Mary Ann Moon

Psoriasis and metabolic syndrome are both associated with high serum levels of leptin, according to a published study of 77 patients at a Taiwanese hospital.

It is possible that the proinflammatory mediators in psoriasis may stimulate leptin expression, which may in turn eventually lead to metabolic dysregulation, wrote Dr. Yi-Ju Chen, of Taichung (Taiwan) Veterans General Hospital, and associates.

It has been found that ischemic heart disease and stroke are significantly more common in psoriasis patients than in the general population. Therefore, the investigators wanted to examine the role of leptin, an adipocyte-derived hormone that helps regulate energy homeostasis, metabolism, and immune-inflammatory processes. They used serum samples from 77 psoriasis patients and 81 control patients matched for age and gender.

The median serum leptin level was found to be significantly higher in psoriasis patients (7,311 pg/mL) than in controls (4,804 pg/mL).

Patient age, severity of psoriasis, presence or absence of psoriatic arthritis, and clinical subtype of psoriasis was found to have no relation to leptin levels. In addition, psoriasis patients who also had metabolic syndrome had significantly higher leptin levels than did psoriasis patients without the metabolic syndrome, Dr. Chen and colleagues reported (Arch. Derm. 2008;144:1571–5).

“It seems that high circulating leptin levels in psoriasis derive not only from adipose tissue but also from an inflammation process,” they wrote.

Psoriasis and metabolic syndrome are both associated with high serum levels of leptin, according to a published study of 77 patients at a Taiwanese hospital.

It is possible that the proinflammatory mediators in psoriasis may stimulate leptin expression, which may in turn eventually lead to metabolic dysregulation, wrote Dr. Yi-Ju Chen, of Taichung (Taiwan) Veterans General Hospital, and associates.

It has been found that ischemic heart disease and stroke are significantly more common in psoriasis patients than in the general population. Therefore, the investigators wanted to examine the role of leptin, an adipocyte-derived hormone that helps regulate energy homeostasis, metabolism, and immune-inflammatory processes. They used serum samples from 77 psoriasis patients and 81 control patients matched for age and gender.

The median serum leptin level was found to be significantly higher in psoriasis patients (7,311 pg/mL) than in controls (4,804 pg/mL).

Patient age, severity of psoriasis, presence or absence of psoriatic arthritis, and clinical subtype of psoriasis was found to have no relation to leptin levels. In addition, psoriasis patients who also had metabolic syndrome had significantly higher leptin levels than did psoriasis patients without the metabolic syndrome, Dr. Chen and colleagues reported (Arch. Derm. 2008;144:1571–5).

“It seems that high circulating leptin levels in psoriasis derive not only from adipose tissue but also from an inflammation process,” they wrote.

Psoriasis and metabolic syndrome are both associated with high serum levels of leptin, according to a published study of 77 patients at a Taiwanese hospital.

It is possible that the proinflammatory mediators in psoriasis may stimulate leptin expression, which may in turn eventually lead to metabolic dysregulation, wrote Dr. Yi-Ju Chen, of Taichung (Taiwan) Veterans General Hospital, and associates.

It has been found that ischemic heart disease and stroke are significantly more common in psoriasis patients than in the general population. Therefore, the investigators wanted to examine the role of leptin, an adipocyte-derived hormone that helps regulate energy homeostasis, metabolism, and immune-inflammatory processes. They used serum samples from 77 psoriasis patients and 81 control patients matched for age and gender.

The median serum leptin level was found to be significantly higher in psoriasis patients (7,311 pg/mL) than in controls (4,804 pg/mL).

Patient age, severity of psoriasis, presence or absence of psoriatic arthritis, and clinical subtype of psoriasis was found to have no relation to leptin levels. In addition, psoriasis patients who also had metabolic syndrome had significantly higher leptin levels than did psoriasis patients without the metabolic syndrome, Dr. Chen and colleagues reported (Arch. Derm. 2008;144:1571–5).

“It seems that high circulating leptin levels in psoriasis derive not only from adipose tissue but also from an inflammation process,” they wrote.

An ad libitum Mediterranean-style diet, supplemented with a daily serving of mixed nuts, appears to decrease the prevalence of metabolic syndrome in older people at high risk for cardiovascular disease, according to Spanish researchers.

In a 1-year study, the diet also lowered the prevalences of hypertriglyceridemia and hypertension, two chief components of the metabolic syndrome. Those beneficial effects were achieved by dietary changes alone; the study subjects did not lose weight or increase their physical activity, said Dr. Jordi Salas-Salvadó of the University of Rovira I Virgili, Reus, Spain, and his associates in the PREDIMED study.

Traditionally, diets recommended to improve health are low in fat and calories, and “generally are not palatable,” the researchers said. The study's results “show that a non-energy-restricted traditional Mediterranean diet enriched with nuts, which is high in fat … and palatable, is a useful tool in managing the metabolic syndrome.”

The PREDIMED (Prevención con Dieta Mediterránea) study is an ongoing multicenter clinical trial involving approximately 9,000 older patients (aged 55–80 years) who are at high risk for cardiovascular disease but as yet show no sign of it.

A subgroup of 1,224 patients was assessed for the report. They were randomly assigned to follow a Mediterranean-style diet supplemented with mixed nuts (primarily walnuts, hazelnuts, and almonds), a Mediterranean-style diet supplemented with virgin olive oil, or a control group.

A total of 61% of the subjects met the criteria for metabolic syndrome, and nearly 45% had type 2 diabetes, the investigators reported.

After 1 year, the rates of elevated triglycerides, high blood pressure, and abdominal obesity were significantly decreased with both dietary interventions, but were not in the control group. Those reductions were more pronounced in the group that followed the Mediterranean-style diet supplemented with nuts.

The overall prevalence of the metabolic syndrome decreased by 14% in the diet-plus-nuts arm of the trial, and by 7% in the diet-plus-olive-oil arm, compared with a 2% reduction in the control group.

“The novelty of our findings is that a positive effect on the metabolic syndrome was achieved by diet alone, in the absence of weight loss or increased energy expenditure in physical activity,” Dr. Salas-Salvado and his associates said (Arch. Intern. Med. 2008;168:2449–58).

Longer follow-up in the study, which is designed to continue for another 3 years, may provide stronger evidence of the cardiovascular benefits of the Mediterranean diet, the investigators added.

Dr. Salas-Salvadó is a nonpaid member of the Scientific Advisory Council of the International Nut Council.

Heart benefits were more pronounced when nuts were included in the diet. ©Marcelo Wain/iStockphoto.com

An ad libitum Mediterranean-style diet, supplemented with a daily serving of mixed nuts, appears to decrease the prevalence of metabolic syndrome in older people at high risk for cardiovascular disease, according to Spanish researchers.

In a 1-year study, the diet also lowered the prevalences of hypertriglyceridemia and hypertension, two chief components of the metabolic syndrome. Those beneficial effects were achieved by dietary changes alone; the study subjects did not lose weight or increase their physical activity, said Dr. Jordi Salas-Salvadó of the University of Rovira I Virgili, Reus, Spain, and his associates in the PREDIMED study.

Traditionally, diets recommended to improve health are low in fat and calories, and “generally are not palatable,” the researchers said. The study's results “show that a non-energy-restricted traditional Mediterranean diet enriched with nuts, which is high in fat … and palatable, is a useful tool in managing the metabolic syndrome.”

The PREDIMED (Prevención con Dieta Mediterránea) study is an ongoing multicenter clinical trial involving approximately 9,000 older patients (aged 55–80 years) who are at high risk for cardiovascular disease but as yet show no sign of it.

A subgroup of 1,224 patients was assessed for the report. They were randomly assigned to follow a Mediterranean-style diet supplemented with mixed nuts (primarily walnuts, hazelnuts, and almonds), a Mediterranean-style diet supplemented with virgin olive oil, or a control group.

A total of 61% of the subjects met the criteria for metabolic syndrome, and nearly 45% had type 2 diabetes, the investigators reported.

After 1 year, the rates of elevated triglycerides, high blood pressure, and abdominal obesity were significantly decreased with both dietary interventions, but were not in the control group. Those reductions were more pronounced in the group that followed the Mediterranean-style diet supplemented with nuts.

The overall prevalence of the metabolic syndrome decreased by 14% in the diet-plus-nuts arm of the trial, and by 7% in the diet-plus-olive-oil arm, compared with a 2% reduction in the control group.

“The novelty of our findings is that a positive effect on the metabolic syndrome was achieved by diet alone, in the absence of weight loss or increased energy expenditure in physical activity,” Dr. Salas-Salvado and his associates said (Arch. Intern. Med. 2008;168:2449–58).

Longer follow-up in the study, which is designed to continue for another 3 years, may provide stronger evidence of the cardiovascular benefits of the Mediterranean diet, the investigators added.

Dr. Salas-Salvadó is a nonpaid member of the Scientific Advisory Council of the International Nut Council.

Heart benefits were more pronounced when nuts were included in the diet. ©Marcelo Wain/iStockphoto.com

An ad libitum Mediterranean-style diet, supplemented with a daily serving of mixed nuts, appears to decrease the prevalence of metabolic syndrome in older people at high risk for cardiovascular disease, according to Spanish researchers.

In a 1-year study, the diet also lowered the prevalences of hypertriglyceridemia and hypertension, two chief components of the metabolic syndrome. Those beneficial effects were achieved by dietary changes alone; the study subjects did not lose weight or increase their physical activity, said Dr. Jordi Salas-Salvadó of the University of Rovira I Virgili, Reus, Spain, and his associates in the PREDIMED study.

Traditionally, diets recommended to improve health are low in fat and calories, and “generally are not palatable,” the researchers said. The study's results “show that a non-energy-restricted traditional Mediterranean diet enriched with nuts, which is high in fat … and palatable, is a useful tool in managing the metabolic syndrome.”

