Mary Ann Moon

Vigorous physical activity – particularly running and aerobics – appears to protect women against developing psoriasis, according to a report published online May 21 in the Archives of Dermatology.

In what the researchers described as the first prospective study to examine the association between physical activity and the onset of psoriasis, women who reported participating in at least 20.9 MET (metabolic equivalent)–hours per week of vigorous exercise – the equivalent of 105 minutes of running or 180 minutes of swimming or playing tennis – showed a 25%-30% lower risk of incident psoriasis, compared with women who reported no vigorous exercise, said Hillary C. Frankel of the department of dermatology at Brigham and Women’s Hospital, Boston, and her associates.

"This amount of vigorous activity is roughly equivalent to the current U.S. Department of Health and Human Services recommendation for greater health benefits," they noted.

Physical activity has been associated with a decreased risk of several disorders that are characterized by systemic inflammation, including type 2 diabetes, colon cancer, coronary artery disease, and breast cancer. Until now, only a few cross-sectional studies have examined the role of physical activity in psoriasis, and those have yielded inconsistent results.

Ms. Frankel and her associates prospectively assessed the relationship between customary physical activity and incident psoriasis using data from the Nurses' Health Study. That study included a longitudinal cohort of more than 116,000 female registered nurses residing in 15 states who were aged 25-42 years at baseline in 1989, and who completed biennial questionnaires about their health.

For this study, the researchers focused on 86,665 participants who did not have psoriasis at baseline and who answered detailed questions about their physical activity in 1991, 1997, and 2001. This included 1,026 study participants who developed psoriasis during the 14-year follow-up period.

The total physical activity score, measured in MET-hours per week, was inversely related to the risk of developing psoriasis in a dose-dependent fashion. The most physically active quintile of the cohort had a relative risk of 0.71 of developing psoriasis, compared with the least-active quintile.

In a separate analysis by type of physical activity, only certain vigorous physical activity was found to be protective against psoriasis.

After adjustment for age, smoking status, alcohol intake, and other vigorous activity, women who ran for more than 1 hour per week had a relative risk of 0.37, compared with those who did not run. Similarly, women who participated in at least 4 hours per week of aerobics had an adjusted relative risk of 0.54, compared with those who did not do aerobics. Both trends were statistically significant.

However, no such association was seen among women who participated in other vigorous activities such as bicycling, swimming, and playing tennis. And walking – regardless of the amount of time devoted to it – was not associated with reduced risk of psoriasis.

"The highly variable intensity at which these activities are performed may account for this finding," the investigators said (Arch. Dermatol. 2012 May 21 [doi:10.1001/archdermatol.2012.943]).

The mechanism by which vigorous exercise might reduce psoriasis risk is not yet known, but "it is biologically plausible that [it] could modulate a state of chronic inflammation and/or immune activation that predisposes women to develop psoriasis," Ms. Frankel and her colleagues said.

Physical activity is known to lower levels of proinflammatory cytokines and elevate levels of anti-inflammatory cytokines. It also has beneficial effects on mood, decreasing anxiety and stress; stress is believed to incite psoriasis by activating the immune system, they added.

This study was supported by the National Institutes of Health and the department of dermatology at Brigham and Women’s Hospital. Study coauthor Dr. Abrar A. Qureshi reported ties to Novartis. No other potential financial conflicts of interest were reported.

Vigorous physical activity – particularly running and aerobics – appears to protect women against developing psoriasis, according to a report published online May 21 in the Archives of Dermatology.

In what the researchers described as the first prospective study to examine the association between physical activity and the onset of psoriasis, women who reported participating in at least 20.9 MET (metabolic equivalent)–hours per week of vigorous exercise – the equivalent of 105 minutes of running or 180 minutes of swimming or playing tennis – showed a 25%-30% lower risk of incident psoriasis, compared with women who reported no vigorous exercise, said Hillary C. Frankel of the department of dermatology at Brigham and Women’s Hospital, Boston, and her associates.

"This amount of vigorous activity is roughly equivalent to the current U.S. Department of Health and Human Services recommendation for greater health benefits," they noted.

Physical activity has been associated with a decreased risk of several disorders that are characterized by systemic inflammation, including type 2 diabetes, colon cancer, coronary artery disease, and breast cancer. Until now, only a few cross-sectional studies have examined the role of physical activity in psoriasis, and those have yielded inconsistent results.

Ms. Frankel and her associates prospectively assessed the relationship between customary physical activity and incident psoriasis using data from the Nurses' Health Study. That study included a longitudinal cohort of more than 116,000 female registered nurses residing in 15 states who were aged 25-42 years at baseline in 1989, and who completed biennial questionnaires about their health.

For this study, the researchers focused on 86,665 participants who did not have psoriasis at baseline and who answered detailed questions about their physical activity in 1991, 1997, and 2001. This included 1,026 study participants who developed psoriasis during the 14-year follow-up period.

The total physical activity score, measured in MET-hours per week, was inversely related to the risk of developing psoriasis in a dose-dependent fashion. The most physically active quintile of the cohort had a relative risk of 0.71 of developing psoriasis, compared with the least-active quintile.

In a separate analysis by type of physical activity, only certain vigorous physical activity was found to be protective against psoriasis.

After adjustment for age, smoking status, alcohol intake, and other vigorous activity, women who ran for more than 1 hour per week had a relative risk of 0.37, compared with those who did not run. Similarly, women who participated in at least 4 hours per week of aerobics had an adjusted relative risk of 0.54, compared with those who did not do aerobics. Both trends were statistically significant.

However, no such association was seen among women who participated in other vigorous activities such as bicycling, swimming, and playing tennis. And walking – regardless of the amount of time devoted to it – was not associated with reduced risk of psoriasis.

"The highly variable intensity at which these activities are performed may account for this finding," the investigators said (Arch. Dermatol. 2012 May 21 [doi:10.1001/archdermatol.2012.943]).

The mechanism by which vigorous exercise might reduce psoriasis risk is not yet known, but "it is biologically plausible that [it] could modulate a state of chronic inflammation and/or immune activation that predisposes women to develop psoriasis," Ms. Frankel and her colleagues said.

Physical activity is known to lower levels of proinflammatory cytokines and elevate levels of anti-inflammatory cytokines. It also has beneficial effects on mood, decreasing anxiety and stress; stress is believed to incite psoriasis by activating the immune system, they added.

This study was supported by the National Institutes of Health and the department of dermatology at Brigham and Women’s Hospital. Study coauthor Dr. Abrar A. Qureshi reported ties to Novartis. No other potential financial conflicts of interest were reported.

Vigorous physical activity – particularly running and aerobics – appears to protect women against developing psoriasis, according to a report published online May 21 in the Archives of Dermatology.

In what the researchers described as the first prospective study to examine the association between physical activity and the onset of psoriasis, women who reported participating in at least 20.9 MET (metabolic equivalent)–hours per week of vigorous exercise – the equivalent of 105 minutes of running or 180 minutes of swimming or playing tennis – showed a 25%-30% lower risk of incident psoriasis, compared with women who reported no vigorous exercise, said Hillary C. Frankel of the department of dermatology at Brigham and Women’s Hospital, Boston, and her associates.

"This amount of vigorous activity is roughly equivalent to the current U.S. Department of Health and Human Services recommendation for greater health benefits," they noted.

Physical activity has been associated with a decreased risk of several disorders that are characterized by systemic inflammation, including type 2 diabetes, colon cancer, coronary artery disease, and breast cancer. Until now, only a few cross-sectional studies have examined the role of physical activity in psoriasis, and those have yielded inconsistent results.

Ms. Frankel and her associates prospectively assessed the relationship between customary physical activity and incident psoriasis using data from the Nurses' Health Study. That study included a longitudinal cohort of more than 116,000 female registered nurses residing in 15 states who were aged 25-42 years at baseline in 1989, and who completed biennial questionnaires about their health.

For this study, the researchers focused on 86,665 participants who did not have psoriasis at baseline and who answered detailed questions about their physical activity in 1991, 1997, and 2001. This included 1,026 study participants who developed psoriasis during the 14-year follow-up period.

The total physical activity score, measured in MET-hours per week, was inversely related to the risk of developing psoriasis in a dose-dependent fashion. The most physically active quintile of the cohort had a relative risk of 0.71 of developing psoriasis, compared with the least-active quintile.

In a separate analysis by type of physical activity, only certain vigorous physical activity was found to be protective against psoriasis.

After adjustment for age, smoking status, alcohol intake, and other vigorous activity, women who ran for more than 1 hour per week had a relative risk of 0.37, compared with those who did not run. Similarly, women who participated in at least 4 hours per week of aerobics had an adjusted relative risk of 0.54, compared with those who did not do aerobics. Both trends were statistically significant.

However, no such association was seen among women who participated in other vigorous activities such as bicycling, swimming, and playing tennis. And walking – regardless of the amount of time devoted to it – was not associated with reduced risk of psoriasis.

"The highly variable intensity at which these activities are performed may account for this finding," the investigators said (Arch. Dermatol. 2012 May 21 [doi:10.1001/archdermatol.2012.943]).

The mechanism by which vigorous exercise might reduce psoriasis risk is not yet known, but "it is biologically plausible that [it] could modulate a state of chronic inflammation and/or immune activation that predisposes women to develop psoriasis," Ms. Frankel and her colleagues said.

Physical activity is known to lower levels of proinflammatory cytokines and elevate levels of anti-inflammatory cytokines. It also has beneficial effects on mood, decreasing anxiety and stress; stress is believed to incite psoriasis by activating the immune system, they added.

This study was supported by the National Institutes of Health and the department of dermatology at Brigham and Women’s Hospital. Study coauthor Dr. Abrar A. Qureshi reported ties to Novartis. No other potential financial conflicts of interest were reported.

Drinking at least one cup of coffee daily may be linked to reduced mortality risks, and people who consume more may enjoy even lower risks, according to a report examining coffee consumption among more than 400,000 people in the May 17 issue of the New England Journal of Medicine.

Compared with men who didn’t drink coffee, those who drank six or more cups per day had a 10% lower risk of death during a median follow-up of 14 years. Compared with women who didn’t drink coffee, those who drank six or more cups per day had a 15% lower risk, reported Neal D. Freedman, Ph.D., of the National Cancer Institute’s Division of Cancer Epidemiology and Genetics, and his associates.

The benefit of coffee consumption was similar between people who predominantly drank decaffeinated and those who predominantly drank caffeinated coffee, so caffeine does not appear to be the component of the beverage that improves mortality, they said.

In previous studies, coffee drinking has been linked to lower rates of diabetes, inflammatory diseases, and stroke. But studies examining a link with heart disease have produced mixed results, and "associations with cancer have generally been null," the researchers noted. Thus, coffee’s association with total mortality has been mixed.

Dr. Freedman and his colleagues used data from the National Institutes of Health–AARP Diet and Health Study to assess the relationship between coffee drinking and both total and cause-specific mortality. The NIH-AARP study involved more than 617,000 subjects aged 50-71 years who were followed from baseline (1995-1996) through 2008, so it had ample power to detect even modest associations, the investigators noted.

For the Diet and Health Study, subjects residing in six states and two cities answered a comprehensive questionnaire about diet and lifestyle at baseline. Dr. Freedman and his associates assessed a subgroup of 229,119 men and 173,141 women from this study population, after excluding those with cancer, heart disease, stroke, or inadequate information on coffee drinking and cigarette smoking.

A total of 33,731 men and 18,784 women died during follow-up. The researchers found a modest inverse association between coffee drinking and total mortality for both sexes (N. Engl. J. Med. 2012;366:1891-1904).

This association was dose dependent. Hazard ratios for death from any cause among men who drank coffee, compared with men who did not, were 0.99 for less than one cup per day, 0.94 for one cup, 0.90 for two to three cups, 0.88 for four to five cups, and 0.90 for six or more cups.

Hazard ratios among women who drank coffee, compared with women who did not, were 1.01 for less than one cup per day, 0.95 for one cup, 0.87 for two to three cups, 0.84 for four to five cups, and 0.85 for six or more cups.

These hazard ratios are similar to those found in several larger, more recent studies, including the Nurses’ Health Study and the Health Professionals Follow-up Study, the investigators said.

In an analysis of the data stratified by the predominant type of coffee consumed, the link between intake and mortality was similar for caffeinated and decaffeinated coffee. This suggests that the mortality benefit is due to some compound contained in coffee other than caffeine, such as antioxidants.

The association also persisted across numerous subgroups of study participants, regardless of age; body mass index; the presence or absence of diabetes; concomitant alcohol consumption; high or low intake of red meat, white meat, fruit, and vegetables; and use or nonuse of hormone replacement therapy.

The strongest inverse associations between coffee drinking and total mortality were found among people who had never smoked (compared with current smokers) and those who reported having very good to excellent overall health (compared with poor to fair health).

