Mary Ann Moon

The massive Women’s Health Initiative estrogen plus progestin clinical trial netted more than $37 billion in savings in the 10 years after it was published, largely by curtailing postmenopausal women’s use of combined hormone therapy, which in turn prevented 126,000 cases of breast cancer and 76,000 cardiovascular events, according to a report published online May 5 in Annals of Internal Medicine.

"The net health yield for women in the United States was approximately 145,000 more quality-of-life-years than would have occurred in the absence of the trial," said Joshua A. Roth, Ph.D., of the public health sciences division, Fred Hutchinson Cancer Research Center and Group Health Research Institute, Seattle, and his associates.

So even though the 2002 trial was one of the most expensive publicly funded studies ever – costing the National Institutes of Health an estimated $260 million in 2012 U.S. dollars – it yielded clinical and economic returns of approximately $140 for every dollar invested in it, they noted.

"Our findings suggest that large public research investments can yield considerable clinical and economic value when targeted to address research questions with great clinical relevance and public health effect," the investigators wrote.

One of the primary debates regarding public funding of research concerns its overall "returns" to society. To estimate the returns of the WHI-EP trial, Dr. Roth and his colleagues developed several mathematical models so they could simulate the 10-year health outcomes of American women aged 50-79 years if the study had never taken place – that is, if it had never been reported that combined hormone therapy (HT) raised the risks of cardiovascular disease, venous thromboembolism, and breast cancer (albeit reducing the risks of fracture and colon cancer).

Publication of those results led to an immediate 50% decrease in the use of combined HT and a continuing decline of 5%-10% per year thereafter, the researchers said.

They compared disease incidence, survival rates, and direct medical expenditures between a "WHI scenario" and a "no WHI scenario" to calculate the net economic and clinical returns of the trial through the year 2012.

Approximately 39.1 million women were eligible for combined HT during the study period. An estimated 5.2 million used combined HT in the WHI scenario, but 9.5 million would have used it if there had never been a WHI, given the usage trends during the years preceding the trial.

Relative to the no-WHI scenario, there were 126,000 fewer cases of breast cancer, 76,000 fewer cases of cardiovascular disease (CVD), and 80,000 fewer cases of venous thromboembolism in the WHI scenario. On the other side of the scale, there also were 263,000 more osteoporotic fractures and 15,000 more cases of colorectal cancer.

"Compared with the no-WHI scenario, the WHI scenario resulted in $35.2 billion in direct medical expenditure savings. Most of the savings came from fewer combined HT users and associated office visits ($26.2 billion), decreased breast cancer incidence ($4.5 billion), and decreased CVD incidence ($2.2 billion), offsetting increases in expenditures for greater fracture incidence ($4.8 billion) and colorectal cancer ($1.0 billion)," Dr. Roth and his associates said (Ann. Intern. Med. 2014;160:594-602).

The WHI scenario, compared with the no-WHI scenario, yielded 145,000 QALYs (quality-adjusted life-years), mainly because of the improved quality of life of women who avoided breast cancer and CVD. This greatly offset the reductions in QALYs that would have been due to increased fractures in the no-WHI scenario.

The net economic return of the WHI was calculated to be $37.1 billion. Savings from reduced use of combined HT drove the early economic value of the trial, and later value was driven by a combination of combined HT expenditure savings and QALY gains.

"This level of value was robust across plausible uncertainty ranges, and remained greater than $20 billion in all simulations that we evaluated," they wrote.

"Our analysis of the economic return from the WHI-EP trial suggests that, in certain circumstances, public investments in large prospective trials with high clinical and public health relevance could provide a similarly large positive rate of return in the long term," the investigators added.

The massive Women’s Health Initiative estrogen plus progestin clinical trial netted more than $37 billion in savings in the 10 years after it was published, largely by curtailing postmenopausal women’s use of combined hormone therapy, which in turn prevented 126,000 cases of breast cancer and 76,000 cardiovascular events, according to a report published online May 5 in Annals of Internal Medicine.

"The net health yield for women in the United States was approximately 145,000 more quality-of-life-years than would have occurred in the absence of the trial," said Joshua A. Roth, Ph.D., of the public health sciences division, Fred Hutchinson Cancer Research Center and Group Health Research Institute, Seattle, and his associates.

So even though the 2002 trial was one of the most expensive publicly funded studies ever – costing the National Institutes of Health an estimated $260 million in 2012 U.S. dollars – it yielded clinical and economic returns of approximately $140 for every dollar invested in it, they noted.

"Our findings suggest that large public research investments can yield considerable clinical and economic value when targeted to address research questions with great clinical relevance and public health effect," the investigators wrote.

One of the primary debates regarding public funding of research concerns its overall "returns" to society. To estimate the returns of the WHI-EP trial, Dr. Roth and his colleagues developed several mathematical models so they could simulate the 10-year health outcomes of American women aged 50-79 years if the study had never taken place – that is, if it had never been reported that combined hormone therapy (HT) raised the risks of cardiovascular disease, venous thromboembolism, and breast cancer (albeit reducing the risks of fracture and colon cancer).

Publication of those results led to an immediate 50% decrease in the use of combined HT and a continuing decline of 5%-10% per year thereafter, the researchers said.

They compared disease incidence, survival rates, and direct medical expenditures between a "WHI scenario" and a "no WHI scenario" to calculate the net economic and clinical returns of the trial through the year 2012.

Approximately 39.1 million women were eligible for combined HT during the study period. An estimated 5.2 million used combined HT in the WHI scenario, but 9.5 million would have used it if there had never been a WHI, given the usage trends during the years preceding the trial.

Relative to the no-WHI scenario, there were 126,000 fewer cases of breast cancer, 76,000 fewer cases of cardiovascular disease (CVD), and 80,000 fewer cases of venous thromboembolism in the WHI scenario. On the other side of the scale, there also were 263,000 more osteoporotic fractures and 15,000 more cases of colorectal cancer.

"Compared with the no-WHI scenario, the WHI scenario resulted in $35.2 billion in direct medical expenditure savings. Most of the savings came from fewer combined HT users and associated office visits ($26.2 billion), decreased breast cancer incidence ($4.5 billion), and decreased CVD incidence ($2.2 billion), offsetting increases in expenditures for greater fracture incidence ($4.8 billion) and colorectal cancer ($1.0 billion)," Dr. Roth and his associates said (Ann. Intern. Med. 2014;160:594-602).

The WHI scenario, compared with the no-WHI scenario, yielded 145,000 QALYs (quality-adjusted life-years), mainly because of the improved quality of life of women who avoided breast cancer and CVD. This greatly offset the reductions in QALYs that would have been due to increased fractures in the no-WHI scenario.

The net economic return of the WHI was calculated to be $37.1 billion. Savings from reduced use of combined HT drove the early economic value of the trial, and later value was driven by a combination of combined HT expenditure savings and QALY gains.

"This level of value was robust across plausible uncertainty ranges, and remained greater than $20 billion in all simulations that we evaluated," they wrote.

"Our analysis of the economic return from the WHI-EP trial suggests that, in certain circumstances, public investments in large prospective trials with high clinical and public health relevance could provide a similarly large positive rate of return in the long term," the investigators added.

The massive Women’s Health Initiative estrogen plus progestin clinical trial netted more than $37 billion in savings in the 10 years after it was published, largely by curtailing postmenopausal women’s use of combined hormone therapy, which in turn prevented 126,000 cases of breast cancer and 76,000 cardiovascular events, according to a report published online May 5 in Annals of Internal Medicine.

"The net health yield for women in the United States was approximately 145,000 more quality-of-life-years than would have occurred in the absence of the trial," said Joshua A. Roth, Ph.D., of the public health sciences division, Fred Hutchinson Cancer Research Center and Group Health Research Institute, Seattle, and his associates.

So even though the 2002 trial was one of the most expensive publicly funded studies ever – costing the National Institutes of Health an estimated $260 million in 2012 U.S. dollars – it yielded clinical and economic returns of approximately $140 for every dollar invested in it, they noted.

"Our findings suggest that large public research investments can yield considerable clinical and economic value when targeted to address research questions with great clinical relevance and public health effect," the investigators wrote.

One of the primary debates regarding public funding of research concerns its overall "returns" to society. To estimate the returns of the WHI-EP trial, Dr. Roth and his colleagues developed several mathematical models so they could simulate the 10-year health outcomes of American women aged 50-79 years if the study had never taken place – that is, if it had never been reported that combined hormone therapy (HT) raised the risks of cardiovascular disease, venous thromboembolism, and breast cancer (albeit reducing the risks of fracture and colon cancer).

Publication of those results led to an immediate 50% decrease in the use of combined HT and a continuing decline of 5%-10% per year thereafter, the researchers said.

They compared disease incidence, survival rates, and direct medical expenditures between a "WHI scenario" and a "no WHI scenario" to calculate the net economic and clinical returns of the trial through the year 2012.

Approximately 39.1 million women were eligible for combined HT during the study period. An estimated 5.2 million used combined HT in the WHI scenario, but 9.5 million would have used it if there had never been a WHI, given the usage trends during the years preceding the trial.

