SCOTTSDALE, ARIZ. – Children and adolescents receiving methotrexate for psoriasis were significantly less likely to experience gastrointestinal side effects when they took a folate supplement every day instead of once weekly or 6 days a week, in a retrospective study of more than 400 pediatric psoriasis patients.

Laboratory abnormalities were significantly more common among children who received a folate supplement 6 days per week rather than daily, noted Inge Bronckers of the department of dermatology, Radboud University, Nijmegen, the Netherlands. “These results support the use of daily folate” in this group of patients,” she said in a poster presentation at the annual meeting of the Society for Investigative Dermatology.

thinkstockphotos.com

Few studies have examined patterns of use or adverse effects of pediatric psoriasis therapies. Although methotrexate is a folate antagonist with related toxicities, whether folate supplementation counteracts the efficacy of methotrexate is also unclear. Because of these uncertainties, some clinicians recommend a supplement 6 days per week, avoiding the day methotrexate is given, while others recommend it daily or once weekly.

To better understand the effects of these regimens, Ms. Inge and her coinvestigators studied 446 children and adolescents who received phototherapy or systemic treatments for moderate to severe psoriasis at 20 centers in the United States, Canada, and Europe between 1990 and 2014. The patients’ average age was 8 years (standard deviation, 4 years); 238 were female and 208 were male.

Among the 390 patients receiving systemic medications, almost 70% were receiving methotrexate, while 27% were being treated with etanercept or another biologic, 15% were using retinoids, 8% were using cyclosporine, and 5% were using fumaric acid. About 19% of patients were receiving more than one of these medications. Methotrexate most often led to nausea (affecting 18% of patients), elevated hepatic transaminases (13%), dyspepsia (7%), and infections (4%), usually of the skin and upper airways. In contrast, biologics most often caused injection-site reactions (19%) and upper airways infections (10%).

Most (253) of the 270 patients on methotrexate had been prescribed folic acid, typically at a dose of about 8 mg/wk, and nearly always in the form of pure folic acid, rather than a multivitamin. Of the patients taking folic acid, about 34% took it 6 days per week, 34% received it daily and 30% – including most patients in Europe – received it once weekly.

Notably, the odds of gastrointestinal side effects were 75% lower for patients who received folic acid daily or 6 days per week, compared with those who received folic acid once a week (odds ratio, 0.25, in both cases; P less than .001), the investigators found. However, laboratory abnormalities were significantly more likely when folic acid was given 6 days a week, compared with daily (OR, 2.31; P = .03) or weekly (OR, 3.9; P = .002). Patients in Europe, who usually received folic acid weekly, were significantly more likely to have methotrexate-related gastrointestinal side effects than were patients in North America (OR, 3.4; P less than .001), and were less likely to have laboratory abnormalities (OR, 0.32; P = .004).

Patients on biologic therapy were less likely to develop laboratory abnormalities or stop treatment because of side effects than were those on other systemic therapies, Ms. Inge and her associates found. Because methotrexate was associated with elevated liver enzymes, it also was dose adjusted more often than other therapies. No patient on any therapy was diagnosed with tuberculosis or malignancy, but three patients on methotrexate had severe adverse effects, including liver disease, methotrexate hypersensitivity pneumonitis, and severe personality changes. In contrast, fumarate was associated with one case each of pericarditis and bone marrow suppression, while one patient on the biologic adalimumab developed appendicitis.

The study underscores the need to monitor the long-term risks of pediatric psoriasis treatments, the researchers concluded. Data and lessons from the study are being used to develop a prospective pediatric psoriasis registry. “If industry joins forces to use this prospective international registry to capture prospective pediatric data, we will ensure early detection of safety signals and facilitate comparative analyses of efficacy and safety,” Ms. Inge said in the poster.

The International Psoriasis Council funded the study. The investigators did not list disclosures.

SCOTTSDALE, ARIZ. – Children and adolescents receiving methotrexate for psoriasis were significantly less likely to experience gastrointestinal side effects when they took a folate supplement every day instead of once weekly or 6 days a week, in a retrospective study of more than 400 pediatric psoriasis patients.

Laboratory abnormalities were significantly more common among children who received a folate supplement 6 days per week rather than daily, noted Inge Bronckers of the department of dermatology, Radboud University, Nijmegen, the Netherlands. “These results support the use of daily folate” in this group of patients,” she said in a poster presentation at the annual meeting of the Society for Investigative Dermatology.

thinkstockphotos.com

Few studies have examined patterns of use or adverse effects of pediatric psoriasis therapies. Although methotrexate is a folate antagonist with related toxicities, whether folate supplementation counteracts the efficacy of methotrexate is also unclear. Because of these uncertainties, some clinicians recommend a supplement 6 days per week, avoiding the day methotrexate is given, while others recommend it daily or once weekly.