When cause-specific mortality was examined, coffee intake was inversely related to most major causes of death in both men and women. Higher coffee consumption was linked to lower mortality due to heart disease, respiratory disease, stroke, injuries and accidents, diabetes, and infections.

However, coffee did not protect against cancer mortality in women, and it showed a borderline positive association with cancer mortality in men.

"Given the observational nature of our study, it is not possible to conclude that the inverse relationship between coffee consumption and mortality reflects cause and effect," the investigators said.

Nevertheless, "our results provide reassurance with respect to the concern that coffee drinking might adversely affect health."

This study was supported by the NIH, the National Cancer Institute, and the NCI’s Division of Cancer Epidemiology and Genetics. No financial conflicts of interest were reported.

Drinking at least one cup of coffee daily may be linked to reduced mortality risks, and people who consume more may enjoy even lower risks, according to a report examining coffee consumption among more than 400,000 people in the May 17 issue of the New England Journal of Medicine.

Compared with men who didn’t drink coffee, those who drank six or more cups per day had a 10% lower risk of death during a median follow-up of 14 years. Compared with women who didn’t drink coffee, those who drank six or more cups per day had a 15% lower risk, reported Neal D. Freedman, Ph.D., of the National Cancer Institute’s Division of Cancer Epidemiology and Genetics, and his associates.

The benefit of coffee consumption was similar between people who predominantly drank decaffeinated and those who predominantly drank caffeinated coffee, so caffeine does not appear to be the component of the beverage that improves mortality, they said.

In previous studies, coffee drinking has been linked to lower rates of diabetes, inflammatory diseases, and stroke. But studies examining a link with heart disease have produced mixed results, and "associations with cancer have generally been null," the researchers noted. Thus, coffee’s association with total mortality has been mixed.

Dr. Freedman and his colleagues used data from the National Institutes of Health–AARP Diet and Health Study to assess the relationship between coffee drinking and both total and cause-specific mortality. The NIH-AARP study involved more than 617,000 subjects aged 50-71 years who were followed from baseline (1995-1996) through 2008, so it had ample power to detect even modest associations, the investigators noted.

For the Diet and Health Study, subjects residing in six states and two cities answered a comprehensive questionnaire about diet and lifestyle at baseline. Dr. Freedman and his associates assessed a subgroup of 229,119 men and 173,141 women from this study population, after excluding those with cancer, heart disease, stroke, or inadequate information on coffee drinking and cigarette smoking.

A total of 33,731 men and 18,784 women died during follow-up. The researchers found a modest inverse association between coffee drinking and total mortality for both sexes (N. Engl. J. Med. 2012;366:1891-1904).

This association was dose dependent. Hazard ratios for death from any cause among men who drank coffee, compared with men who did not, were 0.99 for less than one cup per day, 0.94 for one cup, 0.90 for two to three cups, 0.88 for four to five cups, and 0.90 for six or more cups.

Hazard ratios among women who drank coffee, compared with women who did not, were 1.01 for less than one cup per day, 0.95 for one cup, 0.87 for two to three cups, 0.84 for four to five cups, and 0.85 for six or more cups.

These hazard ratios are similar to those found in several larger, more recent studies, including the Nurses’ Health Study and the Health Professionals Follow-up Study, the investigators said.

In an analysis of the data stratified by the predominant type of coffee consumed, the link between intake and mortality was similar for caffeinated and decaffeinated coffee. This suggests that the mortality benefit is due to some compound contained in coffee other than caffeine, such as antioxidants.

The association also persisted across numerous subgroups of study participants, regardless of age; body mass index; the presence or absence of diabetes; concomitant alcohol consumption; high or low intake of red meat, white meat, fruit, and vegetables; and use or nonuse of hormone replacement therapy.

The strongest inverse associations between coffee drinking and total mortality were found among people who had never smoked (compared with current smokers) and those who reported having very good to excellent overall health (compared with poor to fair health).

When cause-specific mortality was examined, coffee intake was inversely related to most major causes of death in both men and women. Higher coffee consumption was linked to lower mortality due to heart disease, respiratory disease, stroke, injuries and accidents, diabetes, and infections.

However, coffee did not protect against cancer mortality in women, and it showed a borderline positive association with cancer mortality in men.

"Given the observational nature of our study, it is not possible to conclude that the inverse relationship between coffee consumption and mortality reflects cause and effect," the investigators said.

Nevertheless, "our results provide reassurance with respect to the concern that coffee drinking might adversely affect health."

This study was supported by the NIH, the National Cancer Institute, and the NCI’s Division of Cancer Epidemiology and Genetics. No financial conflicts of interest were reported.

Drinking at least one cup of coffee daily may be linked to reduced mortality risks, and people who consume more may enjoy even lower risks, according to a report examining coffee consumption among more than 400,000 people in the May 17 issue of the New England Journal of Medicine.

Compared with men who didn’t drink coffee, those who drank six or more cups per day had a 10% lower risk of death during a median follow-up of 14 years. Compared with women who didn’t drink coffee, those who drank six or more cups per day had a 15% lower risk, reported Neal D. Freedman, Ph.D., of the National Cancer Institute’s Division of Cancer Epidemiology and Genetics, and his associates.

The benefit of coffee consumption was similar between people who predominantly drank decaffeinated and those who predominantly drank caffeinated coffee, so caffeine does not appear to be the component of the beverage that improves mortality, they said.

In previous studies, coffee drinking has been linked to lower rates of diabetes, inflammatory diseases, and stroke. But studies examining a link with heart disease have produced mixed results, and "associations with cancer have generally been null," the researchers noted. Thus, coffee’s association with total mortality has been mixed.

Dr. Freedman and his colleagues used data from the National Institutes of Health–AARP Diet and Health Study to assess the relationship between coffee drinking and both total and cause-specific mortality. The NIH-AARP study involved more than 617,000 subjects aged 50-71 years who were followed from baseline (1995-1996) through 2008, so it had ample power to detect even modest associations, the investigators noted.

For the Diet and Health Study, subjects residing in six states and two cities answered a comprehensive questionnaire about diet and lifestyle at baseline. Dr. Freedman and his associates assessed a subgroup of 229,119 men and 173,141 women from this study population, after excluding those with cancer, heart disease, stroke, or inadequate information on coffee drinking and cigarette smoking.

A total of 33,731 men and 18,784 women died during follow-up. The researchers found a modest inverse association between coffee drinking and total mortality for both sexes (N. Engl. J. Med. 2012;366:1891-1904).

This association was dose dependent. Hazard ratios for death from any cause among men who drank coffee, compared with men who did not, were 0.99 for less than one cup per day, 0.94 for one cup, 0.90 for two to three cups, 0.88 for four to five cups, and 0.90 for six or more cups.

Hazard ratios among women who drank coffee, compared with women who did not, were 1.01 for less than one cup per day, 0.95 for one cup, 0.87 for two to three cups, 0.84 for four to five cups, and 0.85 for six or more cups.

These hazard ratios are similar to those found in several larger, more recent studies, including the Nurses’ Health Study and the Health Professionals Follow-up Study, the investigators said.

In an analysis of the data stratified by the predominant type of coffee consumed, the link between intake and mortality was similar for caffeinated and decaffeinated coffee. This suggests that the mortality benefit is due to some compound contained in coffee other than caffeine, such as antioxidants.

The association also persisted across numerous subgroups of study participants, regardless of age; body mass index; the presence or absence of diabetes; concomitant alcohol consumption; high or low intake of red meat, white meat, fruit, and vegetables; and use or nonuse of hormone replacement therapy.

The strongest inverse associations between coffee drinking and total mortality were found among people who had never smoked (compared with current smokers) and those who reported having very good to excellent overall health (compared with poor to fair health).

When cause-specific mortality was examined, coffee intake was inversely related to most major causes of death in both men and women. Higher coffee consumption was linked to lower mortality due to heart disease, respiratory disease, stroke, injuries and accidents, diabetes, and infections.

However, coffee did not protect against cancer mortality in women, and it showed a borderline positive association with cancer mortality in men.

"Given the observational nature of our study, it is not possible to conclude that the inverse relationship between coffee consumption and mortality reflects cause and effect," the investigators said.

Nevertheless, "our results provide reassurance with respect to the concern that coffee drinking might adversely affect health."

This study was supported by the NIH, the National Cancer Institute, and the NCI’s Division of Cancer Epidemiology and Genetics. No financial conflicts of interest were reported.

A small absolute increase in the risk of cardiovascular death occurs during a 5-day course of azithromycin therapy, according to a report in the May 17 issue of the New England Journal of Medicine.

This rise is most pronounced among the 10% of patients who are already at highest risk for cardiovascular disease, said Wayne A. Ray, Ph.D., of the division of pharmacoepidemiology at Vanderbilt University in Nashville, Tenn., and his associates.

Azithromycin "has been reported to be relatively free of cardiotoxic effects," but it is closely related to erythromycin and clarithromycin, which are known to raise the risk of serious ventricular arrhythmias and sudden cardiac death. In addition, there have been isolated reports of patients with normal heart rhythms developing arrhythmia-related adverse events while taking azithromycin, including 20 cases of torsades de pointes reported to the Food and Drug Administration.

Dr. Ray and his colleagues performed a retrospective cohort study testing their hypothesis that patients taking azithromycin would show a higher rate of cardiovascular death – particularly sudden cardiac death – than would people who were not taking antibiotics and people who were taking different antibiotics.

The researchers analyzed data from the Tennessee Medicaid program on patients aged 30-74 years in 1992 (when azithromycin was first introduced in the United States) through 2006. They compared cardiovascular mortality and all-cause mortality during 347,795 5-day courses of azithromycin vs. 1,391,180 matched-control periods with no antibiotic treatment.

To control for possible confounding by treatment indication, the investigators included a second control group of 1,348,672 prescriptions for amoxicillin; 264,626 for ciprofloxacin; and 193,906 for levofloxacin. The most common indications for both azithromycin and amoxicillin were ear, nose, or throat infections and bronchitis.

Compared with no antibiotic treatment, the use of azithromycin was associated with an increased rate of cardiovascular death (85.2 CV deaths per million courses with azithromycin vs. 29.8 per million courses with no treatment). The hazard ratio for cardiovascular death was 2.88 during a course of azithromycin, compared with no antibiotic therapy.

Similarly, the use of azithromycin was associated with an increased risk of cardiovascular death, compared with amoxicillin treatment, for which the rate was 31.5 CV deaths per million courses.

"As compared with amoxicillin, there were 47 additional cardiovascular deaths per 1 million courses of azithromycin therapy; for patients in the highest decile of baseline risk of CV disease, there were 245 additional cardiac deaths per 1 million courses," Dr. Ray and his associates said (N. Engl. J. Med. 2012;366:1881-90).

Azithromycin raised the risk of sudden cardiac death as well as that of other cardiovascular deaths.

The findings were similar when azithromycin was compared with ciprofloxacin, but mortality risks did not differ significantly between azithromycin and levofloxacin. Levofloxacin "has [a] recognized proarrhythmic potential" and has been linked to increased risk of cardiovascular death in previous studies, Dr. Ray and his associates said.

These increased mortality risks did not persist beyond the 5-day course of treatment, even though concentrations of azithromycin remain elevated in tissue for several more days. This may be because serum concentrations of the drug decline more rapidly, "falling to trough levels within 24 hours" of completing the course of therapy.

"Although our data are consistent with an adverse cardiac effect of azithromycin, they cannot establish a specific causal mechanism," they added.

In a statement May 17, Food and Drug Administration officials noted that the agency is aware of the study and its findings and is reviewing the results; they noted that any new information that results from the FDA review would be shared.*

This study was supported by the National Heart, Lung, and Blood Institute and the Agency for Healthcare Research and Quality Centers for Education and Research on Therapeutics. Dr. Ray reported ties to XL Insurance regarding conjugated estrogens, and providing expert testimony in litigation involving zoledronic acid.

*This story was updated May 17, 2012.

A small absolute increase in the risk of cardiovascular death occurs during a 5-day course of azithromycin therapy, according to a report in the May 17 issue of the New England Journal of Medicine.

This rise is most pronounced among the 10% of patients who are already at highest risk for cardiovascular disease, said Wayne A. Ray, Ph.D., of the division of pharmacoepidemiology at Vanderbilt University in Nashville, Tenn., and his associates.

Azithromycin "has been reported to be relatively free of cardiotoxic effects," but it is closely related to erythromycin and clarithromycin, which are known to raise the risk of serious ventricular arrhythmias and sudden cardiac death. In addition, there have been isolated reports of patients with normal heart rhythms developing arrhythmia-related adverse events while taking azithromycin, including 20 cases of torsades de pointes reported to the Food and Drug Administration.

Dr. Ray and his colleagues performed a retrospective cohort study testing their hypothesis that patients taking azithromycin would show a higher rate of cardiovascular death – particularly sudden cardiac death – than would people who were not taking antibiotics and people who were taking different antibiotics.