The PREDIMED (Prevención con Dieta Mediterránea) study is an ongoing multicenter clinical trial involving approximately 9,000 older patients (aged 55–80 years) who are at high risk for cardiovascular disease but as yet show no sign of it.

A subgroup of 1,224 patients was assessed for the report. They were randomly assigned to follow a Mediterranean-style diet supplemented with mixed nuts (primarily walnuts, hazelnuts, and almonds), a Mediterranean-style diet supplemented with virgin olive oil, or a control group.

A total of 61% of the subjects met the criteria for metabolic syndrome, and nearly 45% had type 2 diabetes, the investigators reported.

After 1 year, the rates of elevated triglycerides, high blood pressure, and abdominal obesity were significantly decreased with both dietary interventions, but were not in the control group. Those reductions were more pronounced in the group that followed the Mediterranean-style diet supplemented with nuts.

The overall prevalence of the metabolic syndrome decreased by 14% in the diet-plus-nuts arm of the trial, and by 7% in the diet-plus-olive-oil arm, compared with a 2% reduction in the control group.

“The novelty of our findings is that a positive effect on the metabolic syndrome was achieved by diet alone, in the absence of weight loss or increased energy expenditure in physical activity,” Dr. Salas-Salvado and his associates said (Arch. Intern. Med. 2008;168:2449–58).

Longer follow-up in the study, which is designed to continue for another 3 years, may provide stronger evidence of the cardiovascular benefits of the Mediterranean diet, the investigators added.

Dr. Salas-Salvadó is a nonpaid member of the Scientific Advisory Council of the International Nut Council.

Heart benefits were more pronounced when nuts were included in the diet. ©Marcelo Wain/iStockphoto.com

Elderly patients who started taking rosiglitazone had higher rates of all-cause mortality and hospitalization for heart failure during the following year than did those who started taking pioglitazone, in a study of nearly 30,000 subjects.

Previous research has suggested that rosiglitazone carries greater cardiovascular risks than pioglitazone, but “to date, only sparse information has become available from head-to-head comparisons between these two drugs,” said Dr. Wolfgang C. Winkelmayer and his associates at Brigham and Women's Hospital, Boston.

They conducted such a comparison in a large cohort of elderly patients with recent-onset type 2 diabetes. “To our knowledge, this is the first study specifically aimed at detecting any differences in relative cardiovascular safety between these two thiazolidinediones in typical elderly patients initiating such therapy.”

The study participants were identified using medical claims data that included comprehensive prescription drug coverage for elderly patients throughout New Jersey and Pennsylvania. The 28,361 patients were older than 65 years when they filled their first prescriptions for pioglitazone (50.3%) or rosiglitazone (49.7%) between 2000 and 2005.

The median time of exposure to the drugs was about 1 year. During that time 1,869 people died.

Rosiglitazone users had significantly higher rates of all-cause mortality. Crude, unadjusted event rates per 1,000 person-years were 60 for pioglitazone and 69 for rosiglitazone initiators, which yielded an unadjusted incident rate ratio of 1.17. After adjustment for patient characteristics, a Cox regression showed a 15% greater mortality rate in patients initiated with rosiglitazone compared those who took pioglitazone.

Use of rosiglitazone also was associated with a 13% greater risk of heart failure, Dr. Winkelmayer and his colleagues reported (Arch. Intern. Med. 2008;168:2368-75).

This association remained robust when the data were analyzed in different statistical models, and it was consistent across important subgroups of patients, such as those who had already begun insulin therapy.

The study was limited in that patients were not randomly assigned to the two drugs, but were given them at the discretion of their treating physicians.

In addition, the study didn't include information on cause of death, so although the findings suggested a higher cardiovascular case fatality rate for rosiglitazone, “we cannot formally examine this possibility,” the authors wrote.

Nevertheless, the results “confirm the safety concerns that have been raised for rosiglitazone, compared with pioglitazone,” they added.

Dr. Winkelmayer has participated, without receiving an honorarium, in the advisory boards of Amgen, Roche, Genzyme, and Fresenius Medical Care. This study was supported by the American Heart Association, Satellite Healthcare Inc., and investigator-initiated grants from Amgen, Fresenius, and GlaxoSmithKline.

Elderly patients who started taking rosiglitazone had higher rates of all-cause mortality and hospitalization for heart failure during the following year than did those who started taking pioglitazone, in a study of nearly 30,000 subjects.

Previous research has suggested that rosiglitazone carries greater cardiovascular risks than pioglitazone, but “to date, only sparse information has become available from head-to-head comparisons between these two drugs,” said Dr. Wolfgang C. Winkelmayer and his associates at Brigham and Women's Hospital, Boston.

They conducted such a comparison in a large cohort of elderly patients with recent-onset type 2 diabetes. “To our knowledge, this is the first study specifically aimed at detecting any differences in relative cardiovascular safety between these two thiazolidinediones in typical elderly patients initiating such therapy.”

The study participants were identified using medical claims data that included comprehensive prescription drug coverage for elderly patients throughout New Jersey and Pennsylvania. The 28,361 patients were older than 65 years when they filled their first prescriptions for pioglitazone (50.3%) or rosiglitazone (49.7%) between 2000 and 2005.

The median time of exposure to the drugs was about 1 year. During that time 1,869 people died.

Rosiglitazone users had significantly higher rates of all-cause mortality. Crude, unadjusted event rates per 1,000 person-years were 60 for pioglitazone and 69 for rosiglitazone initiators, which yielded an unadjusted incident rate ratio of 1.17. After adjustment for patient characteristics, a Cox regression showed a 15% greater mortality rate in patients initiated with rosiglitazone compared those who took pioglitazone.

Use of rosiglitazone also was associated with a 13% greater risk of heart failure, Dr. Winkelmayer and his colleagues reported (Arch. Intern. Med. 2008;168:2368-75).

This association remained robust when the data were analyzed in different statistical models, and it was consistent across important subgroups of patients, such as those who had already begun insulin therapy.

The study was limited in that patients were not randomly assigned to the two drugs, but were given them at the discretion of their treating physicians.

In addition, the study didn't include information on cause of death, so although the findings suggested a higher cardiovascular case fatality rate for rosiglitazone, “we cannot formally examine this possibility,” the authors wrote.

Nevertheless, the results “confirm the safety concerns that have been raised for rosiglitazone, compared with pioglitazone,” they added.

Dr. Winkelmayer has participated, without receiving an honorarium, in the advisory boards of Amgen, Roche, Genzyme, and Fresenius Medical Care. This study was supported by the American Heart Association, Satellite Healthcare Inc., and investigator-initiated grants from Amgen, Fresenius, and GlaxoSmithKline.

Elderly patients who started taking rosiglitazone had higher rates of all-cause mortality and hospitalization for heart failure during the following year than did those who started taking pioglitazone, in a study of nearly 30,000 subjects.

Previous research has suggested that rosiglitazone carries greater cardiovascular risks than pioglitazone, but “to date, only sparse information has become available from head-to-head comparisons between these two drugs,” said Dr. Wolfgang C. Winkelmayer and his associates at Brigham and Women's Hospital, Boston.

They conducted such a comparison in a large cohort of elderly patients with recent-onset type 2 diabetes. “To our knowledge, this is the first study specifically aimed at detecting any differences in relative cardiovascular safety between these two thiazolidinediones in typical elderly patients initiating such therapy.”

The study participants were identified using medical claims data that included comprehensive prescription drug coverage for elderly patients throughout New Jersey and Pennsylvania. The 28,361 patients were older than 65 years when they filled their first prescriptions for pioglitazone (50.3%) or rosiglitazone (49.7%) between 2000 and 2005.

The median time of exposure to the drugs was about 1 year. During that time 1,869 people died.

Rosiglitazone users had significantly higher rates of all-cause mortality. Crude, unadjusted event rates per 1,000 person-years were 60 for pioglitazone and 69 for rosiglitazone initiators, which yielded an unadjusted incident rate ratio of 1.17. After adjustment for patient characteristics, a Cox regression showed a 15% greater mortality rate in patients initiated with rosiglitazone compared those who took pioglitazone.

Use of rosiglitazone also was associated with a 13% greater risk of heart failure, Dr. Winkelmayer and his colleagues reported (Arch. Intern. Med. 2008;168:2368-75).

This association remained robust when the data were analyzed in different statistical models, and it was consistent across important subgroups of patients, such as those who had already begun insulin therapy.

The study was limited in that patients were not randomly assigned to the two drugs, but were given them at the discretion of their treating physicians.

In addition, the study didn't include information on cause of death, so although the findings suggested a higher cardiovascular case fatality rate for rosiglitazone, “we cannot formally examine this possibility,” the authors wrote.

Nevertheless, the results “confirm the safety concerns that have been raised for rosiglitazone, compared with pioglitazone,” they added.

Dr. Winkelmayer has participated, without receiving an honorarium, in the advisory boards of Amgen, Roche, Genzyme, and Fresenius Medical Care. This study was supported by the American Heart Association, Satellite Healthcare Inc., and investigator-initiated grants from Amgen, Fresenius, and GlaxoSmithKline.

The testosterone patch improves sexual function in postmenopausal women who have hypoactive sexual desire disorder, but the patch's long-term safety needs to be studied, according to a report.

The improvement in frequency of satisfying sexual episodes was “numerically modest,” at 1.4 more such episodes per month, but this amount has been shown to be clinically meaningful in previous studies, said Dr. Susan R. Davis of Monash University, Prahran, Victoria, Australia, and her associates.

This is the first large-scale, phase III clinical trial of testosterone therapy that involved postmenopausal women who were not taking concomitant estrogen.

