Mary Ann Moon

Mortality rates of people infected with HIV now approach those of the general population, at least for the first 5 years of the infection, according to a large multinational study.

The gap in mortality rates between people with HIV infection and the general population has narrowed every year since the introduction of highly active antiretroviral therapy in 1996, study investigators reported.

This represents a 94% reduction in excess mortality in recent years, as compared with the time before HAART was available.

However, there still appears to be an excess in mortality as the duration of HIV infection increases.

To compare mortality rates, the investigators used a large data set comprising 21 separate cohorts of HIV-infected subjects whose dates of seroconversion (development of serum antibodies as a result of infection) had been pinned down relatively precisely. These cohorts included 16,534 subjects who were followed for up to 23 years in 10 European countries, Australia, and Canada.

A total of 2,571 of the subjects had died as of the end of 2006, compared with an estimated 235 deaths that would be expected in a matched cohort from the general population. The excess in mortality was most marked during the pre-HAART time period and declined dramatically from 1996 onward, said the investigators, led by Krishnan Bhaskaran of the Medical Research Council Clinical Trials Unit, London.

By the end of the study period in 2006, "there was no evidence of any excess mortality to 5 years from seroconversion in any age group," Mr. Bhaskaran and his associates said (JAMA 2008;300:51-9).

However, some excess mortality was still evident as the duration of HIV infection lengthened to 10 years or more. "It is likely that, even with current standards of HIV management, some long-term excess mortality would remain because problems of toxicity, resistance, and therapy adherence are likely to increase with time," they noted.

Mortality was four times as high among subjects who acquired HIV through intravenous drug use than among those who acquired it through sexual contact. This likely reflects the fact that intravenous drug users are at higher risk than nonusers for mental health-related illness and coinfections, and often have poorer access to and adherence to treatment, the investigators added.

Mortality rates of people infected with HIV now approach those of the general population, at least for the first 5 years of the infection, according to a large multinational study.

The gap in mortality rates between people with HIV infection and the general population has narrowed every year since the introduction of highly active antiretroviral therapy in 1996, study investigators reported.

This represents a 94% reduction in excess mortality in recent years, as compared with the time before HAART was available.

However, there still appears to be an excess in mortality as the duration of HIV infection increases.

To compare mortality rates, the investigators used a large data set comprising 21 separate cohorts of HIV-infected subjects whose dates of seroconversion (development of serum antibodies as a result of infection) had been pinned down relatively precisely. These cohorts included 16,534 subjects who were followed for up to 23 years in 10 European countries, Australia, and Canada.

A total of 2,571 of the subjects had died as of the end of 2006, compared with an estimated 235 deaths that would be expected in a matched cohort from the general population. The excess in mortality was most marked during the pre-HAART time period and declined dramatically from 1996 onward, said the investigators, led by Krishnan Bhaskaran of the Medical Research Council Clinical Trials Unit, London.

By the end of the study period in 2006, "there was no evidence of any excess mortality to 5 years from seroconversion in any age group," Mr. Bhaskaran and his associates said (JAMA 2008;300:51-9).

However, some excess mortality was still evident as the duration of HIV infection lengthened to 10 years or more. "It is likely that, even with current standards of HIV management, some long-term excess mortality would remain because problems of toxicity, resistance, and therapy adherence are likely to increase with time," they noted.

Mortality was four times as high among subjects who acquired HIV through intravenous drug use than among those who acquired it through sexual contact. This likely reflects the fact that intravenous drug users are at higher risk than nonusers for mental health-related illness and coinfections, and often have poorer access to and adherence to treatment, the investigators added.

Mortality rates of people infected with HIV now approach those of the general population, at least for the first 5 years of the infection, according to a large multinational study.

The gap in mortality rates between people with HIV infection and the general population has narrowed every year since the introduction of highly active antiretroviral therapy in 1996, study investigators reported.

This represents a 94% reduction in excess mortality in recent years, as compared with the time before HAART was available.

However, there still appears to be an excess in mortality as the duration of HIV infection increases.

To compare mortality rates, the investigators used a large data set comprising 21 separate cohorts of HIV-infected subjects whose dates of seroconversion (development of serum antibodies as a result of infection) had been pinned down relatively precisely. These cohorts included 16,534 subjects who were followed for up to 23 years in 10 European countries, Australia, and Canada.

A total of 2,571 of the subjects had died as of the end of 2006, compared with an estimated 235 deaths that would be expected in a matched cohort from the general population. The excess in mortality was most marked during the pre-HAART time period and declined dramatically from 1996 onward, said the investigators, led by Krishnan Bhaskaran of the Medical Research Council Clinical Trials Unit, London.

By the end of the study period in 2006, "there was no evidence of any excess mortality to 5 years from seroconversion in any age group," Mr. Bhaskaran and his associates said (JAMA 2008;300:51-9).

However, some excess mortality was still evident as the duration of HIV infection lengthened to 10 years or more. "It is likely that, even with current standards of HIV management, some long-term excess mortality would remain because problems of toxicity, resistance, and therapy adherence are likely to increase with time," they noted.

Mortality was four times as high among subjects who acquired HIV through intravenous drug use than among those who acquired it through sexual contact. This likely reflects the fact that intravenous drug users are at higher risk than nonusers for mental health-related illness and coinfections, and often have poorer access to and adherence to treatment, the investigators added.

Prolonged therapy with pegylated interferon has been found to improve recurrence-free survival in patients with excised stage III melanoma in a randomized phase III trial.

In contrast, survival free of distant metastases was numerically but not statistically significantly better with adjuvant pegylated interferon, and the treatment had no apparent effect on overall survival, Dr. Alexander M. M. Eggermont and his associates reported in the European Organisation for Research and Treatment of Cancer (EORTC) trial 18991 (Lancet 2008;372:117-26).

In an editorial comment that accompanied the report, Dr. Vernon K. Sondak and Dr. Lawrence E. Flaherty wrote that "many patients with melanoma are willing to accept significant toxicity in exchange for a modest improvement in recurrence-free survival, even in the absence of an overall survival effect," (Lancet 2008;372:89-90).

It remains to be seen, however, whether such patients and their physicians will accept 5 years of pegylated interferon treatment "for an absolute benefit in recurrence-free survival of about 6% at 4 years," they noted.

Dr. Eggermont and his colleagues compared the therapy with observation alone in a randomized controlled trial involving 1,256 patients treated at 99 medical centers in 17 countries. All patients had undergone complete excision of stage III melanoma and complete regional lymphadenectomy.

The study was funded by Schering-Plough Research International.

The two study groups were well matched according to disease substage, number of involved lymph nodes, thickness of the primary tumor, and ulceration of the primary tumor. Patients who took interferon received high-dose induction therapy for 8 weeks, followed by once-weekly self-administered subcutaneous injections for an intended duration of 5 years, said Dr. Eggermont, of Erasmus University, Rotterdam, the Netherlands, and his associates.

After a median of 4 years of follow-up, significantly fewer recurrences had developed in the interferon group than in the observation group, with a 6.7% absolute difference in estimated rates of recurrence-free survival. The therapy's benefit was seen early in the course of treatment and remained at a consistent level throughout the study, the investigators said.

However, there was no difference in overall survival between patients who took pegylated interferon and those who did not.

The drug was most effective in patients who had microscopic rather than palpable nodal disease, patients whose involvement was limited to one lymph node, and in patients with ulcerated rather than nonulcerated tumors. These groups accounted for approximately 40% of the treated patients.

One-third of the study subjects who took interferon discontinued the drug because of toxicity. The most common adverse effects were fatigue and depression, which were reported in 25% and 16% of patients, respectively. Anorexia, liver function abnormalities, myalgia, headache, nausea, and fever also were reported.

In their editorial comment, Dr. Sondak of H. Lee Moffitt Cancer Center, Tampa, and Dr. Flaherty of Karmanos Cancer Institute, Detroit, said that a 4-year follow-up "is too short for final conclusions." Further follow-up and more clinical trials are needed. However, they added, "for the large group of patients with melanoma found in their sentinel node, we believe this regimen will be an attractive alternative to high-dose interferon."

Dr. Eggermont, Dr. Sondak, and Dr. Flaherty have all been paid consultants for Schering-Plough.

Prolonged therapy with pegylated interferon has been found to improve recurrence-free survival in patients with excised stage III melanoma in a randomized phase III trial.

In contrast, survival free of distant metastases was numerically but not statistically significantly better with adjuvant pegylated interferon, and the treatment had no apparent effect on overall survival, Dr. Alexander M. M. Eggermont and his associates reported in the European Organisation for Research and Treatment of Cancer (EORTC) trial 18991 (Lancet 2008;372:117-26).

In an editorial comment that accompanied the report, Dr. Vernon K. Sondak and Dr. Lawrence E. Flaherty wrote that "many patients with melanoma are willing to accept significant toxicity in exchange for a modest improvement in recurrence-free survival, even in the absence of an overall survival effect," (Lancet 2008;372:89-90).

It remains to be seen, however, whether such patients and their physicians will accept 5 years of pegylated interferon treatment "for an absolute benefit in recurrence-free survival of about 6% at 4 years," they noted.

Dr. Eggermont and his colleagues compared the therapy with observation alone in a randomized controlled trial involving 1,256 patients treated at 99 medical centers in 17 countries. All patients had undergone complete excision of stage III melanoma and complete regional lymphadenectomy.