The researchers analyzed data from the Tennessee Medicaid program on patients aged 30-74 years in 1992 (when azithromycin was first introduced in the United States) through 2006. They compared cardiovascular mortality and all-cause mortality during 347,795 5-day courses of azithromycin vs. 1,391,180 matched-control periods with no antibiotic treatment.

To control for possible confounding by treatment indication, the investigators included a second control group of 1,348,672 prescriptions for amoxicillin; 264,626 for ciprofloxacin; and 193,906 for levofloxacin. The most common indications for both azithromycin and amoxicillin were ear, nose, or throat infections and bronchitis.

Compared with no antibiotic treatment, the use of azithromycin was associated with an increased rate of cardiovascular death (85.2 CV deaths per million courses with azithromycin vs. 29.8 per million courses with no treatment). The hazard ratio for cardiovascular death was 2.88 during a course of azithromycin, compared with no antibiotic therapy.

Similarly, the use of azithromycin was associated with an increased risk of cardiovascular death, compared with amoxicillin treatment, for which the rate was 31.5 CV deaths per million courses.

"As compared with amoxicillin, there were 47 additional cardiovascular deaths per 1 million courses of azithromycin therapy; for patients in the highest decile of baseline risk of CV disease, there were 245 additional cardiac deaths per 1 million courses," Dr. Ray and his associates said (N. Engl. J. Med. 2012;366:1881-90).

Azithromycin raised the risk of sudden cardiac death as well as that of other cardiovascular deaths.

The findings were similar when azithromycin was compared with ciprofloxacin, but mortality risks did not differ significantly between azithromycin and levofloxacin. Levofloxacin "has [a] recognized proarrhythmic potential" and has been linked to increased risk of cardiovascular death in previous studies, Dr. Ray and his associates said.

These increased mortality risks did not persist beyond the 5-day course of treatment, even though concentrations of azithromycin remain elevated in tissue for several more days. This may be because serum concentrations of the drug decline more rapidly, "falling to trough levels within 24 hours" of completing the course of therapy.

"Although our data are consistent with an adverse cardiac effect of azithromycin, they cannot establish a specific causal mechanism," they added.

In a statement May 17, Food and Drug Administration officials noted that the agency is aware of the study and its findings and is reviewing the results; they noted that any new information that results from the FDA review would be shared.*

This study was supported by the National Heart, Lung, and Blood Institute and the Agency for Healthcare Research and Quality Centers for Education and Research on Therapeutics. Dr. Ray reported ties to XL Insurance regarding conjugated estrogens, and providing expert testimony in litigation involving zoledronic acid.

*This story was updated May 17, 2012.

A small absolute increase in the risk of cardiovascular death occurs during a 5-day course of azithromycin therapy, according to a report in the May 17 issue of the New England Journal of Medicine.

This rise is most pronounced among the 10% of patients who are already at highest risk for cardiovascular disease, said Wayne A. Ray, Ph.D., of the division of pharmacoepidemiology at Vanderbilt University in Nashville, Tenn., and his associates.

Azithromycin "has been reported to be relatively free of cardiotoxic effects," but it is closely related to erythromycin and clarithromycin, which are known to raise the risk of serious ventricular arrhythmias and sudden cardiac death. In addition, there have been isolated reports of patients with normal heart rhythms developing arrhythmia-related adverse events while taking azithromycin, including 20 cases of torsades de pointes reported to the Food and Drug Administration.

Dr. Ray and his colleagues performed a retrospective cohort study testing their hypothesis that patients taking azithromycin would show a higher rate of cardiovascular death – particularly sudden cardiac death – than would people who were not taking antibiotics and people who were taking different antibiotics.

The researchers analyzed data from the Tennessee Medicaid program on patients aged 30-74 years in 1992 (when azithromycin was first introduced in the United States) through 2006. They compared cardiovascular mortality and all-cause mortality during 347,795 5-day courses of azithromycin vs. 1,391,180 matched-control periods with no antibiotic treatment.

To control for possible confounding by treatment indication, the investigators included a second control group of 1,348,672 prescriptions for amoxicillin; 264,626 for ciprofloxacin; and 193,906 for levofloxacin. The most common indications for both azithromycin and amoxicillin were ear, nose, or throat infections and bronchitis.

Compared with no antibiotic treatment, the use of azithromycin was associated with an increased rate of cardiovascular death (85.2 CV deaths per million courses with azithromycin vs. 29.8 per million courses with no treatment). The hazard ratio for cardiovascular death was 2.88 during a course of azithromycin, compared with no antibiotic therapy.

Similarly, the use of azithromycin was associated with an increased risk of cardiovascular death, compared with amoxicillin treatment, for which the rate was 31.5 CV deaths per million courses.

"As compared with amoxicillin, there were 47 additional cardiovascular deaths per 1 million courses of azithromycin therapy; for patients in the highest decile of baseline risk of CV disease, there were 245 additional cardiac deaths per 1 million courses," Dr. Ray and his associates said (N. Engl. J. Med. 2012;366:1881-90).

Azithromycin raised the risk of sudden cardiac death as well as that of other cardiovascular deaths.

The findings were similar when azithromycin was compared with ciprofloxacin, but mortality risks did not differ significantly between azithromycin and levofloxacin. Levofloxacin "has [a] recognized proarrhythmic potential" and has been linked to increased risk of cardiovascular death in previous studies, Dr. Ray and his associates said.

These increased mortality risks did not persist beyond the 5-day course of treatment, even though concentrations of azithromycin remain elevated in tissue for several more days. This may be because serum concentrations of the drug decline more rapidly, "falling to trough levels within 24 hours" of completing the course of therapy.

"Although our data are consistent with an adverse cardiac effect of azithromycin, they cannot establish a specific causal mechanism," they added.

In a statement May 17, Food and Drug Administration officials noted that the agency is aware of the study and its findings and is reviewing the results; they noted that any new information that results from the FDA review would be shared.*

This study was supported by the National Heart, Lung, and Blood Institute and the Agency for Healthcare Research and Quality Centers for Education and Research on Therapeutics. Dr. Ray reported ties to XL Insurance regarding conjugated estrogens, and providing expert testimony in litigation involving zoledronic acid.

*This story was updated May 17, 2012.

Schizophrenia with comorbid panic disorder, also known as panic psychosis, appears to be a distinct subtype of schizophrenia, according to a study published in Psychiatry Research.

Patients who have these two psychiatric disorders concomitantly show distinctive cognitive and neuropsychological features, and likely will prove to have a different prognosis and a different biology from that of other patients with schizophrenia, said Dr. Erica Kirsten Rapp of the Mount Sinai School of Medicine, New York, and her associates.

Panic attacks have been reported in 7.1%-47.5% of patients with schizophrenia, depending on the population surveyed and the techniques used to assess them. Similarly, panic disorder has been reported in 4.2%-35%.

In research a decade ago, patients who had comorbid obsessive-compulsive disorder and schizophrenia appeared to have "a distinct set of clinical symptoms, neuropsychological features, and treatment responses, prompting researchers to suggest the existence of a ‘schizo-obsessive disorder.’ " To assess whether those with comorbid panic disorder and schizophrenia constitute a similar subtype, Dr. Rapp and her colleagues examined 255 inpatients using an extensive battery of cognitive and neuropsychological tests.

In all, 165 of these study subjects were diagnosed as having either schizophrenia or schizoaffective disorder without any accompanying anxiety (the schizophrenia-only group), whereas 39 had comorbid panic disorder (the panic-schizophrenia group) and 51 had a nonpanic anxiety disorder (anxiety-schizophrenia group).

Previous investigators have found higher rates of paranoid schizophrenia among patients with comorbid panic symptoms, so Dr. Rapp and her associates specifically examined the prevalence of paranoia in their study subjects. This prevalence was comparable among the three study groups, with 33.9% of the schizophrenia-only group, 33.3% of the panic-schizophrenia group, and 27.5% of the anxiety-schizophrenia group having paranoia.

Thus, the study findings would not be confounded by a predominance of paranoia in any of the study groups.

The panic-schizophrenia group differed significantly from the schizophrenia-only group in numerous measures. They showed significantly higher IQs, higher verbal IQs, better recall after a delay, more efficient problem-solving and set-switching abilities, better attentional skills, and better verbal fluency. They also performed better than the anxiety-schizophrenia group in problem-solving, attentional skills, and verbal fluency.

"These results suggest that patients with panic and schizophrenia may be more cognitively intact . . . and are less likely to exhibit the level of deficits in executive functioning and overall intelligence that are often considered to be a core feature of schizophrenia," Dr. Rapp and her colleagues said (Psychiatr. Res. 2012 [doi:10.1016/j.psychres.2012.01.017]).

"It is likely that both the presence of panic symptoms and the better neuropsychological performance are precipitated by [the same] underlying neurobiological factor," they added.

One possible candidate for this underlying factor is dopamine, which is known to affect executive functioning, positive symptoms in schizophrenia, and panic symptoms.

The panic-schizophrenia group also reported significantly more dysthymia when they were stabilized on medication than did either of the other study groups. This might be related to the fact that they also demonstrated significantly more insight into their illness than did the other patients, a finding that has been reported previously.

Given the superior cognitive performance and relatively intact executive functioning of the panic-schizophrenia group, this superior insight might indicate "a better capacity for metacognition and self-reflection. ... It may be that once their acute psychoses had resolved, they were more dysphoric about their experiences and prognosis," the researchers said. Still, their research contributes to the theory that patients with panic psychosis might "constitute a distinct group within those with schizophrenia."

This study was supported by the National Institute of Mental Health. No financial conflicts of interest were reported.

Schizophrenia with comorbid panic disorder, also known as panic psychosis, appears to be a distinct subtype of schizophrenia, according to a study published in Psychiatry Research.

Patients who have these two psychiatric disorders concomitantly show distinctive cognitive and neuropsychological features, and likely will prove to have a different prognosis and a different biology from that of other patients with schizophrenia, said Dr. Erica Kirsten Rapp of the Mount Sinai School of Medicine, New York, and her associates.

Panic attacks have been reported in 7.1%-47.5% of patients with schizophrenia, depending on the population surveyed and the techniques used to assess them. Similarly, panic disorder has been reported in 4.2%-35%.

In research a decade ago, patients who had comorbid obsessive-compulsive disorder and schizophrenia appeared to have "a distinct set of clinical symptoms, neuropsychological features, and treatment responses, prompting researchers to suggest the existence of a ‘schizo-obsessive disorder.’ " To assess whether those with comorbid panic disorder and schizophrenia constitute a similar subtype, Dr. Rapp and her colleagues examined 255 inpatients using an extensive battery of cognitive and neuropsychological tests.

In all, 165 of these study subjects were diagnosed as having either schizophrenia or schizoaffective disorder without any accompanying anxiety (the schizophrenia-only group), whereas 39 had comorbid panic disorder (the panic-schizophrenia group) and 51 had a nonpanic anxiety disorder (anxiety-schizophrenia group).

Previous investigators have found higher rates of paranoid schizophrenia among patients with comorbid panic symptoms, so Dr. Rapp and her associates specifically examined the prevalence of paranoia in their study subjects. This prevalence was comparable among the three study groups, with 33.9% of the schizophrenia-only group, 33.3% of the panic-schizophrenia group, and 27.5% of the anxiety-schizophrenia group having paranoia.

Thus, the study findings would not be confounded by a predominance of paranoia in any of the study groups.

The panic-schizophrenia group differed significantly from the schizophrenia-only group in numerous measures. They showed significantly higher IQs, higher verbal IQs, better recall after a delay, more efficient problem-solving and set-switching abilities, better attentional skills, and better verbal fluency. They also performed better than the anxiety-schizophrenia group in problem-solving, attentional skills, and verbal fluency.

"These results suggest that patients with panic and schizophrenia may be more cognitively intact . . . and are less likely to exhibit the level of deficits in executive functioning and overall intelligence that are often considered to be a core feature of schizophrenia," Dr. Rapp and her colleagues said (Psychiatr. Res. 2012 [doi:10.1016/j.psychres.2012.01.017]).

"It is likely that both the presence of panic symptoms and the better neuropsychological performance are precipitated by [the same] underlying neurobiological factor," they added.

One possible candidate for this underlying factor is dopamine, which is known to affect executive functioning, positive symptoms in schizophrenia, and panic symptoms.

The panic-schizophrenia group also reported significantly more dysthymia when they were stabilized on medication than did either of the other study groups. This might be related to the fact that they also demonstrated significantly more insight into their illness than did the other patients, a finding that has been reported previously.

Given the superior cognitive performance and relatively intact executive functioning of the panic-schizophrenia group, this superior insight might indicate "a better capacity for metacognition and self-reflection. ... It may be that once their acute psychoses had resolved, they were more dysphoric about their experiences and prognosis," the researchers said. Still, their research contributes to the theory that patients with panic psychosis might "constitute a distinct group within those with schizophrenia."

This study was supported by the National Institute of Mental Health. No financial conflicts of interest were reported.

