to Gilead Sciences, Merck, GlaxoSmithKline, Genosea, and Nordique.

The cumulative rates of anal, colorectal, and liver cancers are increasing among HIV-positive patients, mainly because in the antiretroviral era they are living long enough for these malignancies to develop, according to a report published online Oct. 5 in Annals of Internal Medicine.

Certain cancers are known to be more common among HIV-infected than among noninfected adults, but it has been uncertain whether this is because of a true increase in incidence or simply to these patients’ greater longevity in recent years, said Michael J. Silverberg, Ph.D., a research scientist at Kaiser Permanente Division of Research, Oakland Calif., and his associates.

The investigators analyzed data from 16 U.S. and Canadian cohorts participating in the North American Cohort Collaboration on Research and Design to compare time trends in cancer incidence between 86,620 adults with HIV and 196,987 demographically similar control subjects without HIV. These study participants were followed from 1996 to 2009 for the development of nine cancers: Kaposi’s sarcoma, non-Hodgkin’s lymphoma, lung cancer, anal cancer, colorectal cancer, liver cancer, oral cavity/pharyngeal cancer, Hodgkin’s lymphoma, and melanoma. As expected, the incidences of all of these malignancies were higher among patients with HIV than among control subjects.

The cumulative incidence of anal, colorectal, and liver cancer increased over time among HIV-positive but not among HIV-negative adults. This was attributed primarily to the declining death rate among HIV-positive patients, which “presumably allowed more persons to survive long enough to have long-term exposure to human papillomavirus infection” in the case of anal cancer and to hepatitis B and C virus infection in the case of liver cancer. In the case of colorectal cancer, rates steadily declined in the control subjects as they have in the general population due to increased screening and earlier detection of lesions with malignant potential. “We hypothesize that this disparity in colorectal cancer trends may be because persons with HIV lag behind” in getting screened for colorectal cancer, Dr. Silverberg and his associates said (Ann Intern Med. 2015 Oct 5. doi: 10.7326/M14-2768).

Kaposi’s sarcoma, non-Hodgkin’s lymphoma, and lung cancer “remain of great concern” among HIV-positive adults, and the investigators calculated that each of these malignancies carry high lifetime (to age 75 years) risks of 1 in 25 in this patient population. “Efforts need to be intensified to promote early, sustained [antiretroviral therapy], the only known approach to prevention of these and possibly other cancer types linked to immunosuppression or inflammation,” they noted.

Time trends in the rates of oral/pharyngeal cancer, Hodgkin’s lymphoma, and melanoma did not differ significantly between patients with HIV and control subjects.

This study was supported by the National Institutes of Health, the Centers for Disease Control and Prevention, the Agency for Healthcare Research and Quality, the Health Resources and Services Administration, the Canadian Institutes of Health Research, the Ontario ministry of Health and Long-Term Care, the government of Alberta, and the National Cancer Institute. Dr. Silverberg reported receiving grants from Pfizer and Merck; his associates reported ties to Gilead Sciences, Merck, GlaxoSmithKline, Genosea, and Nordique.

The cumulative rates of anal, colorectal, and liver cancers are increasing among HIV-positive patients, mainly because in the antiretroviral era they are living long enough for these malignancies to develop, according to a report published online Oct. 5 in Annals of Internal Medicine.

Certain cancers are known to be more common among HIV-infected than among noninfected adults, but it has been uncertain whether this is because of a true increase in incidence or simply to these patients’ greater longevity in recent years, said Michael J. Silverberg, Ph.D., a research scientist at Kaiser Permanente Division of Research, Oakland Calif., and his associates.

The investigators analyzed data from 16 U.S. and Canadian cohorts participating in the North American Cohort Collaboration on Research and Design to compare time trends in cancer incidence between 86,620 adults with HIV and 196,987 demographically similar control subjects without HIV. These study participants were followed from 1996 to 2009 for the development of nine cancers: Kaposi’s sarcoma, non-Hodgkin’s lymphoma, lung cancer, anal cancer, colorectal cancer, liver cancer, oral cavity/pharyngeal cancer, Hodgkin’s lymphoma, and melanoma. As expected, the incidences of all of these malignancies were higher among patients with HIV than among control subjects.

The cumulative incidence of anal, colorectal, and liver cancer increased over time among HIV-positive but not among HIV-negative adults. This was attributed primarily to the declining death rate among HIV-positive patients, which “presumably allowed more persons to survive long enough to have long-term exposure to human papillomavirus infection” in the case of anal cancer and to hepatitis B and C virus infection in the case of liver cancer. In the case of colorectal cancer, rates steadily declined in the control subjects as they have in the general population due to increased screening and earlier detection of lesions with malignant potential. “We hypothesize that this disparity in colorectal cancer trends may be because persons with HIV lag behind” in getting screened for colorectal cancer, Dr. Silverberg and his associates said (Ann Intern Med. 2015 Oct 5. doi: 10.7326/M14-2768).