Relative to the no-WHI scenario, there were 126,000 fewer cases of breast cancer, 76,000 fewer cases of cardiovascular disease (CVD), and 80,000 fewer cases of venous thromboembolism in the WHI scenario. On the other side of the scale, there also were 263,000 more osteoporotic fractures and 15,000 more cases of colorectal cancer.

"Compared with the no-WHI scenario, the WHI scenario resulted in $35.2 billion in direct medical expenditure savings. Most of the savings came from fewer combined HT users and associated office visits ($26.2 billion), decreased breast cancer incidence ($4.5 billion), and decreased CVD incidence ($2.2 billion), offsetting increases in expenditures for greater fracture incidence ($4.8 billion) and colorectal cancer ($1.0 billion)," Dr. Roth and his associates said (Ann. Intern. Med. 2014;160:594-602).

The WHI scenario, compared with the no-WHI scenario, yielded 145,000 QALYs (quality-adjusted life-years), mainly because of the improved quality of life of women who avoided breast cancer and CVD. This greatly offset the reductions in QALYs that would have been due to increased fractures in the no-WHI scenario.

The net economic return of the WHI was calculated to be $37.1 billion. Savings from reduced use of combined HT drove the early economic value of the trial, and later value was driven by a combination of combined HT expenditure savings and QALY gains.

"This level of value was robust across plausible uncertainty ranges, and remained greater than $20 billion in all simulations that we evaluated," they wrote.

"Our analysis of the economic return from the WHI-EP trial suggests that, in certain circumstances, public investments in large prospective trials with high clinical and public health relevance could provide a similarly large positive rate of return in the long term," the investigators added.

Therapy with trastuzumab emtansine – a conjugate containing a recombinant HER2-receptor monoclonal antibody and a maytansinoid, which is now being used in numerous clinical trials involving patients with HER2-positive breast cancer—appears to cause nodular regenerative hyperplasia of the liver leading to portal hypertension in some patients, according to a report published online in the Journal of Clinical Oncology.

Two cases of this complication arising in women with recurrent or metastatic HER2-positive ductal carcinomas who were participating in phase II trials were reported by Dr. Jeremy Force and his associates at Indiana University, Indianapolis.

The first woman (age 66) received trastuzumab emtansine when breast cancer recurred despite initial lumpectomy with axillary lymph node dissection, chemotherapy, and radiation, then recurred again following multiple chemotherapy regimens. Abdominal CT showed a normal-appearing liver before trastuzumab emtansine was initiated. Months later the woman developed worsening abdominal pain and ascites, and noncirrhotic portal hypertension resulting from nodular regenerative hyperplasia was diagnosed. The therapy was discontinued, and the patient remains free of ascites 5 months later (J. Clin. Oncol. 2014 April 28 [doi:10.1200/JCO.2013.49.8543]).

The second woman (age 50) received trastuzumab emtansine when breast cancer metastasized 2 years after bilateral mastectomy and persisted despite multiple chemotherapy regimens. Abdominal CT showed only hepatic steatosis but no evidence of portal hypertension before trastuzumab emtansine was initiated. Within 1 month the patient showed elevated serum aminotransferase and thrombocytopenia but was asymptomatic. A surveillance CT 1 year later showed evidence of portal hypertension, and liver biopsy showed nodular regenerative hyperplasia. The therapy was discontinued, and within 1 month liver test results improved. The patient now shows no signs of ascites or liver decompensation, and thrombocytopenia has resolved.

Clinicians should maintain a high index of suspicion for drug-induced liver injury in patients undergoing treatment with trastuzumab emtansine and consider nodular regenerative hyperplasia if liver test abnormalities or signs of portal hypertension develop. "Early and accurate diagnosis is vital because both liver test abnormalities and portal hypertension seem to be reversible" when the drug is discontinued, Dr. Force and his associates said.

Dr. Force reported no financial conflicts of interest; his associates reported ties to Mochida, Genentech, Merck, Sanofi Aventis, Salix, Abbott, Eli Lilly, Pfizer, Vertex, Bristol-Myers Squibb, Intercept, and Gilead.

Therapy with trastuzumab emtansine – a conjugate containing a recombinant HER2-receptor monoclonal antibody and a maytansinoid, which is now being used in numerous clinical trials involving patients with HER2-positive breast cancer—appears to cause nodular regenerative hyperplasia of the liver leading to portal hypertension in some patients, according to a report published online in the Journal of Clinical Oncology.

Two cases of this complication arising in women with recurrent or metastatic HER2-positive ductal carcinomas who were participating in phase II trials were reported by Dr. Jeremy Force and his associates at Indiana University, Indianapolis.

The first woman (age 66) received trastuzumab emtansine when breast cancer recurred despite initial lumpectomy with axillary lymph node dissection, chemotherapy, and radiation, then recurred again following multiple chemotherapy regimens. Abdominal CT showed a normal-appearing liver before trastuzumab emtansine was initiated. Months later the woman developed worsening abdominal pain and ascites, and noncirrhotic portal hypertension resulting from nodular regenerative hyperplasia was diagnosed. The therapy was discontinued, and the patient remains free of ascites 5 months later (J. Clin. Oncol. 2014 April 28 [doi:10.1200/JCO.2013.49.8543]).

The second woman (age 50) received trastuzumab emtansine when breast cancer metastasized 2 years after bilateral mastectomy and persisted despite multiple chemotherapy regimens. Abdominal CT showed only hepatic steatosis but no evidence of portal hypertension before trastuzumab emtansine was initiated. Within 1 month the patient showed elevated serum aminotransferase and thrombocytopenia but was asymptomatic. A surveillance CT 1 year later showed evidence of portal hypertension, and liver biopsy showed nodular regenerative hyperplasia. The therapy was discontinued, and within 1 month liver test results improved. The patient now shows no signs of ascites or liver decompensation, and thrombocytopenia has resolved.

Clinicians should maintain a high index of suspicion for drug-induced liver injury in patients undergoing treatment with trastuzumab emtansine and consider nodular regenerative hyperplasia if liver test abnormalities or signs of portal hypertension develop. "Early and accurate diagnosis is vital because both liver test abnormalities and portal hypertension seem to be reversible" when the drug is discontinued, Dr. Force and his associates said.

Dr. Force reported no financial conflicts of interest; his associates reported ties to Mochida, Genentech, Merck, Sanofi Aventis, Salix, Abbott, Eli Lilly, Pfizer, Vertex, Bristol-Myers Squibb, Intercept, and Gilead.

Therapy with trastuzumab emtansine – a conjugate containing a recombinant HER2-receptor monoclonal antibody and a maytansinoid, which is now being used in numerous clinical trials involving patients with HER2-positive breast cancer—appears to cause nodular regenerative hyperplasia of the liver leading to portal hypertension in some patients, according to a report published online in the Journal of Clinical Oncology.

Two cases of this complication arising in women with recurrent or metastatic HER2-positive ductal carcinomas who were participating in phase II trials were reported by Dr. Jeremy Force and his associates at Indiana University, Indianapolis.

The first woman (age 66) received trastuzumab emtansine when breast cancer recurred despite initial lumpectomy with axillary lymph node dissection, chemotherapy, and radiation, then recurred again following multiple chemotherapy regimens. Abdominal CT showed a normal-appearing liver before trastuzumab emtansine was initiated. Months later the woman developed worsening abdominal pain and ascites, and noncirrhotic portal hypertension resulting from nodular regenerative hyperplasia was diagnosed. The therapy was discontinued, and the patient remains free of ascites 5 months later (J. Clin. Oncol. 2014 April 28 [doi:10.1200/JCO.2013.49.8543]).

The second woman (age 50) received trastuzumab emtansine when breast cancer metastasized 2 years after bilateral mastectomy and persisted despite multiple chemotherapy regimens. Abdominal CT showed only hepatic steatosis but no evidence of portal hypertension before trastuzumab emtansine was initiated. Within 1 month the patient showed elevated serum aminotransferase and thrombocytopenia but was asymptomatic. A surveillance CT 1 year later showed evidence of portal hypertension, and liver biopsy showed nodular regenerative hyperplasia. The therapy was discontinued, and within 1 month liver test results improved. The patient now shows no signs of ascites or liver decompensation, and thrombocytopenia has resolved.

Clinicians should maintain a high index of suspicion for drug-induced liver injury in patients undergoing treatment with trastuzumab emtansine and consider nodular regenerative hyperplasia if liver test abnormalities or signs of portal hypertension develop. "Early and accurate diagnosis is vital because both liver test abnormalities and portal hypertension seem to be reversible" when the drug is discontinued, Dr. Force and his associates said.

Dr. Force reported no financial conflicts of interest; his associates reported ties to Mochida, Genentech, Merck, Sanofi Aventis, Salix, Abbott, Eli Lilly, Pfizer, Vertex, Bristol-Myers Squibb, Intercept, and Gilead.

Among African American men with abnormal prostate-specific antigen levels or abnormal findings on digital rectal examination of the prostate, biopsies are more likely to detect prostate cancer in those who have vitamin D deficiency than in those who don’t, according to a report published online May 1 in Clinical Cancer Research.

And in both American men of European descent and African American men who have vitamin D deficiency, initial biopsies are more likely to show tumors with high Gleason grade and more advanced clinical stage than are tumor biopsies in men who don’t have vitamin D deficiency, reported Dr. Adam B. Murphy of Northwestern University, Chicago, and his coauthors.