Schizophrenia with comorbid panic disorder, also known as panic psychosis, appears to be a distinct subtype of schizophrenia, according to a study published in Psychiatry Research.

Patients who have these two psychiatric disorders concomitantly show distinctive cognitive and neuropsychological features, and likely will prove to have a different prognosis and a different biology from that of other patients with schizophrenia, said Dr. Erica Kirsten Rapp of the Mount Sinai School of Medicine, New York, and her associates.

Panic attacks have been reported in 7.1%-47.5% of patients with schizophrenia, depending on the population surveyed and the techniques used to assess them. Similarly, panic disorder has been reported in 4.2%-35%.

In research a decade ago, patients who had comorbid obsessive-compulsive disorder and schizophrenia appeared to have "a distinct set of clinical symptoms, neuropsychological features, and treatment responses, prompting researchers to suggest the existence of a ‘schizo-obsessive disorder.’ " To assess whether those with comorbid panic disorder and schizophrenia constitute a similar subtype, Dr. Rapp and her colleagues examined 255 inpatients using an extensive battery of cognitive and neuropsychological tests.

In all, 165 of these study subjects were diagnosed as having either schizophrenia or schizoaffective disorder without any accompanying anxiety (the schizophrenia-only group), whereas 39 had comorbid panic disorder (the panic-schizophrenia group) and 51 had a nonpanic anxiety disorder (anxiety-schizophrenia group).

Previous investigators have found higher rates of paranoid schizophrenia among patients with comorbid panic symptoms, so Dr. Rapp and her associates specifically examined the prevalence of paranoia in their study subjects. This prevalence was comparable among the three study groups, with 33.9% of the schizophrenia-only group, 33.3% of the panic-schizophrenia group, and 27.5% of the anxiety-schizophrenia group having paranoia.

Thus, the study findings would not be confounded by a predominance of paranoia in any of the study groups.

The panic-schizophrenia group differed significantly from the schizophrenia-only group in numerous measures. They showed significantly higher IQs, higher verbal IQs, better recall after a delay, more efficient problem-solving and set-switching abilities, better attentional skills, and better verbal fluency. They also performed better than the anxiety-schizophrenia group in problem-solving, attentional skills, and verbal fluency.

"These results suggest that patients with panic and schizophrenia may be more cognitively intact . . . and are less likely to exhibit the level of deficits in executive functioning and overall intelligence that are often considered to be a core feature of schizophrenia," Dr. Rapp and her colleagues said (Psychiatr. Res. 2012 [doi:10.1016/j.psychres.2012.01.017]).

"It is likely that both the presence of panic symptoms and the better neuropsychological performance are precipitated by [the same] underlying neurobiological factor," they added.

One possible candidate for this underlying factor is dopamine, which is known to affect executive functioning, positive symptoms in schizophrenia, and panic symptoms.

The panic-schizophrenia group also reported significantly more dysthymia when they were stabilized on medication than did either of the other study groups. This might be related to the fact that they also demonstrated significantly more insight into their illness than did the other patients, a finding that has been reported previously.

Given the superior cognitive performance and relatively intact executive functioning of the panic-schizophrenia group, this superior insight might indicate "a better capacity for metacognition and self-reflection. ... It may be that once their acute psychoses had resolved, they were more dysphoric about their experiences and prognosis," the researchers said. Still, their research contributes to the theory that patients with panic psychosis might "constitute a distinct group within those with schizophrenia."

This study was supported by the National Institute of Mental Health. No financial conflicts of interest were reported.

Routine exercise stress echocardiography may not be warranted in asymptomatic patients after coronary revascularization because even though it may identify those at high risk, this does not improve patient outcomes, according to a report published online May 14 in Archives of Internal Medicine.

"Given the very large population of post-PCI and post-CABG patients, careful consideration is warranted before the screening of asymptomatic patients is considered appropriate at any stage after revascularization," said Dr. Serge C. Harb and his associates at the Cleveland Clinic Heart and Vascular Institute.

Exercise stress echocardiography is useful in symptomatic patients after revascularization because it can identify the cause of the symptoms and allow further treatment to relieve them, which is usually highly effective. However, its role in asymptomatic patients is controversial because there is no evidence that identifying problems that cause no symptoms leads to better treatment, nor that treatment improves the course of the disease or patient outcomes.

Dr. Harb and his colleagues assessed the usefulness of exercise stress echocardiography in asymptomatic patients in an observational cohort study of 2,105 consecutive patients referred for such testing to their institute in 2000-2010. Patients were referred "solely at the discretion of individual physicians treating the patient, usually on the basis of concerns regarding risk factor status or incomplete revascularization," the researchers said.

Such testing is considered inappropriate when it is done too soon after the revascularization – less than 2 years after percutaneous coronary intervention (PCI) and less than 5 years after coronary artery bypass graft surgery (CABG). In this study, 1,143 study subjects had undergone PCI (709 referred for "early" and 434 for appropriate stress echocardiography) and 962 had undergone CABG (527 referred for "early" and 435 for appropriate stress echocardiography).

There were five major findings.

First, only 13% of the entire study population showed evidence of ischemia on stress echocardiography – a low yield of positive findings for this expensive procedure, the authors noted.

Second, abnormal results on stress echocardiography were associated with significantly higher risks of overall and cardiac mortality during a mean follow-up of 6 years. Mortality was 8.0% in patients who showed ischemia on stress testing, compared with only 4.1% in those who had no ischemia. However, identifying these high-risk patients made no difference in the eventual outcomes of the study cohort.

Interestingly, there was no distinction in the prognostic usefulness of stress echocardiography between patients who underwent "early" and those who underwent appropriate testing. This suggests that these cutoff times, which were based on expert opinion, are somewhat arbitrary and not useful for prognosis, the investigators said (Arch. Intern. Med. 2012 May 14 [doi:10.1001/archinternmed.2012.1355]).

Third, the main component of stress echocardiography that was found to be predictive was exercise capacity. This indicates that standard exercise testing rather than exercise echocardiography might be sufficient for risk evaluation.

Fourth, when exercise echocardiography did identify evidence of ischemia in a minority of patients, the findings were not acted upon in most cases. Only 33% of the 262 patients with positive results underwent further revascularization. Thus, the test results led to repeat revascularization in only 87 patients out of 2,105 who were tested. That’s because the decision to do repeat revascularization was based more on the development of symptoms after testing rather than on the results of the test.

Fifth, further revascularization procedures did not produce more favorable mortality outcomes.

"Our results suggest that from a prognostic standpoint, a combination of clinical and exercise data is effective in identifying patients at highest risk, even though they are unlikely to benefit from repeat revascularization," Dr. Harb and his associates said.

Dr. Rita F. Redberg, editor of Archives of Internal Medicine, noted that the recommendation "Do not perform serial stress cardiac imaging or advanced noninvasive imaging as part of routine follow-up in asymptomatic patients" is one of the Top 5 recommendationsfor the American College of Cardiology in the American Board of Internal Medicine Foundation’s "Choosing Wisely" campaign. Dr. Redberg, who is professor of medicine and director of Women’s Cardiovascular Services at the University of California, San Francisco, also gave the recommendation a "Less Is More" designation, which highlights areas of health care with no known benefit and definite risks.

Dr. Redberg has no relevant financial disclosures.

Routine exercise stress echocardiography may not be warranted in asymptomatic patients after coronary revascularization because even though it may identify those at high risk, this does not improve patient outcomes, according to a report published online May 14 in Archives of Internal Medicine.

"Given the very large population of post-PCI and post-CABG patients, careful consideration is warranted before the screening of asymptomatic patients is considered appropriate at any stage after revascularization," said Dr. Serge C. Harb and his associates at the Cleveland Clinic Heart and Vascular Institute.

Exercise stress echocardiography is useful in symptomatic patients after revascularization because it can identify the cause of the symptoms and allow further treatment to relieve them, which is usually highly effective. However, its role in asymptomatic patients is controversial because there is no evidence that identifying problems that cause no symptoms leads to better treatment, nor that treatment improves the course of the disease or patient outcomes.

Dr. Harb and his colleagues assessed the usefulness of exercise stress echocardiography in asymptomatic patients in an observational cohort study of 2,105 consecutive patients referred for such testing to their institute in 2000-2010. Patients were referred "solely at the discretion of individual physicians treating the patient, usually on the basis of concerns regarding risk factor status or incomplete revascularization," the researchers said.

Such testing is considered inappropriate when it is done too soon after the revascularization – less than 2 years after percutaneous coronary intervention (PCI) and less than 5 years after coronary artery bypass graft surgery (CABG). In this study, 1,143 study subjects had undergone PCI (709 referred for "early" and 434 for appropriate stress echocardiography) and 962 had undergone CABG (527 referred for "early" and 435 for appropriate stress echocardiography).

There were five major findings.

First, only 13% of the entire study population showed evidence of ischemia on stress echocardiography – a low yield of positive findings for this expensive procedure, the authors noted.

Second, abnormal results on stress echocardiography were associated with significantly higher risks of overall and cardiac mortality during a mean follow-up of 6 years. Mortality was 8.0% in patients who showed ischemia on stress testing, compared with only 4.1% in those who had no ischemia. However, identifying these high-risk patients made no difference in the eventual outcomes of the study cohort.

Interestingly, there was no distinction in the prognostic usefulness of stress echocardiography between patients who underwent "early" and those who underwent appropriate testing. This suggests that these cutoff times, which were based on expert opinion, are somewhat arbitrary and not useful for prognosis, the investigators said (Arch. Intern. Med. 2012 May 14 [doi:10.1001/archinternmed.2012.1355]).

Third, the main component of stress echocardiography that was found to be predictive was exercise capacity. This indicates that standard exercise testing rather than exercise echocardiography might be sufficient for risk evaluation.

Fourth, when exercise echocardiography did identify evidence of ischemia in a minority of patients, the findings were not acted upon in most cases. Only 33% of the 262 patients with positive results underwent further revascularization. Thus, the test results led to repeat revascularization in only 87 patients out of 2,105 who were tested. That’s because the decision to do repeat revascularization was based more on the development of symptoms after testing rather than on the results of the test.

Fifth, further revascularization procedures did not produce more favorable mortality outcomes.

"Our results suggest that from a prognostic standpoint, a combination of clinical and exercise data is effective in identifying patients at highest risk, even though they are unlikely to benefit from repeat revascularization," Dr. Harb and his associates said.

Dr. Rita F. Redberg, editor of Archives of Internal Medicine, noted that the recommendation "Do not perform serial stress cardiac imaging or advanced noninvasive imaging as part of routine follow-up in asymptomatic patients" is one of the Top 5 recommendationsfor the American College of Cardiology in the American Board of Internal Medicine Foundation’s "Choosing Wisely" campaign. Dr. Redberg, who is professor of medicine and director of Women’s Cardiovascular Services at the University of California, San Francisco, also gave the recommendation a "Less Is More" designation, which highlights areas of health care with no known benefit and definite risks.

Dr. Redberg has no relevant financial disclosures.

Routine exercise stress echocardiography may not be warranted in asymptomatic patients after coronary revascularization because even though it may identify those at high risk, this does not improve patient outcomes, according to a report published online May 14 in Archives of Internal Medicine.

"Given the very large population of post-PCI and post-CABG patients, careful consideration is warranted before the screening of asymptomatic patients is considered appropriate at any stage after revascularization," said Dr. Serge C. Harb and his associates at the Cleveland Clinic Heart and Vascular Institute.

Exercise stress echocardiography is useful in symptomatic patients after revascularization because it can identify the cause of the symptoms and allow further treatment to relieve them, which is usually highly effective. However, its role in asymptomatic patients is controversial because there is no evidence that identifying problems that cause no symptoms leads to better treatment, nor that treatment improves the course of the disease or patient outcomes.

Dr. Harb and his colleagues assessed the usefulness of exercise stress echocardiography in asymptomatic patients in an observational cohort study of 2,105 consecutive patients referred for such testing to their institute in 2000-2010. Patients were referred "solely at the discretion of individual physicians treating the patient, usually on the basis of concerns regarding risk factor status or incomplete revascularization," the researchers said.

Such testing is considered inappropriate when it is done too soon after the revascularization – less than 2 years after percutaneous coronary intervention (PCI) and less than 5 years after coronary artery bypass graft surgery (CABG). In this study, 1,143 study subjects had undergone PCI (709 referred for "early" and 434 for appropriate stress echocardiography) and 962 had undergone CABG (527 referred for "early" and 435 for appropriate stress echocardiography).

There were five major findings.

First, only 13% of the entire study population showed evidence of ischemia on stress echocardiography – a low yield of positive findings for this expensive procedure, the authors noted.

Second, abnormal results on stress echocardiography were associated with significantly higher risks of overall and cardiac mortality during a mean follow-up of 6 years. Mortality was 8.0% in patients who showed ischemia on stress testing, compared with only 4.1% in those who had no ischemia. However, identifying these high-risk patients made no difference in the eventual outcomes of the study cohort.