Kaposi’s sarcoma, non-Hodgkin’s lymphoma, and lung cancer “remain of great concern” among HIV-positive adults, and the investigators calculated that each of these malignancies carry high lifetime (to age 75 years) risks of 1 in 25 in this patient population. “Efforts need to be intensified to promote early, sustained [antiretroviral therapy], the only known approach to prevention of these and possibly other cancer types linked to immunosuppression or inflammation,” they noted.

Time trends in the rates of oral/pharyngeal cancer, Hodgkin’s lymphoma, and melanoma did not differ significantly between patients with HIV and control subjects.

This study was supported by the National Institutes of Health, the Centers for Disease Control and Prevention, the Agency for Healthcare Research and Quality, the Health Resources and Services Administration, the Canadian Institutes of Health Research, the Ontario ministry of Health and Long-Term Care, the government of Alberta, and the National Cancer Institute. Dr. Silverberg reported receiving grants from Pfizer and Merck; his associates reported ties to Gilead Sciences, Merck, GlaxoSmithKline, Genosea, and Nordique.

Remote ischemic preconditioning failed to improve outcomes among higher-risk patients undergoing elective cardiac surgery in two separate large clinical trials reported online Oct. 5 in the New England Journal of Medicine.

Both studies clearly showed that the technique did not provide greater protection of the heart, brain, or kidneys than did a sham technique, failing to improve any of the numerous primary or secondary endpoints or to produce a benefit in any of several subgroups of patients.

Remote ischemic preconditioning involves protecting the heart and other organs against surgery-related acute ischemia/reperfusion injury by first applying brief cycles of ischemia and reperfusion to a remote organ or tissue. It is thought that this stimulus produces a blood-borne response that conveys a protective effect from the remote area to the target organs. This remote preconditioning can be accomplished noninvasively by inflating and deflating a standard blood pressure cuff on the upper arm or thigh for brief periods.

Some early studies indicated that using this technique during cardiovascular surgery improved serum cardiac and renal biomarkers, which implied protection of these organs against ischemia/reperfusion injury. But more recent prospective clinical trials have shown no such benefit. None of these studies were adequately powered to assess the effect on hard clinical endpoints, and most were single center, unblinded, and had no standardized anesthesia regimen.

RIPHeart study

To address these study limitations, the RIPHeart Study investigators performed a prospective double-blind controlled trial among 1,385 adults undergoing elective cardiovascular surgery requiring cardiopulmonary bypass at 14 university hospitals in Germany during a 3-year period. The participants had a mean EuroSCORE (European System for Cardiac Operative Risk Evaluation) of 6 or higher, indicating that most of them were at higher than average risk, and all received the same anesthetic, intravenous propofol. A total of 692 patients were randomly assigned to undergo four 5-minute cycles of upper-arm ischemia/reperfusion after being anesthetized and 693 to undergo sham ischemia/reperfusion on a dummy arm hidden by surgical drapes, said Dr. Patrick Meybohm of the department of anesthesiology, intensive care medicine, and pain therapy at University Hospital Frankfurt and his associates.

The primary endpoint – a composite of death from any cause, nonfatal MI, stroke, or acute renal failure before hospital discharge – occurred in 14.3% of the intervention group and 14.6% of the control group, a nonsignificant difference. Furthermore, no significant differences between the two study groups were seen in any of the individual components of this composite measure, or in any secondary endpoints such as duration of mechanical ventilation, ICU length of stay, hospital length of stay, troponin levels, creatinine levels, onset of atrial fibrillation, or incidence of postoperative delirium. All outcome measures remained similar between the two study groups at 30-day, 90-day, and 1-year follow-ups (N Engl J Med 2015 Oct 5. doi: 10.1056/NEJMoa1413579).

In addition, estimated event-free survival at 30 days was 85.2% with the true intervention and 85.0% with the sham intervention, another nonsignificant difference. These estimates remained similar between the two study groups at 90 days and 1 year. The findings of the primary analysis were confirmed in the “completely concordant” per-protocol analysis, Dr. Meybohm and his associates noted.

ERICCA trial

In the Effect of Remote Ischemic Preconditioning on Clinical Outcomes in Patients Undergoing CABG (ERICCA) study, investigators assessed 1,612 adults undergoing on-pump CABG (with or without valve surgery) using blood cardioplegia at 30 cardiac surgery centers in the United Kingdom during a 3-year period. These patients were randomly assigned to undergo remote ischemic preconditioning with a standard blood pressure cuff on the upper arm for four 5-minute cycles (801 participants) or a sham procedure using a deactivated blood pressure cuff (811 participants) before surgery but while anesthetized, said Dr. Derek J. Hausenloy of the Hatter Cardiovascular Institute, University College London, and his associates.