To better understand the effects of these regimens, Ms. Inge and her coinvestigators studied 446 children and adolescents who received phototherapy or systemic treatments for moderate to severe psoriasis at 20 centers in the United States, Canada, and Europe between 1990 and 2014. The patients’ average age was 8 years (standard deviation, 4 years); 238 were female and 208 were male.

Among the 390 patients receiving systemic medications, almost 70% were receiving methotrexate, while 27% were being treated with etanercept or another biologic, 15% were using retinoids, 8% were using cyclosporine, and 5% were using fumaric acid. About 19% of patients were receiving more than one of these medications. Methotrexate most often led to nausea (affecting 18% of patients), elevated hepatic transaminases (13%), dyspepsia (7%), and infections (4%), usually of the skin and upper airways. In contrast, biologics most often caused injection-site reactions (19%) and upper airways infections (10%).

Most (253) of the 270 patients on methotrexate had been prescribed folic acid, typically at a dose of about 8 mg/wk, and nearly always in the form of pure folic acid, rather than a multivitamin. Of the patients taking folic acid, about 34% took it 6 days per week, 34% received it daily and 30% – including most patients in Europe – received it once weekly.

Notably, the odds of gastrointestinal side effects were 75% lower for patients who received folic acid daily or 6 days per week, compared with those who received folic acid once a week (odds ratio, 0.25, in both cases; P less than .001), the investigators found. However, laboratory abnormalities were significantly more likely when folic acid was given 6 days a week, compared with daily (OR, 2.31; P = .03) or weekly (OR, 3.9; P = .002). Patients in Europe, who usually received folic acid weekly, were significantly more likely to have methotrexate-related gastrointestinal side effects than were patients in North America (OR, 3.4; P less than .001), and were less likely to have laboratory abnormalities (OR, 0.32; P = .004).

Patients on biologic therapy were less likely to develop laboratory abnormalities or stop treatment because of side effects than were those on other systemic therapies, Ms. Inge and her associates found. Because methotrexate was associated with elevated liver enzymes, it also was dose adjusted more often than other therapies. No patient on any therapy was diagnosed with tuberculosis or malignancy, but three patients on methotrexate had severe adverse effects, including liver disease, methotrexate hypersensitivity pneumonitis, and severe personality changes. In contrast, fumarate was associated with one case each of pericarditis and bone marrow suppression, while one patient on the biologic adalimumab developed appendicitis.

The study underscores the need to monitor the long-term risks of pediatric psoriasis treatments, the researchers concluded. Data and lessons from the study are being used to develop a prospective pediatric psoriasis registry. “If industry joins forces to use this prospective international registry to capture prospective pediatric data, we will ensure early detection of safety signals and facilitate comparative analyses of efficacy and safety,” Ms. Inge said in the poster.

The International Psoriasis Council funded the study. The investigators did not list disclosures.

SCOTTSDALE, ARIZ. – Children and adolescents receiving methotrexate for psoriasis were significantly less likely to experience gastrointestinal side effects when they took a folate supplement every day instead of once weekly or 6 days a week, in a retrospective study of more than 400 pediatric psoriasis patients.

Laboratory abnormalities were significantly more common among children who received a folate supplement 6 days per week rather than daily, noted Inge Bronckers of the department of dermatology, Radboud University, Nijmegen, the Netherlands. “These results support the use of daily folate” in this group of patients,” she said in a poster presentation at the annual meeting of the Society for Investigative Dermatology.

thinkstockphotos.com

Few studies have examined patterns of use or adverse effects of pediatric psoriasis therapies. Although methotrexate is a folate antagonist with related toxicities, whether folate supplementation counteracts the efficacy of methotrexate is also unclear. Because of these uncertainties, some clinicians recommend a supplement 6 days per week, avoiding the day methotrexate is given, while others recommend it daily or once weekly.

To better understand the effects of these regimens, Ms. Inge and her coinvestigators studied 446 children and adolescents who received phototherapy or systemic treatments for moderate to severe psoriasis at 20 centers in the United States, Canada, and Europe between 1990 and 2014. The patients’ average age was 8 years (standard deviation, 4 years); 238 were female and 208 were male.

Among the 390 patients receiving systemic medications, almost 70% were receiving methotrexate, while 27% were being treated with etanercept or another biologic, 15% were using retinoids, 8% were using cyclosporine, and 5% were using fumaric acid. About 19% of patients were receiving more than one of these medications. Methotrexate most often led to nausea (affecting 18% of patients), elevated hepatic transaminases (13%), dyspepsia (7%), and infections (4%), usually of the skin and upper airways. In contrast, biologics most often caused injection-site reactions (19%) and upper airways infections (10%).