Testosterone without concomitant estrogen may have adverse effects on the breast and endometrium.

In this study, four cases of breast cancer occurred in women on active treatment, compared with no cases in women taking placebo, and vaginal bleeding also was significantly more common with active treatment.

The study involved women aged 20-70 years who had surgically induced menopause of at least 1 year's duration, and women aged 40-70 years who had natural menopause of at least 2 years' duration. The women all had hypoactive sexual desire and were treated at 65 medical centers in the United States, Canada, Australia, the United Kingdom, and Sweden between 2004 and 2006 (N. Engl. J. Med. 2008;359:2005-17).

The study was sponsored by Procter & Gamble Pharmaceuticals Inc., which also was involved in study design and data collection, and conducted the data analysis. Procter & Gamble makes Intrinsa, a testosterone patch that has been approved by the European Medicines Agency for treatment of hypoactive sexual desire.

A Food and Drug Administration advisory committee recommended against approval of the drug for the U.S. market in 2004.

In the study, 814 women were randomly assigned to use a 150-mcg testosterone patch, a 300-mcg testosterone patch, or a placebo patch every day for 1 year.

The efficacy analysis was performed at 24 weeks, after which the effect of testosterone tends to plateau; the safety analysis was performed at 1 year. A total of 71% of the women completed 24 weeks, and 57% completed the full year.

Compared with the placebo group, both groups on active treatment reported significant increases in sexual desire and frequency of satisfying sexual episodes, as well as decreases in personal distress related to sexual function.

The overall incidence of adverse effects was similar among the three groups.

The most common reasons for withdrawal from the study were patch-site reactions and androgenic events, principally the growth of facial hair.

Dr. Davis reports receiving consulting or lecture fees, and grant support, from Procter & Gamble Pharmaceuticals and other firms.

The testosterone patch improves sexual function in postmenopausal women who have hypoactive sexual desire disorder, but the patch's long-term safety needs to be studied, according to a report.

The improvement in frequency of satisfying sexual episodes was “numerically modest,” at 1.4 more such episodes per month, but this amount has been shown to be clinically meaningful in previous studies, said Dr. Susan R. Davis of Monash University, Prahran, Victoria, Australia, and her associates.

This is the first large-scale, phase III clinical trial of testosterone therapy that involved postmenopausal women who were not taking concomitant estrogen.

Testosterone without concomitant estrogen may have adverse effects on the breast and endometrium.

In this study, four cases of breast cancer occurred in women on active treatment, compared with no cases in women taking placebo, and vaginal bleeding also was significantly more common with active treatment.

The study involved women aged 20-70 years who had surgically induced menopause of at least 1 year's duration, and women aged 40-70 years who had natural menopause of at least 2 years' duration. The women all had hypoactive sexual desire and were treated at 65 medical centers in the United States, Canada, Australia, the United Kingdom, and Sweden between 2004 and 2006 (N. Engl. J. Med. 2008;359:2005-17).

The study was sponsored by Procter & Gamble Pharmaceuticals Inc., which also was involved in study design and data collection, and conducted the data analysis. Procter & Gamble makes Intrinsa, a testosterone patch that has been approved by the European Medicines Agency for treatment of hypoactive sexual desire.

A Food and Drug Administration advisory committee recommended against approval of the drug for the U.S. market in 2004.

In the study, 814 women were randomly assigned to use a 150-mcg testosterone patch, a 300-mcg testosterone patch, or a placebo patch every day for 1 year.

The efficacy analysis was performed at 24 weeks, after which the effect of testosterone tends to plateau; the safety analysis was performed at 1 year. A total of 71% of the women completed 24 weeks, and 57% completed the full year.

Compared with the placebo group, both groups on active treatment reported significant increases in sexual desire and frequency of satisfying sexual episodes, as well as decreases in personal distress related to sexual function.

The overall incidence of adverse effects was similar among the three groups.

The most common reasons for withdrawal from the study were patch-site reactions and androgenic events, principally the growth of facial hair.

Dr. Davis reports receiving consulting or lecture fees, and grant support, from Procter & Gamble Pharmaceuticals and other firms.

The testosterone patch improves sexual function in postmenopausal women who have hypoactive sexual desire disorder, but the patch's long-term safety needs to be studied, according to a report.

The improvement in frequency of satisfying sexual episodes was “numerically modest,” at 1.4 more such episodes per month, but this amount has been shown to be clinically meaningful in previous studies, said Dr. Susan R. Davis of Monash University, Prahran, Victoria, Australia, and her associates.

This is the first large-scale, phase III clinical trial of testosterone therapy that involved postmenopausal women who were not taking concomitant estrogen.

Testosterone without concomitant estrogen may have adverse effects on the breast and endometrium.

In this study, four cases of breast cancer occurred in women on active treatment, compared with no cases in women taking placebo, and vaginal bleeding also was significantly more common with active treatment.

The study involved women aged 20-70 years who had surgically induced menopause of at least 1 year's duration, and women aged 40-70 years who had natural menopause of at least 2 years' duration. The women all had hypoactive sexual desire and were treated at 65 medical centers in the United States, Canada, Australia, the United Kingdom, and Sweden between 2004 and 2006 (N. Engl. J. Med. 2008;359:2005-17).

The study was sponsored by Procter & Gamble Pharmaceuticals Inc., which also was involved in study design and data collection, and conducted the data analysis. Procter & Gamble makes Intrinsa, a testosterone patch that has been approved by the European Medicines Agency for treatment of hypoactive sexual desire.

A Food and Drug Administration advisory committee recommended against approval of the drug for the U.S. market in 2004.

In the study, 814 women were randomly assigned to use a 150-mcg testosterone patch, a 300-mcg testosterone patch, or a placebo patch every day for 1 year.

The efficacy analysis was performed at 24 weeks, after which the effect of testosterone tends to plateau; the safety analysis was performed at 1 year. A total of 71% of the women completed 24 weeks, and 57% completed the full year.

Compared with the placebo group, both groups on active treatment reported significant increases in sexual desire and frequency of satisfying sexual episodes, as well as decreases in personal distress related to sexual function.

The overall incidence of adverse effects was similar among the three groups.

The most common reasons for withdrawal from the study were patch-site reactions and androgenic events, principally the growth of facial hair.

Dr. Davis reports receiving consulting or lecture fees, and grant support, from Procter & Gamble Pharmaceuticals and other firms.

The testosterone patch improves sexual function and decreases emotional distress in postmenopausal women who have hypoactive sexual desire disorder, but the patch's long-term safety needs to be assessed, according to an international study of more than 800 women.

“The increase in the frequency of satisfying sexual episodes was modest but appeared to be clinically meaningful,” said Dr. Susan R. Davis of Monash University, Prahran, Victoria, Australia, and her associates.

This is the first large-scale, phase III clinical trial of testosterone therapy that involved postmenopausal women who were not taking concomitant estrogen. The results “indicate that exogenous estrogen or combined estrogen plus progestin are not required for testosterone to be effective in the treatment of hypoactive sexual disorder,” the authors wrote.

However, “additional data are needed to assess the long-term safety of testosterone use in women with estrogen depletion,” they added.

Of particular concern is the possibility that testosterone without concomitant estrogen may have adverse effects on the breast and endometrium. In this study, four cases of breast cancer occurred in women on active treatment, compared with no cases in women taking placebo, and vaginal bleeding also was significantly more common with active treatment.

The study involved women aged 20–70 years who had surgically induced menopause of at least 1 year's duration, and women aged 40–70 years who had natural menopause of at least 2 years' duration. These subjects all had hypoactive sexual desire and were treated at 65 medical centers throughout the United States, Canada, Australia, the United Kingdom, and Sweden between 2004 and 2006.

The study was sponsored by Procter & Gamble Pharmaceuticals Inc., which also was involved in study design and data collection, and conducted the data analysis. Procter & Gamble makes Intrinsa, a testosterone patch that has been approved by the European Medicines Agency for treatment of hypoactive sexual desire. A Food and Drug Administration advisory committee recommended against approval of the drug for the U.S. market in 2004.

In the study, 814 women were randomly assigned to use a 150-mcg testosterone patch, a 300-mcg testosterone patch, or a placebo patch every day for 1 year. The efficacy analysis was performed at 24 weeks, after which the effect of testosterone tends to plateau; the safety analysis was performed at 1 year. A total of 71% of the study subjects completed 24 weeks, and only 57% completed the full year.

Compared with the placebo group, both groups on active treatment reported significant increases in sexual desire and frequency of satisfying sexual episodes, as well as decreases in personal distress related to sexual function.

The improvement in frequency of satisfying sexual episodes was “numerically modest,” at only 1.4 more such episodes per month. However, this amount has been shown to be clinically meaningful in previous studies, Dr. Davis and her associates said (N. Engl. J. Med. 2008;359:2005–17).

Treatment effects did not differ between women who had undergone surgical menopause and those who had undergone natural menopause.

The overall incidence of adverse effects was similar among the three groups. The most common reasons for withdrawal from the study were patch-site reactions and androgenic events, principally the growth of facial hair.

Four women receiving active treatment developed breast cancer, compared with none receiving placebo. The size of the study groups was too small to allow for analysis, and this excess could be the result of chance. But “the possibility of a causal relationship must be considered,” the researchers noted.

Nearly 11% of women with an intact uterus who used the higher dose patch reported vaginal bleeding, compared with fewer than 3% of the other two groups. All women with vaginal bleeding had ultrasonography and/or endometrial biopsy. There were no cases of endometrial hyperplasia or carcinoma.

In an accompanying editorial comment, Julia R. Heiman, Ph.D., of the Kinsey Institute for Sex, Gender, and Reproduction at Indiana University, Bloomington, said that it is reasonable to wonder whether an absolute increase in satisfying sexual episodes of only 1.4 per month is worthwhile.