The primary endpoint – a composite of death from cardiovascular causes, nonfatal MI, coronary revascularization, or stroke within 1 year – was 26.5% with true preconditioning and 27.7% with the sham procedure, a nonsignificant difference. There were no significant differences between the two study groups in any of the individual components of this composite or according to type of anesthesia or the interval between preconditioning and surgical incision.

These findings remained strongly consistent across all subgroups of patients evaluated, regardless of troponin levels, inotrope score, presence or absence of kidney injury, degree of kidney injury, length of ICU stay, length of hospital stay, or performance on 6-minute walk test, Dr. Hausenloy and his associates said (N Engl J Med. 2015 Oct 5. doi: 10.1056/NEJMoa1413534).

In both trials, the rate of adverse effects from remote ischemic preconditioning was the same between the true and the sham procedures, and the only adverse effect considered to be related to preconditioning was an increased incidence of skin petechiae (4.4% vs. 0.2%) in the ERICCA study.

The investigators’ financial disclosures are available at NEJM.org.

Remote ischemic preconditioning failed to improve outcomes among higher-risk patients undergoing elective cardiac surgery in two separate large clinical trials reported online Oct. 5 in the New England Journal of Medicine.

Both studies clearly showed that the technique did not provide greater protection of the heart, brain, or kidneys than did a sham technique, failing to improve any of the numerous primary or secondary endpoints or to produce a benefit in any of several subgroups of patients.

Remote ischemic preconditioning involves protecting the heart and other organs against surgery-related acute ischemia/reperfusion injury by first applying brief cycles of ischemia and reperfusion to a remote organ or tissue. It is thought that this stimulus produces a blood-borne response that conveys a protective effect from the remote area to the target organs. This remote preconditioning can be accomplished noninvasively by inflating and deflating a standard blood pressure cuff on the upper arm or thigh for brief periods.

Some early studies indicated that using this technique during cardiovascular surgery improved serum cardiac and renal biomarkers, which implied protection of these organs against ischemia/reperfusion injury. But more recent prospective clinical trials have shown no such benefit. None of these studies were adequately powered to assess the effect on hard clinical endpoints, and most were single center, unblinded, and had no standardized anesthesia regimen.

RIPHeart study

To address these study limitations, the RIPHeart Study investigators performed a prospective double-blind controlled trial among 1,385 adults undergoing elective cardiovascular surgery requiring cardiopulmonary bypass at 14 university hospitals in Germany during a 3-year period. The participants had a mean EuroSCORE (European System for Cardiac Operative Risk Evaluation) of 6 or higher, indicating that most of them were at higher than average risk, and all received the same anesthetic, intravenous propofol. A total of 692 patients were randomly assigned to undergo four 5-minute cycles of upper-arm ischemia/reperfusion after being anesthetized and 693 to undergo sham ischemia/reperfusion on a dummy arm hidden by surgical drapes, said Dr. Patrick Meybohm of the department of anesthesiology, intensive care medicine, and pain therapy at University Hospital Frankfurt and his associates.

The primary endpoint – a composite of death from any cause, nonfatal MI, stroke, or acute renal failure before hospital discharge – occurred in 14.3% of the intervention group and 14.6% of the control group, a nonsignificant difference. Furthermore, no significant differences between the two study groups were seen in any of the individual components of this composite measure, or in any secondary endpoints such as duration of mechanical ventilation, ICU length of stay, hospital length of stay, troponin levels, creatinine levels, onset of atrial fibrillation, or incidence of postoperative delirium. All outcome measures remained similar between the two study groups at 30-day, 90-day, and 1-year follow-ups (N Engl J Med 2015 Oct 5. doi: 10.1056/NEJMoa1413579).

In addition, estimated event-free survival at 30 days was 85.2% with the true intervention and 85.0% with the sham intervention, another nonsignificant difference. These estimates remained similar between the two study groups at 90 days and 1 year. The findings of the primary analysis were confirmed in the “completely concordant” per-protocol analysis, Dr. Meybohm and his associates noted.

ERICCA trial

In the Effect of Remote Ischemic Preconditioning on Clinical Outcomes in Patients Undergoing CABG (ERICCA) study, investigators assessed 1,612 adults undergoing on-pump CABG (with or without valve surgery) using blood cardioplegia at 30 cardiac surgery centers in the United Kingdom during a 3-year period. These patients were randomly assigned to undergo remote ischemic preconditioning with a standard blood pressure cuff on the upper arm for four 5-minute cycles (801 participants) or a sham procedure using a deactivated blood pressure cuff (811 participants) before surgery but while anesthetized, said Dr. Derek J. Hausenloy of the Hatter Cardiovascular Institute, University College London, and his associates.