Most (253) of the 270 patients on methotrexate had been prescribed folic acid, typically at a dose of about 8 mg/wk, and nearly always in the form of pure folic acid, rather than a multivitamin. Of the patients taking folic acid, about 34% took it 6 days per week, 34% received it daily and 30% – including most patients in Europe – received it once weekly.

Notably, the odds of gastrointestinal side effects were 75% lower for patients who received folic acid daily or 6 days per week, compared with those who received folic acid once a week (odds ratio, 0.25, in both cases; P less than .001), the investigators found. However, laboratory abnormalities were significantly more likely when folic acid was given 6 days a week, compared with daily (OR, 2.31; P = .03) or weekly (OR, 3.9; P = .002). Patients in Europe, who usually received folic acid weekly, were significantly more likely to have methotrexate-related gastrointestinal side effects than were patients in North America (OR, 3.4; P less than .001), and were less likely to have laboratory abnormalities (OR, 0.32; P = .004).

Patients on biologic therapy were less likely to develop laboratory abnormalities or stop treatment because of side effects than were those on other systemic therapies, Ms. Inge and her associates found. Because methotrexate was associated with elevated liver enzymes, it also was dose adjusted more often than other therapies. No patient on any therapy was diagnosed with tuberculosis or malignancy, but three patients on methotrexate had severe adverse effects, including liver disease, methotrexate hypersensitivity pneumonitis, and severe personality changes. In contrast, fumarate was associated with one case each of pericarditis and bone marrow suppression, while one patient on the biologic adalimumab developed appendicitis.

The study underscores the need to monitor the long-term risks of pediatric psoriasis treatments, the researchers concluded. Data and lessons from the study are being used to develop a prospective pediatric psoriasis registry. “If industry joins forces to use this prospective international registry to capture prospective pediatric data, we will ensure early detection of safety signals and facilitate comparative analyses of efficacy and safety,” Ms. Inge said in the poster.

The International Psoriasis Council funded the study. The investigators did not list disclosures.

SCOTTSDALE, ARIZ. – Children and adolescents receiving methotrexate for psoriasis were significantly less likely to experience gastrointestinal side effects when they took a folate supplement every day instead of once weekly or 6 days a week, in a retrospective study of more than 400 pediatric psoriasis patients.

Laboratory abnormalities were significantly more common among children who received a folate supplement 6 days per week rather than daily, noted Inge Bronckers of the department of dermatology, Radboud University, Nijmegen, the Netherlands. “These results support the use of daily folate” in this group of patients,” she said in a poster presentation at the annual meeting of the Society for Investigative Dermatology.

thinkstockphotos.com

Few studies have examined patterns of use or adverse effects of pediatric psoriasis therapies. Although methotrexate is a folate antagonist with related toxicities, whether folate supplementation counteracts the efficacy of methotrexate is also unclear. Because of these uncertainties, some clinicians recommend a supplement 6 days per week, avoiding the day methotrexate is given, while others recommend it daily or once weekly.

To better understand the effects of these regimens, Ms. Inge and her coinvestigators studied 446 children and adolescents who received phototherapy or systemic treatments for moderate to severe psoriasis at 20 centers in the United States, Canada, and Europe between 1990 and 2014. The patients’ average age was 8 years (standard deviation, 4 years); 238 were female and 208 were male.

Among the 390 patients receiving systemic medications, almost 70% were receiving methotrexate, while 27% were being treated with etanercept or another biologic, 15% were using retinoids, 8% were using cyclosporine, and 5% were using fumaric acid. About 19% of patients were receiving more than one of these medications. Methotrexate most often led to nausea (affecting 18% of patients), elevated hepatic transaminases (13%), dyspepsia (7%), and infections (4%), usually of the skin and upper airways. In contrast, biologics most often caused injection-site reactions (19%) and upper airways infections (10%).

Most (253) of the 270 patients on methotrexate had been prescribed folic acid, typically at a dose of about 8 mg/wk, and nearly always in the form of pure folic acid, rather than a multivitamin. Of the patients taking folic acid, about 34% took it 6 days per week, 34% received it daily and 30% – including most patients in Europe – received it once weekly.