The study was funded by Schering-Plough Research International.

The two study groups were well matched according to disease substage, number of involved lymph nodes, thickness of the primary tumor, and ulceration of the primary tumor. Patients who took interferon received high-dose induction therapy for 8 weeks, followed by once-weekly self-administered subcutaneous injections for an intended duration of 5 years, said Dr. Eggermont, of Erasmus University, Rotterdam, the Netherlands, and his associates.

After a median of 4 years of follow-up, significantly fewer recurrences had developed in the interferon group than in the observation group, with a 6.7% absolute difference in estimated rates of recurrence-free survival. The therapy's benefit was seen early in the course of treatment and remained at a consistent level throughout the study, the investigators said.

However, there was no difference in overall survival between patients who took pegylated interferon and those who did not.

The drug was most effective in patients who had microscopic rather than palpable nodal disease, patients whose involvement was limited to one lymph node, and in patients with ulcerated rather than nonulcerated tumors. These groups accounted for approximately 40% of the treated patients.

One-third of the study subjects who took interferon discontinued the drug because of toxicity. The most common adverse effects were fatigue and depression, which were reported in 25% and 16% of patients, respectively. Anorexia, liver function abnormalities, myalgia, headache, nausea, and fever also were reported.

In their editorial comment, Dr. Sondak of H. Lee Moffitt Cancer Center, Tampa, and Dr. Flaherty of Karmanos Cancer Institute, Detroit, said that a 4-year follow-up "is too short for final conclusions." Further follow-up and more clinical trials are needed. However, they added, "for the large group of patients with melanoma found in their sentinel node, we believe this regimen will be an attractive alternative to high-dose interferon."

Dr. Eggermont, Dr. Sondak, and Dr. Flaherty have all been paid consultants for Schering-Plough.

Prolonged therapy with pegylated interferon has been found to improve recurrence-free survival in patients with excised stage III melanoma in a randomized phase III trial.

In contrast, survival free of distant metastases was numerically but not statistically significantly better with adjuvant pegylated interferon, and the treatment had no apparent effect on overall survival, Dr. Alexander M. M. Eggermont and his associates reported in the European Organisation for Research and Treatment of Cancer (EORTC) trial 18991 (Lancet 2008;372:117-26).

In an editorial comment that accompanied the report, Dr. Vernon K. Sondak and Dr. Lawrence E. Flaherty wrote that "many patients with melanoma are willing to accept significant toxicity in exchange for a modest improvement in recurrence-free survival, even in the absence of an overall survival effect," (Lancet 2008;372:89-90).

It remains to be seen, however, whether such patients and their physicians will accept 5 years of pegylated interferon treatment "for an absolute benefit in recurrence-free survival of about 6% at 4 years," they noted.

Dr. Eggermont and his colleagues compared the therapy with observation alone in a randomized controlled trial involving 1,256 patients treated at 99 medical centers in 17 countries. All patients had undergone complete excision of stage III melanoma and complete regional lymphadenectomy.

The study was funded by Schering-Plough Research International.

The two study groups were well matched according to disease substage, number of involved lymph nodes, thickness of the primary tumor, and ulceration of the primary tumor. Patients who took interferon received high-dose induction therapy for 8 weeks, followed by once-weekly self-administered subcutaneous injections for an intended duration of 5 years, said Dr. Eggermont, of Erasmus University, Rotterdam, the Netherlands, and his associates.

After a median of 4 years of follow-up, significantly fewer recurrences had developed in the interferon group than in the observation group, with a 6.7% absolute difference in estimated rates of recurrence-free survival. The therapy's benefit was seen early in the course of treatment and remained at a consistent level throughout the study, the investigators said.

However, there was no difference in overall survival between patients who took pegylated interferon and those who did not.

The drug was most effective in patients who had microscopic rather than palpable nodal disease, patients whose involvement was limited to one lymph node, and in patients with ulcerated rather than nonulcerated tumors. These groups accounted for approximately 40% of the treated patients.

One-third of the study subjects who took interferon discontinued the drug because of toxicity. The most common adverse effects were fatigue and depression, which were reported in 25% and 16% of patients, respectively. Anorexia, liver function abnormalities, myalgia, headache, nausea, and fever also were reported.

In their editorial comment, Dr. Sondak of H. Lee Moffitt Cancer Center, Tampa, and Dr. Flaherty of Karmanos Cancer Institute, Detroit, said that a 4-year follow-up "is too short for final conclusions." Further follow-up and more clinical trials are needed. However, they added, "for the large group of patients with melanoma found in their sentinel node, we believe this regimen will be an attractive alternative to high-dose interferon."

Dr. Eggermont, Dr. Sondak, and Dr. Flaherty have all been paid consultants for Schering-Plough.

More young adults now say that they value the appearance of a tan than have said so in past years, and their increased use of indoor tanning reflects that attitude, according to Dr. June K. Robinson of Northwestern University, Chicago, and her associates.

Researchers surveyed 100 people who appeared to be aged 18-30 years, and were sitting or lying on a Chicago beach in July of last year, about their knowledge of, attitudes toward, and use of indoor tanning, and compared the results with telephone surveys of 1,000 Illinois residents conducted in 1988 and with 958 teenage and young adult Chicagoans in 1994.

The 38 men and 62 women in the present survey were matched for age and sex with 100 subjects in each earlier survey.

The knowledge that tanning can cause melanoma/skin cancer initially decreased from 42% in the 1988 survey to 38% in the 1994 survey but then increased to 87% in 2007, Dr. Robinson and her associates reported (Arch. Dermatol. 2008;144:484-8).

Nevertheless, they said, "in each successive interval, there was an almost equivalent increase in the perception that people looked better with a tan"—from 58% to 69% and finally to 81% in 2007.

Tanning bed use also rose from 1% in 1988 to 26% in 1994 and 27% in 2007.

In all years surveyed, respondents said that they got most of their information about the general safety of indoor tanning beds from their friends or social group (71%-75%) and half reported that they went to a tanning salon for the first time with their friends. Other sources of information included family (18%-21%) and tanning salon workers (23%-24%).

Adolescents and young adults said their most trusted source of information about indoor tanning was the family physician or dermatologist, but only 15% reported that they had ever discussed the issue with their physicians, Dr. Robinson and her associates found.

"Counseling young adult patients to cease indoor tanning represents an opportunity to prevent UV radiation exposure that may cause melanoma," they noted.

More young adults now say that they value the appearance of a tan than have said so in past years, and their increased use of indoor tanning reflects that attitude, according to Dr. June K. Robinson of Northwestern University, Chicago, and her associates.

Researchers surveyed 100 people who appeared to be aged 18-30 years, and were sitting or lying on a Chicago beach in July of last year, about their knowledge of, attitudes toward, and use of indoor tanning, and compared the results with telephone surveys of 1,000 Illinois residents conducted in 1988 and with 958 teenage and young adult Chicagoans in 1994.

The 38 men and 62 women in the present survey were matched for age and sex with 100 subjects in each earlier survey.

The knowledge that tanning can cause melanoma/skin cancer initially decreased from 42% in the 1988 survey to 38% in the 1994 survey but then increased to 87% in 2007, Dr. Robinson and her associates reported (Arch. Dermatol. 2008;144:484-8).

Nevertheless, they said, "in each successive interval, there was an almost equivalent increase in the perception that people looked better with a tan"—from 58% to 69% and finally to 81% in 2007.

Tanning bed use also rose from 1% in 1988 to 26% in 1994 and 27% in 2007.

In all years surveyed, respondents said that they got most of their information about the general safety of indoor tanning beds from their friends or social group (71%-75%) and half reported that they went to a tanning salon for the first time with their friends. Other sources of information included family (18%-21%) and tanning salon workers (23%-24%).

Adolescents and young adults said their most trusted source of information about indoor tanning was the family physician or dermatologist, but only 15% reported that they had ever discussed the issue with their physicians, Dr. Robinson and her associates found.

"Counseling young adult patients to cease indoor tanning represents an opportunity to prevent UV radiation exposure that may cause melanoma," they noted.

More young adults now say that they value the appearance of a tan than have said so in past years, and their increased use of indoor tanning reflects that attitude, according to Dr. June K. Robinson of Northwestern University, Chicago, and her associates.

Researchers surveyed 100 people who appeared to be aged 18-30 years, and were sitting or lying on a Chicago beach in July of last year, about their knowledge of, attitudes toward, and use of indoor tanning, and compared the results with telephone surveys of 1,000 Illinois residents conducted in 1988 and with 958 teenage and young adult Chicagoans in 1994.

The 38 men and 62 women in the present survey were matched for age and sex with 100 subjects in each earlier survey.

The knowledge that tanning can cause melanoma/skin cancer initially decreased from 42% in the 1988 survey to 38% in the 1994 survey but then increased to 87% in 2007, Dr. Robinson and her associates reported (Arch. Dermatol. 2008;144:484-8).

Nevertheless, they said, "in each successive interval, there was an almost equivalent increase in the perception that people looked better with a tan"—from 58% to 69% and finally to 81% in 2007.

Tanning bed use also rose from 1% in 1988 to 26% in 1994 and 27% in 2007.

In all years surveyed, respondents said that they got most of their information about the general safety of indoor tanning beds from their friends or social group (71%-75%) and half reported that they went to a tanning salon for the first time with their friends. Other sources of information included family (18%-21%) and tanning salon workers (23%-24%).