“Although the report does not indicate whether the women were asked whether this change was meaningful for them, a review of the baseline data suggests it probably was, since the mean number of such episodes almost doubled for the high-dose group,” she said (N. Engl. J. Med. 2008;359:2047–9).

The “potentially worrisome” excess of breast cancer cases “cannot be ignored,” Dr. Heiman added.

They “suggest the need for caution in using testosterone until we understand more about its possible link with breast cancer and are better able to predict which patients are more likely to be subject to negative effects.”

Dr. Davis reports receiving consulting or lecture fees from Acrux Ltd., AstraZeneca Oncology Australia, Organon, and Procter & Gamble Pharmaceuticals, as well as grant support from AstraZeneca Pharmaceuticals, Novartis Oncology Australia, and Procter & Gamble Pharmaceuticals. Dr. Heiman reports receiving grant support from Pfizer, Bayer HealthCare, and Zestra Laboratories Inc.

The testosterone patch improves sexual function and decreases emotional distress in postmenopausal women who have hypoactive sexual desire disorder, but the patch's long-term safety needs to be assessed, according to an international study of more than 800 women.

“The increase in the frequency of satisfying sexual episodes was modest but appeared to be clinically meaningful,” said Dr. Susan R. Davis of Monash University, Prahran, Victoria, Australia, and her associates.

This is the first large-scale, phase III clinical trial of testosterone therapy that involved postmenopausal women who were not taking concomitant estrogen. The results “indicate that exogenous estrogen or combined estrogen plus progestin are not required for testosterone to be effective in the treatment of hypoactive sexual disorder,” the authors wrote.

However, “additional data are needed to assess the long-term safety of testosterone use in women with estrogen depletion,” they added.

Of particular concern is the possibility that testosterone without concomitant estrogen may have adverse effects on the breast and endometrium. In this study, four cases of breast cancer occurred in women on active treatment, compared with no cases in women taking placebo, and vaginal bleeding also was significantly more common with active treatment.

The study involved women aged 20–70 years who had surgically induced menopause of at least 1 year's duration, and women aged 40–70 years who had natural menopause of at least 2 years' duration. These subjects all had hypoactive sexual desire and were treated at 65 medical centers throughout the United States, Canada, Australia, the United Kingdom, and Sweden between 2004 and 2006.

The study was sponsored by Procter & Gamble Pharmaceuticals Inc., which also was involved in study design and data collection, and conducted the data analysis. Procter & Gamble makes Intrinsa, a testosterone patch that has been approved by the European Medicines Agency for treatment of hypoactive sexual desire. A Food and Drug Administration advisory committee recommended against approval of the drug for the U.S. market in 2004.

In the study, 814 women were randomly assigned to use a 150-mcg testosterone patch, a 300-mcg testosterone patch, or a placebo patch every day for 1 year. The efficacy analysis was performed at 24 weeks, after which the effect of testosterone tends to plateau; the safety analysis was performed at 1 year. A total of 71% of the study subjects completed 24 weeks, and only 57% completed the full year.

Compared with the placebo group, both groups on active treatment reported significant increases in sexual desire and frequency of satisfying sexual episodes, as well as decreases in personal distress related to sexual function.

The improvement in frequency of satisfying sexual episodes was “numerically modest,” at only 1.4 more such episodes per month. However, this amount has been shown to be clinically meaningful in previous studies, Dr. Davis and her associates said (N. Engl. J. Med. 2008;359:2005–17).

Treatment effects did not differ between women who had undergone surgical menopause and those who had undergone natural menopause.

The overall incidence of adverse effects was similar among the three groups. The most common reasons for withdrawal from the study were patch-site reactions and androgenic events, principally the growth of facial hair.

Four women receiving active treatment developed breast cancer, compared with none receiving placebo. The size of the study groups was too small to allow for analysis, and this excess could be the result of chance. But “the possibility of a causal relationship must be considered,” the researchers noted.

Nearly 11% of women with an intact uterus who used the higher dose patch reported vaginal bleeding, compared with fewer than 3% of the other two groups. All women with vaginal bleeding had ultrasonography and/or endometrial biopsy. There were no cases of endometrial hyperplasia or carcinoma.

In an accompanying editorial comment, Julia R. Heiman, Ph.D., of the Kinsey Institute for Sex, Gender, and Reproduction at Indiana University, Bloomington, said that it is reasonable to wonder whether an absolute increase in satisfying sexual episodes of only 1.4 per month is worthwhile.

“Although the report does not indicate whether the women were asked whether this change was meaningful for them, a review of the baseline data suggests it probably was, since the mean number of such episodes almost doubled for the high-dose group,” she said (N. Engl. J. Med. 2008;359:2047–9).

The “potentially worrisome” excess of breast cancer cases “cannot be ignored,” Dr. Heiman added.

They “suggest the need for caution in using testosterone until we understand more about its possible link with breast cancer and are better able to predict which patients are more likely to be subject to negative effects.”

Dr. Davis reports receiving consulting or lecture fees from Acrux Ltd., AstraZeneca Oncology Australia, Organon, and Procter & Gamble Pharmaceuticals, as well as grant support from AstraZeneca Pharmaceuticals, Novartis Oncology Australia, and Procter & Gamble Pharmaceuticals. Dr. Heiman reports receiving grant support from Pfizer, Bayer HealthCare, and Zestra Laboratories Inc.

The testosterone patch improves sexual function and decreases emotional distress in postmenopausal women who have hypoactive sexual desire disorder, but the patch's long-term safety needs to be assessed, according to an international study of more than 800 women.

“The increase in the frequency of satisfying sexual episodes was modest but appeared to be clinically meaningful,” said Dr. Susan R. Davis of Monash University, Prahran, Victoria, Australia, and her associates.

This is the first large-scale, phase III clinical trial of testosterone therapy that involved postmenopausal women who were not taking concomitant estrogen. The results “indicate that exogenous estrogen or combined estrogen plus progestin are not required for testosterone to be effective in the treatment of hypoactive sexual disorder,” the authors wrote.

However, “additional data are needed to assess the long-term safety of testosterone use in women with estrogen depletion,” they added.

Of particular concern is the possibility that testosterone without concomitant estrogen may have adverse effects on the breast and endometrium. In this study, four cases of breast cancer occurred in women on active treatment, compared with no cases in women taking placebo, and vaginal bleeding also was significantly more common with active treatment.

The study involved women aged 20–70 years who had surgically induced menopause of at least 1 year's duration, and women aged 40–70 years who had natural menopause of at least 2 years' duration. These subjects all had hypoactive sexual desire and were treated at 65 medical centers throughout the United States, Canada, Australia, the United Kingdom, and Sweden between 2004 and 2006.

The study was sponsored by Procter & Gamble Pharmaceuticals Inc., which also was involved in study design and data collection, and conducted the data analysis. Procter & Gamble makes Intrinsa, a testosterone patch that has been approved by the European Medicines Agency for treatment of hypoactive sexual desire. A Food and Drug Administration advisory committee recommended against approval of the drug for the U.S. market in 2004.

In the study, 814 women were randomly assigned to use a 150-mcg testosterone patch, a 300-mcg testosterone patch, or a placebo patch every day for 1 year. The efficacy analysis was performed at 24 weeks, after which the effect of testosterone tends to plateau; the safety analysis was performed at 1 year. A total of 71% of the study subjects completed 24 weeks, and only 57% completed the full year.

Compared with the placebo group, both groups on active treatment reported significant increases in sexual desire and frequency of satisfying sexual episodes, as well as decreases in personal distress related to sexual function.

The improvement in frequency of satisfying sexual episodes was “numerically modest,” at only 1.4 more such episodes per month. However, this amount has been shown to be clinically meaningful in previous studies, Dr. Davis and her associates said (N. Engl. J. Med. 2008;359:2005–17).

Treatment effects did not differ between women who had undergone surgical menopause and those who had undergone natural menopause.

The overall incidence of adverse effects was similar among the three groups. The most common reasons for withdrawal from the study were patch-site reactions and androgenic events, principally the growth of facial hair.

Four women receiving active treatment developed breast cancer, compared with none receiving placebo. The size of the study groups was too small to allow for analysis, and this excess could be the result of chance. But “the possibility of a causal relationship must be considered,” the researchers noted.

Nearly 11% of women with an intact uterus who used the higher dose patch reported vaginal bleeding, compared with fewer than 3% of the other two groups. All women with vaginal bleeding had ultrasonography and/or endometrial biopsy. There were no cases of endometrial hyperplasia or carcinoma.

In an accompanying editorial comment, Julia R. Heiman, Ph.D., of the Kinsey Institute for Sex, Gender, and Reproduction at Indiana University, Bloomington, said that it is reasonable to wonder whether an absolute increase in satisfying sexual episodes of only 1.4 per month is worthwhile.

“Although the report does not indicate whether the women were asked whether this change was meaningful for them, a review of the baseline data suggests it probably was, since the mean number of such episodes almost doubled for the high-dose group,” she said (N. Engl. J. Med. 2008;359:2047–9).

The “potentially worrisome” excess of breast cancer cases “cannot be ignored,” Dr. Heiman added.

They “suggest the need for caution in using testosterone until we understand more about its possible link with breast cancer and are better able to predict which patients are more likely to be subject to negative effects.”

Dr. Davis reports receiving consulting or lecture fees from Acrux Ltd., AstraZeneca Oncology Australia, Organon, and Procter & Gamble Pharmaceuticals, as well as grant support from AstraZeneca Pharmaceuticals, Novartis Oncology Australia, and Procter & Gamble Pharmaceuticals. Dr. Heiman reports receiving grant support from Pfizer, Bayer HealthCare, and Zestra Laboratories Inc.

