Mary Ann Moon

Patients who take hydroxychloroquine for their rheumatoid arthritis symptoms also show a dose-dependent reduction in their risk for developing diabetes, results of a large study suggest.

Diabetes risk decreased by as much as 77% in patients who took the antimalarial drug hydroxychloroquine for more than 4 years, “a finding that is comparable or superior to that of other drugs studied in clinical trials: rosiglitazone, combination hormone therapy, estrogen [only], metformin, acarbose, and ramipril,” the study researchers reported.

This is the first evidence that has ever been reported suggesting that hydroxychloroquine reduces the risk of diabetes in RA patients, wrote Dr. Mary Chester M. Wasko, of the University of Pittsburgh, and her associates.

Antimalarials are known to cause hypoglycemia and are thought to improve insulin secretion and peripheral insulin sensitivity. They “have been explored as an adjunct to insulin and oral hypoglycemic agents for poorly controlled type 2 diabetes,” Dr. Wasko and her associates said.

The investigators studied the possible link between use of hydroxychloroquine and diabetes risk in an established RA cohort with more than 20 years of follow-up.

The 4,905 subjects in this longitudinal observational study were treated at seven RA practice sites across North America from 1976 through 2004. A total of 1,808 reported use of hydroxychloroquine at some time during the study, most of them for an average of 3 years.

Diabetes developed in 70% of the subjects who had never taken the antimalarial drug, compared with only 48% of those who had ever taken it.

Diabetes incidence rates were 8.9 per 1,000 patient-years of observation among those who had never before taken hydroxychloroquine, compared with 5.2 per 1,000 patient-years for those who had taken the drug.

In addition, “the relative risk of developing diabetes progressively declined with increasing time taking hydroxychloroquine,” the investigators said (JAMA 2007;298:187–93).

Patients who did develop diabetes after taking the antimalarial were less likely than were those who hadn't taken it to need oral hypoglycemic medication.

“Hydroxychloroquine use may modify the clinical manifestations of hyperglycemia, or it may attenuate hyperglycemia and reduce the need for medications once this diagnosis is established,” Dr. Wasko and her associates commented.

Although antimalarials do not address RA signs and symptoms as well as other current treatment options, their toxicity profile is better, so they are used for mild to moderate disease and in combination therapy.

Unlike the traditional RA medications, antimalarials are well tolerated, do not require routine laboratory monitoring for toxicity, confer no increased risk of infection or malignancy, and carry “minimal” risk for adversely affecting internal organs when dosing is tailored to body weight, the researchers said.

Even though this study involved only RA patients, the results also may apply to people who do not have RA, because hydroxychloroquine may prove beneficial in preventing diabetes in high-risk members of the general population, the researchers added.

Patients who take hydroxychloroquine for their rheumatoid arthritis symptoms also show a dose-dependent reduction in their risk for developing diabetes, results of a large study suggest.

Diabetes risk decreased by as much as 77% in patients who took the antimalarial drug hydroxychloroquine for more than 4 years, “a finding that is comparable or superior to that of other drugs studied in clinical trials: rosiglitazone, combination hormone therapy, estrogen [only], metformin, acarbose, and ramipril,” the study researchers reported.

This is the first evidence that has ever been reported suggesting that hydroxychloroquine reduces the risk of diabetes in RA patients, wrote Dr. Mary Chester M. Wasko, of the University of Pittsburgh, and her associates.

Antimalarials are known to cause hypoglycemia and are thought to improve insulin secretion and peripheral insulin sensitivity. They “have been explored as an adjunct to insulin and oral hypoglycemic agents for poorly controlled type 2 diabetes,” Dr. Wasko and her associates said.

The investigators studied the possible link between use of hydroxychloroquine and diabetes risk in an established RA cohort with more than 20 years of follow-up.

The 4,905 subjects in this longitudinal observational study were treated at seven RA practice sites across North America from 1976 through 2004. A total of 1,808 reported use of hydroxychloroquine at some time during the study, most of them for an average of 3 years.

Diabetes developed in 70% of the subjects who had never taken the antimalarial drug, compared with only 48% of those who had ever taken it.

Diabetes incidence rates were 8.9 per 1,000 patient-years of observation among those who had never before taken hydroxychloroquine, compared with 5.2 per 1,000 patient-years for those who had taken the drug.

In addition, “the relative risk of developing diabetes progressively declined with increasing time taking hydroxychloroquine,” the investigators said (JAMA 2007;298:187–93).

Patients who did develop diabetes after taking the antimalarial were less likely than were those who hadn't taken it to need oral hypoglycemic medication.

“Hydroxychloroquine use may modify the clinical manifestations of hyperglycemia, or it may attenuate hyperglycemia and reduce the need for medications once this diagnosis is established,” Dr. Wasko and her associates commented.

Although antimalarials do not address RA signs and symptoms as well as other current treatment options, their toxicity profile is better, so they are used for mild to moderate disease and in combination therapy.

Unlike the traditional RA medications, antimalarials are well tolerated, do not require routine laboratory monitoring for toxicity, confer no increased risk of infection or malignancy, and carry “minimal” risk for adversely affecting internal organs when dosing is tailored to body weight, the researchers said.

Even though this study involved only RA patients, the results also may apply to people who do not have RA, because hydroxychloroquine may prove beneficial in preventing diabetes in high-risk members of the general population, the researchers added.

Patients who take hydroxychloroquine for their rheumatoid arthritis symptoms also show a dose-dependent reduction in their risk for developing diabetes, results of a large study suggest.

Diabetes risk decreased by as much as 77% in patients who took the antimalarial drug hydroxychloroquine for more than 4 years, “a finding that is comparable or superior to that of other drugs studied in clinical trials: rosiglitazone, combination hormone therapy, estrogen [only], metformin, acarbose, and ramipril,” the study researchers reported.

This is the first evidence that has ever been reported suggesting that hydroxychloroquine reduces the risk of diabetes in RA patients, wrote Dr. Mary Chester M. Wasko, of the University of Pittsburgh, and her associates.

Antimalarials are known to cause hypoglycemia and are thought to improve insulin secretion and peripheral insulin sensitivity. They “have been explored as an adjunct to insulin and oral hypoglycemic agents for poorly controlled type 2 diabetes,” Dr. Wasko and her associates said.

The investigators studied the possible link between use of hydroxychloroquine and diabetes risk in an established RA cohort with more than 20 years of follow-up.

The 4,905 subjects in this longitudinal observational study were treated at seven RA practice sites across North America from 1976 through 2004. A total of 1,808 reported use of hydroxychloroquine at some time during the study, most of them for an average of 3 years.

Diabetes developed in 70% of the subjects who had never taken the antimalarial drug, compared with only 48% of those who had ever taken it.

Diabetes incidence rates were 8.9 per 1,000 patient-years of observation among those who had never before taken hydroxychloroquine, compared with 5.2 per 1,000 patient-years for those who had taken the drug.

In addition, “the relative risk of developing diabetes progressively declined with increasing time taking hydroxychloroquine,” the investigators said (JAMA 2007;298:187–93).

Patients who did develop diabetes after taking the antimalarial were less likely than were those who hadn't taken it to need oral hypoglycemic medication.

“Hydroxychloroquine use may modify the clinical manifestations of hyperglycemia, or it may attenuate hyperglycemia and reduce the need for medications once this diagnosis is established,” Dr. Wasko and her associates commented.

Although antimalarials do not address RA signs and symptoms as well as other current treatment options, their toxicity profile is better, so they are used for mild to moderate disease and in combination therapy.

Unlike the traditional RA medications, antimalarials are well tolerated, do not require routine laboratory monitoring for toxicity, confer no increased risk of infection or malignancy, and carry “minimal” risk for adversely affecting internal organs when dosing is tailored to body weight, the researchers said.

Even though this study involved only RA patients, the results also may apply to people who do not have RA, because hydroxychloroquine may prove beneficial in preventing diabetes in high-risk members of the general population, the researchers added.

Two large-scale studies of the possible teratogenic effects of selective serotonin reuptake inhibitors have concluded that the absolute risk of birth defects related to the drugs is small.

Neither study could confirm previously reported associations between SSRIs and heart defects. Both suggested that a few individual SSRIs might raise the risk of a few specific defects, but these malformations are so rare that even a large increase in risk would still put the chance of having an affected child at well under 1%, the researchers said in separate reports.

In the first report, Carol Louik, Sc.D., of Boston University's Slone Epidemiology Center, and associates analyzed data from the center's Birth Defects Study, an ongoing case-control surveillance program of a wide range of malformations, which covers areas surrounding Boston, Philadelphia, Toronto, San Diego, and a portion of New York State. The researchers focused on births that occurred between 1993 and 2004, which included 9,849 neonates with malformations and 5,860 neonates without malformations who served as controls.

They found no association between maternal use of SSRIs during pregnancy and heart defects as a whole, nor was there any association with craniosynostosis, omphalocele, or neural tube defects. However, the use of sertraline raised the risk of a single heart defect (cardiac septal defect), based on 13 cases, and the use of paroxetine raised the risk of another single heart defect (right ventricular outflow tract obstruction), based on 6 cases.

In addition, the data “suggested” possible links between sertraline and both anal atresia and limb-reduction defects, and possible links between paroxetine and both neural-tube defects and clubfoot.