Notably, the odds of gastrointestinal side effects were 75% lower for patients who received folic acid daily or 6 days per week, compared with those who received folic acid once a week (odds ratio, 0.25, in both cases; P less than .001), the investigators found. However, laboratory abnormalities were significantly more likely when folic acid was given 6 days a week, compared with daily (OR, 2.31; P = .03) or weekly (OR, 3.9; P = .002). Patients in Europe, who usually received folic acid weekly, were significantly more likely to have methotrexate-related gastrointestinal side effects than were patients in North America (OR, 3.4; P less than .001), and were less likely to have laboratory abnormalities (OR, 0.32; P = .004).

Patients on biologic therapy were less likely to develop laboratory abnormalities or stop treatment because of side effects than were those on other systemic therapies, Ms. Inge and her associates found. Because methotrexate was associated with elevated liver enzymes, it also was dose adjusted more often than other therapies. No patient on any therapy was diagnosed with tuberculosis or malignancy, but three patients on methotrexate had severe adverse effects, including liver disease, methotrexate hypersensitivity pneumonitis, and severe personality changes. In contrast, fumarate was associated with one case each of pericarditis and bone marrow suppression, while one patient on the biologic adalimumab developed appendicitis.

The study underscores the need to monitor the long-term risks of pediatric psoriasis treatments, the researchers concluded. Data and lessons from the study are being used to develop a prospective pediatric psoriasis registry. “If industry joins forces to use this prospective international registry to capture prospective pediatric data, we will ensure early detection of safety signals and facilitate comparative analyses of efficacy and safety,” Ms. Inge said in the poster.

The International Psoriasis Council funded the study. The investigators did not list disclosures.

SCOTTSDALE, ARIZ. – Children and adolescents receiving methotrexate for psoriasis were significantly less likely to experience gastrointestinal side effects when they took a folate supplement every day instead of once weekly or 6 days a week, in a retrospective study of more than 400 pediatric psoriasis patients.

Laboratory abnormalities were significantly more common among children who received a folate supplement 6 days per week rather than daily, noted Inge Bronckers of the department of dermatology, Radboud University, Nijmegen, the Netherlands. “These results support the use of daily folate” in this group of patients,” she said in a poster presentation at the annual meeting of the Society for Investigative Dermatology.

thinkstockphotos.com

Few studies have examined patterns of use or adverse effects of pediatric psoriasis therapies. Although methotrexate is a folate antagonist with related toxicities, whether folate supplementation counteracts the efficacy of methotrexate is also unclear. Because of these uncertainties, some clinicians recommend a supplement 6 days per week, avoiding the day methotrexate is given, while others recommend it daily or once weekly.

To better understand the effects of these regimens, Ms. Inge and her coinvestigators studied 446 children and adolescents who received phototherapy or systemic treatments for moderate to severe psoriasis at 20 centers in the United States, Canada, and Europe between 1990 and 2014. The patients’ average age was 8 years (standard deviation, 4 years); 238 were female and 208 were male.

Among the 390 patients receiving systemic medications, almost 70% were receiving methotrexate, while 27% were being treated with etanercept or another biologic, 15% were using retinoids, 8% were using cyclosporine, and 5% were using fumaric acid. About 19% of patients were receiving more than one of these medications. Methotrexate most often led to nausea (affecting 18% of patients), elevated hepatic transaminases (13%), dyspepsia (7%), and infections (4%), usually of the skin and upper airways. In contrast, biologics most often caused injection-site reactions (19%) and upper airways infections (10%).

Most (253) of the 270 patients on methotrexate had been prescribed folic acid, typically at a dose of about 8 mg/wk, and nearly always in the form of pure folic acid, rather than a multivitamin. Of the patients taking folic acid, about 34% took it 6 days per week, 34% received it daily and 30% – including most patients in Europe – received it once weekly.

Notably, the odds of gastrointestinal side effects were 75% lower for patients who received folic acid daily or 6 days per week, compared with those who received folic acid once a week (odds ratio, 0.25, in both cases; P less than .001), the investigators found. However, laboratory abnormalities were significantly more likely when folic acid was given 6 days a week, compared with daily (OR, 2.31; P = .03) or weekly (OR, 3.9; P = .002). Patients in Europe, who usually received folic acid weekly, were significantly more likely to have methotrexate-related gastrointestinal side effects than were patients in North America (OR, 3.4; P less than .001), and were less likely to have laboratory abnormalities (OR, 0.32; P = .004).

Patients on biologic therapy were less likely to develop laboratory abnormalities or stop treatment because of side effects than were those on other systemic therapies, Ms. Inge and her associates found. Because methotrexate was associated with elevated liver enzymes, it also was dose adjusted more often than other therapies. No patient on any therapy was diagnosed with tuberculosis or malignancy, but three patients on methotrexate had severe adverse effects, including liver disease, methotrexate hypersensitivity pneumonitis, and severe personality changes. In contrast, fumarate was associated with one case each of pericarditis and bone marrow suppression, while one patient on the biologic adalimumab developed appendicitis.