Interestingly, there was no distinction in the prognostic usefulness of stress echocardiography between patients who underwent "early" and those who underwent appropriate testing. This suggests that these cutoff times, which were based on expert opinion, are somewhat arbitrary and not useful for prognosis, the investigators said (Arch. Intern. Med. 2012 May 14 [doi:10.1001/archinternmed.2012.1355]).

Third, the main component of stress echocardiography that was found to be predictive was exercise capacity. This indicates that standard exercise testing rather than exercise echocardiography might be sufficient for risk evaluation.

Fourth, when exercise echocardiography did identify evidence of ischemia in a minority of patients, the findings were not acted upon in most cases. Only 33% of the 262 patients with positive results underwent further revascularization. Thus, the test results led to repeat revascularization in only 87 patients out of 2,105 who were tested. That’s because the decision to do repeat revascularization was based more on the development of symptoms after testing rather than on the results of the test.

Fifth, further revascularization procedures did not produce more favorable mortality outcomes.

"Our results suggest that from a prognostic standpoint, a combination of clinical and exercise data is effective in identifying patients at highest risk, even though they are unlikely to benefit from repeat revascularization," Dr. Harb and his associates said.

Dr. Rita F. Redberg, editor of Archives of Internal Medicine, noted that the recommendation "Do not perform serial stress cardiac imaging or advanced noninvasive imaging as part of routine follow-up in asymptomatic patients" is one of the Top 5 recommendationsfor the American College of Cardiology in the American Board of Internal Medicine Foundation’s "Choosing Wisely" campaign. Dr. Redberg, who is professor of medicine and director of Women’s Cardiovascular Services at the University of California, San Francisco, also gave the recommendation a "Less Is More" designation, which highlights areas of health care with no known benefit and definite risks.

Dr. Redberg has no relevant financial disclosures.

Exposure to "aged" secondhand smoke – even to a small amount and even for a brief time – impairs endothelial function, according to a report in the May 22 issue of the Journal of the American College of Cardiology.

"Aged" secondhand smoke refers to smoke that lingers in an indoor area 30 minutes or more after a smoker has finished a cigarette, and it is known to be more toxic to the respiratory epithelium than is fresh secondhand smoke, said Dr. Paul F. Frey of the division of cardiology, San Francisco General Hospital, and his associates.

The investigators performed a study to determine whether stale secondhand smoke also impairs endothelial function at the relatively low exposure levels that people are likely to encounter in the community setting. Endothelial dysfunction is a key mechanism in all stages of cardiovascular disease, they noted.

painless/Fotolia.com

The typical level of aged secondhand smoke found in smokers’ homes or in restaurants or other public venues that allow smoking is 100 mcg/m³ respirable suspended particles (RSPs), and the typical level found in bars or casinos in which smoke is more concentrated is 400 mcg/m³ RSPs. Dr. Frey and his colleagues assessed the response to 30 minutes of exposure at both of these levels, as well as to filtered smoke-free air, in 33 healthy nonsmoking adults aged 18-40 years.

All the study participants reported no exposure to secondhand smoke during the month preceding the study. None of them had conditions that could adversely affect endothelial function such as diabetes, hypertension, respiratory disease, kidney disease, coronary artery disease, or heart failure.

Endothelial function was assessed using high-resolution ultrasound to measure maximal percent flow-mediated dilation of the brachial artery before and after exposure.

The study participants were exposed to smoke-free air (11 participants), 100 mcg/m³ RSPs (11 participants), or 400 mcg/m³ RSPs (11 participants) in a hooded device attached to a smoking machine. The secondhand smoke was aged for 60 minutes, then routed to the hood for a single 30-minute exposure time. The RSP level was monitored continuously.

Endothelial function was impaired in a dose-dependent fashion at both levels of exposure to aged secondhand smoke. For every 100 mcg/m³ increase in RSP level, maximal percent flow-mediated dilation of the brachial artery decreased by 0.67%, Dr. Frey and his associates said (J. Am. Coll. Cardiol. 2012;59:1908-13).

"Our research strengthens the evidence that secondhand smoke is detrimental to cardiovascular health even at very short exposures and low particulate concentrations," they noted.

The findings highlight the importance of policies that limit the public’s exposure to secondhand smoke, the researchers said.

The study conditions may underestimate the effect of aged secondhand smoke in real-world settings, they added.

The subjects remained at rest throughout their exposure to secondhand smoke and were exposed for only half an hour. In real-world experience, people are exposed for much longer durations and may be physically active during their exposure, which increases minute ventilation. Moreover, "our subjects were healthy and may have been less susceptible to decrements in endothelial function than patients with vascular disease who are at greater risk for secondhand smoke–induced acute cardiovascular events."

This study was supported in part by the Tobacco-Related Disease Research Program and the Flight Attendants Medical Research Institute Bland Lane Center of Excellence on Secondhand Smoke at the University of California, San Francisco. One coauthor reported ties to pharmaceutical companies that develop or market smoking-cessation medications and being a paid expert witness in litigation against tobacco companies.

Exposure to "aged" secondhand smoke – even to a small amount and even for a brief time – impairs endothelial function, according to a report in the May 22 issue of the Journal of the American College of Cardiology.

"Aged" secondhand smoke refers to smoke that lingers in an indoor area 30 minutes or more after a smoker has finished a cigarette, and it is known to be more toxic to the respiratory epithelium than is fresh secondhand smoke, said Dr. Paul F. Frey of the division of cardiology, San Francisco General Hospital, and his associates.

The investigators performed a study to determine whether stale secondhand smoke also impairs endothelial function at the relatively low exposure levels that people are likely to encounter in the community setting. Endothelial dysfunction is a key mechanism in all stages of cardiovascular disease, they noted.

painless/Fotolia.com

The typical level of aged secondhand smoke found in smokers’ homes or in restaurants or other public venues that allow smoking is 100 mcg/m³ respirable suspended particles (RSPs), and the typical level found in bars or casinos in which smoke is more concentrated is 400 mcg/m³ RSPs. Dr. Frey and his colleagues assessed the response to 30 minutes of exposure at both of these levels, as well as to filtered smoke-free air, in 33 healthy nonsmoking adults aged 18-40 years.

All the study participants reported no exposure to secondhand smoke during the month preceding the study. None of them had conditions that could adversely affect endothelial function such as diabetes, hypertension, respiratory disease, kidney disease, coronary artery disease, or heart failure.

Endothelial function was assessed using high-resolution ultrasound to measure maximal percent flow-mediated dilation of the brachial artery before and after exposure.

The study participants were exposed to smoke-free air (11 participants), 100 mcg/m³ RSPs (11 participants), or 400 mcg/m³ RSPs (11 participants) in a hooded device attached to a smoking machine. The secondhand smoke was aged for 60 minutes, then routed to the hood for a single 30-minute exposure time. The RSP level was monitored continuously.

Endothelial function was impaired in a dose-dependent fashion at both levels of exposure to aged secondhand smoke. For every 100 mcg/m³ increase in RSP level, maximal percent flow-mediated dilation of the brachial artery decreased by 0.67%, Dr. Frey and his associates said (J. Am. Coll. Cardiol. 2012;59:1908-13).

"Our research strengthens the evidence that secondhand smoke is detrimental to cardiovascular health even at very short exposures and low particulate concentrations," they noted.

The findings highlight the importance of policies that limit the public’s exposure to secondhand smoke, the researchers said.

The study conditions may underestimate the effect of aged secondhand smoke in real-world settings, they added.

The subjects remained at rest throughout their exposure to secondhand smoke and were exposed for only half an hour. In real-world experience, people are exposed for much longer durations and may be physically active during their exposure, which increases minute ventilation. Moreover, "our subjects were healthy and may have been less susceptible to decrements in endothelial function than patients with vascular disease who are at greater risk for secondhand smoke–induced acute cardiovascular events."

This study was supported in part by the Tobacco-Related Disease Research Program and the Flight Attendants Medical Research Institute Bland Lane Center of Excellence on Secondhand Smoke at the University of California, San Francisco. One coauthor reported ties to pharmaceutical companies that develop or market smoking-cessation medications and being a paid expert witness in litigation against tobacco companies.

Exposure to "aged" secondhand smoke – even to a small amount and even for a brief time – impairs endothelial function, according to a report in the May 22 issue of the Journal of the American College of Cardiology.

"Aged" secondhand smoke refers to smoke that lingers in an indoor area 30 minutes or more after a smoker has finished a cigarette, and it is known to be more toxic to the respiratory epithelium than is fresh secondhand smoke, said Dr. Paul F. Frey of the division of cardiology, San Francisco General Hospital, and his associates.

The investigators performed a study to determine whether stale secondhand smoke also impairs endothelial function at the relatively low exposure levels that people are likely to encounter in the community setting. Endothelial dysfunction is a key mechanism in all stages of cardiovascular disease, they noted.

painless/Fotolia.com

The typical level of aged secondhand smoke found in smokers’ homes or in restaurants or other public venues that allow smoking is 100 mcg/m³ respirable suspended particles (RSPs), and the typical level found in bars or casinos in which smoke is more concentrated is 400 mcg/m³ RSPs. Dr. Frey and his colleagues assessed the response to 30 minutes of exposure at both of these levels, as well as to filtered smoke-free air, in 33 healthy nonsmoking adults aged 18-40 years.

All the study participants reported no exposure to secondhand smoke during the month preceding the study. None of them had conditions that could adversely affect endothelial function such as diabetes, hypertension, respiratory disease, kidney disease, coronary artery disease, or heart failure.

Endothelial function was assessed using high-resolution ultrasound to measure maximal percent flow-mediated dilation of the brachial artery before and after exposure.

The study participants were exposed to smoke-free air (11 participants), 100 mcg/m³ RSPs (11 participants), or 400 mcg/m³ RSPs (11 participants) in a hooded device attached to a smoking machine. The secondhand smoke was aged for 60 minutes, then routed to the hood for a single 30-minute exposure time. The RSP level was monitored continuously.

Endothelial function was impaired in a dose-dependent fashion at both levels of exposure to aged secondhand smoke. For every 100 mcg/m³ increase in RSP level, maximal percent flow-mediated dilation of the brachial artery decreased by 0.67%, Dr. Frey and his associates said (J. Am. Coll. Cardiol. 2012;59:1908-13).

"Our research strengthens the evidence that secondhand smoke is detrimental to cardiovascular health even at very short exposures and low particulate concentrations," they noted.

The findings highlight the importance of policies that limit the public’s exposure to secondhand smoke, the researchers said.

The study conditions may underestimate the effect of aged secondhand smoke in real-world settings, they added.

The subjects remained at rest throughout their exposure to secondhand smoke and were exposed for only half an hour. In real-world experience, people are exposed for much longer durations and may be physically active during their exposure, which increases minute ventilation. Moreover, "our subjects were healthy and may have been less susceptible to decrements in endothelial function than patients with vascular disease who are at greater risk for secondhand smoke–induced acute cardiovascular events."

This study was supported in part by the Tobacco-Related Disease Research Program and the Flight Attendants Medical Research Institute Bland Lane Center of Excellence on Secondhand Smoke at the University of California, San Francisco. One coauthor reported ties to pharmaceutical companies that develop or market smoking-cessation medications and being a paid expert witness in litigation against tobacco companies.

Siblings of people who have schizophrenia are more likely than healthy control subjects to have social anhedonia, to withdraw from social contact, and to report having psychotic experiences, according to a report published online in Schizophrenia Research.

"Our findings suggest that the overlap between [social anhedonia], withdrawal, and positive symptoms ... may ... reflect a shared genetic vulnerability, instead of merely being either a state marker of – or reaction to – psychotic symptoms," said Eva Velthorst of the University of Amsterdam and her associates (Schizophr. Res. 2012 April 30 [doi:10.1016/j.schres.2012.03.022]).

For many years, social disinterest was recognized as a central feature of psychosis vulnerability, Ms. Velthorst and her colleagues wrote. These study results suggest that social anhedonia could be a significant factor in the pathway to psychosis, and that people who develop this cluster of symptoms might be at increased susceptibility for a first psychosis, added Ms. Velthorst, a Ph.D. candidate at the university.

The investigators examined the relationship among social anhedonia, withdrawal, and psychotic experiences using data from a multicenter longitudinal study of people aged 16-50 years residing in the Netherlands and Belgium. They assessed a subgroup of 646 unaffected siblings of schizophrenia patients and 326 healthy controls. Exclusion criteria for healthy controls were a history of psychotic disorder or having a first-degree family member with such a history.

The study subjects were assessed for social anhedonia and withdrawal using the Structured Interview for Schizotypy-Revised, and for psychotic experiences using the Community Assessment of Psychic Experiences. The CAPE, a self-report questionnaire, covers social delusions such as feeling persecuted, bizarre experiences such as receiving messages from the television, and popular beliefs such as believing in telepathy or voodoo.