Despite the relatively large study population, the investigators said they had limited numbers to evaluate associations between rare outcomes and exposures. “We included results based on small numbers of exposed subjects in order to allow other researchers to compare their observations with ours, but we caution that these estimates should not be interpreted as strong evidence of increased risks,” Dr. Louik and associates said (N. Engl. J. Med. 2007;356:2675-83).

In any case, “it is important to keep in perspective that the absolute risks of these rare defects are small. For example, the baseline prevalences of anal atresia and right ventricular outflow tract obstruction defects are each estimated to be about 5.5 cases per 10,000 live births; thus, even if a specific SSRI increased rates by a factor of four, the risk of having an affected child would still be only 0.2%,” they noted.

In the second study, Sura Alwan of the University of British Columbia, Vancouver, and associates analyzed data from the National Birth Defects Prevention Study on infants born between 1997 and 2002 in eight study sites throughout the United States. This included 9,622 neonates with birth defects and 4,092 without birth defects who served as controls.

Again, no associations were found between SSRIs and most of the birth defects assessed, including heart defects as a group. However, a small but significant association was found between paroxetine use and right ventricular outflow tract obstruction, based on six cases.

There also were small but significant associations with anencephaly (based on 9 exposed neonates), craniosynostosis (based on 24 exposed neonates), and omphalocele (based on 11 exposed neonates).

“Our study did not show an increased risk of most birth defects, and SSRI exposure was present in only a small number of cases of certain defects. The absolute risks associated with SSRIs appear small in comparison with the baseline risks of birth defects that exist in every pregnancy,” the researchers reported (N. Engl. J. Med. 2007;356:2684-92).

In an editorial comment accompanying this report, Dr. Michael F. Greene of Massachusetts General Hospital, Boston, said the findings of both studies make it clear that “neither SSRIs as a group nor individual SSRIs are major teratogens.

“Patients and physicians alike would prefer it if there were clear lines separating 'risk' and 'no risk' and if all studies gave consistent results pointing in the same direction. Unfortunately, this is often not the case, and the data to inform potential risks of SSRIs are no exception,” he said (N. Engl. J. Med. 2007;356:2732-3).

Even with the association found between paroxetine and right ventricular outflow obstruction, the malformation is so rare and the number of neonates exposed to the drug so small that the absolute incidence in exposed neonates “is unlikely to exceed 1%, and the incidence of all congenital heart defects is unlikely to exceed 2%,” Dr. Greene noted.

Two large-scale studies of the possible teratogenic effects of selective serotonin reuptake inhibitors have concluded that the absolute risk of birth defects related to the drugs is small.

Neither study could confirm previously reported associations between SSRIs and heart defects. Both suggested that a few individual SSRIs might raise the risk of a few specific defects, but these malformations are so rare that even a large increase in risk would still put the chance of having an affected child at well under 1%, the researchers said in separate reports.

In the first report, Carol Louik, Sc.D., of Boston University's Slone Epidemiology Center, and associates analyzed data from the center's Birth Defects Study, an ongoing case-control surveillance program of a wide range of malformations, which covers areas surrounding Boston, Philadelphia, Toronto, San Diego, and a portion of New York State. The researchers focused on births that occurred between 1993 and 2004, which included 9,849 neonates with malformations and 5,860 neonates without malformations who served as controls.

They found no association between maternal use of SSRIs during pregnancy and heart defects as a whole, nor was there any association with craniosynostosis, omphalocele, or neural tube defects. However, the use of sertraline raised the risk of a single heart defect (cardiac septal defect), based on 13 cases, and the use of paroxetine raised the risk of another single heart defect (right ventricular outflow tract obstruction), based on 6 cases.

In addition, the data “suggested” possible links between sertraline and both anal atresia and limb-reduction defects, and possible links between paroxetine and both neural-tube defects and clubfoot.

Despite the relatively large study population, the investigators said they had limited numbers to evaluate associations between rare outcomes and exposures. “We included results based on small numbers of exposed subjects in order to allow other researchers to compare their observations with ours, but we caution that these estimates should not be interpreted as strong evidence of increased risks,” Dr. Louik and associates said (N. Engl. J. Med. 2007;356:2675-83).

In any case, “it is important to keep in perspective that the absolute risks of these rare defects are small. For example, the baseline prevalences of anal atresia and right ventricular outflow tract obstruction defects are each estimated to be about 5.5 cases per 10,000 live births; thus, even if a specific SSRI increased rates by a factor of four, the risk of having an affected child would still be only 0.2%,” they noted.

In the second study, Sura Alwan of the University of British Columbia, Vancouver, and associates analyzed data from the National Birth Defects Prevention Study on infants born between 1997 and 2002 in eight study sites throughout the United States. This included 9,622 neonates with birth defects and 4,092 without birth defects who served as controls.

Again, no associations were found between SSRIs and most of the birth defects assessed, including heart defects as a group. However, a small but significant association was found between paroxetine use and right ventricular outflow tract obstruction, based on six cases.

There also were small but significant associations with anencephaly (based on 9 exposed neonates), craniosynostosis (based on 24 exposed neonates), and omphalocele (based on 11 exposed neonates).

“Our study did not show an increased risk of most birth defects, and SSRI exposure was present in only a small number of cases of certain defects. The absolute risks associated with SSRIs appear small in comparison with the baseline risks of birth defects that exist in every pregnancy,” the researchers reported (N. Engl. J. Med. 2007;356:2684-92).

In an editorial comment accompanying this report, Dr. Michael F. Greene of Massachusetts General Hospital, Boston, said the findings of both studies make it clear that “neither SSRIs as a group nor individual SSRIs are major teratogens.

“Patients and physicians alike would prefer it if there were clear lines separating 'risk' and 'no risk' and if all studies gave consistent results pointing in the same direction. Unfortunately, this is often not the case, and the data to inform potential risks of SSRIs are no exception,” he said (N. Engl. J. Med. 2007;356:2732-3).

Even with the association found between paroxetine and right ventricular outflow obstruction, the malformation is so rare and the number of neonates exposed to the drug so small that the absolute incidence in exposed neonates “is unlikely to exceed 1%, and the incidence of all congenital heart defects is unlikely to exceed 2%,” Dr. Greene noted.

Two large-scale studies of the possible teratogenic effects of selective serotonin reuptake inhibitors have concluded that the absolute risk of birth defects related to the drugs is small.

Neither study could confirm previously reported associations between SSRIs and heart defects. Both suggested that a few individual SSRIs might raise the risk of a few specific defects, but these malformations are so rare that even a large increase in risk would still put the chance of having an affected child at well under 1%, the researchers said in separate reports.

In the first report, Carol Louik, Sc.D., of Boston University's Slone Epidemiology Center, and associates analyzed data from the center's Birth Defects Study, an ongoing case-control surveillance program of a wide range of malformations, which covers areas surrounding Boston, Philadelphia, Toronto, San Diego, and a portion of New York State. The researchers focused on births that occurred between 1993 and 2004, which included 9,849 neonates with malformations and 5,860 neonates without malformations who served as controls.

They found no association between maternal use of SSRIs during pregnancy and heart defects as a whole, nor was there any association with craniosynostosis, omphalocele, or neural tube defects. However, the use of sertraline raised the risk of a single heart defect (cardiac septal defect), based on 13 cases, and the use of paroxetine raised the risk of another single heart defect (right ventricular outflow tract obstruction), based on 6 cases.

In addition, the data “suggested” possible links between sertraline and both anal atresia and limb-reduction defects, and possible links between paroxetine and both neural-tube defects and clubfoot.

Despite the relatively large study population, the investigators said they had limited numbers to evaluate associations between rare outcomes and exposures. “We included results based on small numbers of exposed subjects in order to allow other researchers to compare their observations with ours, but we caution that these estimates should not be interpreted as strong evidence of increased risks,” Dr. Louik and associates said (N. Engl. J. Med. 2007;356:2675-83).

In any case, “it is important to keep in perspective that the absolute risks of these rare defects are small. For example, the baseline prevalences of anal atresia and right ventricular outflow tract obstruction defects are each estimated to be about 5.5 cases per 10,000 live births; thus, even if a specific SSRI increased rates by a factor of four, the risk of having an affected child would still be only 0.2%,” they noted.

In the second study, Sura Alwan of the University of British Columbia, Vancouver, and associates analyzed data from the National Birth Defects Prevention Study on infants born between 1997 and 2002 in eight study sites throughout the United States. This included 9,622 neonates with birth defects and 4,092 without birth defects who served as controls.

Again, no associations were found between SSRIs and most of the birth defects assessed, including heart defects as a group. However, a small but significant association was found between paroxetine use and right ventricular outflow tract obstruction, based on six cases.

There also were small but significant associations with anencephaly (based on 9 exposed neonates), craniosynostosis (based on 24 exposed neonates), and omphalocele (based on 11 exposed neonates).

“Our study did not show an increased risk of most birth defects, and SSRI exposure was present in only a small number of cases of certain defects. The absolute risks associated with SSRIs appear small in comparison with the baseline risks of birth defects that exist in every pregnancy,” the researchers reported (N. Engl. J. Med. 2007;356:2684-92).