The study underscores the need to monitor the long-term risks of pediatric psoriasis treatments, the researchers concluded. Data and lessons from the study are being used to develop a prospective pediatric psoriasis registry. “If industry joins forces to use this prospective international registry to capture prospective pediatric data, we will ensure early detection of safety signals and facilitate comparative analyses of efficacy and safety,” Ms. Inge said in the poster.

The International Psoriasis Council funded the study. The investigators did not list disclosures.

SCOTTSDALE, ARIZ. – Children and adolescents receiving methotrexate for psoriasis were significantly less likely to experience gastrointestinal side effects when they took a folate supplement every day instead of once weekly or 6 days a week, in a retrospective study of more than 400 pediatric psoriasis patients.

Laboratory abnormalities were significantly more common among children who received a folate supplement 6 days per week rather than daily, noted Inge Bronckers of the department of dermatology, Radboud University, Nijmegen, the Netherlands. “These results support the use of daily folate” in this group of patients,” she said in a poster presentation at the annual meeting of the Society for Investigative Dermatology.

thinkstockphotos.com

Few studies have examined patterns of use or adverse effects of pediatric psoriasis therapies. Although methotrexate is a folate antagonist with related toxicities, whether folate supplementation counteracts the efficacy of methotrexate is also unclear. Because of these uncertainties, some clinicians recommend a supplement 6 days per week, avoiding the day methotrexate is given, while others recommend it daily or once weekly.

To better understand the effects of these regimens, Ms. Inge and her coinvestigators studied 446 children and adolescents who received phototherapy or systemic treatments for moderate to severe psoriasis at 20 centers in the United States, Canada, and Europe between 1990 and 2014. The patients’ average age was 8 years (standard deviation, 4 years); 238 were female and 208 were male.

Among the 390 patients receiving systemic medications, almost 70% were receiving methotrexate, while 27% were being treated with etanercept or another biologic, 15% were using retinoids, 8% were using cyclosporine, and 5% were using fumaric acid. About 19% of patients were receiving more than one of these medications. Methotrexate most often led to nausea (affecting 18% of patients), elevated hepatic transaminases (13%), dyspepsia (7%), and infections (4%), usually of the skin and upper airways. In contrast, biologics most often caused injection-site reactions (19%) and upper airways infections (10%).

Most (253) of the 270 patients on methotrexate had been prescribed folic acid, typically at a dose of about 8 mg/wk, and nearly always in the form of pure folic acid, rather than a multivitamin. Of the patients taking folic acid, about 34% took it 6 days per week, 34% received it daily and 30% – including most patients in Europe – received it once weekly.

Notably, the odds of gastrointestinal side effects were 75% lower for patients who received folic acid daily or 6 days per week, compared with those who received folic acid once a week (odds ratio, 0.25, in both cases; P less than .001), the investigators found. However, laboratory abnormalities were significantly more likely when folic acid was given 6 days a week, compared with daily (OR, 2.31; P = .03) or weekly (OR, 3.9; P = .002). Patients in Europe, who usually received folic acid weekly, were significantly more likely to have methotrexate-related gastrointestinal side effects than were patients in North America (OR, 3.4; P less than .001), and were less likely to have laboratory abnormalities (OR, 0.32; P = .004).

Patients on biologic therapy were less likely to develop laboratory abnormalities or stop treatment because of side effects than were those on other systemic therapies, Ms. Inge and her associates found. Because methotrexate was associated with elevated liver enzymes, it also was dose adjusted more often than other therapies. No patient on any therapy was diagnosed with tuberculosis or malignancy, but three patients on methotrexate had severe adverse effects, including liver disease, methotrexate hypersensitivity pneumonitis, and severe personality changes. In contrast, fumarate was associated with one case each of pericarditis and bone marrow suppression, while one patient on the biologic adalimumab developed appendicitis.

The study underscores the need to monitor the long-term risks of pediatric psoriasis treatments, the researchers concluded. Data and lessons from the study are being used to develop a prospective pediatric psoriasis registry. “If industry joins forces to use this prospective international registry to capture prospective pediatric data, we will ensure early detection of safety signals and facilitate comparative analyses of efficacy and safety,” Ms. Inge said in the poster.

The International Psoriasis Council funded the study. The investigators did not list disclosures.