The primary endpoint – a composite of death from cardiovascular causes, nonfatal MI, coronary revascularization, or stroke within 1 year – was 26.5% with true preconditioning and 27.7% with the sham procedure, a nonsignificant difference. There were no significant differences between the two study groups in any of the individual components of this composite or according to type of anesthesia or the interval between preconditioning and surgical incision.

These findings remained strongly consistent across all subgroups of patients evaluated, regardless of troponin levels, inotrope score, presence or absence of kidney injury, degree of kidney injury, length of ICU stay, length of hospital stay, or performance on 6-minute walk test, Dr. Hausenloy and his associates said (N Engl J Med. 2015 Oct 5. doi: 10.1056/NEJMoa1413534).

In both trials, the rate of adverse effects from remote ischemic preconditioning was the same between the true and the sham procedures, and the only adverse effect considered to be related to preconditioning was an increased incidence of skin petechiae (4.4% vs. 0.2%) in the ERICCA study.

The investigators’ financial disclosures are available at NEJM.org.

Remote ischemic preconditioning failed to improve outcomes among higher-risk patients undergoing elective cardiac surgery in two separate large clinical trials reported online Oct. 5 in the New England Journal of Medicine.

Both studies clearly showed that the technique did not provide greater protection of the heart, brain, or kidneys than did a sham technique, failing to improve any of the numerous primary or secondary endpoints or to produce a benefit in any of several subgroups of patients.

Remote ischemic preconditioning involves protecting the heart and other organs against surgery-related acute ischemia/reperfusion injury by first applying brief cycles of ischemia and reperfusion to a remote organ or tissue. It is thought that this stimulus produces a blood-borne response that conveys a protective effect from the remote area to the target organs. This remote preconditioning can be accomplished noninvasively by inflating and deflating a standard blood pressure cuff on the upper arm or thigh for brief periods.

Some early studies indicated that using this technique during cardiovascular surgery improved serum cardiac and renal biomarkers, which implied protection of these organs against ischemia/reperfusion injury. But more recent prospective clinical trials have shown no such benefit. None of these studies were adequately powered to assess the effect on hard clinical endpoints, and most were single center, unblinded, and had no standardized anesthesia regimen.

RIPHeart study

To address these study limitations, the RIPHeart Study investigators performed a prospective double-blind controlled trial among 1,385 adults undergoing elective cardiovascular surgery requiring cardiopulmonary bypass at 14 university hospitals in Germany during a 3-year period. The participants had a mean EuroSCORE (European System for Cardiac Operative Risk Evaluation) of 6 or higher, indicating that most of them were at higher than average risk, and all received the same anesthetic, intravenous propofol. A total of 692 patients were randomly assigned to undergo four 5-minute cycles of upper-arm ischemia/reperfusion after being anesthetized and 693 to undergo sham ischemia/reperfusion on a dummy arm hidden by surgical drapes, said Dr. Patrick Meybohm of the department of anesthesiology, intensive care medicine, and pain therapy at University Hospital Frankfurt and his associates.

The primary endpoint – a composite of death from any cause, nonfatal MI, stroke, or acute renal failure before hospital discharge – occurred in 14.3% of the intervention group and 14.6% of the control group, a nonsignificant difference. Furthermore, no significant differences between the two study groups were seen in any of the individual components of this composite measure, or in any secondary endpoints such as duration of mechanical ventilation, ICU length of stay, hospital length of stay, troponin levels, creatinine levels, onset of atrial fibrillation, or incidence of postoperative delirium. All outcome measures remained similar between the two study groups at 30-day, 90-day, and 1-year follow-ups (N Engl J Med 2015 Oct 5. doi: 10.1056/NEJMoa1413579).

In addition, estimated event-free survival at 30 days was 85.2% with the true intervention and 85.0% with the sham intervention, another nonsignificant difference. These estimates remained similar between the two study groups at 90 days and 1 year. The findings of the primary analysis were confirmed in the “completely concordant” per-protocol analysis, Dr. Meybohm and his associates noted.

ERICCA trial

In the Effect of Remote Ischemic Preconditioning on Clinical Outcomes in Patients Undergoing CABG (ERICCA) study, investigators assessed 1,612 adults undergoing on-pump CABG (with or without valve surgery) using blood cardioplegia at 30 cardiac surgery centers in the United Kingdom during a 3-year period. These patients were randomly assigned to undergo remote ischemic preconditioning with a standard blood pressure cuff on the upper arm for four 5-minute cycles (801 participants) or a sham procedure using a deactivated blood pressure cuff (811 participants) before surgery but while anesthetized, said Dr. Derek J. Hausenloy of the Hatter Cardiovascular Institute, University College London, and his associates.