In an editorial comment accompanying this report, Dr. Michael F. Greene of Massachusetts General Hospital, Boston, said the findings of both studies make it clear that “neither SSRIs as a group nor individual SSRIs are major teratogens.

“Patients and physicians alike would prefer it if there were clear lines separating 'risk' and 'no risk' and if all studies gave consistent results pointing in the same direction. Unfortunately, this is often not the case, and the data to inform potential risks of SSRIs are no exception,” he said (N. Engl. J. Med. 2007;356:2732-3).

Even with the association found between paroxetine and right ventricular outflow obstruction, the malformation is so rare and the number of neonates exposed to the drug so small that the absolute incidence in exposed neonates “is unlikely to exceed 1%, and the incidence of all congenital heart defects is unlikely to exceed 2%,” Dr. Greene noted.

Eating a small piece of dark chocolate every day reduced systolic and diastolic blood pressure in a randomized, controlled study of older people who had prehypertension or stage 1 hypertension.

The “dose” was too small to adversely affect glucose metabolism or insulin sensitivity, and it did not cause weight gain, German investigators reported in the July 4 issue of the Journal of the American Medical Association.

The magnitude of the chocolate's effect was comparable with that of “comprehensive dietary modifications that have proven efficacy to reduce cardiovascular event rate.”

Moreover, whereas “long-term adherence to complex behavioral changes is often low and requires continuous counseling, [the adoption] of small amounts of flavanol-rich cocoa into the habitual diet is a dietary modification that is easy to adhere to and therefore may be a promising behavioral approach,” wrote Dr. Dirk Taubert and his associates at the University Hospital of Cologne (Germany).

The investigators studied chocolate's effect in 20 men and 24 women aged 55-75 years who were in good general health, except for having prehypertension (blood pressure of 130/85 to 139/89 mm Hg) or stage 1 hypertension (blood pressure of 140/90 to 160/100 mm Hg). The subjects were not taking any antihypertensive medications and had normal plasma lipid and plasma glucose levels.

Study participants were randomly assigned to eat a single 6.3-g dose–1 piece of a 16-piece bar weighing 100 g–of commercially available polyphenol-rich dark chocolate or a similar-sized dose of polyphenol-free white chocolate every day for 18 weeks. They were instructed to eat the candy 2 hours after their evening meal, to abstain from other cocoa products, and to maintain their usual diet and physical activity throughout the course of the clinical trial.

Both systolic and diastolic blood pressure declined steadily over time in the participants who ate dark chocolate, but not in those who ate white chocolate.

By the end of the study, systolic blood pressure had declined by a mean of 2.9 mm Hg, and diastolic pressure by a mean of 1.9 mm Hg; these differences from baseline were statistically significant.

After 18 weeks, all 22 of the subjects in the dark-chocolate group had lower blood pressure readings than at baseline, and 4 (18%) no longer qualified as hypertensive. This corresponds to a 21% relative risk reduction (JAMA 2007;298:49-60).

“Although the magnitude of the [blood pressure] reduction was small, the effects are clinically noteworthy. On a population basis, it has been estimated that a 3-mm Hg reduction in systolic BP would reduce the relative risk of stroke mortality by 8%, of coronary artery disease mortality by 5%, and of all-cause mortality by 4%,” the investigators noted.

“It is likely that the cocoa flavanols in dark chocolate were responsible for the observed effects” on blood pressure, the researchers wrote.

Previous research has suggested that cocoa flavonols may enhance the formation of endothelial nitric oxide, leading to vasodilation.

Study participants ate 6.3 g daily, or 1 piece of a 16-piece bar. Vivian E. Lee/Elsevier Global Medical News

Eating a small piece of dark chocolate every day reduced systolic and diastolic blood pressure in a randomized, controlled study of older people who had prehypertension or stage 1 hypertension.

The “dose” was too small to adversely affect glucose metabolism or insulin sensitivity, and it did not cause weight gain, German investigators reported in the July 4 issue of the Journal of the American Medical Association.

The magnitude of the chocolate's effect was comparable with that of “comprehensive dietary modifications that have proven efficacy to reduce cardiovascular event rate.”

Moreover, whereas “long-term adherence to complex behavioral changes is often low and requires continuous counseling, [the adoption] of small amounts of flavanol-rich cocoa into the habitual diet is a dietary modification that is easy to adhere to and therefore may be a promising behavioral approach,” wrote Dr. Dirk Taubert and his associates at the University Hospital of Cologne (Germany).

The investigators studied chocolate's effect in 20 men and 24 women aged 55-75 years who were in good general health, except for having prehypertension (blood pressure of 130/85 to 139/89 mm Hg) or stage 1 hypertension (blood pressure of 140/90 to 160/100 mm Hg). The subjects were not taking any antihypertensive medications and had normal plasma lipid and plasma glucose levels.

Study participants were randomly assigned to eat a single 6.3-g dose–1 piece of a 16-piece bar weighing 100 g–of commercially available polyphenol-rich dark chocolate or a similar-sized dose of polyphenol-free white chocolate every day for 18 weeks. They were instructed to eat the candy 2 hours after their evening meal, to abstain from other cocoa products, and to maintain their usual diet and physical activity throughout the course of the clinical trial.

Both systolic and diastolic blood pressure declined steadily over time in the participants who ate dark chocolate, but not in those who ate white chocolate.

By the end of the study, systolic blood pressure had declined by a mean of 2.9 mm Hg, and diastolic pressure by a mean of 1.9 mm Hg; these differences from baseline were statistically significant.

After 18 weeks, all 22 of the subjects in the dark-chocolate group had lower blood pressure readings than at baseline, and 4 (18%) no longer qualified as hypertensive. This corresponds to a 21% relative risk reduction (JAMA 2007;298:49-60).

“Although the magnitude of the [blood pressure] reduction was small, the effects are clinically noteworthy. On a population basis, it has been estimated that a 3-mm Hg reduction in systolic BP would reduce the relative risk of stroke mortality by 8%, of coronary artery disease mortality by 5%, and of all-cause mortality by 4%,” the investigators noted.

“It is likely that the cocoa flavanols in dark chocolate were responsible for the observed effects” on blood pressure, the researchers wrote.

Previous research has suggested that cocoa flavonols may enhance the formation of endothelial nitric oxide, leading to vasodilation.

Study participants ate 6.3 g daily, or 1 piece of a 16-piece bar. Vivian E. Lee/Elsevier Global Medical News

Eating a small piece of dark chocolate every day reduced systolic and diastolic blood pressure in a randomized, controlled study of older people who had prehypertension or stage 1 hypertension.

The “dose” was too small to adversely affect glucose metabolism or insulin sensitivity, and it did not cause weight gain, German investigators reported in the July 4 issue of the Journal of the American Medical Association.

The magnitude of the chocolate's effect was comparable with that of “comprehensive dietary modifications that have proven efficacy to reduce cardiovascular event rate.”

Moreover, whereas “long-term adherence to complex behavioral changes is often low and requires continuous counseling, [the adoption] of small amounts of flavanol-rich cocoa into the habitual diet is a dietary modification that is easy to adhere to and therefore may be a promising behavioral approach,” wrote Dr. Dirk Taubert and his associates at the University Hospital of Cologne (Germany).

The investigators studied chocolate's effect in 20 men and 24 women aged 55-75 years who were in good general health, except for having prehypertension (blood pressure of 130/85 to 139/89 mm Hg) or stage 1 hypertension (blood pressure of 140/90 to 160/100 mm Hg). The subjects were not taking any antihypertensive medications and had normal plasma lipid and plasma glucose levels.

Study participants were randomly assigned to eat a single 6.3-g dose–1 piece of a 16-piece bar weighing 100 g–of commercially available polyphenol-rich dark chocolate or a similar-sized dose of polyphenol-free white chocolate every day for 18 weeks. They were instructed to eat the candy 2 hours after their evening meal, to abstain from other cocoa products, and to maintain their usual diet and physical activity throughout the course of the clinical trial.

Both systolic and diastolic blood pressure declined steadily over time in the participants who ate dark chocolate, but not in those who ate white chocolate.

By the end of the study, systolic blood pressure had declined by a mean of 2.9 mm Hg, and diastolic pressure by a mean of 1.9 mm Hg; these differences from baseline were statistically significant.

After 18 weeks, all 22 of the subjects in the dark-chocolate group had lower blood pressure readings than at baseline, and 4 (18%) no longer qualified as hypertensive. This corresponds to a 21% relative risk reduction (JAMA 2007;298:49-60).

“Although the magnitude of the [blood pressure] reduction was small, the effects are clinically noteworthy. On a population basis, it has been estimated that a 3-mm Hg reduction in systolic BP would reduce the relative risk of stroke mortality by 8%, of coronary artery disease mortality by 5%, and of all-cause mortality by 4%,” the investigators noted.

“It is likely that the cocoa flavanols in dark chocolate were responsible for the observed effects” on blood pressure, the researchers wrote.

Previous research has suggested that cocoa flavonols may enhance the formation of endothelial nitric oxide, leading to vasodilation.

Study participants ate 6.3 g daily, or 1 piece of a 16-piece bar. Vivian E. Lee/Elsevier Global Medical News

Two large-scale studies of the possible teratogenic effects of selective serotonin reuptake inhibitors have concluded that the absolute risk of birth defects related to the drugs is small.