Their "novel" findings corroborate "a plethora of in vitro, animal, and clinical data suggesting potential mechanisms for the role of vitamin D in prostate differentiation and tumor progression," the investigators noted.

©Kaspri/Fotolia.com

If vitamin D is involved in prostate cancer initiation or progression, then vitamin D supplements may prove helpful for both primary and secondary prevention, especially in the highest-risk group of African American men, Dr. Murphy and his colleagues said.

The researchers investigated this issue because no prior studies have assessed the association between vitamin D status and prostate biopsy outcomes, even though several have suggested that vitamin D deficiency might explain the disparity between blacks and whites in prostate cancer incidence and survival. "African American men have lower serum vitamin D levels than their European American and Hispanic counterparts, in part due to lower skin synthesis from the ultraviolet-blocking effects of melanin in the skin," Dr. Murphy and his associates said.

They examined these outcomes in an ethnically diverse population of 667 men residing in Chicago, a city with low ultraviolet light exposure. There were 275 European Americans, 273 African Americans, and 119 men of other ethnicities.

The study participants, aged 40-79 years, were enrolled over a 4-year period from five urology clinics. They were undergoing an initial biopsy because of elevated prostate-specific antigen levels and/or abnormal findings on digital rectal exam. Vitamin D status was determined using serum samples collected on the day of biopsy.

Vitamin D deficiency (a 25-hydroxyvitamin D level less than 20 ng/mL) was quite common, affecting 41% of the entire study population. Severe vitamin D deficiency (a 25[OH]D level less than 12 ng/mL) was relatively common, affecting 16%.

Prostate cancer was detected in 383 biopsies.

Vitamin D deficiency was not associated with a biopsy finding of prostate cancer among European American men, but it was strongly associated with a biopsy finding of prostate cancer among African Americans (odds ratio, 2.43). This association remained robust when the data were controlled for patient age, prostate-specific antigen level, family history, and cigarette and alcohol use.

In addition, severe vitamin D deficiency was associated with a higher Gleason score and higher tumor stage in both races, and thus with a higher risk category by National Comprehensive Cancer Network criteria (Clin. Cancer Res. 2014;20:2289-99).

"Our work supports the hypothesis that 25-hydroxyvitamin D is a potential biomarker that plays a clinically significant role in prostate cancer, and it may be a useful modifiable risk factor in the disease. Additionally, differences in 25-hydroxyvitamin D levels may explain ethnic disparities in prostate cancer–specific incidence, morbidity, and mortality," Dr. Murphy and his associates wrote.

This study was supported in part by grants from the National Institutes of Health and the U.S. Department of Defense. Dr. Murphy reported no financial conflicts of interest; one of his coauthors reported ties to Beckman Coulter, DeCode Genetics, and Ohmx.

Among African American men with abnormal prostate-specific antigen levels or abnormal findings on digital rectal examination of the prostate, biopsies are more likely to detect prostate cancer in those who have vitamin D deficiency than in those who don’t, according to a report published online May 1 in Clinical Cancer Research.

And in both American men of European descent and African American men who have vitamin D deficiency, initial biopsies are more likely to show tumors with high Gleason grade and more advanced clinical stage than are tumor biopsies in men who don’t have vitamin D deficiency, reported Dr. Adam B. Murphy of Northwestern University, Chicago, and his coauthors.

Their "novel" findings corroborate "a plethora of in vitro, animal, and clinical data suggesting potential mechanisms for the role of vitamin D in prostate differentiation and tumor progression," the investigators noted.

©Kaspri/Fotolia.com

If vitamin D is involved in prostate cancer initiation or progression, then vitamin D supplements may prove helpful for both primary and secondary prevention, especially in the highest-risk group of African American men, Dr. Murphy and his colleagues said.

The researchers investigated this issue because no prior studies have assessed the association between vitamin D status and prostate biopsy outcomes, even though several have suggested that vitamin D deficiency might explain the disparity between blacks and whites in prostate cancer incidence and survival. "African American men have lower serum vitamin D levels than their European American and Hispanic counterparts, in part due to lower skin synthesis from the ultraviolet-blocking effects of melanin in the skin," Dr. Murphy and his associates said.

They examined these outcomes in an ethnically diverse population of 667 men residing in Chicago, a city with low ultraviolet light exposure. There were 275 European Americans, 273 African Americans, and 119 men of other ethnicities.

The study participants, aged 40-79 years, were enrolled over a 4-year period from five urology clinics. They were undergoing an initial biopsy because of elevated prostate-specific antigen levels and/or abnormal findings on digital rectal exam. Vitamin D status was determined using serum samples collected on the day of biopsy.

Vitamin D deficiency (a 25-hydroxyvitamin D level less than 20 ng/mL) was quite common, affecting 41% of the entire study population. Severe vitamin D deficiency (a 25[OH]D level less than 12 ng/mL) was relatively common, affecting 16%.

Prostate cancer was detected in 383 biopsies.

Vitamin D deficiency was not associated with a biopsy finding of prostate cancer among European American men, but it was strongly associated with a biopsy finding of prostate cancer among African Americans (odds ratio, 2.43). This association remained robust when the data were controlled for patient age, prostate-specific antigen level, family history, and cigarette and alcohol use.

In addition, severe vitamin D deficiency was associated with a higher Gleason score and higher tumor stage in both races, and thus with a higher risk category by National Comprehensive Cancer Network criteria (Clin. Cancer Res. 2014;20:2289-99).

"Our work supports the hypothesis that 25-hydroxyvitamin D is a potential biomarker that plays a clinically significant role in prostate cancer, and it may be a useful modifiable risk factor in the disease. Additionally, differences in 25-hydroxyvitamin D levels may explain ethnic disparities in prostate cancer–specific incidence, morbidity, and mortality," Dr. Murphy and his associates wrote.

This study was supported in part by grants from the National Institutes of Health and the U.S. Department of Defense. Dr. Murphy reported no financial conflicts of interest; one of his coauthors reported ties to Beckman Coulter, DeCode Genetics, and Ohmx.

Among African American men with abnormal prostate-specific antigen levels or abnormal findings on digital rectal examination of the prostate, biopsies are more likely to detect prostate cancer in those who have vitamin D deficiency than in those who don’t, according to a report published online May 1 in Clinical Cancer Research.

And in both American men of European descent and African American men who have vitamin D deficiency, initial biopsies are more likely to show tumors with high Gleason grade and more advanced clinical stage than are tumor biopsies in men who don’t have vitamin D deficiency, reported Dr. Adam B. Murphy of Northwestern University, Chicago, and his coauthors.

Their "novel" findings corroborate "a plethora of in vitro, animal, and clinical data suggesting potential mechanisms for the role of vitamin D in prostate differentiation and tumor progression," the investigators noted.

©Kaspri/Fotolia.com

If vitamin D is involved in prostate cancer initiation or progression, then vitamin D supplements may prove helpful for both primary and secondary prevention, especially in the highest-risk group of African American men, Dr. Murphy and his colleagues said.

The researchers investigated this issue because no prior studies have assessed the association between vitamin D status and prostate biopsy outcomes, even though several have suggested that vitamin D deficiency might explain the disparity between blacks and whites in prostate cancer incidence and survival. "African American men have lower serum vitamin D levels than their European American and Hispanic counterparts, in part due to lower skin synthesis from the ultraviolet-blocking effects of melanin in the skin," Dr. Murphy and his associates said.

They examined these outcomes in an ethnically diverse population of 667 men residing in Chicago, a city with low ultraviolet light exposure. There were 275 European Americans, 273 African Americans, and 119 men of other ethnicities.

The study participants, aged 40-79 years, were enrolled over a 4-year period from five urology clinics. They were undergoing an initial biopsy because of elevated prostate-specific antigen levels and/or abnormal findings on digital rectal exam. Vitamin D status was determined using serum samples collected on the day of biopsy.

Vitamin D deficiency (a 25-hydroxyvitamin D level less than 20 ng/mL) was quite common, affecting 41% of the entire study population. Severe vitamin D deficiency (a 25[OH]D level less than 12 ng/mL) was relatively common, affecting 16%.

Prostate cancer was detected in 383 biopsies.

Vitamin D deficiency was not associated with a biopsy finding of prostate cancer among European American men, but it was strongly associated with a biopsy finding of prostate cancer among African Americans (odds ratio, 2.43). This association remained robust when the data were controlled for patient age, prostate-specific antigen level, family history, and cigarette and alcohol use.

In addition, severe vitamin D deficiency was associated with a higher Gleason score and higher tumor stage in both races, and thus with a higher risk category by National Comprehensive Cancer Network criteria (Clin. Cancer Res. 2014;20:2289-99).

"Our work supports the hypothesis that 25-hydroxyvitamin D is a potential biomarker that plays a clinically significant role in prostate cancer, and it may be a useful modifiable risk factor in the disease. Additionally, differences in 25-hydroxyvitamin D levels may explain ethnic disparities in prostate cancer–specific incidence, morbidity, and mortality," Dr. Murphy and his associates wrote.

This study was supported in part by grants from the National Institutes of Health and the U.S. Department of Defense. Dr. Murphy reported no financial conflicts of interest; one of his coauthors reported ties to Beckman Coulter, DeCode Genetics, and Ohmx.