Ginkgo biloba does not prevent onset of dementia in general or of Alzheimer's disease in particular, according to data from a large, randomized clinical trial.

Basic and observational research has suggested the herbal product should be a promising therapy, but “no adequately designed and powered clinical trial has evaluated the [herb's] safety and effectiveness in the primary prevention of dementia,” said Dr. Steven T. DeKosky of the University of Pittsburgh and his associates in the Ginkgo Evaluation of Memory study.

The National Center for Complementary and Alternative Medicine and the National Institute on Aging, Bethesda, Md., sponsored the study of 3,069 community-dwelling subjects aged 75 and older. They were randomly assigned to receive G. biloba or placebo twice daily and followed for a median of 6 years to track development of dementia (JAMA 2008;300:2253–62).

The G. biloba was a standard formulation used in many of the branded products sold in the United States and was administered at the highest, most commonly used dosage. An expert panel assessed the subjects' cognitive status, focusing on therapy adherence and subject retention, given their advanced age and concomitant morbidity.

A total of 523 subjects developed dementia, including 16% in the placebo group and 18% in the active treatment group, a nonsignificant difference. The rate of total dementia was not significantly different between subjects receiving ginkgo (3.3 cases per 100 person-years) and those receiving placebo (2.9 cases per 100 person-years), neither was the rate of Alzheimer's disease at 3 cases per 100 person-years and 2.6 cases per 100 person-years, respectively.

The findings remained consistent across subgroups of patients categorized by age, sex, and the presence or absence of mild cognitive impairment at baseline. Mortality and the adverse event profiles were similar between the groups, with similar incidence of coronary heart disease events, stroke, and bleeding events.

Because the delay from initial brain changes to clinical dementia is known to be long, it may take many years to manifest an effect of G. biloba, positive or negative, the authors wrote, and they are planning further analysis of brain function and pathology by group using MRIs.

Dr. DeKosky reported receiving grants or research support from Elan Corp., Myriad Genetics Inc., Neurochem Inc., and GlaxoSmithKline, and serving on the advisory boards of or consulting for several additional pharmaceutical companies.

Ginkgo biloba does not prevent onset of dementia in general or of Alzheimer's disease in particular, according to data from a large, randomized clinical trial.

Basic and observational research has suggested the herbal product should be a promising therapy, but “no adequately designed and powered clinical trial has evaluated the [herb's] safety and effectiveness in the primary prevention of dementia,” said Dr. Steven T. DeKosky of the University of Pittsburgh and his associates in the Ginkgo Evaluation of Memory study.

The National Center for Complementary and Alternative Medicine and the National Institute on Aging, Bethesda, Md., sponsored the study of 3,069 community-dwelling subjects aged 75 and older. They were randomly assigned to receive G. biloba or placebo twice daily and followed for a median of 6 years to track development of dementia (JAMA 2008;300:2253–62).

The G. biloba was a standard formulation used in many of the branded products sold in the United States and was administered at the highest, most commonly used dosage. An expert panel assessed the subjects' cognitive status, focusing on therapy adherence and subject retention, given their advanced age and concomitant morbidity.

A total of 523 subjects developed dementia, including 16% in the placebo group and 18% in the active treatment group, a nonsignificant difference. The rate of total dementia was not significantly different between subjects receiving ginkgo (3.3 cases per 100 person-years) and those receiving placebo (2.9 cases per 100 person-years), neither was the rate of Alzheimer's disease at 3 cases per 100 person-years and 2.6 cases per 100 person-years, respectively.

The findings remained consistent across subgroups of patients categorized by age, sex, and the presence or absence of mild cognitive impairment at baseline. Mortality and the adverse event profiles were similar between the groups, with similar incidence of coronary heart disease events, stroke, and bleeding events.

Because the delay from initial brain changes to clinical dementia is known to be long, it may take many years to manifest an effect of G. biloba, positive or negative, the authors wrote, and they are planning further analysis of brain function and pathology by group using MRIs.

Dr. DeKosky reported receiving grants or research support from Elan Corp., Myriad Genetics Inc., Neurochem Inc., and GlaxoSmithKline, and serving on the advisory boards of or consulting for several additional pharmaceutical companies.

Ginkgo biloba does not prevent onset of dementia in general or of Alzheimer's disease in particular, according to data from a large, randomized clinical trial.

Basic and observational research has suggested the herbal product should be a promising therapy, but “no adequately designed and powered clinical trial has evaluated the [herb's] safety and effectiveness in the primary prevention of dementia,” said Dr. Steven T. DeKosky of the University of Pittsburgh and his associates in the Ginkgo Evaluation of Memory study.

The National Center for Complementary and Alternative Medicine and the National Institute on Aging, Bethesda, Md., sponsored the study of 3,069 community-dwelling subjects aged 75 and older. They were randomly assigned to receive G. biloba or placebo twice daily and followed for a median of 6 years to track development of dementia (JAMA 2008;300:2253–62).

The G. biloba was a standard formulation used in many of the branded products sold in the United States and was administered at the highest, most commonly used dosage. An expert panel assessed the subjects' cognitive status, focusing on therapy adherence and subject retention, given their advanced age and concomitant morbidity.

A total of 523 subjects developed dementia, including 16% in the placebo group and 18% in the active treatment group, a nonsignificant difference. The rate of total dementia was not significantly different between subjects receiving ginkgo (3.3 cases per 100 person-years) and those receiving placebo (2.9 cases per 100 person-years), neither was the rate of Alzheimer's disease at 3 cases per 100 person-years and 2.6 cases per 100 person-years, respectively.

The findings remained consistent across subgroups of patients categorized by age, sex, and the presence or absence of mild cognitive impairment at baseline. Mortality and the adverse event profiles were similar between the groups, with similar incidence of coronary heart disease events, stroke, and bleeding events.

Because the delay from initial brain changes to clinical dementia is known to be long, it may take many years to manifest an effect of G. biloba, positive or negative, the authors wrote, and they are planning further analysis of brain function and pathology by group using MRIs.

Dr. DeKosky reported receiving grants or research support from Elan Corp., Myriad Genetics Inc., Neurochem Inc., and GlaxoSmithKline, and serving on the advisory boards of or consulting for several additional pharmaceutical companies.

Extended follow-up of patients in the Adenomatous Polyp Prevention on Vioxx trial confirms the initial finding that rofecoxib raises the risks of myocardial infarction and stroke.

“Small numbers prohibit detailed conclusions about when the increased risk begins and ends, but our data are compatible with an early increase in risk that seems to persist for about 1 year after 3 years of treatment,” reported Dr. John A. Baron of Dartmouth Medical School, Lebanon, N.H., and associates (Lancet 2008 Oct. 14 [doi: 10.1016/S0140–6736(08) 61490–7]).

The APPROVE trial, designed to assess whether rofecoxib (Vioxx) reduced the risk of recurrent colorectal neoplasia, was halted early (in 2004) because the drug appeared to double the risk of cardiovascular toxicity. Rofecoxib was soon withdrawn from the market. The trial, funded by Merck Research Laboratories, was criticized for flaws in its statistical analyses.

Dr. Baron and his associates extended the follow-up to at least 1 year after the drug was discontinued, to further assess rofecoxib's CV toxicity. Follow-up was completed for 1,092 subjects who had taken placebo and 1,074 who had taken rofecoxib.

Thrombotic events occurred in 76 rofecoxib patients and 46 on placebo (overall unadjusted hazard ratio, 1.7). After adjustment for age, sex, aspirin use, and CV risk profile at baseline, the hazard ratio was 1.72 for MI and 2.17 for stroke. Subgroup analyses suggested that rofecoxib particularly affected people already at risk for CV disease, but the data were not conclusive because the number of events was small.

Rofecoxib's cardiovascular toxicity “seems to be a class effect,” since other studies have found similar results with different cyclooxygenase-2 inhibitors. Conventional non-aspirin NSAIDs “may share the same toxicity, to the extent that they are COX-2 selective,” the investigators added.

“All these drugs are effective analgesic and anti-inflammatory agents, and seem to reduce risks of colorectal neoplasia. But these benefits will have to be weighed against their proven or possible cardiovascular risks in assessing their suitability in various clinical settings,” they said.

Dr. Baron received consulting fees from Merck as a member of the trial's steering committee and is a consultant to, and has received research funding, from Bayer.

Extended follow-up of patients in the Adenomatous Polyp Prevention on Vioxx trial confirms the initial finding that rofecoxib raises the risks of myocardial infarction and stroke.

“Small numbers prohibit detailed conclusions about when the increased risk begins and ends, but our data are compatible with an early increase in risk that seems to persist for about 1 year after 3 years of treatment,” reported Dr. John A. Baron of Dartmouth Medical School, Lebanon, N.H., and associates (Lancet 2008 Oct. 14 [doi: 10.1016/S0140–6736(08) 61490–7]).

The APPROVE trial, designed to assess whether rofecoxib (Vioxx) reduced the risk of recurrent colorectal neoplasia, was halted early (in 2004) because the drug appeared to double the risk of cardiovascular toxicity. Rofecoxib was soon withdrawn from the market. The trial, funded by Merck Research Laboratories, was criticized for flaws in its statistical analyses.

Dr. Baron and his associates extended the follow-up to at least 1 year after the drug was discontinued, to further assess rofecoxib's CV toxicity. Follow-up was completed for 1,092 subjects who had taken placebo and 1,074 who had taken rofecoxib.

Thrombotic events occurred in 76 rofecoxib patients and 46 on placebo (overall unadjusted hazard ratio, 1.7). After adjustment for age, sex, aspirin use, and CV risk profile at baseline, the hazard ratio was 1.72 for MI and 2.17 for stroke. Subgroup analyses suggested that rofecoxib particularly affected people already at risk for CV disease, but the data were not conclusive because the number of events was small.