Neither study could confirm previously reported associations between SSRIs and heart defects. Both suggested that a few individual SSRIs might raise the risk of a few specific defects, but these malformations are so rare that even a large increase in risk would still put the chance of having an affected child at well under 1%, the researchers said in separate reports.

In the first report, Carol Louik, Sc.D., of Boston University's Slone Epidemiology Center, and associates analyzed data from the center's Birth Defects Study, an ongoing case-control surveillance program of a wide range of malformations, which covers areas surrounding Boston, Philadelphia, Toronto, San Diego, and a portion of New York State. The researchers focused on births that occurred between 1993 and 2004, which included 9,849 neonates with malformations and 5,860 neonates without malformations who served as controls.

They found no association between maternal use of SSRIs during pregnancy and heart defects as a whole, nor was there any association with craniosynostosis, omphalocele, or neural tube defects. However, the use of sertraline raised the risk of a single heart defect (cardiac septal defect), based on 13 cases, and the use of paroxetine raised the risk of another single heart defect (right ventricular outflow tract obstruction), based on 6 cases.

In addition, the data “suggested” possible links between sertraline and both anal atresia and limb-reduction defects, and possible links between paroxetine and both neural-tube defects and clubfoot.

Despite the relatively large study population, the investigators said they had limited numbers to evaluate associations between rare outcomes and exposures. “We included results based on small numbers of exposed subjects in order to allow other researchers to compare their observations with ours, but we caution that these estimates should not be interpreted as strong evidence of increased risks,” Dr. Louik and associates said (N. Engl. J. Med. 2007;356:2675–83).

In any case, “it is important to keep in perspective that the absolute risks of these rare defects are small. For example, the baseline prevalences of anal atresia and right ventricular outflow tract obstruction defects are each estimated to be about 5.5 cases per 10,000 live births; thus, even if a specific SSRI increased rates by a factor of four, the risk of having an affected child would still be only 0.2%,” they noted.

In the second study, Sura Alwan of the University of British Columbia, Vancouver, and associates analyzed data from the National Birth Defects Prevention Study on infants born between 1997 and 2002 in eight study sites throughout the United States. This included 9,622 neonates with birth defects and 4,092 without birth defects who served as controls.

Again, no associations were found between SSRIs and most of the birth defects assessed, including heart defects as a group. However, a small but significant association was found between paroxetine use and right ventricular outflow tract obstruction, based on six cases.

There also were small but significant associations with anencephaly (based on 9 exposed neonates), craniosynostosis (based on 24 exposed neonates), and omphalocele (based on 11 exposed neonates).

“Our study did not show an increased risk of most birth defects, and SSRI exposure was present in only a small number of cases of certain defects. The absolute risks associated with SSRIs appear small in comparison with the baseline risks of birth defects that exist in every pregnancy,” the researchers reported (N. Engl. J. Med. 2007;356:2684–92).

In an editorial comment accompanying this report, Dr. Michael F. Greene of Massachusetts General Hospital, Boston, said the findings of both studies make it clear that “neither SSRIs as a group nor individual SSRIs are major teratogens.” Even with the association found between paroxetine and right ventricular outflow obstruction, the malformation is so rare and the number of neonates exposed to the drug so small that the absolute incidence in exposed neonates “is unlikely to exceed 1%, and the incidence of all congenital heart defects is unlikely to exceed 2%,” he noted (N. Engl. J. Med. 2007;356:2732–3).

Two large-scale studies of the possible teratogenic effects of selective serotonin reuptake inhibitors have concluded that the absolute risk of birth defects related to the drugs is small.

Neither study could confirm previously reported associations between SSRIs and heart defects. Both suggested that a few individual SSRIs might raise the risk of a few specific defects, but these malformations are so rare that even a large increase in risk would still put the chance of having an affected child at well under 1%, the researchers said in separate reports.

In the first report, Carol Louik, Sc.D., of Boston University's Slone Epidemiology Center, and associates analyzed data from the center's Birth Defects Study, an ongoing case-control surveillance program of a wide range of malformations, which covers areas surrounding Boston, Philadelphia, Toronto, San Diego, and a portion of New York State. The researchers focused on births that occurred between 1993 and 2004, which included 9,849 neonates with malformations and 5,860 neonates without malformations who served as controls.

They found no association between maternal use of SSRIs during pregnancy and heart defects as a whole, nor was there any association with craniosynostosis, omphalocele, or neural tube defects. However, the use of sertraline raised the risk of a single heart defect (cardiac septal defect), based on 13 cases, and the use of paroxetine raised the risk of another single heart defect (right ventricular outflow tract obstruction), based on 6 cases.

In addition, the data “suggested” possible links between sertraline and both anal atresia and limb-reduction defects, and possible links between paroxetine and both neural-tube defects and clubfoot.

Despite the relatively large study population, the investigators said they had limited numbers to evaluate associations between rare outcomes and exposures. “We included results based on small numbers of exposed subjects in order to allow other researchers to compare their observations with ours, but we caution that these estimates should not be interpreted as strong evidence of increased risks,” Dr. Louik and associates said (N. Engl. J. Med. 2007;356:2675–83).

In any case, “it is important to keep in perspective that the absolute risks of these rare defects are small. For example, the baseline prevalences of anal atresia and right ventricular outflow tract obstruction defects are each estimated to be about 5.5 cases per 10,000 live births; thus, even if a specific SSRI increased rates by a factor of four, the risk of having an affected child would still be only 0.2%,” they noted.

In the second study, Sura Alwan of the University of British Columbia, Vancouver, and associates analyzed data from the National Birth Defects Prevention Study on infants born between 1997 and 2002 in eight study sites throughout the United States. This included 9,622 neonates with birth defects and 4,092 without birth defects who served as controls.

Again, no associations were found between SSRIs and most of the birth defects assessed, including heart defects as a group. However, a small but significant association was found between paroxetine use and right ventricular outflow tract obstruction, based on six cases.

There also were small but significant associations with anencephaly (based on 9 exposed neonates), craniosynostosis (based on 24 exposed neonates), and omphalocele (based on 11 exposed neonates).

“Our study did not show an increased risk of most birth defects, and SSRI exposure was present in only a small number of cases of certain defects. The absolute risks associated with SSRIs appear small in comparison with the baseline risks of birth defects that exist in every pregnancy,” the researchers reported (N. Engl. J. Med. 2007;356:2684–92).

In an editorial comment accompanying this report, Dr. Michael F. Greene of Massachusetts General Hospital, Boston, said the findings of both studies make it clear that “neither SSRIs as a group nor individual SSRIs are major teratogens.” Even with the association found between paroxetine and right ventricular outflow obstruction, the malformation is so rare and the number of neonates exposed to the drug so small that the absolute incidence in exposed neonates “is unlikely to exceed 1%, and the incidence of all congenital heart defects is unlikely to exceed 2%,” he noted (N. Engl. J. Med. 2007;356:2732–3).

Two large-scale studies of the possible teratogenic effects of selective serotonin reuptake inhibitors have concluded that the absolute risk of birth defects related to the drugs is small.

Neither study could confirm previously reported associations between SSRIs and heart defects. Both suggested that a few individual SSRIs might raise the risk of a few specific defects, but these malformations are so rare that even a large increase in risk would still put the chance of having an affected child at well under 1%, the researchers said in separate reports.

In the first report, Carol Louik, Sc.D., of Boston University's Slone Epidemiology Center, and associates analyzed data from the center's Birth Defects Study, an ongoing case-control surveillance program of a wide range of malformations, which covers areas surrounding Boston, Philadelphia, Toronto, San Diego, and a portion of New York State. The researchers focused on births that occurred between 1993 and 2004, which included 9,849 neonates with malformations and 5,860 neonates without malformations who served as controls.

They found no association between maternal use of SSRIs during pregnancy and heart defects as a whole, nor was there any association with craniosynostosis, omphalocele, or neural tube defects. However, the use of sertraline raised the risk of a single heart defect (cardiac septal defect), based on 13 cases, and the use of paroxetine raised the risk of another single heart defect (right ventricular outflow tract obstruction), based on 6 cases.

In addition, the data “suggested” possible links between sertraline and both anal atresia and limb-reduction defects, and possible links between paroxetine and both neural-tube defects and clubfoot.

Despite the relatively large study population, the investigators said they had limited numbers to evaluate associations between rare outcomes and exposures. “We included results based on small numbers of exposed subjects in order to allow other researchers to compare their observations with ours, but we caution that these estimates should not be interpreted as strong evidence of increased risks,” Dr. Louik and associates said (N. Engl. J. Med. 2007;356:2675–83).

In any case, “it is important to keep in perspective that the absolute risks of these rare defects are small. For example, the baseline prevalences of anal atresia and right ventricular outflow tract obstruction defects are each estimated to be about 5.5 cases per 10,000 live births; thus, even if a specific SSRI increased rates by a factor of four, the risk of having an affected child would still be only 0.2%,” they noted.

In the second study, Sura Alwan of the University of British Columbia, Vancouver, and associates analyzed data from the National Birth Defects Prevention Study on infants born between 1997 and 2002 in eight study sites throughout the United States. This included 9,622 neonates with birth defects and 4,092 without birth defects who served as controls.