Among African American men with abnormal prostate-specific antigen levels or abnormal findings on digital rectal examination of the prostate, biopsies are more likely to detect prostate cancer in those who have vitamin D deficiency than in those who don’t, according to a report published online May 1 in Clinical Cancer Research.

And in both American men of European descent and African American men who have vitamin D deficiency, initial biopsies are more likely to show tumors with high Gleason grade and more advanced clinical stage than are tumor biopsies in men who don’t have vitamin D deficiency, reported Dr. Adam B. Murphy of Northwestern University, Chicago, and his coauthors.

Their "novel" findings corroborate "a plethora of in vitro, animal, and clinical data suggesting potential mechanisms for the role of vitamin D in prostate differentiation and tumor progression," the investigators noted.

©Kaspri/Fotolia.com

If vitamin D is involved in prostate cancer initiation or progression, then vitamin D supplements may prove helpful for both primary and secondary prevention, especially in the highest-risk group of African American men, Dr. Murphy and his colleagues said.

The researchers investigated this issue because no prior studies have assessed the association between vitamin D status and prostate biopsy outcomes, even though several have suggested that vitamin D deficiency might explain the disparity between blacks and whites in prostate cancer incidence and survival. "African American men have lower serum vitamin D levels than their European American and Hispanic counterparts, in part due to lower skin synthesis from the ultraviolet-blocking effects of melanin in the skin," Dr. Murphy and his associates said.

They examined these outcomes in an ethnically diverse population of 667 men residing in Chicago, a city with low ultraviolet light exposure. There were 275 European Americans, 273 African Americans, and 119 men of other ethnicities.

The study participants, aged 40-79 years, were enrolled over a 4-year period from five urology clinics. They were undergoing an initial biopsy because of elevated prostate-specific antigen levels and/or abnormal findings on digital rectal exam. Vitamin D status was determined using serum samples collected on the day of biopsy.

Vitamin D deficiency (a 25-hydroxyvitamin D level less than 20 ng/mL) was quite common, affecting 41% of the entire study population. Severe vitamin D deficiency (a 25[OH]D level less than 12 ng/mL) was relatively common, affecting 16%.

Prostate cancer was detected in 383 biopsies.

Vitamin D deficiency was not associated with a biopsy finding of prostate cancer among European American men, but it was strongly associated with a biopsy finding of prostate cancer among African Americans (odds ratio, 2.43). This association remained robust when the data were controlled for patient age, prostate-specific antigen level, family history, and cigarette and alcohol use.

In addition, severe vitamin D deficiency was associated with a higher Gleason score and higher tumor stage in both races, and thus with a higher risk category by National Comprehensive Cancer Network criteria (Clin. Cancer Res. 2014;20:2289-99).

"Our work supports the hypothesis that 25-hydroxyvitamin D is a potential biomarker that plays a clinically significant role in prostate cancer, and it may be a useful modifiable risk factor in the disease. Additionally, differences in 25-hydroxyvitamin D levels may explain ethnic disparities in prostate cancer–specific incidence, morbidity, and mortality," Dr. Murphy and his associates wrote.

This study was supported in part by grants from the National Institutes of Health and the U.S. Department of Defense. Dr. Murphy reported no financial conflicts of interest; one of his coauthors reported ties to Beckman Coulter, DeCode Genetics, and Ohmx.

Among African American men with abnormal prostate-specific antigen levels or abnormal findings on digital rectal examination of the prostate, biopsies are more likely to detect prostate cancer in those who have vitamin D deficiency than in those who don’t, according to a report published online May 1 in Clinical Cancer Research.

And in both American men of European descent and African American men who have vitamin D deficiency, initial biopsies are more likely to show tumors with high Gleason grade and more advanced clinical stage than are tumor biopsies in men who don’t have vitamin D deficiency, reported Dr. Adam B. Murphy of Northwestern University, Chicago, and his coauthors.

Their "novel" findings corroborate "a plethora of in vitro, animal, and clinical data suggesting potential mechanisms for the role of vitamin D in prostate differentiation and tumor progression," the investigators noted.

©Kaspri/Fotolia.com

If vitamin D is involved in prostate cancer initiation or progression, then vitamin D supplements may prove helpful for both primary and secondary prevention, especially in the highest-risk group of African American men, Dr. Murphy and his colleagues said.

The researchers investigated this issue because no prior studies have assessed the association between vitamin D status and prostate biopsy outcomes, even though several have suggested that vitamin D deficiency might explain the disparity between blacks and whites in prostate cancer incidence and survival. "African American men have lower serum vitamin D levels than their European American and Hispanic counterparts, in part due to lower skin synthesis from the ultraviolet-blocking effects of melanin in the skin," Dr. Murphy and his associates said.

They examined these outcomes in an ethnically diverse population of 667 men residing in Chicago, a city with low ultraviolet light exposure. There were 275 European Americans, 273 African Americans, and 119 men of other ethnicities.

The study participants, aged 40-79 years, were enrolled over a 4-year period from five urology clinics. They were undergoing an initial biopsy because of elevated prostate-specific antigen levels and/or abnormal findings on digital rectal exam. Vitamin D status was determined using serum samples collected on the day of biopsy.

Vitamin D deficiency (a 25-hydroxyvitamin D level less than 20 ng/mL) was quite common, affecting 41% of the entire study population. Severe vitamin D deficiency (a 25[OH]D level less than 12 ng/mL) was relatively common, affecting 16%.

Prostate cancer was detected in 383 biopsies.

Vitamin D deficiency was not associated with a biopsy finding of prostate cancer among European American men, but it was strongly associated with a biopsy finding of prostate cancer among African Americans (odds ratio, 2.43). This association remained robust when the data were controlled for patient age, prostate-specific antigen level, family history, and cigarette and alcohol use.

In addition, severe vitamin D deficiency was associated with a higher Gleason score and higher tumor stage in both races, and thus with a higher risk category by National Comprehensive Cancer Network criteria (Clin. Cancer Res. 2014;20:2289-99).

"Our work supports the hypothesis that 25-hydroxyvitamin D is a potential biomarker that plays a clinically significant role in prostate cancer, and it may be a useful modifiable risk factor in the disease. Additionally, differences in 25-hydroxyvitamin D levels may explain ethnic disparities in prostate cancer–specific incidence, morbidity, and mortality," Dr. Murphy and his associates wrote.

This study was supported in part by grants from the National Institutes of Health and the U.S. Department of Defense. Dr. Murphy reported no financial conflicts of interest; one of his coauthors reported ties to Beckman Coulter, DeCode Genetics, and Ohmx.

Among African American men with abnormal prostate-specific antigen levels or abnormal findings on digital rectal examination of the prostate, biopsies are more likely to detect prostate cancer in those who have vitamin D deficiency than in those who don’t, according to a report published online May 1 in Clinical Cancer Research.

And in both American men of European descent and African American men who have vitamin D deficiency, initial biopsies are more likely to show tumors with high Gleason grade and more advanced clinical stage than are tumor biopsies in men who don’t have vitamin D deficiency, reported Dr. Adam B. Murphy of Northwestern University, Chicago, and his coauthors.

Their "novel" findings corroborate "a plethora of in vitro, animal, and clinical data suggesting potential mechanisms for the role of vitamin D in prostate differentiation and tumor progression," the investigators noted.

©Kaspri/Fotolia.com

If vitamin D is involved in prostate cancer initiation or progression, then vitamin D supplements may prove helpful for both primary and secondary prevention, especially in the highest-risk group of African American men, Dr. Murphy and his colleagues said.

The researchers investigated this issue because no prior studies have assessed the association between vitamin D status and prostate biopsy outcomes, even though several have suggested that vitamin D deficiency might explain the disparity between blacks and whites in prostate cancer incidence and survival. "African American men have lower serum vitamin D levels than their European American and Hispanic counterparts, in part due to lower skin synthesis from the ultraviolet-blocking effects of melanin in the skin," Dr. Murphy and his associates said.

They examined these outcomes in an ethnically diverse population of 667 men residing in Chicago, a city with low ultraviolet light exposure. There were 275 European Americans, 273 African Americans, and 119 men of other ethnicities.

The study participants, aged 40-79 years, were enrolled over a 4-year period from five urology clinics. They were undergoing an initial biopsy because of elevated prostate-specific antigen levels and/or abnormal findings on digital rectal exam. Vitamin D status was determined using serum samples collected on the day of biopsy.

Vitamin D deficiency (a 25-hydroxyvitamin D level less than 20 ng/mL) was quite common, affecting 41% of the entire study population. Severe vitamin D deficiency (a 25[OH]D level less than 12 ng/mL) was relatively common, affecting 16%.

Prostate cancer was detected in 383 biopsies.

Vitamin D deficiency was not associated with a biopsy finding of prostate cancer among European American men, but it was strongly associated with a biopsy finding of prostate cancer among African Americans (odds ratio, 2.43). This association remained robust when the data were controlled for patient age, prostate-specific antigen level, family history, and cigarette and alcohol use.

In addition, severe vitamin D deficiency was associated with a higher Gleason score and higher tumor stage in both races, and thus with a higher risk category by National Comprehensive Cancer Network criteria (Clin. Cancer Res. 2014;20:2289-99).