Rofecoxib's cardiovascular toxicity “seems to be a class effect,” since other studies have found similar results with different cyclooxygenase-2 inhibitors. Conventional non-aspirin NSAIDs “may share the same toxicity, to the extent that they are COX-2 selective,” the investigators added.

“All these drugs are effective analgesic and anti-inflammatory agents, and seem to reduce risks of colorectal neoplasia. But these benefits will have to be weighed against their proven or possible cardiovascular risks in assessing their suitability in various clinical settings,” they said.

Dr. Baron received consulting fees from Merck as a member of the trial's steering committee and is a consultant to, and has received research funding, from Bayer.

Extended follow-up of patients in the Adenomatous Polyp Prevention on Vioxx trial confirms the initial finding that rofecoxib raises the risks of myocardial infarction and stroke.

“Small numbers prohibit detailed conclusions about when the increased risk begins and ends, but our data are compatible with an early increase in risk that seems to persist for about 1 year after 3 years of treatment,” reported Dr. John A. Baron of Dartmouth Medical School, Lebanon, N.H., and associates (Lancet 2008 Oct. 14 [doi: 10.1016/S0140–6736(08) 61490–7]).

The APPROVE trial, designed to assess whether rofecoxib (Vioxx) reduced the risk of recurrent colorectal neoplasia, was halted early (in 2004) because the drug appeared to double the risk of cardiovascular toxicity. Rofecoxib was soon withdrawn from the market. The trial, funded by Merck Research Laboratories, was criticized for flaws in its statistical analyses.

Dr. Baron and his associates extended the follow-up to at least 1 year after the drug was discontinued, to further assess rofecoxib's CV toxicity. Follow-up was completed for 1,092 subjects who had taken placebo and 1,074 who had taken rofecoxib.

Thrombotic events occurred in 76 rofecoxib patients and 46 on placebo (overall unadjusted hazard ratio, 1.7). After adjustment for age, sex, aspirin use, and CV risk profile at baseline, the hazard ratio was 1.72 for MI and 2.17 for stroke. Subgroup analyses suggested that rofecoxib particularly affected people already at risk for CV disease, but the data were not conclusive because the number of events was small.

Rofecoxib's cardiovascular toxicity “seems to be a class effect,” since other studies have found similar results with different cyclooxygenase-2 inhibitors. Conventional non-aspirin NSAIDs “may share the same toxicity, to the extent that they are COX-2 selective,” the investigators added.

“All these drugs are effective analgesic and anti-inflammatory agents, and seem to reduce risks of colorectal neoplasia. But these benefits will have to be weighed against their proven or possible cardiovascular risks in assessing their suitability in various clinical settings,” they said.

Dr. Baron received consulting fees from Merck as a member of the trial's steering committee and is a consultant to, and has received research funding, from Bayer.

Giving patients with ST-segment elevation myocardial infarction a cyclosporine bolus at the time of reperfusion appears to reduce infarct size by about 40%, researchers in a small proof-of-concept trial reported.

The study results “support the argument that reperfusion necrosis is a major component of infarct size after prolonged ischemia and reperfusion,” said Dr. Christophe Piot of Hôpital Arnaud de Villeneuve, Montpellier, France, and associates (N. Engl. J. Med. 2008;359:473–81).

Cyclosporine has shown promise in limiting reperfusion injury in preclinical studies. The investigators conducted their prospective, multicenter trial in 58 patients with acute ST-segment elevation MI who were slated for percutaneous coronary intervention. Both the size of the infarct and the size of the area considered to be at risk were estimated by measuring the circumferential extent of abnormally contracting segments on angiography.

After coronary angiography was performed, but before stent placement, the patients were randomly assigned to receive a single IV bolus of either cyclosporine (30 subjects) or normal saline (28 control subjects).

Infarct size after reperfusion, as measured by release of serum creatine kinase, was significantly reduced in the cyclosporine group but not in the control group. The difference “represents a reduction in the infarct size of approximately 40%,” the investigators said.

When the subjects were categorized according to the size of the area at risk, the infarcts that developed in those given cyclosporine were consistently smaller than those that developed in control subjects.

In a subgroup of 27 patients who underwent MRI, the absolute mass of the area of delayed hyperenhancement was 20% smaller in those given cyclosporine than in control subjects.

No adverse events were attributed to cyclosporine.

Giving patients with ST-segment elevation myocardial infarction a cyclosporine bolus at the time of reperfusion appears to reduce infarct size by about 40%, researchers in a small proof-of-concept trial reported.

The study results “support the argument that reperfusion necrosis is a major component of infarct size after prolonged ischemia and reperfusion,” said Dr. Christophe Piot of Hôpital Arnaud de Villeneuve, Montpellier, France, and associates (N. Engl. J. Med. 2008;359:473–81).

Cyclosporine has shown promise in limiting reperfusion injury in preclinical studies. The investigators conducted their prospective, multicenter trial in 58 patients with acute ST-segment elevation MI who were slated for percutaneous coronary intervention. Both the size of the infarct and the size of the area considered to be at risk were estimated by measuring the circumferential extent of abnormally contracting segments on angiography.

After coronary angiography was performed, but before stent placement, the patients were randomly assigned to receive a single IV bolus of either cyclosporine (30 subjects) or normal saline (28 control subjects).

Infarct size after reperfusion, as measured by release of serum creatine kinase, was significantly reduced in the cyclosporine group but not in the control group. The difference “represents a reduction in the infarct size of approximately 40%,” the investigators said.

When the subjects were categorized according to the size of the area at risk, the infarcts that developed in those given cyclosporine were consistently smaller than those that developed in control subjects.

In a subgroup of 27 patients who underwent MRI, the absolute mass of the area of delayed hyperenhancement was 20% smaller in those given cyclosporine than in control subjects.

No adverse events were attributed to cyclosporine.

Giving patients with ST-segment elevation myocardial infarction a cyclosporine bolus at the time of reperfusion appears to reduce infarct size by about 40%, researchers in a small proof-of-concept trial reported.

The study results “support the argument that reperfusion necrosis is a major component of infarct size after prolonged ischemia and reperfusion,” said Dr. Christophe Piot of Hôpital Arnaud de Villeneuve, Montpellier, France, and associates (N. Engl. J. Med. 2008;359:473–81).

Cyclosporine has shown promise in limiting reperfusion injury in preclinical studies. The investigators conducted their prospective, multicenter trial in 58 patients with acute ST-segment elevation MI who were slated for percutaneous coronary intervention. Both the size of the infarct and the size of the area considered to be at risk were estimated by measuring the circumferential extent of abnormally contracting segments on angiography.

After coronary angiography was performed, but before stent placement, the patients were randomly assigned to receive a single IV bolus of either cyclosporine (30 subjects) or normal saline (28 control subjects).

Infarct size after reperfusion, as measured by release of serum creatine kinase, was significantly reduced in the cyclosporine group but not in the control group. The difference “represents a reduction in the infarct size of approximately 40%,” the investigators said.

When the subjects were categorized according to the size of the area at risk, the infarcts that developed in those given cyclosporine were consistently smaller than those that developed in control subjects.

In a subgroup of 27 patients who underwent MRI, the absolute mass of the area of delayed hyperenhancement was 20% smaller in those given cyclosporine than in control subjects.

No adverse events were attributed to cyclosporine.

A wide variety of prescription and nonprescription medications and nutritional supplements are at the root of drug-induced liver injury in the United States.

Moreover, combinations of potentially hepatotoxic agents, rather than single agents, account for at least 20% of cases reported to the Drug-Induced Liver Injury Network (DILIN), a registry of clinically significant cases and a repository of biological specimens established in 2003. The registry is run cooperatively by the National Institutes of Health and five academic clinical centers.

That percentage is much higher than was reported in a recent European study, and it may reflect greater use of medications in the U.S. population, Dr. Naga Chalasani and his colleagues reported (J. Gastro. 2008 December [Epub doi:10.1053/j.gastro.2008.09.011]).

Dr. Chalsani, professor of medicine at Indiana University, Indianapolis, and his associates described the cases and short-term outcomes of the first 300 subjects reported to this registry and enrolled in an ongoing prospective study. The researchers hope the registry and study will furnish data for further research on the etiology and prevention of drug-induced liver injury.

The 300 subjects were enrolled in 2004–2007. Of the group, 93% were adults, including 18% who were older than 65 years. The severity of liver damage was judged to be mild in 27%, moderate in 19%, moderate requiring hospitalization in 33%, severe in 15%, and severe requiring transplant or precipitating death in 6%.

Single prescription medication was the likely cause of the liver injury in 73% of the cases. Multiple prescription medications or a combination of prescription medicine and dietary supplements were the cause in 18%. Single or multiple dietary supplements were the cause in the remaining 9%.

Dietary supplements that caused liver injury included those taken to build muscle, lose weight, cure insomnia, prevent colds, boost energy, and control menopausal symptoms. Many patients were using multiple dietary supplements and, even when a single dietary supplement caused the liver damage, it often contained multiple herbal or nutritional components.

Among prescription medicines, antimicrobials (including antibacterials, antivirals, and antifungals) were the most frequent offenders, causing liver damage in over 45% of cases. This finding is in accord with the results of previous studies.

The reason why antimicrobials have such a propensity to cause liver damage is not yet known. It may be related to the generally high usage of antimicrobials in the U.S. population, or it may be that patients' underlying infection and inflammation confer increased susceptibility to liver injury, Dr. Chalsani and his associates said.

CNS agents such as antiepileptics, antidepressants, and antipsychotics were the likely cause of liver damage in 15% of cases, immunomodulatory agents were the likely cause in 5%, analgesics in 5%, antineoplastic drugs in 4%, antihypertensives in 5%, and lipid-lowering agents in 3%.