A small but significant association was found among the three symptoms in the sibling group but not in the control subjects, suggesting that social anhedonia and withdrawal might be a marker of vulnerability to psychosis.

"Further prospective research is needed to clarify how [social anhedonia], withdrawal, and positive symptoms interact precisely in the trajectory to a first psychosis, and such research may eventually contribute to a better psychosis prediction," Ms. Velthorst and her colleagues said.

Future research also could open the door to possible interventions, testing whether social activity and engagement reduce the likelihood of progressing to a first psychotic episode, they added.

This study was supported by the Dutch Health Research Group, Lundbeck, AstraZeneca, Eli Lilly, and Janssen-Cilag. No financial conflicts of interest were reported.

Siblings of people who have schizophrenia are more likely than healthy control subjects to have social anhedonia, to withdraw from social contact, and to report having psychotic experiences, according to a report published online in Schizophrenia Research.

"Our findings suggest that the overlap between [social anhedonia], withdrawal, and positive symptoms ... may ... reflect a shared genetic vulnerability, instead of merely being either a state marker of – or reaction to – psychotic symptoms," said Eva Velthorst of the University of Amsterdam and her associates (Schizophr. Res. 2012 April 30 [doi:10.1016/j.schres.2012.03.022]).

For many years, social disinterest was recognized as a central feature of psychosis vulnerability, Ms. Velthorst and her colleagues wrote. These study results suggest that social anhedonia could be a significant factor in the pathway to psychosis, and that people who develop this cluster of symptoms might be at increased susceptibility for a first psychosis, added Ms. Velthorst, a Ph.D. candidate at the university.

The investigators examined the relationship among social anhedonia, withdrawal, and psychotic experiences using data from a multicenter longitudinal study of people aged 16-50 years residing in the Netherlands and Belgium. They assessed a subgroup of 646 unaffected siblings of schizophrenia patients and 326 healthy controls. Exclusion criteria for healthy controls were a history of psychotic disorder or having a first-degree family member with such a history.

The study subjects were assessed for social anhedonia and withdrawal using the Structured Interview for Schizotypy-Revised, and for psychotic experiences using the Community Assessment of Psychic Experiences. The CAPE, a self-report questionnaire, covers social delusions such as feeling persecuted, bizarre experiences such as receiving messages from the television, and popular beliefs such as believing in telepathy or voodoo.

A small but significant association was found among the three symptoms in the sibling group but not in the control subjects, suggesting that social anhedonia and withdrawal might be a marker of vulnerability to psychosis.

"Further prospective research is needed to clarify how [social anhedonia], withdrawal, and positive symptoms interact precisely in the trajectory to a first psychosis, and such research may eventually contribute to a better psychosis prediction," Ms. Velthorst and her colleagues said.

Future research also could open the door to possible interventions, testing whether social activity and engagement reduce the likelihood of progressing to a first psychotic episode, they added.

This study was supported by the Dutch Health Research Group, Lundbeck, AstraZeneca, Eli Lilly, and Janssen-Cilag. No financial conflicts of interest were reported.

Siblings of people who have schizophrenia are more likely than healthy control subjects to have social anhedonia, to withdraw from social contact, and to report having psychotic experiences, according to a report published online in Schizophrenia Research.

"Our findings suggest that the overlap between [social anhedonia], withdrawal, and positive symptoms ... may ... reflect a shared genetic vulnerability, instead of merely being either a state marker of – or reaction to – psychotic symptoms," said Eva Velthorst of the University of Amsterdam and her associates (Schizophr. Res. 2012 April 30 [doi:10.1016/j.schres.2012.03.022]).

For many years, social disinterest was recognized as a central feature of psychosis vulnerability, Ms. Velthorst and her colleagues wrote. These study results suggest that social anhedonia could be a significant factor in the pathway to psychosis, and that people who develop this cluster of symptoms might be at increased susceptibility for a first psychosis, added Ms. Velthorst, a Ph.D. candidate at the university.

The investigators examined the relationship among social anhedonia, withdrawal, and psychotic experiences using data from a multicenter longitudinal study of people aged 16-50 years residing in the Netherlands and Belgium. They assessed a subgroup of 646 unaffected siblings of schizophrenia patients and 326 healthy controls. Exclusion criteria for healthy controls were a history of psychotic disorder or having a first-degree family member with such a history.

The study subjects were assessed for social anhedonia and withdrawal using the Structured Interview for Schizotypy-Revised, and for psychotic experiences using the Community Assessment of Psychic Experiences. The CAPE, a self-report questionnaire, covers social delusions such as feeling persecuted, bizarre experiences such as receiving messages from the television, and popular beliefs such as believing in telepathy or voodoo.

A small but significant association was found among the three symptoms in the sibling group but not in the control subjects, suggesting that social anhedonia and withdrawal might be a marker of vulnerability to psychosis.

"Further prospective research is needed to clarify how [social anhedonia], withdrawal, and positive symptoms interact precisely in the trajectory to a first psychosis, and such research may eventually contribute to a better psychosis prediction," Ms. Velthorst and her colleagues said.

Future research also could open the door to possible interventions, testing whether social activity and engagement reduce the likelihood of progressing to a first psychotic episode, they added.

This study was supported by the Dutch Health Research Group, Lundbeck, AstraZeneca, Eli Lilly, and Janssen-Cilag. No financial conflicts of interest were reported.

Many patients continue to use proton pump inhibitors after pH testing shows that they do not have acid reflux, Dr. Andrew J. Gawron and his colleagues reported in the June issue of Clinical Gastroenterology and Hepatology.

In this cross-sectional, observational study, investigators conducted phone interviews with 90 patients who had received negative results on pH testing months to years earlier (mean of 25.0 months). Of these 90 people, fully 42% (38 patients), were still taking PPIs.

Most of these patients reported having persistent, troublesome symptoms every day, and "a significant proportion" had scores on the GerdQ that would be considered diagnostic of gastroesophageal reflux disease (GERD), said Dr. Gawron of the division of gastroenterology and hepatology and the Institute for Healthcare Studies at Northwestern University, Chicago, and his associates (Clin. Gastro. Hepatol. 2012 Feb. 23 [doi:10.1016/j.cgh.2012.02.012]).

Only 17 patients (19%) remembered being instructed to discontinue their PPI after receiving their test results, and only 15 had documentation of this instruction in their charts. Patients who continued taking PPIs were slightly older than those who stopped their PPIs after negative pH testing (50.3 vs. 46.8 years, respectively).

The study findings suggest that clinicians should improve their patient counseling methods and be more systematic in their approach to patients whose reflux testing yields negative results. The study’s conclusions also "highlight the need for improved strategies to identify alternative diagnoses and treatments for patients whose symptoms are inadequately relieved by PPIs," the investigators said.

Overuse of PPIs has been demonstrated in numerous studies. In the current study, Dr. Gawron and his colleagues reviewed the records of 90 patients who had been referred for ambulatory pH testing in 2006-2010, using endoscopy plus either 48-hour Bravo pH monitoring (66 subjects) or multichannel intraluminal impedance-pH testing (24 subjects). All had received negative results indicating that they did not have GERD.

These patients were later contacted by phone and completed the GerdQ, a questionnaire that quantifies GERD symptoms and their impact on daily life. The GerdQ has shown similar accuracy to a gastroenterologist’s assessment in diagnosing GERD, the researchers noted.

The study subjects also completed a telephone questionnaire regarding their general health status.

In all, 38 patients said they were currently using PPIs, and 13 were taking their PPI twice a day, despite their negative results on pH testing. Most used esomeprazole (13 subjects) or omeprazole (11 subjects).

A total of 56% of the subjects who continued to take PPIs had positive scores on the GerdQ, which would indicate that they did have GERD. In contrast, only 21% of the subjects who discontinued PPIs had positive GerdQ scores.

Mean age, sex, race, body mass index, marital status, income, and education level were similar between patients who continued taking PPIs and those who did not. Also, there were no differences between the two groups in outpatient visits to either primary care or gastroenterology physicians, use of medication for depression or anxiety, or general health status.

The only clinical or demographic factor that appeared to differ between the two groups was alcohol intake: 90% of patients who were not taking a PPI reported alcohol use, while only 63% of those who were taking a PPI did so. This suggests that symptoms were bothersome enough for patients who continued taking PPIs that they reduced their alcohol consumption.

Although PPIs are often prescribed for gastroprotection in patients who are taking concomitant aspirin or NSAID therapy, this did not account for the continued use of PPIs in this study population. Only 12 patients reported taking aspirin and only 8 reported taking NSAIDs.

This study was supported by the U.S. Public Health Service and the Agency for Healthcare Research and Quality. Dr. Gawron reported no financial conflicts of interest. His coauthors reported ties to AstraZeneca, Eisai, EndoGastric Solutions, Ironwood, Torax, Reckitt Benckiser, Given, Sandhill, Shire, and Crospon.

Many patients continue to use proton pump inhibitors after pH testing shows that they do not have acid reflux, Dr. Andrew J. Gawron and his colleagues reported in the June issue of Clinical Gastroenterology and Hepatology.

In this cross-sectional, observational study, investigators conducted phone interviews with 90 patients who had received negative results on pH testing months to years earlier (mean of 25.0 months). Of these 90 people, fully 42% (38 patients), were still taking PPIs.

Most of these patients reported having persistent, troublesome symptoms every day, and "a significant proportion" had scores on the GerdQ that would be considered diagnostic of gastroesophageal reflux disease (GERD), said Dr. Gawron of the division of gastroenterology and hepatology and the Institute for Healthcare Studies at Northwestern University, Chicago, and his associates (Clin. Gastro. Hepatol. 2012 Feb. 23 [doi:10.1016/j.cgh.2012.02.012]).

Only 17 patients (19%) remembered being instructed to discontinue their PPI after receiving their test results, and only 15 had documentation of this instruction in their charts. Patients who continued taking PPIs were slightly older than those who stopped their PPIs after negative pH testing (50.3 vs. 46.8 years, respectively).

The study findings suggest that clinicians should improve their patient counseling methods and be more systematic in their approach to patients whose reflux testing yields negative results. The study’s conclusions also "highlight the need for improved strategies to identify alternative diagnoses and treatments for patients whose symptoms are inadequately relieved by PPIs," the investigators said.

Overuse of PPIs has been demonstrated in numerous studies. In the current study, Dr. Gawron and his colleagues reviewed the records of 90 patients who had been referred for ambulatory pH testing in 2006-2010, using endoscopy plus either 48-hour Bravo pH monitoring (66 subjects) or multichannel intraluminal impedance-pH testing (24 subjects). All had received negative results indicating that they did not have GERD.

These patients were later contacted by phone and completed the GerdQ, a questionnaire that quantifies GERD symptoms and their impact on daily life. The GerdQ has shown similar accuracy to a gastroenterologist’s assessment in diagnosing GERD, the researchers noted.

The study subjects also completed a telephone questionnaire regarding their general health status.

In all, 38 patients said they were currently using PPIs, and 13 were taking their PPI twice a day, despite their negative results on pH testing. Most used esomeprazole (13 subjects) or omeprazole (11 subjects).

A total of 56% of the subjects who continued to take PPIs had positive scores on the GerdQ, which would indicate that they did have GERD. In contrast, only 21% of the subjects who discontinued PPIs had positive GerdQ scores.

Mean age, sex, race, body mass index, marital status, income, and education level were similar between patients who continued taking PPIs and those who did not. Also, there were no differences between the two groups in outpatient visits to either primary care or gastroenterology physicians, use of medication for depression or anxiety, or general health status.

The only clinical or demographic factor that appeared to differ between the two groups was alcohol intake: 90% of patients who were not taking a PPI reported alcohol use, while only 63% of those who were taking a PPI did so. This suggests that symptoms were bothersome enough for patients who continued taking PPIs that they reduced their alcohol consumption.

Although PPIs are often prescribed for gastroprotection in patients who are taking concomitant aspirin or NSAID therapy, this did not account for the continued use of PPIs in this study population. Only 12 patients reported taking aspirin and only 8 reported taking NSAIDs.

This study was supported by the U.S. Public Health Service and the Agency for Healthcare Research and Quality. Dr. Gawron reported no financial conflicts of interest. His coauthors reported ties to AstraZeneca, Eisai, EndoGastric Solutions, Ironwood, Torax, Reckitt Benckiser, Given, Sandhill, Shire, and Crospon.

Many patients continue to use proton pump inhibitors after pH testing shows that they do not have acid reflux, Dr. Andrew J. Gawron and his colleagues reported in the June issue of Clinical Gastroenterology and Hepatology.

In this cross-sectional, observational study, investigators conducted phone interviews with 90 patients who had received negative results on pH testing months to years earlier (mean of 25.0 months). Of these 90 people, fully 42% (38 patients), were still taking PPIs.