"Our work supports the hypothesis that 25-hydroxyvitamin D is a potential biomarker that plays a clinically significant role in prostate cancer, and it may be a useful modifiable risk factor in the disease. Additionally, differences in 25-hydroxyvitamin D levels may explain ethnic disparities in prostate cancer–specific incidence, morbidity, and mortality," Dr. Murphy and his associates wrote.

This study was supported in part by grants from the National Institutes of Health and the U.S. Department of Defense. Dr. Murphy reported no financial conflicts of interest; one of his coauthors reported ties to Beckman Coulter, DeCode Genetics, and Ohmx.

Nearly six of every seven patients presenting to U.S. emergency departments with acute heart failure are admitted. This means acute heart failure is "a major challenge" to emergency departments nationwide and consumes a sizeable portion of their resources.

"Strategies to reduce this clinical and economic burden are needed," said Dr. Alan B. Storrow of the department of emergency medicine, Vanderbilt University, Nashville, and his associates.

The investigators performed a retrospective cohort study to quantify the burden of acute heart failure on emergency medical care because "it is important ... to focus individual and health system strategies to address [these] challenges before they become overwhelming." To do so, they analyzed information from the Nationwide Emergency Department Sample, "the largest all-payer ED [emergency department] database in the United States," which contains 25-30 million records of ED visits for more than 950 hospitals.

For this study, the researchers assessed an average of 958,167 annual ED visits for acute heart failure over a 5-year period. They excluded patients with cardiogenic shock, unspecified shock, intubation, noninvasive ventilation, or acute myocardial infarction because such patients wouldn’t have been eligible for discharge from the ED, which was an important outcome for this analysis.

Overall, 83.7% of acute heart failure patients who presented to the ED were admitted for hospitalization. The median length of stay was 3.4 days. Median ED charges rose over time, from $1,075 to $1,558 per person (JACC Heart Failure 2014 April 30 [doi:10.1016/j.jchf.2014.01.006]).

Patients who presented to EDs at academic hospitals were 1.5 times more likely to be admitted than were those who presented to nonacademic hospitals.

Admission rates also varied with geographic location of the hospital. Patients who presented to EDs in the Northeast region of the country were the most likely to be admitted (90% admission rate), while those in the West were the least likely (79% admission rate).

Uninsured patients were admitted less often than insured patients, even though they were more likely to have significant comorbidities. However, uninsured patients who were admitted underwent more diagnostic and therapeutic procedures than did insured patients.

"These data strongly suggest the ED is increasingly being relied on to evaluate more complex patients, some of whom previously received care as outpatients, or were directly admitted from an outpatient setting. ... As a result, emergency physicians increasingly serve as the major decision makers for approximately one-half of all U.S. inpatient admissions," Dr. Storrow and his associates noted.

In addition, "Emergency physicians’ tolerance of ‘risk’ in relation to ED discharge decisions, especially for patients they do not have an ongoing relationship with, is likely lower than for other caregivers," they said.

Alternatives to admission must be considered, at least for a subset of patients who present to EDs with acute heart failure. For example, patients who are found not to have high-risk features could be managed for 24-48 hours in an observation unit or discharged home. "Exploring these alternative strategies is crucial because the prevalence of chronic heart failure, and ED presentations for acute heart failure, are expected to increase over the next decade," Dr. Storrow and his colleagues said.

They added that this study probably underestimated the burden of acute heart failure on EDs because some patients likely received primary diagnoses of pneumonia, chronic obstructive pulmonary disease, asthma, or pulmonary embolus, with acute heart failure listed only as a supporting diagnosis. Such patients wouldn’t have been included in the analysis.

This study was supported by the National Heart, Lung, and Blood Institute and the National Center for Advancing Translational Sciences. Dr. Storrow reported receiving grants from Abbott and Roche Diagnostics and is a consultant for Abbott, Astellas, and Novartis; his associates reported ties to numerous industry sources.

Nearly six of every seven patients presenting to U.S. emergency departments with acute heart failure are admitted. This means acute heart failure is "a major challenge" to emergency departments nationwide and consumes a sizeable portion of their resources.

"Strategies to reduce this clinical and economic burden are needed," said Dr. Alan B. Storrow of the department of emergency medicine, Vanderbilt University, Nashville, and his associates.

The investigators performed a retrospective cohort study to quantify the burden of acute heart failure on emergency medical care because "it is important ... to focus individual and health system strategies to address [these] challenges before they become overwhelming." To do so, they analyzed information from the Nationwide Emergency Department Sample, "the largest all-payer ED [emergency department] database in the United States," which contains 25-30 million records of ED visits for more than 950 hospitals.

For this study, the researchers assessed an average of 958,167 annual ED visits for acute heart failure over a 5-year period. They excluded patients with cardiogenic shock, unspecified shock, intubation, noninvasive ventilation, or acute myocardial infarction because such patients wouldn’t have been eligible for discharge from the ED, which was an important outcome for this analysis.

Overall, 83.7% of acute heart failure patients who presented to the ED were admitted for hospitalization. The median length of stay was 3.4 days. Median ED charges rose over time, from $1,075 to $1,558 per person (JACC Heart Failure 2014 April 30 [doi:10.1016/j.jchf.2014.01.006]).

Patients who presented to EDs at academic hospitals were 1.5 times more likely to be admitted than were those who presented to nonacademic hospitals.

Admission rates also varied with geographic location of the hospital. Patients who presented to EDs in the Northeast region of the country were the most likely to be admitted (90% admission rate), while those in the West were the least likely (79% admission rate).

Uninsured patients were admitted less often than insured patients, even though they were more likely to have significant comorbidities. However, uninsured patients who were admitted underwent more diagnostic and therapeutic procedures than did insured patients.

"These data strongly suggest the ED is increasingly being relied on to evaluate more complex patients, some of whom previously received care as outpatients, or were directly admitted from an outpatient setting. ... As a result, emergency physicians increasingly serve as the major decision makers for approximately one-half of all U.S. inpatient admissions," Dr. Storrow and his associates noted.

In addition, "Emergency physicians’ tolerance of ‘risk’ in relation to ED discharge decisions, especially for patients they do not have an ongoing relationship with, is likely lower than for other caregivers," they said.

Alternatives to admission must be considered, at least for a subset of patients who present to EDs with acute heart failure. For example, patients who are found not to have high-risk features could be managed for 24-48 hours in an observation unit or discharged home. "Exploring these alternative strategies is crucial because the prevalence of chronic heart failure, and ED presentations for acute heart failure, are expected to increase over the next decade," Dr. Storrow and his colleagues said.

They added that this study probably underestimated the burden of acute heart failure on EDs because some patients likely received primary diagnoses of pneumonia, chronic obstructive pulmonary disease, asthma, or pulmonary embolus, with acute heart failure listed only as a supporting diagnosis. Such patients wouldn’t have been included in the analysis.

This study was supported by the National Heart, Lung, and Blood Institute and the National Center for Advancing Translational Sciences. Dr. Storrow reported receiving grants from Abbott and Roche Diagnostics and is a consultant for Abbott, Astellas, and Novartis; his associates reported ties to numerous industry sources.

Nearly six of every seven patients presenting to U.S. emergency departments with acute heart failure are admitted. This means acute heart failure is "a major challenge" to emergency departments nationwide and consumes a sizeable portion of their resources.

"Strategies to reduce this clinical and economic burden are needed," said Dr. Alan B. Storrow of the department of emergency medicine, Vanderbilt University, Nashville, and his associates.

The investigators performed a retrospective cohort study to quantify the burden of acute heart failure on emergency medical care because "it is important ... to focus individual and health system strategies to address [these] challenges before they become overwhelming." To do so, they analyzed information from the Nationwide Emergency Department Sample, "the largest all-payer ED [emergency department] database in the United States," which contains 25-30 million records of ED visits for more than 950 hospitals.

For this study, the researchers assessed an average of 958,167 annual ED visits for acute heart failure over a 5-year period. They excluded patients with cardiogenic shock, unspecified shock, intubation, noninvasive ventilation, or acute myocardial infarction because such patients wouldn’t have been eligible for discharge from the ED, which was an important outcome for this analysis.

Overall, 83.7% of acute heart failure patients who presented to the ED were admitted for hospitalization. The median length of stay was 3.4 days. Median ED charges rose over time, from $1,075 to $1,558 per person (JACC Heart Failure 2014 April 30 [doi:10.1016/j.jchf.2014.01.006]).

Patients who presented to EDs at academic hospitals were 1.5 times more likely to be admitted than were those who presented to nonacademic hospitals.

Admission rates also varied with geographic location of the hospital. Patients who presented to EDs in the Northeast region of the country were the most likely to be admitted (90% admission rate), while those in the West were the least likely (79% admission rate).

Uninsured patients were admitted less often than insured patients, even though they were more likely to have significant comorbidities. However, uninsured patients who were admitted underwent more diagnostic and therapeutic procedures than did insured patients.

"These data strongly suggest the ED is increasingly being relied on to evaluate more complex patients, some of whom previously received care as outpatients, or were directly admitted from an outpatient setting. ... As a result, emergency physicians increasingly serve as the major decision makers for approximately one-half of all U.S. inpatient admissions," Dr. Storrow and his associates noted.

In addition, "Emergency physicians’ tolerance of ‘risk’ in relation to ED discharge decisions, especially for patients they do not have an ongoing relationship with, is likely lower than for other caregivers," they said.