Adolescents and young adults said their most trusted source of information about indoor tanning was the family physician or dermatologist, but only 15% reported that they had ever discussed the issue with their physicians, Dr. Robinson and her associates found.

"Counseling young adult patients to cease indoor tanning represents an opportunity to prevent UV radiation exposure that may cause melanoma," they noted.

The selective 5-hydroxytryptamine receptor agonist prucalopride improved the rate of spontaneous, complete bowel movements in patients with severe chronic constipation, researchers reported.

Over 12 weeks of treatment in the phase III clinical trial, prucalopride also reduced the frequency and severity of abdominal and stool symptoms, and it significantly improved quality of life, compared with placebo, according to Dr. Michael Camilleri of the Mayo Clinic, Rochester, Minn., and his associates.

However, there is concern about potential cardiac risks with the drug, which is “similar in function to cisapride and tegaserod, two constipation-reducing drugs that were voluntarily removed from the market after warnings from the Food and Drug Administration about life-threatening cardiac side effects,” Dr. Arthur J. Moss of the University of Rochester (N.Y.) said in an editorial comment accompanying the report.

There are additional concerns about the 9-year delay in publishing the results.

The trial was designed by Johnson & Johnson in 1998 and conducted in 1998–1999, but the final analysis was done by a Belgian company, Movetis NV, in 2007, after Movetis purchased the drug.

“It is not known why clinical trials with prucalopride were temporarily suspended around 2001, or why it took so long to bring this study to publication,” Dr. Moss noted (N. Engl. J. Med. 2008;358:2402-3).

The study was conducted at 38 U.S. medical centers and involved 620 patients who had two or fewer spontaneous, complete bowel movements per week for a minimum of 6 months.

Patients had hard or very hard stools, a sensation of incomplete evacuation, or straining during defecation at least 25% of the time.

In all, 207 patients were randomly assigned to receive 2 mg of prucalopride, 204 patients received 4 mg of prucalopride, and 209 patients received placebo orally once a day for 3 months. The percentage of patients whose bowel function normalized to three or more spontaneous, complete bowel movements per week was 31% with the 2-mg dose, and 28% with the 4-mg dose of prucalopride, a difference that was not statistically significant.

The percentages were significantly greater than the 12% of subjects in the placebo group whose bowel function normalized, Dr. Camilleri and his associates said (N. Engl. J. Med. 2008;358:2344-54).

Similarly, the percentage of patients who reported an increase in the number of spontaneous, complete bowel movements per week was 47% with 2 mg prucalopride and 47% with 4 mg prucalopride, compared with 26% with placebo, the investigators reported.

Patients in both active-treatment groups also were able to decrease their use of “rescue” laxatives by approximately half during the study.

Quality of life improved in 45% of patients taking 2 mg prucalopride and in 49% of those taking 4 mg, compared with 24% of those patients taking placebo.

Adverse events occurred in 80% of patients taking 2 mg of prucalopride, in 78% of patients taking 4 mg, and in 71% of patients taking placebo. The most frequent adverse events were abdominal pain, headache, nausea, and diarrhea.

Adverse events led to treatment stoppage in 8.2% of patients on 2 mg of prucalopride, in 8% of patients on 4 mg, and in 2% of those on placebo. Three patients discontinued treatment because of adverse events that included cardiovascular events.

“Further assessment of the cardiovascular safety of prucalopride in other trials is required to ensure that rare adverse cardiovascular effects are ruled out,” the investigators said.

In his editorial comment, Dr. Moss concurred. “More complete clinical, electrophysiological, and pharmacokinetic data are required before this drug can be brought to market for the treatment of chronic constipation,” he said.

ELSEVIER GLOBAL MEDICAL NEWS

The selective 5-hydroxytryptamine receptor agonist prucalopride improved the rate of spontaneous, complete bowel movements in patients with severe chronic constipation, researchers reported.

Over 12 weeks of treatment in the phase III clinical trial, prucalopride also reduced the frequency and severity of abdominal and stool symptoms, and it significantly improved quality of life, compared with placebo, according to Dr. Michael Camilleri of the Mayo Clinic, Rochester, Minn., and his associates.

However, there is concern about potential cardiac risks with the drug, which is “similar in function to cisapride and tegaserod, two constipation-reducing drugs that were voluntarily removed from the market after warnings from the Food and Drug Administration about life-threatening cardiac side effects,” Dr. Arthur J. Moss of the University of Rochester (N.Y.) said in an editorial comment accompanying the report.

There are additional concerns about the 9-year delay in publishing the results.

The trial was designed by Johnson & Johnson in 1998 and conducted in 1998–1999, but the final analysis was done by a Belgian company, Movetis NV, in 2007, after Movetis purchased the drug.

“It is not known why clinical trials with prucalopride were temporarily suspended around 2001, or why it took so long to bring this study to publication,” Dr. Moss noted (N. Engl. J. Med. 2008;358:2402-3).

The study was conducted at 38 U.S. medical centers and involved 620 patients who had two or fewer spontaneous, complete bowel movements per week for a minimum of 6 months.

Patients had hard or very hard stools, a sensation of incomplete evacuation, or straining during defecation at least 25% of the time.

In all, 207 patients were randomly assigned to receive 2 mg of prucalopride, 204 patients received 4 mg of prucalopride, and 209 patients received placebo orally once a day for 3 months. The percentage of patients whose bowel function normalized to three or more spontaneous, complete bowel movements per week was 31% with the 2-mg dose, and 28% with the 4-mg dose of prucalopride, a difference that was not statistically significant.

The percentages were significantly greater than the 12% of subjects in the placebo group whose bowel function normalized, Dr. Camilleri and his associates said (N. Engl. J. Med. 2008;358:2344-54).

Similarly, the percentage of patients who reported an increase in the number of spontaneous, complete bowel movements per week was 47% with 2 mg prucalopride and 47% with 4 mg prucalopride, compared with 26% with placebo, the investigators reported.

Patients in both active-treatment groups also were able to decrease their use of “rescue” laxatives by approximately half during the study.

Quality of life improved in 45% of patients taking 2 mg prucalopride and in 49% of those taking 4 mg, compared with 24% of those patients taking placebo.

Adverse events occurred in 80% of patients taking 2 mg of prucalopride, in 78% of patients taking 4 mg, and in 71% of patients taking placebo. The most frequent adverse events were abdominal pain, headache, nausea, and diarrhea.

Adverse events led to treatment stoppage in 8.2% of patients on 2 mg of prucalopride, in 8% of patients on 4 mg, and in 2% of those on placebo. Three patients discontinued treatment because of adverse events that included cardiovascular events.

“Further assessment of the cardiovascular safety of prucalopride in other trials is required to ensure that rare adverse cardiovascular effects are ruled out,” the investigators said.

In his editorial comment, Dr. Moss concurred. “More complete clinical, electrophysiological, and pharmacokinetic data are required before this drug can be brought to market for the treatment of chronic constipation,” he said.

ELSEVIER GLOBAL MEDICAL NEWS

The selective 5-hydroxytryptamine receptor agonist prucalopride improved the rate of spontaneous, complete bowel movements in patients with severe chronic constipation, researchers reported.

Over 12 weeks of treatment in the phase III clinical trial, prucalopride also reduced the frequency and severity of abdominal and stool symptoms, and it significantly improved quality of life, compared with placebo, according to Dr. Michael Camilleri of the Mayo Clinic, Rochester, Minn., and his associates.

However, there is concern about potential cardiac risks with the drug, which is “similar in function to cisapride and tegaserod, two constipation-reducing drugs that were voluntarily removed from the market after warnings from the Food and Drug Administration about life-threatening cardiac side effects,” Dr. Arthur J. Moss of the University of Rochester (N.Y.) said in an editorial comment accompanying the report.

There are additional concerns about the 9-year delay in publishing the results.

The trial was designed by Johnson & Johnson in 1998 and conducted in 1998–1999, but the final analysis was done by a Belgian company, Movetis NV, in 2007, after Movetis purchased the drug.

“It is not known why clinical trials with prucalopride were temporarily suspended around 2001, or why it took so long to bring this study to publication,” Dr. Moss noted (N. Engl. J. Med. 2008;358:2402-3).

The study was conducted at 38 U.S. medical centers and involved 620 patients who had two or fewer spontaneous, complete bowel movements per week for a minimum of 6 months.

Patients had hard or very hard stools, a sensation of incomplete evacuation, or straining during defecation at least 25% of the time.

In all, 207 patients were randomly assigned to receive 2 mg of prucalopride, 204 patients received 4 mg of prucalopride, and 209 patients received placebo orally once a day for 3 months. The percentage of patients whose bowel function normalized to three or more spontaneous, complete bowel movements per week was 31% with the 2-mg dose, and 28% with the 4-mg dose of prucalopride, a difference that was not statistically significant.

The percentages were significantly greater than the 12% of subjects in the placebo group whose bowel function normalized, Dr. Camilleri and his associates said (N. Engl. J. Med. 2008;358:2344-54).

Similarly, the percentage of patients who reported an increase in the number of spontaneous, complete bowel movements per week was 47% with 2 mg prucalopride and 47% with 4 mg prucalopride, compared with 26% with placebo, the investigators reported.

Patients in both active-treatment groups also were able to decrease their use of “rescue” laxatives by approximately half during the study.