Again, no associations were found between SSRIs and most of the birth defects assessed, including heart defects as a group. However, a small but significant association was found between paroxetine use and right ventricular outflow tract obstruction, based on six cases.

There also were small but significant associations with anencephaly (based on 9 exposed neonates), craniosynostosis (based on 24 exposed neonates), and omphalocele (based on 11 exposed neonates).

“Our study did not show an increased risk of most birth defects, and SSRI exposure was present in only a small number of cases of certain defects. The absolute risks associated with SSRIs appear small in comparison with the baseline risks of birth defects that exist in every pregnancy,” the researchers reported (N. Engl. J. Med. 2007;356:2684–92).

In an editorial comment accompanying this report, Dr. Michael F. Greene of Massachusetts General Hospital, Boston, said the findings of both studies make it clear that “neither SSRIs as a group nor individual SSRIs are major teratogens.” Even with the association found between paroxetine and right ventricular outflow obstruction, the malformation is so rare and the number of neonates exposed to the drug so small that the absolute incidence in exposed neonates “is unlikely to exceed 1%, and the incidence of all congenital heart defects is unlikely to exceed 2%,” he noted (N. Engl. J. Med. 2007;356:2732–3).

Women who initiated hormone therapy during their 50s showed a lower prevalence of coronary plaque and less extensive calcification 8 years later than did those who took placebo, reported Dr. JoAnn E. Manson and her associates in the WHI-CACS trial.

The findings support the hypothesis that estrogen therapy is cardioprotective in younger but not older postmenopausal women. They “provide some reassurance that estrogen is unlikely to have an adverse effect on the risk of coronary events among women who have recently undergone menopause and are considering hormone therapy for the treatment of menopausal symptoms,” the researchers said.

A total of 1,064 women, who had been age 50–59 years at randomization for Women's Health Initiative and were recruited to participate in The WHI-Coronary Artery Calcium Study, underwent CT assessment of coronary plaque at a mean age of 65 years, approximately 8 years after they had been randomized to receive either estrogen or placebo. The intention-to-treat analysis showed that women who had taken estrogen therapy were 42% less likely to have high levels of coronary calcification than were women who had taken placebo.

In the subgroup of subjects who had been most adherent to the study medication for at least 5 years, those who had taken estrogen were 61% less likely to have high levels of coronary calcification than were those who had taken placebo, the investigators said (N. Engl. J. Med. 2007;356:2591–602).

Subjects who took active medication also showed less extensive coronary calcification than did the placebo group.

“It is possible that estrogen could reduce coronary artery calcium scores but still increase the risk of clinical CHD events, owing to adverse effects on thrombosis and plaque rupture, which are more likely in older women with advanced stages of atherosclerosis. Such a duality of effects would not necessarily apply to younger women with lower burdens of atherosclerosis,” Dr. Manson and her associates said.

The investigators stressed that these new findings should not alter current hormone therapy recommendations.

Women who initiated hormone therapy during their 50s showed a lower prevalence of coronary plaque and less extensive calcification 8 years later than did those who took placebo, reported Dr. JoAnn E. Manson and her associates in the WHI-CACS trial.

The findings support the hypothesis that estrogen therapy is cardioprotective in younger but not older postmenopausal women. They “provide some reassurance that estrogen is unlikely to have an adverse effect on the risk of coronary events among women who have recently undergone menopause and are considering hormone therapy for the treatment of menopausal symptoms,” the researchers said.

A total of 1,064 women, who had been age 50–59 years at randomization for Women's Health Initiative and were recruited to participate in The WHI-Coronary Artery Calcium Study, underwent CT assessment of coronary plaque at a mean age of 65 years, approximately 8 years after they had been randomized to receive either estrogen or placebo. The intention-to-treat analysis showed that women who had taken estrogen therapy were 42% less likely to have high levels of coronary calcification than were women who had taken placebo.

In the subgroup of subjects who had been most adherent to the study medication for at least 5 years, those who had taken estrogen were 61% less likely to have high levels of coronary calcification than were those who had taken placebo, the investigators said (N. Engl. J. Med. 2007;356:2591–602).

Subjects who took active medication also showed less extensive coronary calcification than did the placebo group.

“It is possible that estrogen could reduce coronary artery calcium scores but still increase the risk of clinical CHD events, owing to adverse effects on thrombosis and plaque rupture, which are more likely in older women with advanced stages of atherosclerosis. Such a duality of effects would not necessarily apply to younger women with lower burdens of atherosclerosis,” Dr. Manson and her associates said.

The investigators stressed that these new findings should not alter current hormone therapy recommendations.

Women who initiated hormone therapy during their 50s showed a lower prevalence of coronary plaque and less extensive calcification 8 years later than did those who took placebo, reported Dr. JoAnn E. Manson and her associates in the WHI-CACS trial.

The findings support the hypothesis that estrogen therapy is cardioprotective in younger but not older postmenopausal women. They “provide some reassurance that estrogen is unlikely to have an adverse effect on the risk of coronary events among women who have recently undergone menopause and are considering hormone therapy for the treatment of menopausal symptoms,” the researchers said.

A total of 1,064 women, who had been age 50–59 years at randomization for Women's Health Initiative and were recruited to participate in The WHI-Coronary Artery Calcium Study, underwent CT assessment of coronary plaque at a mean age of 65 years, approximately 8 years after they had been randomized to receive either estrogen or placebo. The intention-to-treat analysis showed that women who had taken estrogen therapy were 42% less likely to have high levels of coronary calcification than were women who had taken placebo.

In the subgroup of subjects who had been most adherent to the study medication for at least 5 years, those who had taken estrogen were 61% less likely to have high levels of coronary calcification than were those who had taken placebo, the investigators said (N. Engl. J. Med. 2007;356:2591–602).

Subjects who took active medication also showed less extensive coronary calcification than did the placebo group.

“It is possible that estrogen could reduce coronary artery calcium scores but still increase the risk of clinical CHD events, owing to adverse effects on thrombosis and plaque rupture, which are more likely in older women with advanced stages of atherosclerosis. Such a duality of effects would not necessarily apply to younger women with lower burdens of atherosclerosis,” Dr. Manson and her associates said.

The investigators stressed that these new findings should not alter current hormone therapy recommendations.

Symptom-driven “rescue” use of a single inhaler containing beclomethasone plus albuterol was as effective at controlling mild persistent asthma as was regular twice-daily use of inhaled beclomethasone alone in a prospective, randomized study.

As-needed use of the combination inhaler led to significantly lower cumulative exposure to corticosteroids. In addition, “symptom-driven use of inhaled beclomethasone and albuterol may overcome one of the major problems in the treatment of chronic diseases such as asthma: poor compliance,” the investigators wrote.

Dr. Alberto Papi of the University of Ferrara (Italy) and colleagues compared outcomes with four different inhaler treatments in a 6-month study of 393 adults with mild persistent asthma who were treated at 25 centers in Europe in 2002–2004. The participants were randomly assigned to one of four treatment groups: as-needed combination therapy (250 mcg beclomethasone and 100 mcg albuterol in a single inhaler), regular twice daily combination therapy plus albuterol as needed, regular beclomethasone therapy (250 mcg twice daily) and albuterol as needed, or placebo twice daily plus albuterol as needed.

After 6 months, morning peak expiratory flow rate (primary outcome measure) did not differ significantly between the as-needed combination therapy group and the regular twice-daily beclomethasone or regular combination therapy groups, suggesting “mild persistent asthma may not require regular treatment with inhaled corticosteroids, but rather only as-needed use of an inhaled corticosteroid and an inhaled bronchodilator” (N. Engl. J. Med. 2007;356:2040–52). Chiesi Farmaceutici funded the study.

Symptom-driven “rescue” use of a single inhaler containing beclomethasone plus albuterol was as effective at controlling mild persistent asthma as was regular twice-daily use of inhaled beclomethasone alone in a prospective, randomized study.

As-needed use of the combination inhaler led to significantly lower cumulative exposure to corticosteroids. In addition, “symptom-driven use of inhaled beclomethasone and albuterol may overcome one of the major problems in the treatment of chronic diseases such as asthma: poor compliance,” the investigators wrote.

Dr. Alberto Papi of the University of Ferrara (Italy) and colleagues compared outcomes with four different inhaler treatments in a 6-month study of 393 adults with mild persistent asthma who were treated at 25 centers in Europe in 2002–2004. The participants were randomly assigned to one of four treatment groups: as-needed combination therapy (250 mcg beclomethasone and 100 mcg albuterol in a single inhaler), regular twice daily combination therapy plus albuterol as needed, regular beclomethasone therapy (250 mcg twice daily) and albuterol as needed, or placebo twice daily plus albuterol as needed.

After 6 months, morning peak expiratory flow rate (primary outcome measure) did not differ significantly between the as-needed combination therapy group and the regular twice-daily beclomethasone or regular combination therapy groups, suggesting “mild persistent asthma may not require regular treatment with inhaled corticosteroids, but rather only as-needed use of an inhaled corticosteroid and an inhaled bronchodilator” (N. Engl. J. Med. 2007;356:2040–52). Chiesi Farmaceutici funded the study.