The primary endpoint – a composite of death from cardiovascular causes, nonfatal MI, coronary revascularization, or stroke within 1 year – was 26.5% with true preconditioning and 27.7% with the sham procedure, a nonsignificant difference. There were no significant differences between the two study groups in any of the individual components of this composite or according to type of anesthesia or the interval between preconditioning and surgical incision.

These findings remained strongly consistent across all subgroups of patients evaluated, regardless of troponin levels, inotrope score, presence or absence of kidney injury, degree of kidney injury, length of ICU stay, length of hospital stay, or performance on 6-minute walk test, Dr. Hausenloy and his associates said (N Engl J Med. 2015 Oct 5. doi: 10.1056/NEJMoa1413534).

In both trials, the rate of adverse effects from remote ischemic preconditioning was the same between the true and the sham procedures, and the only adverse effect considered to be related to preconditioning was an increased incidence of skin petechiae (4.4% vs. 0.2%) in the ERICCA study.

The investigators’ financial disclosures are available at NEJM.org.

Anti-TNF therapy for inflammatory bowel disease appears to double the relative risk of developing central demyelinating disease, though the absolute risk remains small, according to a preliminary report published online Oct. 5 in JAMA Internal Medicine.

Previous case reports have suggested a possible association between anti-TNF agents taken for IBD and later development of demyelinating diseases, but a definitive link has been difficult to establish because of the rarity of these disorders and the suspicion that there already may be an underlying association between IBD and demyelinating disease.

So researchers examined the issue by analyzing data from nationwide Danish health registries for IBD patients and medication exposure. They identified 4,504 patients treated during a 14-year period who had IBD and took anti-TNF agents, and 16,429 IBD patients matched for sex, age, and IBD duration who did not take the medications, according to Dr. Nynne Nyboe Andersen, of the department of epidemiology research, Statens Serum Institut, Copenhagen, and her associates.

Eleven patients in the exposed group had central demyelinating events: multiple sclerosis (2 patients), optic neuritis (5 patients), or other central demyelinating disease (4 patients). For exposed patients, there were 7.5 events per 10,000 person-years.

In comparison, 17 patients in the unexposed group had central demyelinating events: multiple sclerosis (5 patients), optic neuritis (6 patients), transverse myelitis (1 patient), or other central demyelinating disease (5 patients). In this group there were 3.3 events per 10,000 person-years.

The hazard ratio for developing central demyelinating disease after exposure to anti-TNF agents was 2.19, the investigators wrote (JAMA Intern Med. 2015 Oct 5, doi:10.1001/jamainternmed.2015.5396.).

These preliminary findings represent the first report of this association and must be confirmed in future studies, according to the researchers.

“If true, the observed association could either be attributed to the unmasking of a latent demyelinating disease or to the emergence of a de novo demyelinating disease,” Dr. Nyboe Andersen and her associates wrote in the research letter.

The study was supported by the Lundbeck Foundation, Women in Science, the Beckett Foundation, the Danish Colitis Crohn Association, and the Danish Council for Independent Research. Dr. Nyboe Andersen reported receiving travel and speaking fees from MSD and speaking fees from Ferring, and one of her associates reported receiving travel and speaking fees from AbbVie.

Anti-TNF therapy for inflammatory bowel disease appears to double the relative risk of developing central demyelinating disease, though the absolute risk remains small, according to a preliminary report published online Oct. 5 in JAMA Internal Medicine.

Previous case reports have suggested a possible association between anti-TNF agents taken for IBD and later development of demyelinating diseases, but a definitive link has been difficult to establish because of the rarity of these disorders and the suspicion that there already may be an underlying association between IBD and demyelinating disease.

So researchers examined the issue by analyzing data from nationwide Danish health registries for IBD patients and medication exposure. They identified 4,504 patients treated during a 14-year period who had IBD and took anti-TNF agents, and 16,429 IBD patients matched for sex, age, and IBD duration who did not take the medications, according to Dr. Nynne Nyboe Andersen, of the department of epidemiology research, Statens Serum Institut, Copenhagen, and her associates.

Eleven patients in the exposed group had central demyelinating events: multiple sclerosis (2 patients), optic neuritis (5 patients), or other central demyelinating disease (4 patients). For exposed patients, there were 7.5 events per 10,000 person-years.

In comparison, 17 patients in the unexposed group had central demyelinating events: multiple sclerosis (5 patients), optic neuritis (6 patients), transverse myelitis (1 patient), or other central demyelinating disease (5 patients). In this group there were 3.3 events per 10,000 person-years.

The hazard ratio for developing central demyelinating disease after exposure to anti-TNF agents was 2.19, the investigators wrote (JAMA Intern Med. 2015 Oct 5, doi:10.1001/jamainternmed.2015.5396.).