Quality of life improved in 45% of patients taking 2 mg prucalopride and in 49% of those taking 4 mg, compared with 24% of those patients taking placebo.

Adverse events occurred in 80% of patients taking 2 mg of prucalopride, in 78% of patients taking 4 mg, and in 71% of patients taking placebo. The most frequent adverse events were abdominal pain, headache, nausea, and diarrhea.

Adverse events led to treatment stoppage in 8.2% of patients on 2 mg of prucalopride, in 8% of patients on 4 mg, and in 2% of those on placebo. Three patients discontinued treatment because of adverse events that included cardiovascular events.

“Further assessment of the cardiovascular safety of prucalopride in other trials is required to ensure that rare adverse cardiovascular effects are ruled out,” the investigators said.

In his editorial comment, Dr. Moss concurred. “More complete clinical, electrophysiological, and pharmacokinetic data are required before this drug can be brought to market for the treatment of chronic constipation,” he said.

ELSEVIER GLOBAL MEDICAL NEWS

Type 2 diabetes and depressive symptoms have a bidirectional association: People with diabetes are at increased risk of developing depressive symptoms, and those with depressive symptoms are at increased risk of developing diabetes, according to a report in the June 18 issue of the Journal of the American Medical Association.

These results, from a population-based longitudinal study that followed approximately 5,000 middle-aged subjects for up to 5 years, are the first to demonstrate a bidirectional association between “these two serious long-term diseases,” said Dr. Sherita Hill Golden of Johns Hopkins University, Baltimore, and her associates.

The findings suggest that interventions targeting depression may complement diabetes prevention strategies, and that patients who already have diabetes perhaps should be screened for depressive symptoms, the investigators noted (JAMA 2008;299:2751-9).

They examined the relationship between diabetes and depression using data from a multicenter longitudinal cohort study of men and women whose mean age was in the 60s and who resided in six U.S. communities. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale, a 20-item questionnaire designed to evaluate such symptoms in community populations.

Among subjects who had no depressive symptoms at baseline, those with type 2 diabetes were at significantly higher risk for developing depressive symptoms during follow-up, independent of their body mass index, socioeconomic status, and comorbidities.

It is possible that the psychological stress of managing diabetes may lead to depression, or that the complications and comorbidities of the disease may increase depressive symptoms, Dr. Golden and her associates said.

In addition, subjects who had depressive symptoms at baseline were at modestly increased risk of developing diabetes during follow-up, independent of sociodemographic, economic, and metabolic factors.

The National Heart, Lung, and Blood Institute was a sponsor of this study. Dr. Golden serves on the Merck Clinical Diabetes Advisory Board and has received an unrestricted educational grant from Novo Nordisk in the past.

Type 2 diabetes and depressive symptoms have a bidirectional association: People with diabetes are at increased risk of developing depressive symptoms, and those with depressive symptoms are at increased risk of developing diabetes, according to a report in the June 18 issue of the Journal of the American Medical Association.

These results, from a population-based longitudinal study that followed approximately 5,000 middle-aged subjects for up to 5 years, are the first to demonstrate a bidirectional association between “these two serious long-term diseases,” said Dr. Sherita Hill Golden of Johns Hopkins University, Baltimore, and her associates.

The findings suggest that interventions targeting depression may complement diabetes prevention strategies, and that patients who already have diabetes perhaps should be screened for depressive symptoms, the investigators noted (JAMA 2008;299:2751-9).

They examined the relationship between diabetes and depression using data from a multicenter longitudinal cohort study of men and women whose mean age was in the 60s and who resided in six U.S. communities. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale, a 20-item questionnaire designed to evaluate such symptoms in community populations.

Among subjects who had no depressive symptoms at baseline, those with type 2 diabetes were at significantly higher risk for developing depressive symptoms during follow-up, independent of their body mass index, socioeconomic status, and comorbidities.

It is possible that the psychological stress of managing diabetes may lead to depression, or that the complications and comorbidities of the disease may increase depressive symptoms, Dr. Golden and her associates said.

In addition, subjects who had depressive symptoms at baseline were at modestly increased risk of developing diabetes during follow-up, independent of sociodemographic, economic, and metabolic factors.

The National Heart, Lung, and Blood Institute was a sponsor of this study. Dr. Golden serves on the Merck Clinical Diabetes Advisory Board and has received an unrestricted educational grant from Novo Nordisk in the past.

Type 2 diabetes and depressive symptoms have a bidirectional association: People with diabetes are at increased risk of developing depressive symptoms, and those with depressive symptoms are at increased risk of developing diabetes, according to a report in the June 18 issue of the Journal of the American Medical Association.

These results, from a population-based longitudinal study that followed approximately 5,000 middle-aged subjects for up to 5 years, are the first to demonstrate a bidirectional association between “these two serious long-term diseases,” said Dr. Sherita Hill Golden of Johns Hopkins University, Baltimore, and her associates.

The findings suggest that interventions targeting depression may complement diabetes prevention strategies, and that patients who already have diabetes perhaps should be screened for depressive symptoms, the investigators noted (JAMA 2008;299:2751-9).

They examined the relationship between diabetes and depression using data from a multicenter longitudinal cohort study of men and women whose mean age was in the 60s and who resided in six U.S. communities. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale, a 20-item questionnaire designed to evaluate such symptoms in community populations.

Among subjects who had no depressive symptoms at baseline, those with type 2 diabetes were at significantly higher risk for developing depressive symptoms during follow-up, independent of their body mass index, socioeconomic status, and comorbidities.

It is possible that the psychological stress of managing diabetes may lead to depression, or that the complications and comorbidities of the disease may increase depressive symptoms, Dr. Golden and her associates said.

In addition, subjects who had depressive symptoms at baseline were at modestly increased risk of developing diabetes during follow-up, independent of sociodemographic, economic, and metabolic factors.

The National Heart, Lung, and Blood Institute was a sponsor of this study. Dr. Golden serves on the Merck Clinical Diabetes Advisory Board and has received an unrestricted educational grant from Novo Nordisk in the past.

Postpartum depression affected 12%–20% of mothers surveyed in the most recent report from the Centers for Disease Control and Prevention's Pregnancy Risk Assessment Monitoring System (PRAMS).

These proportions are somewhat higher than the 10%–15% of mothers generally thought to be affected by postpartum depression within 1 year of giving birth, Kate Brett, Ph.D., and associates in the Office of Analysis and Epidemiology, National Center for Health Statistics.

PRAMS is an ongoing population-based surveillance project that collects data on mothers' attitudes and experiences before, during, and after delivery of a live infant. It targets subjects who are representative of women who have recently delivered in 17 participating states.

In an analysis of the data collected in 2004–2005—the most recent period for which data were available—Dr. Brett and her colleagues found that four characteristics were significantly associated with postpartum depression in all 17 states: young maternal age, low levels of maternal education, single marital status, and Medicaid coverage for delivery.

Five potential risk factors also were associated with postpartum depression: maternal tobacco use during the last trimester, physical abuse before or during the pregnancy, partner-related stress during the pregnancy, traumatic stress during the pregnancy, and financial stress during the pregnancy.

In addition, delivering a low-birth-weight infant was significantly associated with postpartum depression in 14 states.

In the current survey, 11.8% of new mothers in Maine and 11.8% in Vermont reported postpartum depression, compared with about 20.4% of mothers in New Mexico. Oregon and Minneapolis were also clustered in the lower ranges, with 12.2%, and 12.7%, respectively, of new mothers reporting symptoms, whereas in South Carolina and North Carolina, 19.5% and 19.0%, respectively, reported symptoms.

The associations with young maternal age and partner-related stress or physical abuse have been reported in previous research. In contrast, the associations with low-birth-weight infants, tobacco use during pregnancy, and traumatic or financial stress have not been identified before, the investigators said (MMWR 2008;57:361-6).

These findings can be used to tailor screening and interventions so that they target mothers at highest risk for postpartum depression. For example, “adolescent mothers or women who received Medicaid for their delivery are examples of subsets of the population” who can be easily identified at delivery and referred for treatment, the CDC said.

Postpartum depression affected 12%–20% of mothers surveyed in the most recent report from the Centers for Disease Control and Prevention's Pregnancy Risk Assessment Monitoring System (PRAMS).

These proportions are somewhat higher than the 10%–15% of mothers generally thought to be affected by postpartum depression within 1 year of giving birth, Kate Brett, Ph.D., and associates in the Office of Analysis and Epidemiology, National Center for Health Statistics.

PRAMS is an ongoing population-based surveillance project that collects data on mothers' attitudes and experiences before, during, and after delivery of a live infant. It targets subjects who are representative of women who have recently delivered in 17 participating states.

In an analysis of the data collected in 2004–2005—the most recent period for which data were available—Dr. Brett and her colleagues found that four characteristics were significantly associated with postpartum depression in all 17 states: young maternal age, low levels of maternal education, single marital status, and Medicaid coverage for delivery.

Five potential risk factors also were associated with postpartum depression: maternal tobacco use during the last trimester, physical abuse before or during the pregnancy, partner-related stress during the pregnancy, traumatic stress during the pregnancy, and financial stress during the pregnancy.

In addition, delivering a low-birth-weight infant was significantly associated with postpartum depression in 14 states.