Symptom-driven “rescue” use of a single inhaler containing beclomethasone plus albuterol was as effective at controlling mild persistent asthma as was regular twice-daily use of inhaled beclomethasone alone in a prospective, randomized study.

As-needed use of the combination inhaler led to significantly lower cumulative exposure to corticosteroids. In addition, “symptom-driven use of inhaled beclomethasone and albuterol may overcome one of the major problems in the treatment of chronic diseases such as asthma: poor compliance,” the investigators wrote.

Dr. Alberto Papi of the University of Ferrara (Italy) and colleagues compared outcomes with four different inhaler treatments in a 6-month study of 393 adults with mild persistent asthma who were treated at 25 centers in Europe in 2002–2004. The participants were randomly assigned to one of four treatment groups: as-needed combination therapy (250 mcg beclomethasone and 100 mcg albuterol in a single inhaler), regular twice daily combination therapy plus albuterol as needed, regular beclomethasone therapy (250 mcg twice daily) and albuterol as needed, or placebo twice daily plus albuterol as needed.

After 6 months, morning peak expiratory flow rate (primary outcome measure) did not differ significantly between the as-needed combination therapy group and the regular twice-daily beclomethasone or regular combination therapy groups, suggesting “mild persistent asthma may not require regular treatment with inhaled corticosteroids, but rather only as-needed use of an inhaled corticosteroid and an inhaled bronchodilator” (N. Engl. J. Med. 2007;356:2040–52). Chiesi Farmaceutici funded the study.

Urban adolescent girls who have been hit or physically hurt by a boyfriend in the past year are 60% more likely to attempt suicide than those who have not, reported Dr. Elyse Olshen of Columbia University, New York, and her associates.

For urban adolescent boys, date violence does not raise the risk of attempted suicide, but a history of being sexually assaulted does. And for both boys and girls, those who say they are gay, lesbian, bisexual, or unsure of their sexual orientation are more likely to attempt suicide than are those who identify themselves as heterosexual.

Clinicians “should have a low threshold for referring these at-risk teenagers for mental health services,” the researchers said. One way to avoid these problems is to routinely screen urban youths for these risk factors, they said.

Dr. Olshen and her associates examined the relationships among dating violence, sexual assault, and suicide attempts using data from the 2005 National Youth Risk Behavior Survey, a biennial survey of public high school students conducted in states and localities across the United States and supported by the Centers for Disease Control and Prevention. They analyzed the results from a New York City sample that was predominantly African American and Hispanic–representative of that city's general high school population and generalizable to urban youth populations throughout the United States.

A total of 8,080 students from 87 New York City schools answered the anonymous and voluntary 99-item questionnaire. A total of 40% of girls and 24% of boys reported persistent sadness during the preceding year, and about 20% of girls and 10% of boys reported suicidal ideation.

Nearly 12% of girls and more than 7% of boys reported one or more serious suicide attempts in the preceding year, the investigators said (Arch. Pediatr. Adolesc. Med. 2007;161:539–45).

Nearly 10% of girls and more than 5% of boys reported a lifetime history of sexual assault. The prevalence of dating violence in the preceding year was nearly 11% among girls and nearly 10% among boys.

Recent dating violence was associated with a 60% higher risk of attempted suicide among girls. “This association is similar in magnitude to that reported among predominantly white adolescent girls” in studies from two New England states, which suggests that there are no major racial or ethnic differences in the relationship between violent or sexual victimization and suicide attempts, Dr. Olshen and her associates said.

For adolescent boys, recent dating violence was not associated with suicide attempts, but a history of sexual victimization was. “These marked differences between adolescent boys and girls are striking and bear further investigation,” the researchers noted.

Urban adolescent girls who have been hit or physically hurt by a boyfriend in the past year are 60% more likely to attempt suicide than those who have not, reported Dr. Elyse Olshen of Columbia University, New York, and her associates.

For urban adolescent boys, date violence does not raise the risk of attempted suicide, but a history of being sexually assaulted does. And for both boys and girls, those who say they are gay, lesbian, bisexual, or unsure of their sexual orientation are more likely to attempt suicide than are those who identify themselves as heterosexual.

Clinicians “should have a low threshold for referring these at-risk teenagers for mental health services,” the researchers said. One way to avoid these problems is to routinely screen urban youths for these risk factors, they said.

Dr. Olshen and her associates examined the relationships among dating violence, sexual assault, and suicide attempts using data from the 2005 National Youth Risk Behavior Survey, a biennial survey of public high school students conducted in states and localities across the United States and supported by the Centers for Disease Control and Prevention. They analyzed the results from a New York City sample that was predominantly African American and Hispanic–representative of that city's general high school population and generalizable to urban youth populations throughout the United States.

A total of 8,080 students from 87 New York City schools answered the anonymous and voluntary 99-item questionnaire. A total of 40% of girls and 24% of boys reported persistent sadness during the preceding year, and about 20% of girls and 10% of boys reported suicidal ideation.

Nearly 12% of girls and more than 7% of boys reported one or more serious suicide attempts in the preceding year, the investigators said (Arch. Pediatr. Adolesc. Med. 2007;161:539–45).

Nearly 10% of girls and more than 5% of boys reported a lifetime history of sexual assault. The prevalence of dating violence in the preceding year was nearly 11% among girls and nearly 10% among boys.

Recent dating violence was associated with a 60% higher risk of attempted suicide among girls. “This association is similar in magnitude to that reported among predominantly white adolescent girls” in studies from two New England states, which suggests that there are no major racial or ethnic differences in the relationship between violent or sexual victimization and suicide attempts, Dr. Olshen and her associates said.

For adolescent boys, recent dating violence was not associated with suicide attempts, but a history of sexual victimization was. “These marked differences between adolescent boys and girls are striking and bear further investigation,” the researchers noted.

Urban adolescent girls who have been hit or physically hurt by a boyfriend in the past year are 60% more likely to attempt suicide than those who have not, reported Dr. Elyse Olshen of Columbia University, New York, and her associates.

For urban adolescent boys, date violence does not raise the risk of attempted suicide, but a history of being sexually assaulted does. And for both boys and girls, those who say they are gay, lesbian, bisexual, or unsure of their sexual orientation are more likely to attempt suicide than are those who identify themselves as heterosexual.

Clinicians “should have a low threshold for referring these at-risk teenagers for mental health services,” the researchers said. One way to avoid these problems is to routinely screen urban youths for these risk factors, they said.

Dr. Olshen and her associates examined the relationships among dating violence, sexual assault, and suicide attempts using data from the 2005 National Youth Risk Behavior Survey, a biennial survey of public high school students conducted in states and localities across the United States and supported by the Centers for Disease Control and Prevention. They analyzed the results from a New York City sample that was predominantly African American and Hispanic–representative of that city's general high school population and generalizable to urban youth populations throughout the United States.

A total of 8,080 students from 87 New York City schools answered the anonymous and voluntary 99-item questionnaire. A total of 40% of girls and 24% of boys reported persistent sadness during the preceding year, and about 20% of girls and 10% of boys reported suicidal ideation.

Nearly 12% of girls and more than 7% of boys reported one or more serious suicide attempts in the preceding year, the investigators said (Arch. Pediatr. Adolesc. Med. 2007;161:539–45).

Nearly 10% of girls and more than 5% of boys reported a lifetime history of sexual assault. The prevalence of dating violence in the preceding year was nearly 11% among girls and nearly 10% among boys.

Recent dating violence was associated with a 60% higher risk of attempted suicide among girls. “This association is similar in magnitude to that reported among predominantly white adolescent girls” in studies from two New England states, which suggests that there are no major racial or ethnic differences in the relationship between violent or sexual victimization and suicide attempts, Dr. Olshen and her associates said.

For adolescent boys, recent dating violence was not associated with suicide attempts, but a history of sexual victimization was. “These marked differences between adolescent boys and girls are striking and bear further investigation,” the researchers noted.

Breast MRI prompts beneficial changes in the surgical management of approximately 10% of women with newly diagnosed breast cancer, Dr. Karl Y. Bilimoria and his associates reported.

Preoperative breast MRI detected additional, otherwise undetectable malignancies in either the ipsilateral or the contralateral breast in 1 of 10 subjects in a study of 155 women with newly diagnosed breast cancer.

Still, the imaging procedure also carried a “considerable” 80% false-positive rate, heightening patient anxiety and leading to further diagnostic work-ups that ultimately proved to be unnecessary, wrote Dr. Bilimoria and his associates at Northwestern University, Chicago.

Of even more concern was the fact that the MRI results prompted more extensive surgery than originally planned in several cases in which it was later found that the less extensive surgery would have sufficed. These included two ipsilateral mastectomies and three contralateral prophylactic mastectomies that later proved to have been unnecessary.

To determine how routine breast MRI would affect surgical management of newly diagnosed breast cancer, the researchers reviewed data from 155 women aged 34–75 years who were diagnosed and treated by a single surgeon in 2005–2006. All had undergone “exhaustive” evaluation by mammography and ultrasonography, then biopsy of the suspicious lesion, after which a surgical plan had been developed (Arch. Surg. 2007;142:441–7).

At that juncture, bilateral breast MRI was performed. If any additional lesions were detected, the patient had second-look ultrasonography or mammography, followed in some cases by biopsy of the MRI-detected lesion. The original surgical plan could then be altered according to the results of these exams.