These preliminary findings represent the first report of this association and must be confirmed in future studies, according to the researchers.

“If true, the observed association could either be attributed to the unmasking of a latent demyelinating disease or to the emergence of a de novo demyelinating disease,” Dr. Nyboe Andersen and her associates wrote in the research letter.

The study was supported by the Lundbeck Foundation, Women in Science, the Beckett Foundation, the Danish Colitis Crohn Association, and the Danish Council for Independent Research. Dr. Nyboe Andersen reported receiving travel and speaking fees from MSD and speaking fees from Ferring, and one of her associates reported receiving travel and speaking fees from AbbVie.

Anti-TNF therapy for inflammatory bowel disease appears to double the relative risk of developing central demyelinating disease, though the absolute risk remains small, according to a preliminary report published online Oct. 5 in JAMA Internal Medicine.

Previous case reports have suggested a possible association between anti-TNF agents taken for IBD and later development of demyelinating diseases, but a definitive link has been difficult to establish because of the rarity of these disorders and the suspicion that there already may be an underlying association between IBD and demyelinating disease.

So researchers examined the issue by analyzing data from nationwide Danish health registries for IBD patients and medication exposure. They identified 4,504 patients treated during a 14-year period who had IBD and took anti-TNF agents, and 16,429 IBD patients matched for sex, age, and IBD duration who did not take the medications, according to Dr. Nynne Nyboe Andersen, of the department of epidemiology research, Statens Serum Institut, Copenhagen, and her associates.

Eleven patients in the exposed group had central demyelinating events: multiple sclerosis (2 patients), optic neuritis (5 patients), or other central demyelinating disease (4 patients). For exposed patients, there were 7.5 events per 10,000 person-years.

In comparison, 17 patients in the unexposed group had central demyelinating events: multiple sclerosis (5 patients), optic neuritis (6 patients), transverse myelitis (1 patient), or other central demyelinating disease (5 patients). In this group there were 3.3 events per 10,000 person-years.

The hazard ratio for developing central demyelinating disease after exposure to anti-TNF agents was 2.19, the investigators wrote (JAMA Intern Med. 2015 Oct 5, doi:10.1001/jamainternmed.2015.5396.).

These preliminary findings represent the first report of this association and must be confirmed in future studies, according to the researchers.

“If true, the observed association could either be attributed to the unmasking of a latent demyelinating disease or to the emergence of a de novo demyelinating disease,” Dr. Nyboe Andersen and her associates wrote in the research letter.

The study was supported by the Lundbeck Foundation, Women in Science, the Beckett Foundation, the Danish Colitis Crohn Association, and the Danish Council for Independent Research. Dr. Nyboe Andersen reported receiving travel and speaking fees from MSD and speaking fees from Ferring, and one of her associates reported receiving travel and speaking fees from AbbVie.

Reduced-nicotine cigarettes decreased tobacco dependence and the number of cigarettes smoked, with very little evidence of withdrawal or compensatory smoking, in a preliminary study reported online Oct. 1 in the New England Journal of Medicine.

Moreover, study participants who smoked very-low-nicotine cigarettes for the 6-week study were twice as likely to report that they attempted to quit 1 month later, compared with participants who smoked their usual brand or control cigarettes that had the usual nicotine content.

©painless/Fotolia.com

Reduced-nicotine cigarettes differ from “light” cigarettes in that the latter don’t actually reduce the nicotine content of the tobacco but instead increase ventilation of the cigarette – a strategy that is often circumvented by smokers who cover the ventilation holes or increase the number of cigarettes they smoke, said Eric C. Donny, Ph.D., of the department of psychology, University of Pittsburgh, and his associates.

The U.S. Food and Drug Administration recently was granted the authority to reduce, but not eliminate, nicotine in cigarettes if such action were deemed likely to benefit public health. However, no large-scale clinical trials have yet been performed to assess the potential benefit to public health.

Dr. Donny and his associates, supported by the National Institute on Drug Abuse and the FDA Center for Tobacco Products, conducted a double-blind, randomized trial at 10 sites comparing cigarettes with five levels of nicotine content among 839 adult smokers who were not planning to quit in the near future.

The study participants were assigned to smoke their usual brand of cigarettes (118 study subjects); control cigarettes containing the usual 15.8 mg of nicotine/g of tobacco (119 subjects); or experimental reduced-nicotine cigarettes containing 5.2 mg/g of nicotine (122 subjects), 2.4 mg/g (119 subjects), 1.3 mg/g (119 subjects), or 0.4 mg/g (242 subjects).

All the cigarettes were provided free of charge, and the smokers were paid for participating in the study. The dropout rate was only 8% at week 6 and did not differ significantly among the study groups.