In the current survey, 11.8% of new mothers in Maine and 11.8% in Vermont reported postpartum depression, compared with about 20.4% of mothers in New Mexico. Oregon and Minneapolis were also clustered in the lower ranges, with 12.2%, and 12.7%, respectively, of new mothers reporting symptoms, whereas in South Carolina and North Carolina, 19.5% and 19.0%, respectively, reported symptoms.

The associations with young maternal age and partner-related stress or physical abuse have been reported in previous research. In contrast, the associations with low-birth-weight infants, tobacco use during pregnancy, and traumatic or financial stress have not been identified before, the investigators said (MMWR 2008;57:361-6).

These findings can be used to tailor screening and interventions so that they target mothers at highest risk for postpartum depression. For example, “adolescent mothers or women who received Medicaid for their delivery are examples of subsets of the population” who can be easily identified at delivery and referred for treatment, the CDC said.

Postpartum depression affected 12%–20% of mothers surveyed in the most recent report from the Centers for Disease Control and Prevention's Pregnancy Risk Assessment Monitoring System (PRAMS).

These proportions are somewhat higher than the 10%–15% of mothers generally thought to be affected by postpartum depression within 1 year of giving birth, Kate Brett, Ph.D., and associates in the Office of Analysis and Epidemiology, National Center for Health Statistics.

PRAMS is an ongoing population-based surveillance project that collects data on mothers' attitudes and experiences before, during, and after delivery of a live infant. It targets subjects who are representative of women who have recently delivered in 17 participating states.

In an analysis of the data collected in 2004–2005—the most recent period for which data were available—Dr. Brett and her colleagues found that four characteristics were significantly associated with postpartum depression in all 17 states: young maternal age, low levels of maternal education, single marital status, and Medicaid coverage for delivery.

Five potential risk factors also were associated with postpartum depression: maternal tobacco use during the last trimester, physical abuse before or during the pregnancy, partner-related stress during the pregnancy, traumatic stress during the pregnancy, and financial stress during the pregnancy.

In addition, delivering a low-birth-weight infant was significantly associated with postpartum depression in 14 states.

In the current survey, 11.8% of new mothers in Maine and 11.8% in Vermont reported postpartum depression, compared with about 20.4% of mothers in New Mexico. Oregon and Minneapolis were also clustered in the lower ranges, with 12.2%, and 12.7%, respectively, of new mothers reporting symptoms, whereas in South Carolina and North Carolina, 19.5% and 19.0%, respectively, reported symptoms.

The associations with young maternal age and partner-related stress or physical abuse have been reported in previous research. In contrast, the associations with low-birth-weight infants, tobacco use during pregnancy, and traumatic or financial stress have not been identified before, the investigators said (MMWR 2008;57:361-6).

These findings can be used to tailor screening and interventions so that they target mothers at highest risk for postpartum depression. For example, “adolescent mothers or women who received Medicaid for their delivery are examples of subsets of the population” who can be easily identified at delivery and referred for treatment, the CDC said.

Patients with irritable bowel syndrome and fructose malabsorption appeared to benefit from a diet that restricted intake of fructose and fructans, Susan J. Shepherd and her colleagues reported in an article appearing in the July 2008 issue of Clinical Gastroenterology and Hepatology.

In the 25-patient study, the diet led to “marked and sustained global improvement in gastrointestinal symptoms,” researchers noted. A subsequent study of the patients revealed that symptom relief was not specific to restricted intake of fructose, but was achieved by limiting the intake of poorly absorbed short-chain carbohydrates.

These findings “represent the first high-level evidence” that poorly absorbed short-chain carbohydrates—fructose and fructans—are dietary triggers for the symptoms of irritable bowel syndrome (IBS) in patients who also have fructose malabsorption.

The results also demonstrate that restricting intake of these substances may lead to durable symptomatic improvement, wrote Ms. Shepherd, a dietician at Australia's Monash University, Clayton, Victoria, and her colleagues.

They theorized that, because many abdominal symptoms may originate from bowel distension, addressing factors that contribute to the distension would improve symptoms. In the current study, the researchers focused on osmotic load within the lumen and fermentative gas content.

Poorly absorbed short-chain carbohydrates, including fructose and lactose, are highly fermentable. They exert a strong osmotic effect in people who have malabsorption of these two sugars—about 40% of the population in the case of fructose, and between 15% to 100% of the population for lactose.

To minimize or eliminate intake of poorly absorbed short-chain carbohydrates, the investigators created a diet that omitted fruits containing more fructose than glucose, such as apples, pears, and watermelon; vegetables containing fructan, such as onions, leeks, asparagus, and artichokes; wheat products that contain fructan, such as breads and pasta; foods that contain sorbitol, such as stone fruits; and foods that contain raffinose, such as legumes, lentils, cabbage, and brussels sprouts.

In addition, the diet omitted foods that contain lactose in diets for patients who also had lactose malabsorption.

The study group consisted of 21 women and 4 men aged 22–63 years who had had IBS for a median of 9 years, as well as fructose malabsorption. They adopted this rigorous diet for 3–36 months. Their food was provided for them, with a daily energy content of 8, 10, or 12 mJ/day, according to their individual needs. Patients were also given a list of alternative foods they could substitute while dining out.

All of the patients on the diet achieved sustained improvement in their GI symptoms, the investigators said.

The subjects then were challenged in a double-blind crossover fashion with four orange-flavored test drinks that were identical in appearance, prepared by mixing either fructose, fructans, fructose plus fructans, or glucose powders with 500 mL of water. The glucose drink served as a placebo, since glucose is rapidly and completely absorbed.

The subjects were instructed to drink these three times a day for 2 weeks, starting at a low dose (50 mL per meal) and increasing to a high dose (170 mL per meal).

All IBS symptoms were significantly more frequent and more severe after ingestion of the fructose, fructans, and combined fructose-fructans drinks than with the glucose drink. In contrast, non-IBS symptoms such as tiredness did not differ between the treatment and glucose groups.

The IBS symptoms became more intense as the doses of the fructose, fructans, and combined fructose-fructans drinks increased, but there were no such changes with increasing doses of the glucose drink. The fructose-fructans combination caused more severe symptoms than fructose alone.

The results show that restricting intake of fructose and fructans may lead to durable improvement of GI symptoms, and that poorly absorbed short-chain carbohydrates in general, rather than free fructose specifically, are an important trigger of IBS symptoms, wrote the authors.

Ms. Shepherd disclosed that she has published cookbooks concerning fructose malabsorption and celiac disease.

Patients with irritable bowel syndrome and fructose malabsorption appeared to benefit from a diet that restricted intake of fructose and fructans, Susan J. Shepherd and her colleagues reported in an article appearing in the July 2008 issue of Clinical Gastroenterology and Hepatology.

In the 25-patient study, the diet led to “marked and sustained global improvement in gastrointestinal symptoms,” researchers noted. A subsequent study of the patients revealed that symptom relief was not specific to restricted intake of fructose, but was achieved by limiting the intake of poorly absorbed short-chain carbohydrates.

These findings “represent the first high-level evidence” that poorly absorbed short-chain carbohydrates—fructose and fructans—are dietary triggers for the symptoms of irritable bowel syndrome (IBS) in patients who also have fructose malabsorption.

The results also demonstrate that restricting intake of these substances may lead to durable symptomatic improvement, wrote Ms. Shepherd, a dietician at Australia's Monash University, Clayton, Victoria, and her colleagues.

They theorized that, because many abdominal symptoms may originate from bowel distension, addressing factors that contribute to the distension would improve symptoms. In the current study, the researchers focused on osmotic load within the lumen and fermentative gas content.

Poorly absorbed short-chain carbohydrates, including fructose and lactose, are highly fermentable. They exert a strong osmotic effect in people who have malabsorption of these two sugars—about 40% of the population in the case of fructose, and between 15% to 100% of the population for lactose.

To minimize or eliminate intake of poorly absorbed short-chain carbohydrates, the investigators created a diet that omitted fruits containing more fructose than glucose, such as apples, pears, and watermelon; vegetables containing fructan, such as onions, leeks, asparagus, and artichokes; wheat products that contain fructan, such as breads and pasta; foods that contain sorbitol, such as stone fruits; and foods that contain raffinose, such as legumes, lentils, cabbage, and brussels sprouts.

In addition, the diet omitted foods that contain lactose in diets for patients who also had lactose malabsorption.

The study group consisted of 21 women and 4 men aged 22–63 years who had had IBS for a median of 9 years, as well as fructose malabsorption. They adopted this rigorous diet for 3–36 months. Their food was provided for them, with a daily energy content of 8, 10, or 12 mJ/day, according to their individual needs. Patients were also given a list of alternative foods they could substitute while dining out.

All of the patients on the diet achieved sustained improvement in their GI symptoms, the investigators said.

The subjects then were challenged in a double-blind crossover fashion with four orange-flavored test drinks that were identical in appearance, prepared by mixing either fructose, fructans, fructose plus fructans, or glucose powders with 500 mL of water. The glucose drink served as a placebo, since glucose is rapidly and completely absorbed.

The subjects were instructed to drink these three times a day for 2 weeks, starting at a low dose (50 mL per meal) and increasing to a high dose (170 mL per meal).

All IBS symptoms were significantly more frequent and more severe after ingestion of the fructose, fructans, and combined fructose-fructans drinks than with the glucose drink. In contrast, non-IBS symptoms such as tiredness did not differ between the treatment and glucose groups.