Alternatives to admission must be considered, at least for a subset of patients who present to EDs with acute heart failure. For example, patients who are found not to have high-risk features could be managed for 24-48 hours in an observation unit or discharged home. "Exploring these alternative strategies is crucial because the prevalence of chronic heart failure, and ED presentations for acute heart failure, are expected to increase over the next decade," Dr. Storrow and his colleagues said.

They added that this study probably underestimated the burden of acute heart failure on EDs because some patients likely received primary diagnoses of pneumonia, chronic obstructive pulmonary disease, asthma, or pulmonary embolus, with acute heart failure listed only as a supporting diagnosis. Such patients wouldn’t have been included in the analysis.

This study was supported by the National Heart, Lung, and Blood Institute and the National Center for Advancing Translational Sciences. Dr. Storrow reported receiving grants from Abbott and Roche Diagnostics and is a consultant for Abbott, Astellas, and Novartis; his associates reported ties to numerous industry sources.

Children, adolescents, and young adults with depression who begin taking SSRIs at "higher than modal" doses appear to be at twice the risk for suicide as patients aged 25 years and older who do so, according to a report published online April 28 in JAMA Internal Medicine.

In what they described as "the first prospective cohort study to examine the relation between dose of antidepressants and the risk of deliberate self-harm," investigators assessed nationally representative data from health care plans for 162,625 patients aged 10-64 years who were diagnosed as having depression and initiated citalopram, sertraline, or fluoxetine therapy during a 12-year period. These patients were categorized by whether they started on the most commonly prescribed (modal) doses of these agents or on higher than modal doses that still were not in excess of the recommended maximum dose, said Dr. Matthew Miller of the department of health policy and management, Harvard School of Public Health, Boston, and his associates.

These two study groups were well balanced for sex, depression severity, and suicidal ideation at baseline. In the 10- to 24-year-old age range, 142 patients attempted suicide within 1 year; the rate was 14.7 suicide events per 1,000 person-years in those who started selective serotonin reuptake inhibitors (SSRIs) at modal doses, but more than twice as high – 31.5 suicide events per 1,000 person-years – in those who started at high modal doses. In comparison, among older adults these rates were only 2.8 per 1,000 person-years in those who started SSRIs at modal doses and 3.2 per 1,000 person-years in those who started at high modal doses, the investigators reported (JAMA Intern. Med. 2014 April 28 [doi:10.1001/jamainternmed.2014.1053]).

"In our primary analysis of the 10- to 24-year-old cohort, for every 1,000 patients initiating high-dose therapy, there were approximately seven more [suicide] events over the first 90 days of treatment ... compared with modal-dose initiators. The corresponding number needed to harm was 136. For the older cohort, the risk difference was essentially zero," Dr. Miller and his associates wrote.

In effect, "we expect approximately one additional [suicide] event for every 136 patients 10-24 years of age who are treated with high-dose therapy instead of modal-dose therapy," they noted.

"Considered in light of recent meta-analyses concluding that the efficacy of antidepressant therapy for youth seems to be modest, and separate evidence that dose is generally unrelated to the therapeutic efficacy of antidepressants, our findings offer clinicians an additional incentive to avoid initiating pharmacotherapy at high therapeutic doses and to monitor all patients starting antidepressants, especially youth, for several months and regardless of history of deliberate self-harm," Dr. Miller and his colleagues said.

Another notable finding in this study was that for nearly half of all patients who initiated SSRI therapy at high modal doses, the prescriptions were written by internists or general physicians. Among patients aged 24 years and younger, internists/general physicians wrote about one-third of high modal-dose prescriptions, pediatricians wrote 10%, and psychiatrists/psychologists wrote 30%. This "underscores the relevance of our findings to clinicians caring for patients in both specialty and nonspecialty settings," they added.

The investigators cited several limitations. For example, their analysis is based on administrative data, which means that antidepressant adherence was not measured directly.

This study was supported in part by the National Institute of Mental Health, the National institute on Aging, and the Agency for Healthcare Research and Quality. Dr. Miller reported no financial conflicts of interest; one of his associates was supported in part by GlaxoSmithKline, Merck, and Sanofi.

Children, adolescents, and young adults with depression who begin taking SSRIs at "higher than modal" doses appear to be at twice the risk for suicide as patients aged 25 years and older who do so, according to a report published online April 28 in JAMA Internal Medicine.

In what they described as "the first prospective cohort study to examine the relation between dose of antidepressants and the risk of deliberate self-harm," investigators assessed nationally representative data from health care plans for 162,625 patients aged 10-64 years who were diagnosed as having depression and initiated citalopram, sertraline, or fluoxetine therapy during a 12-year period. These patients were categorized by whether they started on the most commonly prescribed (modal) doses of these agents or on higher than modal doses that still were not in excess of the recommended maximum dose, said Dr. Matthew Miller of the department of health policy and management, Harvard School of Public Health, Boston, and his associates.

These two study groups were well balanced for sex, depression severity, and suicidal ideation at baseline. In the 10- to 24-year-old age range, 142 patients attempted suicide within 1 year; the rate was 14.7 suicide events per 1,000 person-years in those who started selective serotonin reuptake inhibitors (SSRIs) at modal doses, but more than twice as high – 31.5 suicide events per 1,000 person-years – in those who started at high modal doses. In comparison, among older adults these rates were only 2.8 per 1,000 person-years in those who started SSRIs at modal doses and 3.2 per 1,000 person-years in those who started at high modal doses, the investigators reported (JAMA Intern. Med. 2014 April 28 [doi:10.1001/jamainternmed.2014.1053]).

"In our primary analysis of the 10- to 24-year-old cohort, for every 1,000 patients initiating high-dose therapy, there were approximately seven more [suicide] events over the first 90 days of treatment ... compared with modal-dose initiators. The corresponding number needed to harm was 136. For the older cohort, the risk difference was essentially zero," Dr. Miller and his associates wrote.

In effect, "we expect approximately one additional [suicide] event for every 136 patients 10-24 years of age who are treated with high-dose therapy instead of modal-dose therapy," they noted.

"Considered in light of recent meta-analyses concluding that the efficacy of antidepressant therapy for youth seems to be modest, and separate evidence that dose is generally unrelated to the therapeutic efficacy of antidepressants, our findings offer clinicians an additional incentive to avoid initiating pharmacotherapy at high therapeutic doses and to monitor all patients starting antidepressants, especially youth, for several months and regardless of history of deliberate self-harm," Dr. Miller and his colleagues said.

Another notable finding in this study was that for nearly half of all patients who initiated SSRI therapy at high modal doses, the prescriptions were written by internists or general physicians. Among patients aged 24 years and younger, internists/general physicians wrote about one-third of high modal-dose prescriptions, pediatricians wrote 10%, and psychiatrists/psychologists wrote 30%. This "underscores the relevance of our findings to clinicians caring for patients in both specialty and nonspecialty settings," they added.

The investigators cited several limitations. For example, their analysis is based on administrative data, which means that antidepressant adherence was not measured directly.

This study was supported in part by the National Institute of Mental Health, the National institute on Aging, and the Agency for Healthcare Research and Quality. Dr. Miller reported no financial conflicts of interest; one of his associates was supported in part by GlaxoSmithKline, Merck, and Sanofi.

Children, adolescents, and young adults with depression who begin taking SSRIs at "higher than modal" doses appear to be at twice the risk for suicide as patients aged 25 years and older who do so, according to a report published online April 28 in JAMA Internal Medicine.

In what they described as "the first prospective cohort study to examine the relation between dose of antidepressants and the risk of deliberate self-harm," investigators assessed nationally representative data from health care plans for 162,625 patients aged 10-64 years who were diagnosed as having depression and initiated citalopram, sertraline, or fluoxetine therapy during a 12-year period. These patients were categorized by whether they started on the most commonly prescribed (modal) doses of these agents or on higher than modal doses that still were not in excess of the recommended maximum dose, said Dr. Matthew Miller of the department of health policy and management, Harvard School of Public Health, Boston, and his associates.

These two study groups were well balanced for sex, depression severity, and suicidal ideation at baseline. In the 10- to 24-year-old age range, 142 patients attempted suicide within 1 year; the rate was 14.7 suicide events per 1,000 person-years in those who started selective serotonin reuptake inhibitors (SSRIs) at modal doses, but more than twice as high – 31.5 suicide events per 1,000 person-years – in those who started at high modal doses. In comparison, among older adults these rates were only 2.8 per 1,000 person-years in those who started SSRIs at modal doses and 3.2 per 1,000 person-years in those who started at high modal doses, the investigators reported (JAMA Intern. Med. 2014 April 28 [doi:10.1001/jamainternmed.2014.1053]).

"In our primary analysis of the 10- to 24-year-old cohort, for every 1,000 patients initiating high-dose therapy, there were approximately seven more [suicide] events over the first 90 days of treatment ... compared with modal-dose initiators. The corresponding number needed to harm was 136. For the older cohort, the risk difference was essentially zero," Dr. Miller and his associates wrote.

In effect, "we expect approximately one additional [suicide] event for every 136 patients 10-24 years of age who are treated with high-dose therapy instead of modal-dose therapy," they noted.