The primary outcome – the average number of cigarettes smoked per day during week 6 – was markedly higher with the usual-brand group (22.2) and the control-cigarette group (21.3) than it was with the three lowest-nicotine groups (16.5, 16.3, and 14.9, respectively). That represents a reduction of 23%-30% in the number of cigarettes smoked in the latter three groups.

Tobacco dependence, as measured by the Wisconsin Inventory of Smoking Dependence Motives and the Fagerstrom Test for Nicotine Dependence, also was markedly lower with reduced-nicotine cigarettes.

Withdrawal symptoms did not increase; and during a brief voluntary abstinence period, smokers in the three lowest-nicotine groups actually reported fewer cravings than did those in the higher-nicotine groups, the investigators said (N Engl J Med. 2015 Oct 1;373[14]:1340-9).

At follow-up 30 days after completing the study, 34.7% of the participants who had smoked cigarettes with 0.4 mg/g of nicotine reported attempting to quit smoking, compared with 17% of those who had smoked cigarettes with 15.8 mg/g. In addition, participants who had smoked cigarettes with 1.3 mg/g or 0.4 mg/g of nicotine were still smoking significantly fewer cigarettes per day, even though the study had ended.

“In summary, these data suggest that if nicotine content is adequately reduced, smokers may benefit by smoking fewer cigarettes and experiencing less nicotine dependence, with few negative consequences,” Dr. Donny and his associates wrote. “If confirmed in longer-term studies, these findings suggest that, when combined with other tobacco-control policies (e.g., taxation and expanded access to treatment), limiting the nicotine content of cigarettes ... could improve public health.”

The study authors added that a longer clinical trial is now underway to further assess reduced-nicotine cigarettes.

NIDA and the FDA Center for Tobacco Products supported the study. Dr. Donny reported having no relevant financial disclosures. Two of his associates reported ties to Pfizer, and two reported serving as expert witnesses regarding addiction litigation against tobacco companies.

Reduced-nicotine cigarettes decreased tobacco dependence and the number of cigarettes smoked, with very little evidence of withdrawal or compensatory smoking, in a preliminary study reported online Oct. 1 in the New England Journal of Medicine.

Moreover, study participants who smoked very-low-nicotine cigarettes for the 6-week study were twice as likely to report that they attempted to quit 1 month later, compared with participants who smoked their usual brand or control cigarettes that had the usual nicotine content.

©painless/Fotolia.com

Reduced-nicotine cigarettes differ from “light” cigarettes in that the latter don’t actually reduce the nicotine content of the tobacco but instead increase ventilation of the cigarette – a strategy that is often circumvented by smokers who cover the ventilation holes or increase the number of cigarettes they smoke, said Eric C. Donny, Ph.D., of the department of psychology, University of Pittsburgh, and his associates.

The U.S. Food and Drug Administration recently was granted the authority to reduce, but not eliminate, nicotine in cigarettes if such action were deemed likely to benefit public health. However, no large-scale clinical trials have yet been performed to assess the potential benefit to public health.

Dr. Donny and his associates, supported by the National Institute on Drug Abuse and the FDA Center for Tobacco Products, conducted a double-blind, randomized trial at 10 sites comparing cigarettes with five levels of nicotine content among 839 adult smokers who were not planning to quit in the near future.

The study participants were assigned to smoke their usual brand of cigarettes (118 study subjects); control cigarettes containing the usual 15.8 mg of nicotine/g of tobacco (119 subjects); or experimental reduced-nicotine cigarettes containing 5.2 mg/g of nicotine (122 subjects), 2.4 mg/g (119 subjects), 1.3 mg/g (119 subjects), or 0.4 mg/g (242 subjects).

All the cigarettes were provided free of charge, and the smokers were paid for participating in the study. The dropout rate was only 8% at week 6 and did not differ significantly among the study groups.

The primary outcome – the average number of cigarettes smoked per day during week 6 – was markedly higher with the usual-brand group (22.2) and the control-cigarette group (21.3) than it was with the three lowest-nicotine groups (16.5, 16.3, and 14.9, respectively). That represents a reduction of 23%-30% in the number of cigarettes smoked in the latter three groups.

Tobacco dependence, as measured by the Wisconsin Inventory of Smoking Dependence Motives and the Fagerstrom Test for Nicotine Dependence, also was markedly lower with reduced-nicotine cigarettes.

Withdrawal symptoms did not increase; and during a brief voluntary abstinence period, smokers in the three lowest-nicotine groups actually reported fewer cravings than did those in the higher-nicotine groups, the investigators said (N Engl J Med. 2015 Oct 1;373[14]:1340-9).