The IBS symptoms became more intense as the doses of the fructose, fructans, and combined fructose-fructans drinks increased, but there were no such changes with increasing doses of the glucose drink. The fructose-fructans combination caused more severe symptoms than fructose alone.

The results show that restricting intake of fructose and fructans may lead to durable improvement of GI symptoms, and that poorly absorbed short-chain carbohydrates in general, rather than free fructose specifically, are an important trigger of IBS symptoms, wrote the authors.

Ms. Shepherd disclosed that she has published cookbooks concerning fructose malabsorption and celiac disease.

Patients with irritable bowel syndrome and fructose malabsorption appeared to benefit from a diet that restricted intake of fructose and fructans, Susan J. Shepherd and her colleagues reported in an article appearing in the July 2008 issue of Clinical Gastroenterology and Hepatology.

In the 25-patient study, the diet led to “marked and sustained global improvement in gastrointestinal symptoms,” researchers noted. A subsequent study of the patients revealed that symptom relief was not specific to restricted intake of fructose, but was achieved by limiting the intake of poorly absorbed short-chain carbohydrates.

These findings “represent the first high-level evidence” that poorly absorbed short-chain carbohydrates—fructose and fructans—are dietary triggers for the symptoms of irritable bowel syndrome (IBS) in patients who also have fructose malabsorption.

The results also demonstrate that restricting intake of these substances may lead to durable symptomatic improvement, wrote Ms. Shepherd, a dietician at Australia's Monash University, Clayton, Victoria, and her colleagues.

They theorized that, because many abdominal symptoms may originate from bowel distension, addressing factors that contribute to the distension would improve symptoms. In the current study, the researchers focused on osmotic load within the lumen and fermentative gas content.

Poorly absorbed short-chain carbohydrates, including fructose and lactose, are highly fermentable. They exert a strong osmotic effect in people who have malabsorption of these two sugars—about 40% of the population in the case of fructose, and between 15% to 100% of the population for lactose.

To minimize or eliminate intake of poorly absorbed short-chain carbohydrates, the investigators created a diet that omitted fruits containing more fructose than glucose, such as apples, pears, and watermelon; vegetables containing fructan, such as onions, leeks, asparagus, and artichokes; wheat products that contain fructan, such as breads and pasta; foods that contain sorbitol, such as stone fruits; and foods that contain raffinose, such as legumes, lentils, cabbage, and brussels sprouts.

In addition, the diet omitted foods that contain lactose in diets for patients who also had lactose malabsorption.

The study group consisted of 21 women and 4 men aged 22–63 years who had had IBS for a median of 9 years, as well as fructose malabsorption. They adopted this rigorous diet for 3–36 months. Their food was provided for them, with a daily energy content of 8, 10, or 12 mJ/day, according to their individual needs. Patients were also given a list of alternative foods they could substitute while dining out.

All of the patients on the diet achieved sustained improvement in their GI symptoms, the investigators said.

The subjects then were challenged in a double-blind crossover fashion with four orange-flavored test drinks that were identical in appearance, prepared by mixing either fructose, fructans, fructose plus fructans, or glucose powders with 500 mL of water. The glucose drink served as a placebo, since glucose is rapidly and completely absorbed.

The subjects were instructed to drink these three times a day for 2 weeks, starting at a low dose (50 mL per meal) and increasing to a high dose (170 mL per meal).

All IBS symptoms were significantly more frequent and more severe after ingestion of the fructose, fructans, and combined fructose-fructans drinks than with the glucose drink. In contrast, non-IBS symptoms such as tiredness did not differ between the treatment and glucose groups.

The IBS symptoms became more intense as the doses of the fructose, fructans, and combined fructose-fructans drinks increased, but there were no such changes with increasing doses of the glucose drink. The fructose-fructans combination caused more severe symptoms than fructose alone.

The results show that restricting intake of fructose and fructans may lead to durable improvement of GI symptoms, and that poorly absorbed short-chain carbohydrates in general, rather than free fructose specifically, are an important trigger of IBS symptoms, wrote the authors.

Ms. Shepherd disclosed that she has published cookbooks concerning fructose malabsorption and celiac disease.

Ambulatory patients with heart failure tend to substantially overestimate their life expectancy, especially those who are younger or who have severe disease, according to the findings of a survey.

Their misperception could “fundamentally influence medical decision making regarding medications, devices, transplantation, and end-of-life care,” said Dr. Larry A. Allen of Duke Clinical Research Institute, Durham, N.C., and his associates.

The researchers surveyed 122 patients with a broad spectrum of heart failure severity to determine their understanding of their prognoses. “Despite advances in care, the prognosis for patients with symptomatic HF remains poor, with a median life expectancy of less than 5 years,” they noted.

Most of the study subjects had longstanding chronic heart failure and comorbid conditions such as hypertension and diabetes. The sample was racially diverse and included a large number of elderly people.

The patient predictions were compared with those obtained using the Seattle Heart Failure Model, a prognostic tool that calculates life expectancy based on clinical characteristics, medications, device use, and results of diagnostic testing.

A total of 9% of the subjects believed their heart failure would be cured, and another 51% believed they would always have heart failure but nevertheless would have a normal life expectancy. Only 36% indicated that heart failure would likely shorten their lives.

A total of 63% of patients markedly overestimated their life expectancy, thinking they'd survive a median of 40% longer than predicted by the clinical prognostic tool, Dr. Allen and his associates said (JAMA 2008;299:2533–42).

Patients also predicted they would live a median of another 13 years. In contrast, the clinical model predicted a median survival of 10 years. The model came close to predicting actual survival rates at 1 and 3 years of follow-up. Mortality at 3 years was 29%.

The younger the patient, the longer they estimated their life expectancies to be. However, the model predicted similar life expectancies across all age groups.

Similarly, patients who had advanced symptoms gave themselves the same prognosis, as did patients with minimal symptoms, predicting great longevity despite the objective severity of their disease.

There was no difference in the accuracy of patient predictions between the 45 patients who reported they had discussed a prognosis with their clinicians and the 76 patients who said they had not.

The study could not address the reasons for the disconnect, but it seems likely that inadequate communication between providers and patients plays a role. Also, “individuals' predictions of longer life expectancy for themselves may simply reflect hope,” they added.

Whatever the reason, patient perception of prognosis warrants further attention, because it “may refine decision making around resuscitation preferences, adherence to medical therapy, and consideration of advanced HF therapies such as implantable cardioverter-defibrillators, cardiac transplantation, or mechanical cardiac support,” Dr. Allen and his associates noted.

In an editorial accompanying the report, Dr. Clyde W. Yancy agreed. “Another reason precise awareness of survival may be important is embedded in the 'time trade-off' construct,” noted Dr. Yancy of the heart and vascular institute at Baylor University Medical Center, Dallas. “Knowing that survival is limited, patients with advanced disease might opt for comfort measures or an enhanced quality of life, even at the expense of shortened survival” (JAMA 2008;299:2566–7).

Patients with advanced disease might opt for comfort measures over enhanced survival. DR. YANCY

Ambulatory patients with heart failure tend to substantially overestimate their life expectancy, especially those who are younger or who have severe disease, according to the findings of a survey.

Their misperception could “fundamentally influence medical decision making regarding medications, devices, transplantation, and end-of-life care,” said Dr. Larry A. Allen of Duke Clinical Research Institute, Durham, N.C., and his associates.

The researchers surveyed 122 patients with a broad spectrum of heart failure severity to determine their understanding of their prognoses. “Despite advances in care, the prognosis for patients with symptomatic HF remains poor, with a median life expectancy of less than 5 years,” they noted.

Most of the study subjects had longstanding chronic heart failure and comorbid conditions such as hypertension and diabetes. The sample was racially diverse and included a large number of elderly people.

The patient predictions were compared with those obtained using the Seattle Heart Failure Model, a prognostic tool that calculates life expectancy based on clinical characteristics, medications, device use, and results of diagnostic testing.

A total of 9% of the subjects believed their heart failure would be cured, and another 51% believed they would always have heart failure but nevertheless would have a normal life expectancy. Only 36% indicated that heart failure would likely shorten their lives.

A total of 63% of patients markedly overestimated their life expectancy, thinking they'd survive a median of 40% longer than predicted by the clinical prognostic tool, Dr. Allen and his associates said (JAMA 2008;299:2533–42).

Patients also predicted they would live a median of another 13 years. In contrast, the clinical model predicted a median survival of 10 years. The model came close to predicting actual survival rates at 1 and 3 years of follow-up. Mortality at 3 years was 29%.

The younger the patient, the longer they estimated their life expectancies to be. However, the model predicted similar life expectancies across all age groups.

Similarly, patients who had advanced symptoms gave themselves the same prognosis, as did patients with minimal symptoms, predicting great longevity despite the objective severity of their disease.

There was no difference in the accuracy of patient predictions between the 45 patients who reported they had discussed a prognosis with their clinicians and the 76 patients who said they had not.

The study could not address the reasons for the disconnect, but it seems likely that inadequate communication between providers and patients plays a role. Also, “individuals' predictions of longer life expectancy for themselves may simply reflect hope,” they added.

Whatever the reason, patient perception of prognosis warrants further attention, because it “may refine decision making around resuscitation preferences, adherence to medical therapy, and consideration of advanced HF therapies such as implantable cardioverter-defibrillators, cardiac transplantation, or mechanical cardiac support,” Dr. Allen and his associates noted.