The most common single prescription drugs that caused liver injury in registry patients were amoxicillin/clavulanate (23 cases), nitrofurantoin (13 cases), isoniazid (13 cases), and trimethoprim-sulfa-methoxazole (13 cases).

This observational study did provide information “of practical relevance in monitoring and counseling patients with drug-induced liver injury,” the investigators noted.

First, serum bilirubin reached its peak an average of 1 week after diagnosis, regardless of the patient's age, the pattern of liver injury, or the causative agent. In patients who developed jaundice, the condition took nearly a month on average to resolve; jaundice took even longer to resolve in elderly patients and in those whose liver injury was caused by dietary supplements rather than by medications.

Second, diabetes was a strong independent risk factor for severe drug-induced liver injury. Diabetes has not been considered as a possible confounding factor in previous studies of drug-induced liver injury, Dr. Chalsani and his associates said.

Third, acute hepatitis C infection should be thoroughly ruled out before attributing a case of acute liver injury to acute drug exposure. Several patients in this series had liver damage thought to be unrelated to acute hepatitis C because they initially tested negative for the virus and reported no risk factors. However, they later seroconverted.

“As better diagnostic tests become available for specific causes of acute liver injury, more cases of suspected drug-induced liver injury may be found to have other etiologies,” the investigators noted.

The DILIN and this study were supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Chalsani is a paid consultant to Takeda Pharmaceuticals, AtheroGenics Inc., Advanced Life Sciences, Kari Bio, Metabasis, Pfizer Inc., and Eli Lilly & Co. He received grant support from Debiovision Inc. and Sanofi-Aventis. On his behalf, Indiana University has initiated contract negotiations with Gilead Sciences Inc. and Pfizer for conducting clinical trials unrelated to drug-induced liver injury. In addition, Dr. Chalsani has served as a defendant's expert witness for a product liability litigation involving suspected drug-induced liver injury.

A wide variety of prescription and nonprescription medications and nutritional supplements are at the root of drug-induced liver injury in the United States.

Moreover, combinations of potentially hepatotoxic agents, rather than single agents, account for at least 20% of cases reported to the Drug-Induced Liver Injury Network (DILIN), a registry of clinically significant cases and a repository of biological specimens established in 2003. The registry is run cooperatively by the National Institutes of Health and five academic clinical centers.

That percentage is much higher than was reported in a recent European study, and it may reflect greater use of medications in the U.S. population, Dr. Naga Chalasani and his colleagues reported (J. Gastro. 2008 December [Epub doi:10.1053/j.gastro.2008.09.011]).

Dr. Chalsani, professor of medicine at Indiana University, Indianapolis, and his associates described the cases and short-term outcomes of the first 300 subjects reported to this registry and enrolled in an ongoing prospective study. The researchers hope the registry and study will furnish data for further research on the etiology and prevention of drug-induced liver injury.

The 300 subjects were enrolled in 2004–2007. Of the group, 93% were adults, including 18% who were older than 65 years. The severity of liver damage was judged to be mild in 27%, moderate in 19%, moderate requiring hospitalization in 33%, severe in 15%, and severe requiring transplant or precipitating death in 6%.

Single prescription medication was the likely cause of the liver injury in 73% of the cases. Multiple prescription medications or a combination of prescription medicine and dietary supplements were the cause in 18%. Single or multiple dietary supplements were the cause in the remaining 9%.

Dietary supplements that caused liver injury included those taken to build muscle, lose weight, cure insomnia, prevent colds, boost energy, and control menopausal symptoms. Many patients were using multiple dietary supplements and, even when a single dietary supplement caused the liver damage, it often contained multiple herbal or nutritional components.

Among prescription medicines, antimicrobials (including antibacterials, antivirals, and antifungals) were the most frequent offenders, causing liver damage in over 45% of cases. This finding is in accord with the results of previous studies.

The reason why antimicrobials have such a propensity to cause liver damage is not yet known. It may be related to the generally high usage of antimicrobials in the U.S. population, or it may be that patients' underlying infection and inflammation confer increased susceptibility to liver injury, Dr. Chalsani and his associates said.

CNS agents such as antiepileptics, antidepressants, and antipsychotics were the likely cause of liver damage in 15% of cases, immunomodulatory agents were the likely cause in 5%, analgesics in 5%, antineoplastic drugs in 4%, antihypertensives in 5%, and lipid-lowering agents in 3%.

The most common single prescription drugs that caused liver injury in registry patients were amoxicillin/clavulanate (23 cases), nitrofurantoin (13 cases), isoniazid (13 cases), and trimethoprim-sulfa-methoxazole (13 cases).

This observational study did provide information “of practical relevance in monitoring and counseling patients with drug-induced liver injury,” the investigators noted.

First, serum bilirubin reached its peak an average of 1 week after diagnosis, regardless of the patient's age, the pattern of liver injury, or the causative agent. In patients who developed jaundice, the condition took nearly a month on average to resolve; jaundice took even longer to resolve in elderly patients and in those whose liver injury was caused by dietary supplements rather than by medications.

Second, diabetes was a strong independent risk factor for severe drug-induced liver injury. Diabetes has not been considered as a possible confounding factor in previous studies of drug-induced liver injury, Dr. Chalsani and his associates said.

Third, acute hepatitis C infection should be thoroughly ruled out before attributing a case of acute liver injury to acute drug exposure. Several patients in this series had liver damage thought to be unrelated to acute hepatitis C because they initially tested negative for the virus and reported no risk factors. However, they later seroconverted.

“As better diagnostic tests become available for specific causes of acute liver injury, more cases of suspected drug-induced liver injury may be found to have other etiologies,” the investigators noted.

The DILIN and this study were supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Chalsani is a paid consultant to Takeda Pharmaceuticals, AtheroGenics Inc., Advanced Life Sciences, Kari Bio, Metabasis, Pfizer Inc., and Eli Lilly & Co. He received grant support from Debiovision Inc. and Sanofi-Aventis. On his behalf, Indiana University has initiated contract negotiations with Gilead Sciences Inc. and Pfizer for conducting clinical trials unrelated to drug-induced liver injury. In addition, Dr. Chalsani has served as a defendant's expert witness for a product liability litigation involving suspected drug-induced liver injury.

A wide variety of prescription and nonprescription medications and nutritional supplements are at the root of drug-induced liver injury in the United States.

Moreover, combinations of potentially hepatotoxic agents, rather than single agents, account for at least 20% of cases reported to the Drug-Induced Liver Injury Network (DILIN), a registry of clinically significant cases and a repository of biological specimens established in 2003. The registry is run cooperatively by the National Institutes of Health and five academic clinical centers.

That percentage is much higher than was reported in a recent European study, and it may reflect greater use of medications in the U.S. population, Dr. Naga Chalasani and his colleagues reported (J. Gastro. 2008 December [Epub doi:10.1053/j.gastro.2008.09.011]).

Dr. Chalsani, professor of medicine at Indiana University, Indianapolis, and his associates described the cases and short-term outcomes of the first 300 subjects reported to this registry and enrolled in an ongoing prospective study. The researchers hope the registry and study will furnish data for further research on the etiology and prevention of drug-induced liver injury.

The 300 subjects were enrolled in 2004–2007. Of the group, 93% were adults, including 18% who were older than 65 years. The severity of liver damage was judged to be mild in 27%, moderate in 19%, moderate requiring hospitalization in 33%, severe in 15%, and severe requiring transplant or precipitating death in 6%.

Single prescription medication was the likely cause of the liver injury in 73% of the cases. Multiple prescription medications or a combination of prescription medicine and dietary supplements were the cause in 18%. Single or multiple dietary supplements were the cause in the remaining 9%.

Dietary supplements that caused liver injury included those taken to build muscle, lose weight, cure insomnia, prevent colds, boost energy, and control menopausal symptoms. Many patients were using multiple dietary supplements and, even when a single dietary supplement caused the liver damage, it often contained multiple herbal or nutritional components.

Among prescription medicines, antimicrobials (including antibacterials, antivirals, and antifungals) were the most frequent offenders, causing liver damage in over 45% of cases. This finding is in accord with the results of previous studies.

The reason why antimicrobials have such a propensity to cause liver damage is not yet known. It may be related to the generally high usage of antimicrobials in the U.S. population, or it may be that patients' underlying infection and inflammation confer increased susceptibility to liver injury, Dr. Chalsani and his associates said.

CNS agents such as antiepileptics, antidepressants, and antipsychotics were the likely cause of liver damage in 15% of cases, immunomodulatory agents were the likely cause in 5%, analgesics in 5%, antineoplastic drugs in 4%, antihypertensives in 5%, and lipid-lowering agents in 3%.

The most common single prescription drugs that caused liver injury in registry patients were amoxicillin/clavulanate (23 cases), nitrofurantoin (13 cases), isoniazid (13 cases), and trimethoprim-sulfa-methoxazole (13 cases).

This observational study did provide information “of practical relevance in monitoring and counseling patients with drug-induced liver injury,” the investigators noted.

First, serum bilirubin reached its peak an average of 1 week after diagnosis, regardless of the patient's age, the pattern of liver injury, or the causative agent. In patients who developed jaundice, the condition took nearly a month on average to resolve; jaundice took even longer to resolve in elderly patients and in those whose liver injury was caused by dietary supplements rather than by medications.

Second, diabetes was a strong independent risk factor for severe drug-induced liver injury. Diabetes has not been considered as a possible confounding factor in previous studies of drug-induced liver injury, Dr. Chalsani and his associates said.

Third, acute hepatitis C infection should be thoroughly ruled out before attributing a case of acute liver injury to acute drug exposure. Several patients in this series had liver damage thought to be unrelated to acute hepatitis C because they initially tested negative for the virus and reported no risk factors. However, they later seroconverted.