Overall, breast MRI changed the surgical plan in 36 (23%) of the study subjects. Ten women who initially were scheduled for breast-conserving therapy were “upgraded” to mastectomy, and 21 required a wider excision but still were able to have a lumpectomy. The remaining five had an MRI-detected lesion in the contralateral breast and underwent prophylactic mastectomy.

Pathologic findings showed that switching to more extensive surgery was appropriate because suspicious lesions proved to be malignant in 8 of the 10 who upgraded to mastectomy, 5 of the 21 who upgraded to wider excision, and 2 of the 5 who had prophylactic mastectomy of the contralateral breast. Thus, the change in surgical plan was deemed “beneficial” in 42% of the women who had such a change, which was approximately 10% of the entire study population, Dr. Bilimoria and his associates said.

“Therefore, 10 women must undergo a breast MRI for 1 to have a beneficial change in management,” they said.

The overall false-positive rate in this study was 80%, because 58 of the 73 MRI-detected suspicious lesions proved to be benign.

The researchers acknowledged that some experts would consider many of the malignant MRI-detected lesions to be clinically irrelevant. “However, if we believe that it is important to clear lumpectomy margins of microscopic disease to minimize the risk of local recurrence, it would follow that small foci detected on MRI also warrant identification and excision,” they said.

In a written discussion accompanying this report, Dr. Baiba J. Grube of Yale University, New Haven, Conn., said that although the authors deemed changes in the surgery plan to be “beneficial” if suspicious lesions proved to be malignant, clinicians should do so only if the surgical “upgrades” improved patient survival or quality of life—two factors that were not addressed in this study (Arch. Surg. 2007;142:445–6).

Breast MRI prompts beneficial changes in the surgical management of approximately 10% of women with newly diagnosed breast cancer, Dr. Karl Y. Bilimoria and his associates reported.

Preoperative breast MRI detected additional, otherwise undetectable malignancies in either the ipsilateral or the contralateral breast in 1 of 10 subjects in a study of 155 women with newly diagnosed breast cancer.

Still, the imaging procedure also carried a “considerable” 80% false-positive rate, heightening patient anxiety and leading to further diagnostic work-ups that ultimately proved to be unnecessary, wrote Dr. Bilimoria and his associates at Northwestern University, Chicago.

Of even more concern was the fact that the MRI results prompted more extensive surgery than originally planned in several cases in which it was later found that the less extensive surgery would have sufficed. These included two ipsilateral mastectomies and three contralateral prophylactic mastectomies that later proved to have been unnecessary.

To determine how routine breast MRI would affect surgical management of newly diagnosed breast cancer, the researchers reviewed data from 155 women aged 34–75 years who were diagnosed and treated by a single surgeon in 2005–2006. All had undergone “exhaustive” evaluation by mammography and ultrasonography, then biopsy of the suspicious lesion, after which a surgical plan had been developed (Arch. Surg. 2007;142:441–7).

At that juncture, bilateral breast MRI was performed. If any additional lesions were detected, the patient had second-look ultrasonography or mammography, followed in some cases by biopsy of the MRI-detected lesion. The original surgical plan could then be altered according to the results of these exams.

Overall, breast MRI changed the surgical plan in 36 (23%) of the study subjects. Ten women who initially were scheduled for breast-conserving therapy were “upgraded” to mastectomy, and 21 required a wider excision but still were able to have a lumpectomy. The remaining five had an MRI-detected lesion in the contralateral breast and underwent prophylactic mastectomy.

Pathologic findings showed that switching to more extensive surgery was appropriate because suspicious lesions proved to be malignant in 8 of the 10 who upgraded to mastectomy, 5 of the 21 who upgraded to wider excision, and 2 of the 5 who had prophylactic mastectomy of the contralateral breast. Thus, the change in surgical plan was deemed “beneficial” in 42% of the women who had such a change, which was approximately 10% of the entire study population, Dr. Bilimoria and his associates said.

“Therefore, 10 women must undergo a breast MRI for 1 to have a beneficial change in management,” they said.

The overall false-positive rate in this study was 80%, because 58 of the 73 MRI-detected suspicious lesions proved to be benign.

The researchers acknowledged that some experts would consider many of the malignant MRI-detected lesions to be clinically irrelevant. “However, if we believe that it is important to clear lumpectomy margins of microscopic disease to minimize the risk of local recurrence, it would follow that small foci detected on MRI also warrant identification and excision,” they said.

In a written discussion accompanying this report, Dr. Baiba J. Grube of Yale University, New Haven, Conn., said that although the authors deemed changes in the surgery plan to be “beneficial” if suspicious lesions proved to be malignant, clinicians should do so only if the surgical “upgrades” improved patient survival or quality of life—two factors that were not addressed in this study (Arch. Surg. 2007;142:445–6).

Breast MRI prompts beneficial changes in the surgical management of approximately 10% of women with newly diagnosed breast cancer, Dr. Karl Y. Bilimoria and his associates reported.

Preoperative breast MRI detected additional, otherwise undetectable malignancies in either the ipsilateral or the contralateral breast in 1 of 10 subjects in a study of 155 women with newly diagnosed breast cancer.

Still, the imaging procedure also carried a “considerable” 80% false-positive rate, heightening patient anxiety and leading to further diagnostic work-ups that ultimately proved to be unnecessary, wrote Dr. Bilimoria and his associates at Northwestern University, Chicago.

Of even more concern was the fact that the MRI results prompted more extensive surgery than originally planned in several cases in which it was later found that the less extensive surgery would have sufficed. These included two ipsilateral mastectomies and three contralateral prophylactic mastectomies that later proved to have been unnecessary.

To determine how routine breast MRI would affect surgical management of newly diagnosed breast cancer, the researchers reviewed data from 155 women aged 34–75 years who were diagnosed and treated by a single surgeon in 2005–2006. All had undergone “exhaustive” evaluation by mammography and ultrasonography, then biopsy of the suspicious lesion, after which a surgical plan had been developed (Arch. Surg. 2007;142:441–7).

At that juncture, bilateral breast MRI was performed. If any additional lesions were detected, the patient had second-look ultrasonography or mammography, followed in some cases by biopsy of the MRI-detected lesion. The original surgical plan could then be altered according to the results of these exams.

Overall, breast MRI changed the surgical plan in 36 (23%) of the study subjects. Ten women who initially were scheduled for breast-conserving therapy were “upgraded” to mastectomy, and 21 required a wider excision but still were able to have a lumpectomy. The remaining five had an MRI-detected lesion in the contralateral breast and underwent prophylactic mastectomy.

Pathologic findings showed that switching to more extensive surgery was appropriate because suspicious lesions proved to be malignant in 8 of the 10 who upgraded to mastectomy, 5 of the 21 who upgraded to wider excision, and 2 of the 5 who had prophylactic mastectomy of the contralateral breast. Thus, the change in surgical plan was deemed “beneficial” in 42% of the women who had such a change, which was approximately 10% of the entire study population, Dr. Bilimoria and his associates said.

“Therefore, 10 women must undergo a breast MRI for 1 to have a beneficial change in management,” they said.

The overall false-positive rate in this study was 80%, because 58 of the 73 MRI-detected suspicious lesions proved to be benign.

The researchers acknowledged that some experts would consider many of the malignant MRI-detected lesions to be clinically irrelevant. “However, if we believe that it is important to clear lumpectomy margins of microscopic disease to minimize the risk of local recurrence, it would follow that small foci detected on MRI also warrant identification and excision,” they said.

In a written discussion accompanying this report, Dr. Baiba J. Grube of Yale University, New Haven, Conn., said that although the authors deemed changes in the surgery plan to be “beneficial” if suspicious lesions proved to be malignant, clinicians should do so only if the surgical “upgrades” improved patient survival or quality of life—two factors that were not addressed in this study (Arch. Surg. 2007;142:445–6).

High intakes of calcium and vitamin D were associated with lower breast cancer risk in premenopausal women in a large prospective study of more than 30,000 women.

The decreased risk appears to be most pronounced with aggressive breast tumors, study researchers wrote.

Animal studies have suggested that calcium and vitamin D may protect against breast cancer, but epidemiologic studies of the issue in humans have yielded conflicting results.

Jennifer Lin, Ph.D., of Harvard Medical School, Boston, and her associates used data from the Women's Health Study to examine intakes of the two nutrients in relation to breast cancer risk in more than 10,000 premenopausal and 20,000 postmenopausal subjects who were followed for an average of 10 years.

During that interval, 276 premenopausal and 743 postmenopausal women developed incident cases of invasive breast cancer.

Mean intakes of total calcium and vitamin D were 1,021 mg/day and 353 IU/day, respectively.

Among premenopausal women, there was a moderate association between lower risk of breast cancer and higher consumption of dietary and supplemental calcium and vitamin D.

When the women were divided into quintiles based on consumption, the multivariate hazard ratios in the highest quintile group relative to the lowest one were 0.61 for total calcium and 0.65 for total vitamin D intake.

This association was most pronounced in women who had cancers larger than 2 cm, poorly differentiated tumors, or positive lymph nodes (Arch. Intern. Med. 2007;167:1050–9).