At follow-up 30 days after completing the study, 34.7% of the participants who had smoked cigarettes with 0.4 mg/g of nicotine reported attempting to quit smoking, compared with 17% of those who had smoked cigarettes with 15.8 mg/g. In addition, participants who had smoked cigarettes with 1.3 mg/g or 0.4 mg/g of nicotine were still smoking significantly fewer cigarettes per day, even though the study had ended.

“In summary, these data suggest that if nicotine content is adequately reduced, smokers may benefit by smoking fewer cigarettes and experiencing less nicotine dependence, with few negative consequences,” Dr. Donny and his associates wrote. “If confirmed in longer-term studies, these findings suggest that, when combined with other tobacco-control policies (e.g., taxation and expanded access to treatment), limiting the nicotine content of cigarettes ... could improve public health.”

The study authors added that a longer clinical trial is now underway to further assess reduced-nicotine cigarettes.

NIDA and the FDA Center for Tobacco Products supported the study. Dr. Donny reported having no relevant financial disclosures. Two of his associates reported ties to Pfizer, and two reported serving as expert witnesses regarding addiction litigation against tobacco companies.

Reduced-nicotine cigarettes decreased tobacco dependence and the number of cigarettes smoked, with very little evidence of withdrawal or compensatory smoking, in a preliminary study reported online Oct. 1 in the New England Journal of Medicine.

Moreover, study participants who smoked very-low-nicotine cigarettes for the 6-week study were twice as likely to report that they attempted to quit 1 month later, compared with participants who smoked their usual brand or control cigarettes that had the usual nicotine content.

©painless/Fotolia.com

Reduced-nicotine cigarettes differ from “light” cigarettes in that the latter don’t actually reduce the nicotine content of the tobacco but instead increase ventilation of the cigarette – a strategy that is often circumvented by smokers who cover the ventilation holes or increase the number of cigarettes they smoke, said Eric C. Donny, Ph.D., of the department of psychology, University of Pittsburgh, and his associates.

The U.S. Food and Drug Administration recently was granted the authority to reduce, but not eliminate, nicotine in cigarettes if such action were deemed likely to benefit public health. However, no large-scale clinical trials have yet been performed to assess the potential benefit to public health.

Dr. Donny and his associates, supported by the National Institute on Drug Abuse and the FDA Center for Tobacco Products, conducted a double-blind, randomized trial at 10 sites comparing cigarettes with five levels of nicotine content among 839 adult smokers who were not planning to quit in the near future.

The study participants were assigned to smoke their usual brand of cigarettes (118 study subjects); control cigarettes containing the usual 15.8 mg of nicotine/g of tobacco (119 subjects); or experimental reduced-nicotine cigarettes containing 5.2 mg/g of nicotine (122 subjects), 2.4 mg/g (119 subjects), 1.3 mg/g (119 subjects), or 0.4 mg/g (242 subjects).

All the cigarettes were provided free of charge, and the smokers were paid for participating in the study. The dropout rate was only 8% at week 6 and did not differ significantly among the study groups.

The primary outcome – the average number of cigarettes smoked per day during week 6 – was markedly higher with the usual-brand group (22.2) and the control-cigarette group (21.3) than it was with the three lowest-nicotine groups (16.5, 16.3, and 14.9, respectively). That represents a reduction of 23%-30% in the number of cigarettes smoked in the latter three groups.

Tobacco dependence, as measured by the Wisconsin Inventory of Smoking Dependence Motives and the Fagerstrom Test for Nicotine Dependence, also was markedly lower with reduced-nicotine cigarettes.

Withdrawal symptoms did not increase; and during a brief voluntary abstinence period, smokers in the three lowest-nicotine groups actually reported fewer cravings than did those in the higher-nicotine groups, the investigators said (N Engl J Med. 2015 Oct 1;373[14]:1340-9).

At follow-up 30 days after completing the study, 34.7% of the participants who had smoked cigarettes with 0.4 mg/g of nicotine reported attempting to quit smoking, compared with 17% of those who had smoked cigarettes with 15.8 mg/g. In addition, participants who had smoked cigarettes with 1.3 mg/g or 0.4 mg/g of nicotine were still smoking significantly fewer cigarettes per day, even though the study had ended.

“In summary, these data suggest that if nicotine content is adequately reduced, smokers may benefit by smoking fewer cigarettes and experiencing less nicotine dependence, with few negative consequences,” Dr. Donny and his associates wrote. “If confirmed in longer-term studies, these findings suggest that, when combined with other tobacco-control policies (e.g., taxation and expanded access to treatment), limiting the nicotine content of cigarettes ... could improve public health.”

The study authors added that a longer clinical trial is now underway to further assess reduced-nicotine cigarettes.

NIDA and the FDA Center for Tobacco Products supported the study. Dr. Donny reported having no relevant financial disclosures. Two of his associates reported ties to Pfizer, and two reported serving as expert witnesses regarding addiction litigation against tobacco companies.