"Considered in light of recent meta-analyses concluding that the efficacy of antidepressant therapy for youth seems to be modest, and separate evidence that dose is generally unrelated to the therapeutic efficacy of antidepressants, our findings offer clinicians an additional incentive to avoid initiating pharmacotherapy at high therapeutic doses and to monitor all patients starting antidepressants, especially youth, for several months and regardless of history of deliberate self-harm," Dr. Miller and his colleagues said.

Another notable finding in this study was that for nearly half of all patients who initiated SSRI therapy at high modal doses, the prescriptions were written by internists or general physicians. Among patients aged 24 years and younger, internists/general physicians wrote about one-third of high modal-dose prescriptions, pediatricians wrote 10%, and psychiatrists/psychologists wrote 30%. This "underscores the relevance of our findings to clinicians caring for patients in both specialty and nonspecialty settings," they added.

The investigators cited several limitations. For example, their analysis is based on administrative data, which means that antidepressant adherence was not measured directly.

This study was supported in part by the National Institute of Mental Health, the National institute on Aging, and the Agency for Healthcare Research and Quality. Dr. Miller reported no financial conflicts of interest; one of his associates was supported in part by GlaxoSmithKline, Merck, and Sanofi.

Among patients who don’t have diabetes, high-normal hemoglobin A1C levels (at or above 5.8%) are strongly correlated with the risk of coronary artery disease, according to a report published online April 21 in the American Journal of Preventive Medicine.

In what they described as the first large-scale study to assess the relationships among A1C, CAD, and carotid intima-medial thickness, researchers enrolled 1,703 consecutive patients undergoing either elective or urgent coronary angiography at a single medical center during a 5-year period. These nondiabetic patients were divided into tertiles according to their A1C levels: low (less than 5.5%), intermediate (5.5%-5.79%), or high (5.8% or higher), reported Dr. Monica Verdoia of the cardiology department, Maggiore della Carita Hospital, Novara (Italy), and her associates.

A1C was significantly associated in a dose-dependent fashion with the prevalence of CAD on angiography (odds ratio, 1.33). CAD prevalence was 66.9% in patients who had low-normal A1C, 73.7% in those with intermediate A1C, and 78.6% in those with high-normal A1C. This association remained robust after the data were adjusted to account for many confounding factors, including patient age and sex; the presence or absence of hypertension, hypercholesterolemia, renal failure, and previous myocardial infarction; and the use or nonuse of medications including angiotensin receptor blockers, beta-blockers, nitrates, statins, or diuretics, the investigators said (Am. J. Prev. Med. 2014 April 21 [doi: 10.1016/j.amepre.2014.02.002]).

This strong association between high-normal A1C and CAD prevalence persisted across every high-risk subgroup that was assessed. A1C also was independently and strongly associated with carotid intima-medial thickness and the prevalence of carotid plaques on ultrasonography.

The best cutoff value for predicting the presence of significant CAD was determined to be 5.8%. Even though this level is within the normal range, it "should be regarded as a risk factor for atherosclerosis," Dr. Verdoia and her associates said.

Future research is needed to confirm these findings and to assess whether more aggressive preventive strategies, such as lifestyle changes, the use of statins, or antiplatelet therapies, might reduce the development and progression of atherosclerosis in such patients, they added.

Dr. Verdoia and her associates reported no financial conflicts of interest.

Among patients who don’t have diabetes, high-normal hemoglobin A1C levels (at or above 5.8%) are strongly correlated with the risk of coronary artery disease, according to a report published online April 21 in the American Journal of Preventive Medicine.

In what they described as the first large-scale study to assess the relationships among A1C, CAD, and carotid intima-medial thickness, researchers enrolled 1,703 consecutive patients undergoing either elective or urgent coronary angiography at a single medical center during a 5-year period. These nondiabetic patients were divided into tertiles according to their A1C levels: low (less than 5.5%), intermediate (5.5%-5.79%), or high (5.8% or higher), reported Dr. Monica Verdoia of the cardiology department, Maggiore della Carita Hospital, Novara (Italy), and her associates.

A1C was significantly associated in a dose-dependent fashion with the prevalence of CAD on angiography (odds ratio, 1.33). CAD prevalence was 66.9% in patients who had low-normal A1C, 73.7% in those with intermediate A1C, and 78.6% in those with high-normal A1C. This association remained robust after the data were adjusted to account for many confounding factors, including patient age and sex; the presence or absence of hypertension, hypercholesterolemia, renal failure, and previous myocardial infarction; and the use or nonuse of medications including angiotensin receptor blockers, beta-blockers, nitrates, statins, or diuretics, the investigators said (Am. J. Prev. Med. 2014 April 21 [doi: 10.1016/j.amepre.2014.02.002]).

This strong association between high-normal A1C and CAD prevalence persisted across every high-risk subgroup that was assessed. A1C also was independently and strongly associated with carotid intima-medial thickness and the prevalence of carotid plaques on ultrasonography.

The best cutoff value for predicting the presence of significant CAD was determined to be 5.8%. Even though this level is within the normal range, it "should be regarded as a risk factor for atherosclerosis," Dr. Verdoia and her associates said.

Future research is needed to confirm these findings and to assess whether more aggressive preventive strategies, such as lifestyle changes, the use of statins, or antiplatelet therapies, might reduce the development and progression of atherosclerosis in such patients, they added.

Dr. Verdoia and her associates reported no financial conflicts of interest.

Among patients who don’t have diabetes, high-normal hemoglobin A1C levels (at or above 5.8%) are strongly correlated with the risk of coronary artery disease, according to a report published online April 21 in the American Journal of Preventive Medicine.

In what they described as the first large-scale study to assess the relationships among A1C, CAD, and carotid intima-medial thickness, researchers enrolled 1,703 consecutive patients undergoing either elective or urgent coronary angiography at a single medical center during a 5-year period. These nondiabetic patients were divided into tertiles according to their A1C levels: low (less than 5.5%), intermediate (5.5%-5.79%), or high (5.8% or higher), reported Dr. Monica Verdoia of the cardiology department, Maggiore della Carita Hospital, Novara (Italy), and her associates.

A1C was significantly associated in a dose-dependent fashion with the prevalence of CAD on angiography (odds ratio, 1.33). CAD prevalence was 66.9% in patients who had low-normal A1C, 73.7% in those with intermediate A1C, and 78.6% in those with high-normal A1C. This association remained robust after the data were adjusted to account for many confounding factors, including patient age and sex; the presence or absence of hypertension, hypercholesterolemia, renal failure, and previous myocardial infarction; and the use or nonuse of medications including angiotensin receptor blockers, beta-blockers, nitrates, statins, or diuretics, the investigators said (Am. J. Prev. Med. 2014 April 21 [doi: 10.1016/j.amepre.2014.02.002]).

This strong association between high-normal A1C and CAD prevalence persisted across every high-risk subgroup that was assessed. A1C also was independently and strongly associated with carotid intima-medial thickness and the prevalence of carotid plaques on ultrasonography.

The best cutoff value for predicting the presence of significant CAD was determined to be 5.8%. Even though this level is within the normal range, it "should be regarded as a risk factor for atherosclerosis," Dr. Verdoia and her associates said.

Future research is needed to confirm these findings and to assess whether more aggressive preventive strategies, such as lifestyle changes, the use of statins, or antiplatelet therapies, might reduce the development and progression of atherosclerosis in such patients, they added.

Dr. Verdoia and her associates reported no financial conflicts of interest.

Among patients who don’t have diabetes, high-normal hemoglobin A1c levels (at or above 5.8%) are strongly correlated with the risk of coronary artery disease, according to a report published online April 21 in the American Journal of Preventive Medicine.

In what they described as the first large-scale study to assess the relationships among HbA_1c, CAD, and carotid intima-medial thickness, researchers enrolled 1,703 consecutive patients undergoing either elective or urgent coronary angiography at a single medical center during a 5-year period. These nondiabetic patients were divided into tertiles according to their HbA_1c levels: low (less than 5.5%), intermediate (5.5%-5.79%), or high (5.8% or higher), reported Dr. Monica Verdoia of the cardiology department, Maggiore della Carita Hospital, Novara (Italy), and her associates.

HbA_1c was significantly associated in a dose-dependent fashion with the prevalence of CAD on angiography (odds ratio, 1.33). CAD prevalence was 66.9% in patients who had low-normal HbA_1c, 73.7% in those with intermediate HbA_1c, and 78.6% in those with high-normal HbA_1c. This association remained robust after the data were adjusted to account for many confounding factors, including patient age and sex; the presence or absence of hypertension, hypercholesterolemia, renal failure, and previous myocardial infarction; and the use or nonuse of medications including angiotensin receptor blockers, beta-blockers, nitrates, statins, or diuretics, the investigators said (Am. J. Prev. Med. 2014 April 21 [doi: 10.1016/j.amepre.2014.02.002]).

This strong association between high-normal HbA_1c and CAD prevalence persisted across every high-risk subgroup that was assessed. HbA_1c also was independently and strongly associated with carotid intima-medial thickness and the prevalence of carotid plaques on ultrasonography.

The best cutoff value for predicting the presence of significant CAD was determined to be 5.8%. Even though this level is within the normal range, it "should be regarded as a risk factor for atherosclerosis," Dr. Verdoia and her associates said.