In an editorial accompanying the report, Dr. Clyde W. Yancy agreed. “Another reason precise awareness of survival may be important is embedded in the 'time trade-off' construct,” noted Dr. Yancy of the heart and vascular institute at Baylor University Medical Center, Dallas. “Knowing that survival is limited, patients with advanced disease might opt for comfort measures or an enhanced quality of life, even at the expense of shortened survival” (JAMA 2008;299:2566–7).

Patients with advanced disease might opt for comfort measures over enhanced survival. DR. YANCY

Ambulatory patients with heart failure tend to substantially overestimate their life expectancy, especially those who are younger or who have severe disease, according to the findings of a survey.

Their misperception could “fundamentally influence medical decision making regarding medications, devices, transplantation, and end-of-life care,” said Dr. Larry A. Allen of Duke Clinical Research Institute, Durham, N.C., and his associates.

The researchers surveyed 122 patients with a broad spectrum of heart failure severity to determine their understanding of their prognoses. “Despite advances in care, the prognosis for patients with symptomatic HF remains poor, with a median life expectancy of less than 5 years,” they noted.

Most of the study subjects had longstanding chronic heart failure and comorbid conditions such as hypertension and diabetes. The sample was racially diverse and included a large number of elderly people.

The patient predictions were compared with those obtained using the Seattle Heart Failure Model, a prognostic tool that calculates life expectancy based on clinical characteristics, medications, device use, and results of diagnostic testing.

A total of 9% of the subjects believed their heart failure would be cured, and another 51% believed they would always have heart failure but nevertheless would have a normal life expectancy. Only 36% indicated that heart failure would likely shorten their lives.

A total of 63% of patients markedly overestimated their life expectancy, thinking they'd survive a median of 40% longer than predicted by the clinical prognostic tool, Dr. Allen and his associates said (JAMA 2008;299:2533–42).

Patients also predicted they would live a median of another 13 years. In contrast, the clinical model predicted a median survival of 10 years. The model came close to predicting actual survival rates at 1 and 3 years of follow-up. Mortality at 3 years was 29%.

The younger the patient, the longer they estimated their life expectancies to be. However, the model predicted similar life expectancies across all age groups.

Similarly, patients who had advanced symptoms gave themselves the same prognosis, as did patients with minimal symptoms, predicting great longevity despite the objective severity of their disease.

There was no difference in the accuracy of patient predictions between the 45 patients who reported they had discussed a prognosis with their clinicians and the 76 patients who said they had not.

The study could not address the reasons for the disconnect, but it seems likely that inadequate communication between providers and patients plays a role. Also, “individuals' predictions of longer life expectancy for themselves may simply reflect hope,” they added.

Whatever the reason, patient perception of prognosis warrants further attention, because it “may refine decision making around resuscitation preferences, adherence to medical therapy, and consideration of advanced HF therapies such as implantable cardioverter-defibrillators, cardiac transplantation, or mechanical cardiac support,” Dr. Allen and his associates noted.

In an editorial accompanying the report, Dr. Clyde W. Yancy agreed. “Another reason precise awareness of survival may be important is embedded in the 'time trade-off' construct,” noted Dr. Yancy of the heart and vascular institute at Baylor University Medical Center, Dallas. “Knowing that survival is limited, patients with advanced disease might opt for comfort measures or an enhanced quality of life, even at the expense of shortened survival” (JAMA 2008;299:2566–7).

Patients with advanced disease might opt for comfort measures over enhanced survival. DR. YANCY

A single dose of methylnaltrexone relieved opioid-induced constipation three times more often than did placebo in a phase III clinical trial of 133 terminally ill patients, investigators have reported.

The treatment did not interfere with analgesia or cause opioid withdrawal, according to Dr. Jay Thomas of San Diego Hospice and the Institute for Palliative Medicine, San Diego, and his associates.

Since opioid-induced constipation is primarily mediated by peripheral opioid receptors, the researchers hypothesized that selective blockade of these receptors “might relieve constipation without compromising the centrally mediated effects of opioid analgesia or precipitating withdrawal.” Methylnaltrexone, produced by N-methylation of the opioid antagonist naltrexone, has a limited ability to cross the blood-brain barrier and thus acts primarily in the periphery.

Dr. Thomas and his associates compared subcutaneous injections of methylnaltrexone with placebo in a double-blind trial at 27 U.S. and Canadian nursing homes, hospices, and palliative care centers.

The 133 patients (median age 71 years) were taking a median opioid dose of 100 mg of oral morphine equivalent and had constipation that failed to respond to a median of two classes of laxative therapy (N. Engl. J. Med. 2008;358:2332–43).

Patients were randomly assigned to receive injections of methylnaltrexone (62 subjects) or placebo (71 subjects) on alternate days for 2 weeks. The study was supported by Progenics Pharmaceuticals Inc.

Within 4 hours of receiving the first dose, 48% of subjects in the methylnaltrexone group defecated, compared with 15% in the placebo group. Over the course of the trial, the proportion of patients who defecated three or more times per week was significantly higher with methylnaltrexone (68%) than with placebo (45%).

In addition, the median time to defecation after the first dose was 6.3 hours with methylnaltrexone, compared with more than 48 hours in the placebo group. Most responders were able to defecate within 1 hour of the injection, and half were able to do so within 30 minutes–a significantly more predictable onset of action than is typically seen with standard laxative treatments, the investigators noted.

Moreover, “more patients in the methylnaltrexone group than in the placebo group had reductions in the difficulty of laxation and distress associated with constipation,” Dr. Thomas and his associates said.

In a subjective assessment, the majority of patients given methylnaltrexone reported that their bowel status had improved with therapy, while the majority of those given placebo reported that their bowel status was unchanged.

At the conclusion of the double-blind phase of the trial, 89 patients opted to receive methylnaltrexone for up to 3 months in an open-label extension of the study. The drug's efficacy persisted throughout this phase of the study, the investigators said.

Mild or moderate abdominal pain and flatulence were the most common adverse events reported. The rates of both adverse events and treatment discontinuation were similarly low in both groups.

Approximately half of patients did not respond to the first dose of methylnaltrexone. It is possible that in at least some of these cases, constipation may have been a result of causes other than opioid use. These include “immobility, decreased oral intake, a low-fiber diet, metabolic and endocrine imbalances, neurologic disorders, concomitant drug side effects, inadequate toileting arrangements, sedation, depression, and advanced age,” Dr. Thomas and his associates noted.

Progenics Pharmaceuticals is collaborating with Wyeth Pharmaceuticals in submitting to the Food and Drug Administration subcutaneous methylnaltrexone for treating opioid-induced constipation in patients receiving palliative care. Dr. Thomas disclosed that he has received consulting and lecture fees, and served on advisory boards for Wyeth Pharmaceuticals.

Most responders were able to defecate within 1 hour of the injection of methylnaltrexone. DR. THOMAS

A single dose of methylnaltrexone relieved opioid-induced constipation three times more often than did placebo in a phase III clinical trial of 133 terminally ill patients, investigators have reported.

The treatment did not interfere with analgesia or cause opioid withdrawal, according to Dr. Jay Thomas of San Diego Hospice and the Institute for Palliative Medicine, San Diego, and his associates.

Since opioid-induced constipation is primarily mediated by peripheral opioid receptors, the researchers hypothesized that selective blockade of these receptors “might relieve constipation without compromising the centrally mediated effects of opioid analgesia or precipitating withdrawal.” Methylnaltrexone, produced by N-methylation of the opioid antagonist naltrexone, has a limited ability to cross the blood-brain barrier and thus acts primarily in the periphery.

Dr. Thomas and his associates compared subcutaneous injections of methylnaltrexone with placebo in a double-blind trial at 27 U.S. and Canadian nursing homes, hospices, and palliative care centers.

The 133 patients (median age 71 years) were taking a median opioid dose of 100 mg of oral morphine equivalent and had constipation that failed to respond to a median of two classes of laxative therapy (N. Engl. J. Med. 2008;358:2332–43).

Patients were randomly assigned to receive injections of methylnaltrexone (62 subjects) or placebo (71 subjects) on alternate days for 2 weeks. The study was supported by Progenics Pharmaceuticals Inc.

Within 4 hours of receiving the first dose, 48% of subjects in the methylnaltrexone group defecated, compared with 15% in the placebo group. Over the course of the trial, the proportion of patients who defecated three or more times per week was significantly higher with methylnaltrexone (68%) than with placebo (45%).

In addition, the median time to defecation after the first dose was 6.3 hours with methylnaltrexone, compared with more than 48 hours in the placebo group. Most responders were able to defecate within 1 hour of the injection, and half were able to do so within 30 minutes–a significantly more predictable onset of action than is typically seen with standard laxative treatments, the investigators noted.

Moreover, “more patients in the methylnaltrexone group than in the placebo group had reductions in the difficulty of laxation and distress associated with constipation,” Dr. Thomas and his associates said.

In a subjective assessment, the majority of patients given methylnaltrexone reported that their bowel status had improved with therapy, while the majority of those given placebo reported that their bowel status was unchanged.

At the conclusion of the double-blind phase of the trial, 89 patients opted to receive methylnaltrexone for up to 3 months in an open-label extension of the study. The drug's efficacy persisted throughout this phase of the study, the investigators said.

Mild or moderate abdominal pain and flatulence were the most common adverse events reported. The rates of both adverse events and treatment discontinuation were similarly low in both groups.