Most of these patients reported having persistent, troublesome symptoms every day, and "a significant proportion" had scores on the GerdQ that would be considered diagnostic of gastroesophageal reflux disease (GERD), said Dr. Gawron of the division of gastroenterology and hepatology and the Institute for Healthcare Studies at Northwestern University, Chicago, and his associates (Clin. Gastro. Hepatol. 2012 Feb. 23 [doi:10.1016/j.cgh.2012.02.012]).

Only 17 patients (19%) remembered being instructed to discontinue their PPI after receiving their test results, and only 15 had documentation of this instruction in their charts. Patients who continued taking PPIs were slightly older than those who stopped their PPIs after negative pH testing (50.3 vs. 46.8 years, respectively).

The study findings suggest that clinicians should improve their patient counseling methods and be more systematic in their approach to patients whose reflux testing yields negative results. The study’s conclusions also "highlight the need for improved strategies to identify alternative diagnoses and treatments for patients whose symptoms are inadequately relieved by PPIs," the investigators said.

Overuse of PPIs has been demonstrated in numerous studies. In the current study, Dr. Gawron and his colleagues reviewed the records of 90 patients who had been referred for ambulatory pH testing in 2006-2010, using endoscopy plus either 48-hour Bravo pH monitoring (66 subjects) or multichannel intraluminal impedance-pH testing (24 subjects). All had received negative results indicating that they did not have GERD.

These patients were later contacted by phone and completed the GerdQ, a questionnaire that quantifies GERD symptoms and their impact on daily life. The GerdQ has shown similar accuracy to a gastroenterologist’s assessment in diagnosing GERD, the researchers noted.

The study subjects also completed a telephone questionnaire regarding their general health status.

In all, 38 patients said they were currently using PPIs, and 13 were taking their PPI twice a day, despite their negative results on pH testing. Most used esomeprazole (13 subjects) or omeprazole (11 subjects).

A total of 56% of the subjects who continued to take PPIs had positive scores on the GerdQ, which would indicate that they did have GERD. In contrast, only 21% of the subjects who discontinued PPIs had positive GerdQ scores.

Mean age, sex, race, body mass index, marital status, income, and education level were similar between patients who continued taking PPIs and those who did not. Also, there were no differences between the two groups in outpatient visits to either primary care or gastroenterology physicians, use of medication for depression or anxiety, or general health status.

The only clinical or demographic factor that appeared to differ between the two groups was alcohol intake: 90% of patients who were not taking a PPI reported alcohol use, while only 63% of those who were taking a PPI did so. This suggests that symptoms were bothersome enough for patients who continued taking PPIs that they reduced their alcohol consumption.

Although PPIs are often prescribed for gastroprotection in patients who are taking concomitant aspirin or NSAID therapy, this did not account for the continued use of PPIs in this study population. Only 12 patients reported taking aspirin and only 8 reported taking NSAIDs.

This study was supported by the U.S. Public Health Service and the Agency for Healthcare Research and Quality. Dr. Gawron reported no financial conflicts of interest. His coauthors reported ties to AstraZeneca, Eisai, EndoGastric Solutions, Ironwood, Torax, Reckitt Benckiser, Given, Sandhill, Shire, and Crospon.

The consumption of fish rich in n-3 polyunsaturated fatty acids was inversely related to the risk of developing hepatocellular carcinoma in a population-based study of Japanese adults, Dr. Norie Sawada and colleagues reported in the June issue of Gastroenterology.

In addition, higher intake of several individual n-3 polyunsaturated fatty acids (PUFAs) – particularly eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid – also correlated with lower hepatocellular carcinoma (HCC) risk.

© Suprijono Suharjoto/Fotolia.com

The associations were dose dependent for intake of n-3 PUFA-rich fish and for intake of individual fatty acids, said Dr. Sawada of the National Cancer Center, Tokyo, and associates.

Dietary n-3 PUFAs, also called omega-3 PUFAs, have long been thought to lower the risk of developing several cancers, but few studies have examined a potential protective effect against liver cancer in particular. One recent prospective study in the United States showed an inverse association between consumption of "white meat," including fish, and liver cancer, but other studies have found no such correlation.

Dr. Sawada and colleagues examined the issue by analyzing data from a large cohort study launched in the 1990s and supervised by the Japanese department of public health. The investigators analyzed detailed dietary data from 90,296 adults who were aged 40-69 years at baseline and were followed for an average of 11 years.

The study subjects completed questionnaires regarding their usual intake of 138 food items during the previous year, using standard portions or units of consumption. Nineteen items on the questionnaire asked about dietary fish and shellfish, which in Japan includes salted fish; dried fish; canned tuna, salmon, or trout; and bonito, tuna, cod, sea bream, mackerel, sardine, mackerel pike, roe, eel, squid, octopus, prawn, clam, crab, vivipara, as well as various fish pastes.

The investigators used the subjects’ responses to calculate daily fish consumption. They also calculated daily intake of all n-3 PUFAS combined, and intake of four individual fatty acids. They separately calculated the consumption of fish rich in n-3 PUFAs, namely salmon, trout, sea bream, mackerel, sardine, mackerel pike, and eel.

Blood samples that had been taken during general health check-ups were screened for hepatitis C antibodies and hepatitis B surface antigen to determine whether the subjects were carrying hepatitis C or B.

A total of 398 cases of incident HCC developed during follow-up (Gastroenterology 2012 Feb. 20 [doi:10.1053/j.gastro.2012.02.018]).

Total fish consumption showed a weak inverse association with risk of HCC, with a multivariable hazard ratio of .64 for highest vs. lowest quintile (95% confidence interval, 0.41 to 1.02, P for trend = .07). The association reached statistical significance when the analysis was confined to fish rich in n-3 PUFAs with a HR of 0.64 (95% CI, .42 to .96, P for trend = .04).

Strong, dose-dependent inverse associations also were found between HCC risk and dietary intake of eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid.

These results did not change substantially when the data were adjusted to account for subject age, sex, smoking status, and body mass index. The findings also persisted across several subgroups of patients such as alcohol drinkers and coffee drinkers.

The inverse association between consumption of fish high in n-3 PUFAs and HCC risk also was strong in the subgroups of patients positive for hepatitis B or hepatitis C.

The reasons underlying this protective effect against liver cancer are not yet known. It is likely that the anti-inflammatory properties of polyunsaturated fatty acids play a role, "given that HCC is an inflammation-related cancer which has a background of chronic inflammation triggered by exposure to hepatitis virus infection or toxic compounds such as ethanol," Dr. Sawada and associates said.

This study was somewhat limited in that it was necessary to estimate the consumption of fish and individual fatty acids rather than measuring these amounts directly. Also, the dietary data were based on subjects’ self-report at only a single time point.

The study was supported by the National Cancer Center Research and Development Fund and the Ministry of Health, Labor, and Welfare of Japan, both in Tokyo. The authors reported no financial conflicts of interest.

The consumption of fish rich in n-3 polyunsaturated fatty acids was inversely related to the risk of developing hepatocellular carcinoma in a population-based study of Japanese adults, Dr. Norie Sawada and colleagues reported in the June issue of Gastroenterology.

In addition, higher intake of several individual n-3 polyunsaturated fatty acids (PUFAs) – particularly eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid – also correlated with lower hepatocellular carcinoma (HCC) risk.

© Suprijono Suharjoto/Fotolia.com

The associations were dose dependent for intake of n-3 PUFA-rich fish and for intake of individual fatty acids, said Dr. Sawada of the National Cancer Center, Tokyo, and associates.

Dietary n-3 PUFAs, also called omega-3 PUFAs, have long been thought to lower the risk of developing several cancers, but few studies have examined a potential protective effect against liver cancer in particular. One recent prospective study in the United States showed an inverse association between consumption of "white meat," including fish, and liver cancer, but other studies have found no such correlation.

Dr. Sawada and colleagues examined the issue by analyzing data from a large cohort study launched in the 1990s and supervised by the Japanese department of public health. The investigators analyzed detailed dietary data from 90,296 adults who were aged 40-69 years at baseline and were followed for an average of 11 years.

The study subjects completed questionnaires regarding their usual intake of 138 food items during the previous year, using standard portions or units of consumption. Nineteen items on the questionnaire asked about dietary fish and shellfish, which in Japan includes salted fish; dried fish; canned tuna, salmon, or trout; and bonito, tuna, cod, sea bream, mackerel, sardine, mackerel pike, roe, eel, squid, octopus, prawn, clam, crab, vivipara, as well as various fish pastes.

The investigators used the subjects’ responses to calculate daily fish consumption. They also calculated daily intake of all n-3 PUFAS combined, and intake of four individual fatty acids. They separately calculated the consumption of fish rich in n-3 PUFAs, namely salmon, trout, sea bream, mackerel, sardine, mackerel pike, and eel.

Blood samples that had been taken during general health check-ups were screened for hepatitis C antibodies and hepatitis B surface antigen to determine whether the subjects were carrying hepatitis C or B.

A total of 398 cases of incident HCC developed during follow-up (Gastroenterology 2012 Feb. 20 [doi:10.1053/j.gastro.2012.02.018]).

Total fish consumption showed a weak inverse association with risk of HCC, with a multivariable hazard ratio of .64 for highest vs. lowest quintile (95% confidence interval, 0.41 to 1.02, P for trend = .07). The association reached statistical significance when the analysis was confined to fish rich in n-3 PUFAs with a HR of 0.64 (95% CI, .42 to .96, P for trend = .04).

Strong, dose-dependent inverse associations also were found between HCC risk and dietary intake of eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid.

These results did not change substantially when the data were adjusted to account for subject age, sex, smoking status, and body mass index. The findings also persisted across several subgroups of patients such as alcohol drinkers and coffee drinkers.

The inverse association between consumption of fish high in n-3 PUFAs and HCC risk also was strong in the subgroups of patients positive for hepatitis B or hepatitis C.

The reasons underlying this protective effect against liver cancer are not yet known. It is likely that the anti-inflammatory properties of polyunsaturated fatty acids play a role, "given that HCC is an inflammation-related cancer which has a background of chronic inflammation triggered by exposure to hepatitis virus infection or toxic compounds such as ethanol," Dr. Sawada and associates said.

This study was somewhat limited in that it was necessary to estimate the consumption of fish and individual fatty acids rather than measuring these amounts directly. Also, the dietary data were based on subjects’ self-report at only a single time point.

The study was supported by the National Cancer Center Research and Development Fund and the Ministry of Health, Labor, and Welfare of Japan, both in Tokyo. The authors reported no financial conflicts of interest.

The consumption of fish rich in n-3 polyunsaturated fatty acids was inversely related to the risk of developing hepatocellular carcinoma in a population-based study of Japanese adults, Dr. Norie Sawada and colleagues reported in the June issue of Gastroenterology.

In addition, higher intake of several individual n-3 polyunsaturated fatty acids (PUFAs) – particularly eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid – also correlated with lower hepatocellular carcinoma (HCC) risk.

© Suprijono Suharjoto/Fotolia.com

The associations were dose dependent for intake of n-3 PUFA-rich fish and for intake of individual fatty acids, said Dr. Sawada of the National Cancer Center, Tokyo, and associates.

Dietary n-3 PUFAs, also called omega-3 PUFAs, have long been thought to lower the risk of developing several cancers, but few studies have examined a potential protective effect against liver cancer in particular. One recent prospective study in the United States showed an inverse association between consumption of "white meat," including fish, and liver cancer, but other studies have found no such correlation.

Dr. Sawada and colleagues examined the issue by analyzing data from a large cohort study launched in the 1990s and supervised by the Japanese department of public health. The investigators analyzed detailed dietary data from 90,296 adults who were aged 40-69 years at baseline and were followed for an average of 11 years.

The study subjects completed questionnaires regarding their usual intake of 138 food items during the previous year, using standard portions or units of consumption. Nineteen items on the questionnaire asked about dietary fish and shellfish, which in Japan includes salted fish; dried fish; canned tuna, salmon, or trout; and bonito, tuna, cod, sea bream, mackerel, sardine, mackerel pike, roe, eel, squid, octopus, prawn, clam, crab, vivipara, as well as various fish pastes.

The investigators used the subjects’ responses to calculate daily fish consumption. They also calculated daily intake of all n-3 PUFAS combined, and intake of four individual fatty acids. They separately calculated the consumption of fish rich in n-3 PUFAs, namely salmon, trout, sea bream, mackerel, sardine, mackerel pike, and eel.

Blood samples that had been taken during general health check-ups were screened for hepatitis C antibodies and hepatitis B surface antigen to determine whether the subjects were carrying hepatitis C or B.

A total of 398 cases of incident HCC developed during follow-up (Gastroenterology 2012 Feb. 20 [doi:10.1053/j.gastro.2012.02.018]).

Total fish consumption showed a weak inverse association with risk of HCC, with a multivariable hazard ratio of .64 for highest vs. lowest quintile (95% confidence interval, 0.41 to 1.02, P for trend = .07). The association reached statistical significance when the analysis was confined to fish rich in n-3 PUFAs with a HR of 0.64 (95% CI, .42 to .96, P for trend = .04).