Future research is needed to confirm these findings and to assess whether more aggressive preventive strategies, such as lifestyle changes, the use of statins, or antiplatelet therapies, might reduce the development and progression of atherosclerosis in such patients, they added.

Dr. Verdoia and her associates reported no financial conflicts of interest.

Among patients who don’t have diabetes, high-normal hemoglobin A1c levels (at or above 5.8%) are strongly correlated with the risk of coronary artery disease, according to a report published online April 21 in the American Journal of Preventive Medicine.

In what they described as the first large-scale study to assess the relationships among HbA_1c, CAD, and carotid intima-medial thickness, researchers enrolled 1,703 consecutive patients undergoing either elective or urgent coronary angiography at a single medical center during a 5-year period. These nondiabetic patients were divided into tertiles according to their HbA_1c levels: low (less than 5.5%), intermediate (5.5%-5.79%), or high (5.8% or higher), reported Dr. Monica Verdoia of the cardiology department, Maggiore della Carita Hospital, Novara (Italy), and her associates.

HbA_1c was significantly associated in a dose-dependent fashion with the prevalence of CAD on angiography (odds ratio, 1.33). CAD prevalence was 66.9% in patients who had low-normal HbA_1c, 73.7% in those with intermediate HbA_1c, and 78.6% in those with high-normal HbA_1c. This association remained robust after the data were adjusted to account for many confounding factors, including patient age and sex; the presence or absence of hypertension, hypercholesterolemia, renal failure, and previous myocardial infarction; and the use or nonuse of medications including angiotensin receptor blockers, beta-blockers, nitrates, statins, or diuretics, the investigators said (Am. J. Prev. Med. 2014 April 21 [doi: 10.1016/j.amepre.2014.02.002]).

This strong association between high-normal HbA_1c and CAD prevalence persisted across every high-risk subgroup that was assessed. HbA_1c also was independently and strongly associated with carotid intima-medial thickness and the prevalence of carotid plaques on ultrasonography.

The best cutoff value for predicting the presence of significant CAD was determined to be 5.8%. Even though this level is within the normal range, it "should be regarded as a risk factor for atherosclerosis," Dr. Verdoia and her associates said.

Future research is needed to confirm these findings and to assess whether more aggressive preventive strategies, such as lifestyle changes, the use of statins, or antiplatelet therapies, might reduce the development and progression of atherosclerosis in such patients, they added.

Dr. Verdoia and her associates reported no financial conflicts of interest.

Among patients who don’t have diabetes, high-normal hemoglobin A1c levels (at or above 5.8%) are strongly correlated with the risk of coronary artery disease, according to a report published online April 21 in the American Journal of Preventive Medicine.

In what they described as the first large-scale study to assess the relationships among HbA_1c, CAD, and carotid intima-medial thickness, researchers enrolled 1,703 consecutive patients undergoing either elective or urgent coronary angiography at a single medical center during a 5-year period. These nondiabetic patients were divided into tertiles according to their HbA_1c levels: low (less than 5.5%), intermediate (5.5%-5.79%), or high (5.8% or higher), reported Dr. Monica Verdoia of the cardiology department, Maggiore della Carita Hospital, Novara (Italy), and her associates.

HbA_1c was significantly associated in a dose-dependent fashion with the prevalence of CAD on angiography (odds ratio, 1.33). CAD prevalence was 66.9% in patients who had low-normal HbA_1c, 73.7% in those with intermediate HbA_1c, and 78.6% in those with high-normal HbA_1c. This association remained robust after the data were adjusted to account for many confounding factors, including patient age and sex; the presence or absence of hypertension, hypercholesterolemia, renal failure, and previous myocardial infarction; and the use or nonuse of medications including angiotensin receptor blockers, beta-blockers, nitrates, statins, or diuretics, the investigators said (Am. J. Prev. Med. 2014 April 21 [doi: 10.1016/j.amepre.2014.02.002]).

This strong association between high-normal HbA_1c and CAD prevalence persisted across every high-risk subgroup that was assessed. HbA_1c also was independently and strongly associated with carotid intima-medial thickness and the prevalence of carotid plaques on ultrasonography.

The best cutoff value for predicting the presence of significant CAD was determined to be 5.8%. Even though this level is within the normal range, it "should be regarded as a risk factor for atherosclerosis," Dr. Verdoia and her associates said.

Future research is needed to confirm these findings and to assess whether more aggressive preventive strategies, such as lifestyle changes, the use of statins, or antiplatelet therapies, might reduce the development and progression of atherosclerosis in such patients, they added.

Dr. Verdoia and her associates reported no financial conflicts of interest.

High dietary intake of animal protein was associated with a modestly elevated risk of type 2 diabetes among women in an international case-control study published online in Diabetes Care.

Investigators assessed the self-reported dietary intakes of 26,253 adults from eight European countries participating in EPIC-InterAct, a large study of behavioral and genetic factors that correlate with the development of type 2 diabetes. A total of 11,637 study subjects developed incident type 2 diabetes and 14,616 did not during a mean follow-up of 12 years, said Dr. Monique van Nielen of the division of human nutrition, Wageningen (the Netherlands) University, and her associates.

©camij/Thinkstockphotos.com

A high intake of total protein was associated with a 13% higher incidence of type 2 diabetes than was a low protein intake among women but not among men. Further analysis showed that animal, not plant, protein accounted for almost all of this association, they reported.

Among women only, for every 10-g increase in the consumption of animal protein the incidence of diabetes rose 5%. This amount is equivalent to approximately a 50-g serving of meat or fish or a glass of milk. No specific type of animal protein accounted for this association, since serial analyses excluding meat, fish, and dairy foods did not alter the results, Dr. van Nielen and her associates said (Diabetes Care 2014 April 10 [doi:10.2337/dc13-2627]).

"In contrast to suggested beneficial short-term effects of dietary protein on glycemic control, our study found that habitually high intake of protein increases type 2 diabetes risk," they noted. Although the mechanism underlying this association is not yet known, it may be advisable to limit isoenergetic diets high in dietary, especially animal, proteins, they said.

This study was funded by the European Union and numerous government and independent sources in all participating countries. No financial conflicts of interest were reported.

High dietary intake of animal protein was associated with a modestly elevated risk of type 2 diabetes among women in an international case-control study published online in Diabetes Care.

Investigators assessed the self-reported dietary intakes of 26,253 adults from eight European countries participating in EPIC-InterAct, a large study of behavioral and genetic factors that correlate with the development of type 2 diabetes. A total of 11,637 study subjects developed incident type 2 diabetes and 14,616 did not during a mean follow-up of 12 years, said Dr. Monique van Nielen of the division of human nutrition, Wageningen (the Netherlands) University, and her associates.

©camij/Thinkstockphotos.com

A high intake of total protein was associated with a 13% higher incidence of type 2 diabetes than was a low protein intake among women but not among men. Further analysis showed that animal, not plant, protein accounted for almost all of this association, they reported.

Among women only, for every 10-g increase in the consumption of animal protein the incidence of diabetes rose 5%. This amount is equivalent to approximately a 50-g serving of meat or fish or a glass of milk. No specific type of animal protein accounted for this association, since serial analyses excluding meat, fish, and dairy foods did not alter the results, Dr. van Nielen and her associates said (Diabetes Care 2014 April 10 [doi:10.2337/dc13-2627]).

"In contrast to suggested beneficial short-term effects of dietary protein on glycemic control, our study found that habitually high intake of protein increases type 2 diabetes risk," they noted. Although the mechanism underlying this association is not yet known, it may be advisable to limit isoenergetic diets high in dietary, especially animal, proteins, they said.

This study was funded by the European Union and numerous government and independent sources in all participating countries. No financial conflicts of interest were reported.

High dietary intake of animal protein was associated with a modestly elevated risk of type 2 diabetes among women in an international case-control study published online in Diabetes Care.

Investigators assessed the self-reported dietary intakes of 26,253 adults from eight European countries participating in EPIC-InterAct, a large study of behavioral and genetic factors that correlate with the development of type 2 diabetes. A total of 11,637 study subjects developed incident type 2 diabetes and 14,616 did not during a mean follow-up of 12 years, said Dr. Monique van Nielen of the division of human nutrition, Wageningen (the Netherlands) University, and her associates.

©camij/Thinkstockphotos.com

A high intake of total protein was associated with a 13% higher incidence of type 2 diabetes than was a low protein intake among women but not among men. Further analysis showed that animal, not plant, protein accounted for almost all of this association, they reported.

Among women only, for every 10-g increase in the consumption of animal protein the incidence of diabetes rose 5%. This amount is equivalent to approximately a 50-g serving of meat or fish or a glass of milk. No specific type of animal protein accounted for this association, since serial analyses excluding meat, fish, and dairy foods did not alter the results, Dr. van Nielen and her associates said (Diabetes Care 2014 April 10 [doi:10.2337/dc13-2627]).

"In contrast to suggested beneficial short-term effects of dietary protein on glycemic control, our study found that habitually high intake of protein increases type 2 diabetes risk," they noted. Although the mechanism underlying this association is not yet known, it may be advisable to limit isoenergetic diets high in dietary, especially animal, proteins, they said.

This study was funded by the European Union and numerous government and independent sources in all participating countries. No financial conflicts of interest were reported.