Approximately half of patients did not respond to the first dose of methylnaltrexone. It is possible that in at least some of these cases, constipation may have been a result of causes other than opioid use. These include “immobility, decreased oral intake, a low-fiber diet, metabolic and endocrine imbalances, neurologic disorders, concomitant drug side effects, inadequate toileting arrangements, sedation, depression, and advanced age,” Dr. Thomas and his associates noted.

Progenics Pharmaceuticals is collaborating with Wyeth Pharmaceuticals in submitting to the Food and Drug Administration subcutaneous methylnaltrexone for treating opioid-induced constipation in patients receiving palliative care. Dr. Thomas disclosed that he has received consulting and lecture fees, and served on advisory boards for Wyeth Pharmaceuticals.

Most responders were able to defecate within 1 hour of the injection of methylnaltrexone. DR. THOMAS

A single dose of methylnaltrexone relieved opioid-induced constipation three times more often than did placebo in a phase III clinical trial of 133 terminally ill patients, investigators have reported.

The treatment did not interfere with analgesia or cause opioid withdrawal, according to Dr. Jay Thomas of San Diego Hospice and the Institute for Palliative Medicine, San Diego, and his associates.

Since opioid-induced constipation is primarily mediated by peripheral opioid receptors, the researchers hypothesized that selective blockade of these receptors “might relieve constipation without compromising the centrally mediated effects of opioid analgesia or precipitating withdrawal.” Methylnaltrexone, produced by N-methylation of the opioid antagonist naltrexone, has a limited ability to cross the blood-brain barrier and thus acts primarily in the periphery.

Dr. Thomas and his associates compared subcutaneous injections of methylnaltrexone with placebo in a double-blind trial at 27 U.S. and Canadian nursing homes, hospices, and palliative care centers.

The 133 patients (median age 71 years) were taking a median opioid dose of 100 mg of oral morphine equivalent and had constipation that failed to respond to a median of two classes of laxative therapy (N. Engl. J. Med. 2008;358:2332–43).

Patients were randomly assigned to receive injections of methylnaltrexone (62 subjects) or placebo (71 subjects) on alternate days for 2 weeks. The study was supported by Progenics Pharmaceuticals Inc.

Within 4 hours of receiving the first dose, 48% of subjects in the methylnaltrexone group defecated, compared with 15% in the placebo group. Over the course of the trial, the proportion of patients who defecated three or more times per week was significantly higher with methylnaltrexone (68%) than with placebo (45%).

In addition, the median time to defecation after the first dose was 6.3 hours with methylnaltrexone, compared with more than 48 hours in the placebo group. Most responders were able to defecate within 1 hour of the injection, and half were able to do so within 30 minutes–a significantly more predictable onset of action than is typically seen with standard laxative treatments, the investigators noted.

Moreover, “more patients in the methylnaltrexone group than in the placebo group had reductions in the difficulty of laxation and distress associated with constipation,” Dr. Thomas and his associates said.

In a subjective assessment, the majority of patients given methylnaltrexone reported that their bowel status had improved with therapy, while the majority of those given placebo reported that their bowel status was unchanged.

At the conclusion of the double-blind phase of the trial, 89 patients opted to receive methylnaltrexone for up to 3 months in an open-label extension of the study. The drug's efficacy persisted throughout this phase of the study, the investigators said.

Mild or moderate abdominal pain and flatulence were the most common adverse events reported. The rates of both adverse events and treatment discontinuation were similarly low in both groups.

Approximately half of patients did not respond to the first dose of methylnaltrexone. It is possible that in at least some of these cases, constipation may have been a result of causes other than opioid use. These include “immobility, decreased oral intake, a low-fiber diet, metabolic and endocrine imbalances, neurologic disorders, concomitant drug side effects, inadequate toileting arrangements, sedation, depression, and advanced age,” Dr. Thomas and his associates noted.

Progenics Pharmaceuticals is collaborating with Wyeth Pharmaceuticals in submitting to the Food and Drug Administration subcutaneous methylnaltrexone for treating opioid-induced constipation in patients receiving palliative care. Dr. Thomas disclosed that he has received consulting and lecture fees, and served on advisory boards for Wyeth Pharmaceuticals.

Most responders were able to defecate within 1 hour of the injection of methylnaltrexone. DR. THOMAS

Smoking is associated with a decline in reasoning ability and with memory deficit as early as in middle age, according to a study of more than 5,000 people.

People who quit smoking before they reach middle age, however, show little of this adverse effect on cognition, according to Severine Sabia of the National Institute for Health and Medical Research at Paul Brousse Hospital in Villejuif, France, and her associates.

Previous studies concluded that smoking is a risk factor for dementia in older adults; it is thought to act primarily through its adverse effect on the vasculature. In this study, the investigators used data from the Whitehall II study to examine the relation of smoking to earlier cognitive impairment, before the onset of dementia.

“Cognition in midlife is clinically relevant because research suggests that individuals with mild cognitive impairment progress to clinically diagnosed dementia at an accelerated rate,” Ms. Sabia and her associates noted (Arch. Intern. Med. 2008;168:1165–73).

The Whitehall II study was a longitudinal assessment of socioeconomic factors and health among more than 10,000 British civil servants aged 35–55 years at baseline in 1985–1988.

The subjects were followed at intervals through 2002–2004.

For this study, data were analyzed for a subset of 5,388 participants who underwent evaluation of cognitive function and who furnished a complete smoking history. Short-term verbal memory, inductive reasoning, vocabulary, and verbal fluency were assessed using a battery of standardized tests.

The study participants were categorized as never smokers (2,543 subjects), current smokers (815 subjects), long-term exsmokers (1,519 subjects who had quit before 1985), and recent exsmokers (511 subjects who quit smoking after the study began).

Current smokers were more likely to show deficits, as well as a decline over time in the performance of memory, reasoning, and verbal fluency tasks, than were never smokers.

However, the investigators found no dose-response relationship between the number of pack-years of smoking and cognitive decline.

Smoking is associated with a decline in reasoning ability and with memory deficit as early as in middle age, according to a study of more than 5,000 people.

People who quit smoking before they reach middle age, however, show little of this adverse effect on cognition, according to Severine Sabia of the National Institute for Health and Medical Research at Paul Brousse Hospital in Villejuif, France, and her associates.

Previous studies concluded that smoking is a risk factor for dementia in older adults; it is thought to act primarily through its adverse effect on the vasculature. In this study, the investigators used data from the Whitehall II study to examine the relation of smoking to earlier cognitive impairment, before the onset of dementia.

“Cognition in midlife is clinically relevant because research suggests that individuals with mild cognitive impairment progress to clinically diagnosed dementia at an accelerated rate,” Ms. Sabia and her associates noted (Arch. Intern. Med. 2008;168:1165–73).

The Whitehall II study was a longitudinal assessment of socioeconomic factors and health among more than 10,000 British civil servants aged 35–55 years at baseline in 1985–1988.

The subjects were followed at intervals through 2002–2004.

For this study, data were analyzed for a subset of 5,388 participants who underwent evaluation of cognitive function and who furnished a complete smoking history. Short-term verbal memory, inductive reasoning, vocabulary, and verbal fluency were assessed using a battery of standardized tests.

The study participants were categorized as never smokers (2,543 subjects), current smokers (815 subjects), long-term exsmokers (1,519 subjects who had quit before 1985), and recent exsmokers (511 subjects who quit smoking after the study began).

Current smokers were more likely to show deficits, as well as a decline over time in the performance of memory, reasoning, and verbal fluency tasks, than were never smokers.

However, the investigators found no dose-response relationship between the number of pack-years of smoking and cognitive decline.

Smoking is associated with a decline in reasoning ability and with memory deficit as early as in middle age, according to a study of more than 5,000 people.

People who quit smoking before they reach middle age, however, show little of this adverse effect on cognition, according to Severine Sabia of the National Institute for Health and Medical Research at Paul Brousse Hospital in Villejuif, France, and her associates.

Previous studies concluded that smoking is a risk factor for dementia in older adults; it is thought to act primarily through its adverse effect on the vasculature. In this study, the investigators used data from the Whitehall II study to examine the relation of smoking to earlier cognitive impairment, before the onset of dementia.

“Cognition in midlife is clinically relevant because research suggests that individuals with mild cognitive impairment progress to clinically diagnosed dementia at an accelerated rate,” Ms. Sabia and her associates noted (Arch. Intern. Med. 2008;168:1165–73).

The Whitehall II study was a longitudinal assessment of socioeconomic factors and health among more than 10,000 British civil servants aged 35–55 years at baseline in 1985–1988.

The subjects were followed at intervals through 2002–2004.

For this study, data were analyzed for a subset of 5,388 participants who underwent evaluation of cognitive function and who furnished a complete smoking history. Short-term verbal memory, inductive reasoning, vocabulary, and verbal fluency were assessed using a battery of standardized tests.

The study participants were categorized as never smokers (2,543 subjects), current smokers (815 subjects), long-term exsmokers (1,519 subjects who had quit before 1985), and recent exsmokers (511 subjects who quit smoking after the study began).

Current smokers were more likely to show deficits, as well as a decline over time in the performance of memory, reasoning, and verbal fluency tasks, than were never smokers.

However, the investigators found no dose-response relationship between the number of pack-years of smoking and cognitive decline.