To the Editor: I read with great interest the article by Thomas et al, “Interpreting SPRINT: How low should you go?”¹

Hypertension is the most prevalent modifiable risk factor, affecting almost one in every three people in the United States.² Moreover, only half of people with hypertension have their blood pressure under control to the current standard of lower than 140/90 mm Hg.² The Systolic Blood Pressure Intervention Trial (SPRINT) tested a lower goal systolic pressure, ie, less than 120 mm Hg, and found it more beneficial than the standard goal of less than 140 mm Hg.³

A drawback of SPRINT that Thomas et al did not address in their interpretation of the trial is that the two study groups were not homogeneous in terms of the antihypertensive drugs used. Antihypertensive drugs do not only lower blood pressure—some of them have additional pleiotropic effects, making their use more advantageous in special situations. For example, renin-angiotensin-aldosterone system (RAAS) blockers—ie, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists—are disease-modfying drugs in heart failure, as are certain beta-blockers.⁴ The cardiovascular benefit seen in the intensive-treatment group in SPRINT compared with the standard-therapy group was primarily due to a reduction in heart failure (a 38% relative risk reduction, P = .0002),³ for which RAAS blockers and beta-adrenergic blocking drugs have been shown consistently to be beneficial. But the intensive- and standard-therapy groups were not homogeneous in terms of the use of RAAS blockers and beta-blockers.

So, was the cardiovascular benefit attained in the intensive-treatment group in SPRINT due to the benefit of lower blood pressure or to the drugs used?

To the Editor: I read with great interest the article by Thomas et al, “Interpreting SPRINT: How low should you go?”¹

Hypertension is the most prevalent modifiable risk factor, affecting almost one in every three people in the United States.² Moreover, only half of people with hypertension have their blood pressure under control to the current standard of lower than 140/90 mm Hg.² The Systolic Blood Pressure Intervention Trial (SPRINT) tested a lower goal systolic pressure, ie, less than 120 mm Hg, and found it more beneficial than the standard goal of less than 140 mm Hg.³

A drawback of SPRINT that Thomas et al did not address in their interpretation of the trial is that the two study groups were not homogeneous in terms of the antihypertensive drugs used. Antihypertensive drugs do not only lower blood pressure—some of them have additional pleiotropic effects, making their use more advantageous in special situations. For example, renin-angiotensin-aldosterone system (RAAS) blockers—ie, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists—are disease-modfying drugs in heart failure, as are certain beta-blockers.⁴ The cardiovascular benefit seen in the intensive-treatment group in SPRINT compared with the standard-therapy group was primarily due to a reduction in heart failure (a 38% relative risk reduction, P = .0002),³ for which RAAS blockers and beta-adrenergic blocking drugs have been shown consistently to be beneficial. But the intensive- and standard-therapy groups were not homogeneous in terms of the use of RAAS blockers and beta-blockers.

So, was the cardiovascular benefit attained in the intensive-treatment group in SPRINT due to the benefit of lower blood pressure or to the drugs used?

To the Editor: I read with great interest the article by Thomas et al, “Interpreting SPRINT: How low should you go?”¹

Hypertension is the most prevalent modifiable risk factor, affecting almost one in every three people in the United States.² Moreover, only half of people with hypertension have their blood pressure under control to the current standard of lower than 140/90 mm Hg.² The Systolic Blood Pressure Intervention Trial (SPRINT) tested a lower goal systolic pressure, ie, less than 120 mm Hg, and found it more beneficial than the standard goal of less than 140 mm Hg.³

A drawback of SPRINT that Thomas et al did not address in their interpretation of the trial is that the two study groups were not homogeneous in terms of the antihypertensive drugs used. Antihypertensive drugs do not only lower blood pressure—some of them have additional pleiotropic effects, making their use more advantageous in special situations. For example, renin-angiotensin-aldosterone system (RAAS) blockers—ie, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists—are disease-modfying drugs in heart failure, as are certain beta-blockers.⁴ The cardiovascular benefit seen in the intensive-treatment group in SPRINT compared with the standard-therapy group was primarily due to a reduction in heart failure (a 38% relative risk reduction, P = .0002),³ for which RAAS blockers and beta-adrenergic blocking drugs have been shown consistently to be beneficial. But the intensive- and standard-therapy groups were not homogeneous in terms of the use of RAAS blockers and beta-blockers.

So, was the cardiovascular benefit attained in the intensive-treatment group in SPRINT due to the benefit of lower blood pressure or to the drugs used?

A day in the psychiatry clinic? No—just scenes from that high-stakes festival of intense human competitiveness gone awry: the current presidential election. Alas, we have no FDA-approved treatments for any of these unusual political behaviors.

More stunning is how blind some loyal voters are to the flaws of their candidate of choice. They seem to be joyfully intoxicated by sharing the unusual beliefs of the candidate, in a cultish folie en masse of epidemic proportion.