“As better diagnostic tests become available for specific causes of acute liver injury, more cases of suspected drug-induced liver injury may be found to have other etiologies,” the investigators noted.

The DILIN and this study were supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Chalsani is a paid consultant to Takeda Pharmaceuticals, AtheroGenics Inc., Advanced Life Sciences, Kari Bio, Metabasis, Pfizer Inc., and Eli Lilly & Co. He received grant support from Debiovision Inc. and Sanofi-Aventis. On his behalf, Indiana University has initiated contract negotiations with Gilead Sciences Inc. and Pfizer for conducting clinical trials unrelated to drug-induced liver injury. In addition, Dr. Chalsani has served as a defendant's expert witness for a product liability litigation involving suspected drug-induced liver injury.

Autism prevalence in three Western states has been linked to precipitation there, so that the heavier the precipitation, the higher the prevalence of the disorder among genetically vulnerable children, a report in the Archives of Pediatric and Adolescent Medicine shows.

This finding supports the hypothesis that an environmental trigger may play a significant role in autism, affecting children who are already genetically predisposed to the disorder.

“Our results clearly are not definitive … but [they] are consistent with the hypothesis, and, therefore, further research focused on establishing whether such a trigger exists and on identifying it is warranted,” said Michael Waldman, Ph.D., of the Johnson Graduate School of Management, Cornell University, Ithaca, N.Y., and his associates.

The investigators noted that several state surveys overseen by the U.S. Department of Education and a recent Centers for Disease Control and Prevention study all indicated that autism prevalence is higher in certain northern regions of the country, and lower in dry areas of the south and southwest.

They assessed a possible correlation with precipitation in Washington, Oregon, and California, where regions west of the mountains receive almost four times as much precipitation as do regions to the east. Using regression analysis, the investigators found that autism prevalence was higher in counties that received abundant precipitation. It also was higher for birth cohorts that received above-average precipitation relative to the usual amount in that county, Dr. Waldman and his associates said.

“The magnitude of the measured relationships is substantial,” they noted (Arch. Pediatr. Adolesc. Med. 2008;162:1026-34).

They are not proposing that autism is related to rain and snow per se, but that it may be related to indoor activities or exposures that are increased during bad weather.

For example, early, excessive television and video viewing has been associated with psychopathological traits such as poor language and cognitive development. It may be that this exposure produces only mild health consequences in most children but produces more serious problems such as autism in genetically vulnerable children.

“Another possibility is that vitamin D deficiency is an environmental trigger for autism,” the researchers wrote. Higher precipitation means less exposure to sunshine, the major source of vitamin D, and vitamin D deficiency “can lead to reduced levels in the developing brain of calcitriol, a critical neurosteroid involved in brain development,” they added.

Any environmental trigger that is associated with indoor activities could be at fault, including household chemicals. And it also is possible that precipitation is more directly involved, by transporting chemicals in the upper atmosphere to the ground, for example. Or high precipitation may promote the overgrowth of weeds or expansion of the insect population, which in turn increase the use of pesticides, they wrote.

In an accompanying editorial, Dr. Noel S. Weiss of the University of Washington, Seattle, noted that the study findings are “tentative” and were intended to prompt further research into environmental triggers, not to implicate rainfall itself.

“The primary audience of Waldman et al is not the practicing pediatrician, and certainly, it is not a member of the public at large. These individuals cannot take away any practical message from it. Rather, the primary target is an investigator interested in the causes of autism, someone who might be able to test one or more of the etiologic hypotheses that derive from [the study],” he said (Arch. Pediatr. Adolesc. Med. 2008:162;1095-6).

The researchers “have made it clear that the message the public should take from their data regarding precipitation and autism is … 'No call for alarm, stay tuned,'” Dr. Weiss wrote.

Autism prevalence in three Western states has been linked to precipitation there, so that the heavier the precipitation, the higher the prevalence of the disorder among genetically vulnerable children, a report in the Archives of Pediatric and Adolescent Medicine shows.

This finding supports the hypothesis that an environmental trigger may play a significant role in autism, affecting children who are already genetically predisposed to the disorder.

“Our results clearly are not definitive … but [they] are consistent with the hypothesis, and, therefore, further research focused on establishing whether such a trigger exists and on identifying it is warranted,” said Michael Waldman, Ph.D., of the Johnson Graduate School of Management, Cornell University, Ithaca, N.Y., and his associates.

The investigators noted that several state surveys overseen by the U.S. Department of Education and a recent Centers for Disease Control and Prevention study all indicated that autism prevalence is higher in certain northern regions of the country, and lower in dry areas of the south and southwest.

They assessed a possible correlation with precipitation in Washington, Oregon, and California, where regions west of the mountains receive almost four times as much precipitation as do regions to the east. Using regression analysis, the investigators found that autism prevalence was higher in counties that received abundant precipitation. It also was higher for birth cohorts that received above-average precipitation relative to the usual amount in that county, Dr. Waldman and his associates said.

“The magnitude of the measured relationships is substantial,” they noted (Arch. Pediatr. Adolesc. Med. 2008;162:1026-34).

They are not proposing that autism is related to rain and snow per se, but that it may be related to indoor activities or exposures that are increased during bad weather.

For example, early, excessive television and video viewing has been associated with psychopathological traits such as poor language and cognitive development. It may be that this exposure produces only mild health consequences in most children but produces more serious problems such as autism in genetically vulnerable children.

“Another possibility is that vitamin D deficiency is an environmental trigger for autism,” the researchers wrote. Higher precipitation means less exposure to sunshine, the major source of vitamin D, and vitamin D deficiency “can lead to reduced levels in the developing brain of calcitriol, a critical neurosteroid involved in brain development,” they added.

Any environmental trigger that is associated with indoor activities could be at fault, including household chemicals. And it also is possible that precipitation is more directly involved, by transporting chemicals in the upper atmosphere to the ground, for example. Or high precipitation may promote the overgrowth of weeds or expansion of the insect population, which in turn increase the use of pesticides, they wrote.

In an accompanying editorial, Dr. Noel S. Weiss of the University of Washington, Seattle, noted that the study findings are “tentative” and were intended to prompt further research into environmental triggers, not to implicate rainfall itself.

“The primary audience of Waldman et al is not the practicing pediatrician, and certainly, it is not a member of the public at large. These individuals cannot take away any practical message from it. Rather, the primary target is an investigator interested in the causes of autism, someone who might be able to test one or more of the etiologic hypotheses that derive from [the study],” he said (Arch. Pediatr. Adolesc. Med. 2008:162;1095-6).

The researchers “have made it clear that the message the public should take from their data regarding precipitation and autism is … 'No call for alarm, stay tuned,'” Dr. Weiss wrote.

Autism prevalence in three Western states has been linked to precipitation there, so that the heavier the precipitation, the higher the prevalence of the disorder among genetically vulnerable children, a report in the Archives of Pediatric and Adolescent Medicine shows.

This finding supports the hypothesis that an environmental trigger may play a significant role in autism, affecting children who are already genetically predisposed to the disorder.

“Our results clearly are not definitive … but [they] are consistent with the hypothesis, and, therefore, further research focused on establishing whether such a trigger exists and on identifying it is warranted,” said Michael Waldman, Ph.D., of the Johnson Graduate School of Management, Cornell University, Ithaca, N.Y., and his associates.

The investigators noted that several state surveys overseen by the U.S. Department of Education and a recent Centers for Disease Control and Prevention study all indicated that autism prevalence is higher in certain northern regions of the country, and lower in dry areas of the south and southwest.

They assessed a possible correlation with precipitation in Washington, Oregon, and California, where regions west of the mountains receive almost four times as much precipitation as do regions to the east. Using regression analysis, the investigators found that autism prevalence was higher in counties that received abundant precipitation. It also was higher for birth cohorts that received above-average precipitation relative to the usual amount in that county, Dr. Waldman and his associates said.

“The magnitude of the measured relationships is substantial,” they noted (Arch. Pediatr. Adolesc. Med. 2008;162:1026-34).

They are not proposing that autism is related to rain and snow per se, but that it may be related to indoor activities or exposures that are increased during bad weather.

For example, early, excessive television and video viewing has been associated with psychopathological traits such as poor language and cognitive development. It may be that this exposure produces only mild health consequences in most children but produces more serious problems such as autism in genetically vulnerable children.

“Another possibility is that vitamin D deficiency is an environmental trigger for autism,” the researchers wrote. Higher precipitation means less exposure to sunshine, the major source of vitamin D, and vitamin D deficiency “can lead to reduced levels in the developing brain of calcitriol, a critical neurosteroid involved in brain development,” they added.

Any environmental trigger that is associated with indoor activities could be at fault, including household chemicals. And it also is possible that precipitation is more directly involved, by transporting chemicals in the upper atmosphere to the ground, for example. Or high precipitation may promote the overgrowth of weeds or expansion of the insect population, which in turn increase the use of pesticides, they wrote.

In an accompanying editorial, Dr. Noel S. Weiss of the University of Washington, Seattle, noted that the study findings are “tentative” and were intended to prompt further research into environmental triggers, not to implicate rainfall itself.

“The primary audience of Waldman et al is not the practicing pediatrician, and certainly, it is not a member of the public at large. These individuals cannot take away any practical message from it. Rather, the primary target is an investigator interested in the causes of autism, someone who might be able to test one or more of the etiologic hypotheses that derive from [the study],” he said (Arch. Pediatr. Adolesc. Med. 2008:162;1095-6).

The researchers “have made it clear that the message the public should take from their data regarding precipitation and autism is … 'No call for alarm, stay tuned,'” Dr. Weiss wrote.