In contrast, among who were postmenopausal, consumption of calcium and vitamin D were not inversely associated with breast cancer, and tumor characteristics did not influence the relationship.

The reason why these nutrients may be linked to breast cancer risk only before menopause remains unknown, Dr. Lin and her associates said.

Research suggests that vitamin D may inhibit “late events of breast tumorigenesis,” and it also may enhance apoptosis and reduce the proliferation of tumor cells.

Similarly, calcium is thought to slow the progression of breast cancer by inhibiting the secretion of certain proteins that play a key role in the growth of advanced tumors and metastasis, they added.

These nutrients appear to lower breast cancer risk, but only before menopause. Lynda Banzi/Elsevier Global Medical News

High intakes of calcium and vitamin D were associated with lower breast cancer risk in premenopausal women in a large prospective study of more than 30,000 women.

The decreased risk appears to be most pronounced with aggressive breast tumors, study researchers wrote.

Animal studies have suggested that calcium and vitamin D may protect against breast cancer, but epidemiologic studies of the issue in humans have yielded conflicting results.

Jennifer Lin, Ph.D., of Harvard Medical School, Boston, and her associates used data from the Women's Health Study to examine intakes of the two nutrients in relation to breast cancer risk in more than 10,000 premenopausal and 20,000 postmenopausal subjects who were followed for an average of 10 years.

During that interval, 276 premenopausal and 743 postmenopausal women developed incident cases of invasive breast cancer.

Mean intakes of total calcium and vitamin D were 1,021 mg/day and 353 IU/day, respectively.

Among premenopausal women, there was a moderate association between lower risk of breast cancer and higher consumption of dietary and supplemental calcium and vitamin D.

When the women were divided into quintiles based on consumption, the multivariate hazard ratios in the highest quintile group relative to the lowest one were 0.61 for total calcium and 0.65 for total vitamin D intake.

This association was most pronounced in women who had cancers larger than 2 cm, poorly differentiated tumors, or positive lymph nodes (Arch. Intern. Med. 2007;167:1050–9).

In contrast, among who were postmenopausal, consumption of calcium and vitamin D were not inversely associated with breast cancer, and tumor characteristics did not influence the relationship.

The reason why these nutrients may be linked to breast cancer risk only before menopause remains unknown, Dr. Lin and her associates said.

Research suggests that vitamin D may inhibit “late events of breast tumorigenesis,” and it also may enhance apoptosis and reduce the proliferation of tumor cells.

Similarly, calcium is thought to slow the progression of breast cancer by inhibiting the secretion of certain proteins that play a key role in the growth of advanced tumors and metastasis, they added.

These nutrients appear to lower breast cancer risk, but only before menopause. Lynda Banzi/Elsevier Global Medical News

High intakes of calcium and vitamin D were associated with lower breast cancer risk in premenopausal women in a large prospective study of more than 30,000 women.

The decreased risk appears to be most pronounced with aggressive breast tumors, study researchers wrote.

Animal studies have suggested that calcium and vitamin D may protect against breast cancer, but epidemiologic studies of the issue in humans have yielded conflicting results.

Jennifer Lin, Ph.D., of Harvard Medical School, Boston, and her associates used data from the Women's Health Study to examine intakes of the two nutrients in relation to breast cancer risk in more than 10,000 premenopausal and 20,000 postmenopausal subjects who were followed for an average of 10 years.

During that interval, 276 premenopausal and 743 postmenopausal women developed incident cases of invasive breast cancer.

Mean intakes of total calcium and vitamin D were 1,021 mg/day and 353 IU/day, respectively.

Among premenopausal women, there was a moderate association between lower risk of breast cancer and higher consumption of dietary and supplemental calcium and vitamin D.

When the women were divided into quintiles based on consumption, the multivariate hazard ratios in the highest quintile group relative to the lowest one were 0.61 for total calcium and 0.65 for total vitamin D intake.

This association was most pronounced in women who had cancers larger than 2 cm, poorly differentiated tumors, or positive lymph nodes (Arch. Intern. Med. 2007;167:1050–9).

In contrast, among who were postmenopausal, consumption of calcium and vitamin D were not inversely associated with breast cancer, and tumor characteristics did not influence the relationship.

The reason why these nutrients may be linked to breast cancer risk only before menopause remains unknown, Dr. Lin and her associates said.

Research suggests that vitamin D may inhibit “late events of breast tumorigenesis,” and it also may enhance apoptosis and reduce the proliferation of tumor cells.

Similarly, calcium is thought to slow the progression of breast cancer by inhibiting the secretion of certain proteins that play a key role in the growth of advanced tumors and metastasis, they added.

These nutrients appear to lower breast cancer risk, but only before menopause. Lynda Banzi/Elsevier Global Medical News

High intake of cereal fiber is associated with a reduced risk of type 2 diabetes, independent of risk factors related to age, sex, and lifestyle, reported Dr. Matthias B. Schulze and his associates at the German Institute of Human Nutrition, in Potsdam-Rehbruecke.

In contrast, intake of fruit fiber and vegetable fiber are not significantly associated with diabetes risk, the researchers said.

Dr. Schulze and his associates analyzed data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study to examine the relationship between fiber consumption and diabetes risk. The EPIC study is a multicenter cohort diet study in members of the general European population first recruited in 1994–1998, when they were aged 35–65 years.

A subgroup of subjects in the Potsdam portion of the study was followed every 2–3 years to identify incident cases of diabetes. Dr. Schulze and his associates assessed 25,067 of these subjects. There were 844 incident cases of diabetes identified during a mean of 7 years of follow-up.

The study subjects were divided into quintiles according to their fiber intake. Cereal fiber consumption was inversely associated with diabetes risk. The relative risk for diabetes was 0.73 for subjects in the highest quintile of cereal fiber consumption, compared with those in the lowest quintile, the investigators said (Arch. Intern. Med. 2007;167:956–65).

In contrast, total fiber, fruit fiber, and vegetable fiber intake were not associated, either positively or negatively, with diabetes risk.

Dr. Schulze and his associates also conducted a meta-analysis of nine cohort studies concerning fiber intake and eight concerning magnesium intake and diabetes risk. The meta-analysis “showed an inverse association for cereal fiber and magnesium, but no beneficial effect of other fiber sources,” they noted.

High intake of cereal fiber is associated with a reduced risk of type 2 diabetes, independent of risk factors related to age, sex, and lifestyle, reported Dr. Matthias B. Schulze and his associates at the German Institute of Human Nutrition, in Potsdam-Rehbruecke.

In contrast, intake of fruit fiber and vegetable fiber are not significantly associated with diabetes risk, the researchers said.

Dr. Schulze and his associates analyzed data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study to examine the relationship between fiber consumption and diabetes risk. The EPIC study is a multicenter cohort diet study in members of the general European population first recruited in 1994–1998, when they were aged 35–65 years.

A subgroup of subjects in the Potsdam portion of the study was followed every 2–3 years to identify incident cases of diabetes. Dr. Schulze and his associates assessed 25,067 of these subjects. There were 844 incident cases of diabetes identified during a mean of 7 years of follow-up.

The study subjects were divided into quintiles according to their fiber intake. Cereal fiber consumption was inversely associated with diabetes risk. The relative risk for diabetes was 0.73 for subjects in the highest quintile of cereal fiber consumption, compared with those in the lowest quintile, the investigators said (Arch. Intern. Med. 2007;167:956–65).

In contrast, total fiber, fruit fiber, and vegetable fiber intake were not associated, either positively or negatively, with diabetes risk.

Dr. Schulze and his associates also conducted a meta-analysis of nine cohort studies concerning fiber intake and eight concerning magnesium intake and diabetes risk. The meta-analysis “showed an inverse association for cereal fiber and magnesium, but no beneficial effect of other fiber sources,” they noted.

High intake of cereal fiber is associated with a reduced risk of type 2 diabetes, independent of risk factors related to age, sex, and lifestyle, reported Dr. Matthias B. Schulze and his associates at the German Institute of Human Nutrition, in Potsdam-Rehbruecke.

In contrast, intake of fruit fiber and vegetable fiber are not significantly associated with diabetes risk, the researchers said.

Dr. Schulze and his associates analyzed data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study to examine the relationship between fiber consumption and diabetes risk. The EPIC study is a multicenter cohort diet study in members of the general European population first recruited in 1994–1998, when they were aged 35–65 years.

A subgroup of subjects in the Potsdam portion of the study was followed every 2–3 years to identify incident cases of diabetes. Dr. Schulze and his associates assessed 25,067 of these subjects. There were 844 incident cases of diabetes identified during a mean of 7 years of follow-up.

The study subjects were divided into quintiles according to their fiber intake. Cereal fiber consumption was inversely associated with diabetes risk. The relative risk for diabetes was 0.73 for subjects in the highest quintile of cereal fiber consumption, compared with those in the lowest quintile, the investigators said (Arch. Intern. Med. 2007;167:956–65).

In contrast, total fiber, fruit fiber, and vegetable fiber intake were not associated, either positively or negatively, with diabetes risk.

Dr. Schulze and his associates also conducted a meta-analysis of nine cohort studies concerning fiber intake and eight concerning magnesium intake and diabetes risk. The meta-analysis “showed an inverse association for cereal fiber and magnesium, but no beneficial effect of other fiber sources,” they noted.