Other (rational) voters are stunned and jarred by what they see and hear; they appear to be in need of Rx: an intellectual antiemetic.

The rise of uber-narcissism
A certain amount of narcissism is, understandably, necessary to run for the nation’s highest office and to believe, against all odds, that winning is certain despite microscopic favorability in the polls. In this election cycle, the cup of narcissism has run over; yet, to adoring fans, narcissism only adds a wondrous halo to their candidate.

The history of the United States is rife with similar behavior by elected officials, including our revered Founding Fathers.¹ But today’s psychiatrists, witnessing this national charade, are perplexed and question the rationality of the national psyche. Established rules for seeking the Presidency have been demolished and the show goes on as if heightened narcissism is the new normal in human behavior.

Giving voice to my colleagues’ consternation
Here are a few thoughts that might cross the mind of psychiatrists as they watch, with a frown and pursed lips, this unconventional election cycle:

From a psychoanalytic perspective, the id has left the ego in its dust, and the super-ego went home to hide.

When boorishness trumps civility, hillaryous consequences ensue.

The gullibility of voters deserves serious scientific study. Jeste and Harris² reviewed the evidence for a neurobiology of wisdom; The National Institutes of Health should fund research into how some voters believe the candidate of their choice will provide them with everything they wish. The chicken in every pot expands to 100 in every pot, and money grows on trees (at least on 1% of the forest!).

From an evolutionary standpoint, survival of the fittest has become survival of the most bombastic.

The zeitgeist reflects an electorate that oscillates agonizingly from surprise to anger to cynicism to disgust.

The traditional internal conflict (studied by political scientists) of choosing between 2 reasonably meritorious candidates has been transformed into a conflict over whether to vote at all.

This is the least nuanced presidential campaign—ever.

All decision-making in politics is unconscious, political scientist Jon A. Krosnick proposed. In this election, however, candidates’ enunciations are so overt that it’s hard to believe there’s anything left in the unconscious. Freud spoke of the “primary process” arising from the unconscious; he definitely was not referring to the primary process we experienced during this election cycle.

From a neuropsychiatric perspective, the limbic system has kicked the cortex in the metaphorical derrière in this election campaign.

Unabashed display of character flaws, personal shortcomings, and biases prove that anyone can run for president in a democracy, and that some voters will display a flight of reason and vote for a flawed candidate.

Even an inept demagogue can be misperceived as a savior by followers. Some voters could use a few sessions of insight-oriented therapy or cognitive-behavioral therapy for their unrealistic expectations.

It is dizzying, mentally, to watch candidates’ verbal acrobatics as they try to pass several litmus tests to satisfy disparate demands of sundry constituencies and mendaciously flip-flop on many issues—ignoring the fact that everything they have said was recorded or videotaped. Intellectual transvestism is a political sin, and sinners abound.

Oh, for a Jenner, Pasteur, or Sabin to discover vaccines for the intellect
Writing this editorial has been therapeutic. It feels good to ventilate about this bizarre election process that has the nation in its grip. I would feel much better if neuroscientists would develop and license vaccines that would broadly inoculate candidates against demagoguery, dishonesty, and pandering and voters against mind-boggling gullibility.

That would make elections so boring. But also so on-label….

A day in the psychiatry clinic? No—just scenes from that high-stakes festival of intense human competitiveness gone awry: the current presidential election. Alas, we have no FDA-approved treatments for any of these unusual political behaviors.

More stunning is how blind some loyal voters are to the flaws of their candidate of choice. They seem to be joyfully intoxicated by sharing the unusual beliefs of the candidate, in a cultish folie en masse of epidemic proportion.

Other (rational) voters are stunned and jarred by what they see and hear; they appear to be in need of Rx: an intellectual antiemetic.

The rise of uber-narcissism
A certain amount of narcissism is, understandably, necessary to run for the nation’s highest office and to believe, against all odds, that winning is certain despite microscopic favorability in the polls. In this election cycle, the cup of narcissism has run over; yet, to adoring fans, narcissism only adds a wondrous halo to their candidate.

The history of the United States is rife with similar behavior by elected officials, including our revered Founding Fathers.¹ But today’s psychiatrists, witnessing this national charade, are perplexed and question the rationality of the national psyche. Established rules for seeking the Presidency have been demolished and the show goes on as if heightened narcissism is the new normal in human behavior.

Giving voice to my colleagues’ consternation
Here are a few thoughts that might cross the mind of psychiatrists as they watch, with a frown and pursed lips, this unconventional election cycle:

From a psychoanalytic perspective, the id has left the ego in its dust, and the super-ego went home to hide.