Strong, dose-dependent inverse associations also were found between HCC risk and dietary intake of eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid.

These results did not change substantially when the data were adjusted to account for subject age, sex, smoking status, and body mass index. The findings also persisted across several subgroups of patients such as alcohol drinkers and coffee drinkers.

The inverse association between consumption of fish high in n-3 PUFAs and HCC risk also was strong in the subgroups of patients positive for hepatitis B or hepatitis C.

The reasons underlying this protective effect against liver cancer are not yet known. It is likely that the anti-inflammatory properties of polyunsaturated fatty acids play a role, "given that HCC is an inflammation-related cancer which has a background of chronic inflammation triggered by exposure to hepatitis virus infection or toxic compounds such as ethanol," Dr. Sawada and associates said.

This study was somewhat limited in that it was necessary to estimate the consumption of fish and individual fatty acids rather than measuring these amounts directly. Also, the dietary data were based on subjects’ self-report at only a single time point.

The study was supported by the National Cancer Center Research and Development Fund and the Ministry of Health, Labor, and Welfare of Japan, both in Tokyo. The authors reported no financial conflicts of interest.

Rivaroxaban was noninferior to standard treatment at preventing a recurrence of pulmonary embolism in an international open-label trial reported online in the New England Journal of Medicine and presented simultaneously at the annual meeting of the American College of Cardiology.

Rates of adverse bleeding events with rivaroxaban were similar to those with the more complex standard therapy of enoxaparin plus a vitamin K antagonist, a regimen that requires INR (international normalized ratio) monitoring, said Dr. Harry R. Buller of the department of vascular medicine at the University of Amsterdam and his associates in the EINSTEIN-PE clinical trial.

The study, sponsored by Bayer HealthCare and Janssen Pharmaceuticals, involved 4,832 adults with acute symptomatic pulmonary embolism (PE), with or without deep vein thrombosis (DVT), who were treated at 263 sites in 38 countries in 2007-2011.

In all, 2,419 study subjects were randomly assigned to receive oral rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) and 2,413 to receive enoxaparin (1 mg/kg twice daily, which was discontinued when the INR reached 2.0 or greater for 2 consecutive days after at least 5 days of therapy) plus either warfarin or acenocoumarol at a dosage adjusted to maintain an INR of 2.0-3.0.

All study subjects were treated for durations of 3, 6, or 12 months, according to the wishes of their treating physicians and in keeping with current practice. The mean duration of treatment was approximately 9 months.

In the standard treatment group, the INR was in the therapeutic range 62.7% of the time. The INR was not measured in the rivaroxaban group, but adherence to therapy was high in 94.2% of patients.

The primary efficacy outcome they followed was symptomatic recurrent venous thromboembolism, a composite of fatal and nonfatal PE or DVT. This occurred in 50 patients (2.1%) receiving rivaroxaban and 44 (1.8%) receiving standard therapy, which met the criterion for noninferiority, the investigators said (N. Engl. J. Med. 2012 March 26 [doi:10.1056/NEJMoa1113572]).

During the initial 3-week period of intensive rivaroxaban therapy, the primary efficacy outcome occurred in 18 patients (0.7%) of the rivaroxaban group and in 21 patients (0.9%) in the standard therapy group.

The efficacy results were similar in a per-protocol analysis and in an intention-to-treat analysis.

The primary safety outcome followed was clinically relevant bleeding, and it occurred in 249 subjects (10.3%) in the rivaroxaban group and in 274 (11.4%) in the standard treatment group.

In particular, major bleeding events occurred in 26 patients (1.1%) taking rivaroxaban and 52 (2.2%) taking standard treatment.

During the initial 3-week period of intensive rivaroxaban therapy, bleeding rates were similar between the two study groups.

Over the full course of treatment, "there were fewer episodes of intracranial bleeding or bleeding in critical areas in the rivaroxaban group than in the standard therapy group," Dr. Buller and his colleagues said.

With regard to other safety outcomes, the rates of acute coronary events were similar between the two study groups, at 0.6% with rivaroxaban and 0.9% with standard therapy. And abnormal findings on liver function tests were seen in 0.2% of both groups.

"The suggestion that rivaroxaban can be administered at the same dose in all patients without laboratory monitoring has raised concern," so the researchers performed multiple subgroup analyses to examine whether any particular patient group was at increased risk while taking the drug.

They found that the rates of recurrent venous thromboembolism and of adverse bleeding events were similar between patients taking rivaroxaban and those on standard therapy regardless of age, sex, obesity status, level of renal function, and the extent of initial PE.

"We believe that our population is representative of the spectrum of patients who present with symptomatic PE," the investigators said, noting that nearly 25% of the study population had extensive PE and 13% had limited PE. Moreover, almost 25% also had concomitant DVT.

This study was supported by Bayer HealthCare and Janssen Pharmaceuticals. Dr. Buller reported ties to ICTOM/Bayer HealthCare, Sanofi-Aventis, Boehringer Ingelheim, Pfizer, GlaxoSmithKline, and Daiichi Sankyo, and his associates reported ties to numerous industry sources.

Rivaroxaban was noninferior to standard treatment at preventing a recurrence of pulmonary embolism in an international open-label trial reported online in the New England Journal of Medicine and presented simultaneously at the annual meeting of the American College of Cardiology.

Rates of adverse bleeding events with rivaroxaban were similar to those with the more complex standard therapy of enoxaparin plus a vitamin K antagonist, a regimen that requires INR (international normalized ratio) monitoring, said Dr. Harry R. Buller of the department of vascular medicine at the University of Amsterdam and his associates in the EINSTEIN-PE clinical trial.

The study, sponsored by Bayer HealthCare and Janssen Pharmaceuticals, involved 4,832 adults with acute symptomatic pulmonary embolism (PE), with or without deep vein thrombosis (DVT), who were treated at 263 sites in 38 countries in 2007-2011.

In all, 2,419 study subjects were randomly assigned to receive oral rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) and 2,413 to receive enoxaparin (1 mg/kg twice daily, which was discontinued when the INR reached 2.0 or greater for 2 consecutive days after at least 5 days of therapy) plus either warfarin or acenocoumarol at a dosage adjusted to maintain an INR of 2.0-3.0.

All study subjects were treated for durations of 3, 6, or 12 months, according to the wishes of their treating physicians and in keeping with current practice. The mean duration of treatment was approximately 9 months.

In the standard treatment group, the INR was in the therapeutic range 62.7% of the time. The INR was not measured in the rivaroxaban group, but adherence to therapy was high in 94.2% of patients.

The primary efficacy outcome they followed was symptomatic recurrent venous thromboembolism, a composite of fatal and nonfatal PE or DVT. This occurred in 50 patients (2.1%) receiving rivaroxaban and 44 (1.8%) receiving standard therapy, which met the criterion for noninferiority, the investigators said (N. Engl. J. Med. 2012 March 26 [doi:10.1056/NEJMoa1113572]).

During the initial 3-week period of intensive rivaroxaban therapy, the primary efficacy outcome occurred in 18 patients (0.7%) of the rivaroxaban group and in 21 patients (0.9%) in the standard therapy group.

The efficacy results were similar in a per-protocol analysis and in an intention-to-treat analysis.

The primary safety outcome followed was clinically relevant bleeding, and it occurred in 249 subjects (10.3%) in the rivaroxaban group and in 274 (11.4%) in the standard treatment group.

In particular, major bleeding events occurred in 26 patients (1.1%) taking rivaroxaban and 52 (2.2%) taking standard treatment.

During the initial 3-week period of intensive rivaroxaban therapy, bleeding rates were similar between the two study groups.

Over the full course of treatment, "there were fewer episodes of intracranial bleeding or bleeding in critical areas in the rivaroxaban group than in the standard therapy group," Dr. Buller and his colleagues said.

With regard to other safety outcomes, the rates of acute coronary events were similar between the two study groups, at 0.6% with rivaroxaban and 0.9% with standard therapy. And abnormal findings on liver function tests were seen in 0.2% of both groups.

"The suggestion that rivaroxaban can be administered at the same dose in all patients without laboratory monitoring has raised concern," so the researchers performed multiple subgroup analyses to examine whether any particular patient group was at increased risk while taking the drug.

They found that the rates of recurrent venous thromboembolism and of adverse bleeding events were similar between patients taking rivaroxaban and those on standard therapy regardless of age, sex, obesity status, level of renal function, and the extent of initial PE.

"We believe that our population is representative of the spectrum of patients who present with symptomatic PE," the investigators said, noting that nearly 25% of the study population had extensive PE and 13% had limited PE. Moreover, almost 25% also had concomitant DVT.

This study was supported by Bayer HealthCare and Janssen Pharmaceuticals. Dr. Buller reported ties to ICTOM/Bayer HealthCare, Sanofi-Aventis, Boehringer Ingelheim, Pfizer, GlaxoSmithKline, and Daiichi Sankyo, and his associates reported ties to numerous industry sources.

Rivaroxaban was noninferior to standard treatment at preventing a recurrence of pulmonary embolism in an international open-label trial reported online in the New England Journal of Medicine and presented simultaneously at the annual meeting of the American College of Cardiology.

Rates of adverse bleeding events with rivaroxaban were similar to those with the more complex standard therapy of enoxaparin plus a vitamin K antagonist, a regimen that requires INR (international normalized ratio) monitoring, said Dr. Harry R. Buller of the department of vascular medicine at the University of Amsterdam and his associates in the EINSTEIN-PE clinical trial.

The study, sponsored by Bayer HealthCare and Janssen Pharmaceuticals, involved 4,832 adults with acute symptomatic pulmonary embolism (PE), with or without deep vein thrombosis (DVT), who were treated at 263 sites in 38 countries in 2007-2011.

In all, 2,419 study subjects were randomly assigned to receive oral rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) and 2,413 to receive enoxaparin (1 mg/kg twice daily, which was discontinued when the INR reached 2.0 or greater for 2 consecutive days after at least 5 days of therapy) plus either warfarin or acenocoumarol at a dosage adjusted to maintain an INR of 2.0-3.0.

All study subjects were treated for durations of 3, 6, or 12 months, according to the wishes of their treating physicians and in keeping with current practice. The mean duration of treatment was approximately 9 months.

In the standard treatment group, the INR was in the therapeutic range 62.7% of the time. The INR was not measured in the rivaroxaban group, but adherence to therapy was high in 94.2% of patients.

The primary efficacy outcome they followed was symptomatic recurrent venous thromboembolism, a composite of fatal and nonfatal PE or DVT. This occurred in 50 patients (2.1%) receiving rivaroxaban and 44 (1.8%) receiving standard therapy, which met the criterion for noninferiority, the investigators said (N. Engl. J. Med. 2012 March 26 [doi:10.1056/NEJMoa1113572]).

During the initial 3-week period of intensive rivaroxaban therapy, the primary efficacy outcome occurred in 18 patients (0.7%) of the rivaroxaban group and in 21 patients (0.9%) in the standard therapy group.

The efficacy results were similar in a per-protocol analysis and in an intention-to-treat analysis.

The primary safety outcome followed was clinically relevant bleeding, and it occurred in 249 subjects (10.3%) in the rivaroxaban group and in 274 (11.4%) in the standard treatment group.

In particular, major bleeding events occurred in 26 patients (1.1%) taking rivaroxaban and 52 (2.2%) taking standard treatment.

During the initial 3-week period of intensive rivaroxaban therapy, bleeding rates were similar between the two study groups.

Over the full course of treatment, "there were fewer episodes of intracranial bleeding or bleeding in critical areas in the rivaroxaban group than in the standard therapy group," Dr. Buller and his colleagues said.

With regard to other safety outcomes, the rates of acute coronary events were similar between the two study groups, at 0.6% with rivaroxaban and 0.9% with standard therapy. And abnormal findings on liver function tests were seen in 0.2% of both groups.

"The suggestion that rivaroxaban can be administered at the same dose in all patients without laboratory monitoring has raised concern," so the researchers performed multiple subgroup analyses to examine whether any particular patient group was at increased risk while taking the drug.

They found that the rates of recurrent venous thromboembolism and of adverse bleeding events were similar between patients taking rivaroxaban and those on standard therapy regardless of age, sex, obesity status, level of renal function, and the extent of initial PE.

"We believe that our population is representative of the spectrum of patients who present with symptomatic PE," the investigators said, noting that nearly 25% of the study population had extensive PE and 13% had limited PE. Moreover, almost 25% also had concomitant DVT.

This study was supported by Bayer HealthCare and Janssen Pharmaceuticals. Dr. Buller reported ties to ICTOM/Bayer HealthCare, Sanofi-Aventis, Boehringer Ingelheim, Pfizer, GlaxoSmithKline, and Daiichi Sankyo, and his associates reported ties to numerous industry sources.