When boorishness trumps civility, hillaryous consequences ensue.

The gullibility of voters deserves serious scientific study. Jeste and Harris² reviewed the evidence for a neurobiology of wisdom; The National Institutes of Health should fund research into how some voters believe the candidate of their choice will provide them with everything they wish. The chicken in every pot expands to 100 in every pot, and money grows on trees (at least on 1% of the forest!).

From an evolutionary standpoint, survival of the fittest has become survival of the most bombastic.

The zeitgeist reflects an electorate that oscillates agonizingly from surprise to anger to cynicism to disgust.

The traditional internal conflict (studied by political scientists) of choosing between 2 reasonably meritorious candidates has been transformed into a conflict over whether to vote at all.

This is the least nuanced presidential campaign—ever.

All decision-making in politics is unconscious, political scientist Jon A. Krosnick proposed. In this election, however, candidates’ enunciations are so overt that it’s hard to believe there’s anything left in the unconscious. Freud spoke of the “primary process” arising from the unconscious; he definitely was not referring to the primary process we experienced during this election cycle.

From a neuropsychiatric perspective, the limbic system has kicked the cortex in the metaphorical derrière in this election campaign.

Unabashed display of character flaws, personal shortcomings, and biases prove that anyone can run for president in a democracy, and that some voters will display a flight of reason and vote for a flawed candidate.

Even an inept demagogue can be misperceived as a savior by followers. Some voters could use a few sessions of insight-oriented therapy or cognitive-behavioral therapy for their unrealistic expectations.

It is dizzying, mentally, to watch candidates’ verbal acrobatics as they try to pass several litmus tests to satisfy disparate demands of sundry constituencies and mendaciously flip-flop on many issues—ignoring the fact that everything they have said was recorded or videotaped. Intellectual transvestism is a political sin, and sinners abound.

Oh, for a Jenner, Pasteur, or Sabin to discover vaccines for the intellect
Writing this editorial has been therapeutic. It feels good to ventilate about this bizarre election process that has the nation in its grip. I would feel much better if neuroscientists would develop and license vaccines that would broadly inoculate candidates against demagoguery, dishonesty, and pandering and voters against mind-boggling gullibility.

That would make elections so boring. But also so on-label….

A day in the psychiatry clinic? No—just scenes from that high-stakes festival of intense human competitiveness gone awry: the current presidential election. Alas, we have no FDA-approved treatments for any of these unusual political behaviors.

More stunning is how blind some loyal voters are to the flaws of their candidate of choice. They seem to be joyfully intoxicated by sharing the unusual beliefs of the candidate, in a cultish folie en masse of epidemic proportion.

Other (rational) voters are stunned and jarred by what they see and hear; they appear to be in need of Rx: an intellectual antiemetic.

The rise of uber-narcissism
A certain amount of narcissism is, understandably, necessary to run for the nation’s highest office and to believe, against all odds, that winning is certain despite microscopic favorability in the polls. In this election cycle, the cup of narcissism has run over; yet, to adoring fans, narcissism only adds a wondrous halo to their candidate.

The history of the United States is rife with similar behavior by elected officials, including our revered Founding Fathers.¹ But today’s psychiatrists, witnessing this national charade, are perplexed and question the rationality of the national psyche. Established rules for seeking the Presidency have been demolished and the show goes on as if heightened narcissism is the new normal in human behavior.

Giving voice to my colleagues’ consternation
Here are a few thoughts that might cross the mind of psychiatrists as they watch, with a frown and pursed lips, this unconventional election cycle:

From a psychoanalytic perspective, the id has left the ego in its dust, and the super-ego went home to hide.

When boorishness trumps civility, hillaryous consequences ensue.

The gullibility of voters deserves serious scientific study. Jeste and Harris² reviewed the evidence for a neurobiology of wisdom; The National Institutes of Health should fund research into how some voters believe the candidate of their choice will provide them with everything they wish. The chicken in every pot expands to 100 in every pot, and money grows on trees (at least on 1% of the forest!).

From an evolutionary standpoint, survival of the fittest has become survival of the most bombastic.

The zeitgeist reflects an electorate that oscillates agonizingly from surprise to anger to cynicism to disgust.

The traditional internal conflict (studied by political scientists) of choosing between 2 reasonably meritorious candidates has been transformed into a conflict over whether to vote at all.

This is the least nuanced presidential campaign—ever.

All decision-making in politics is unconscious, political scientist Jon A. Krosnick proposed. In this election, however, candidates’ enunciations are so overt that it’s hard to believe there’s anything left in the unconscious. Freud spoke of the “primary process” arising from the unconscious; he definitely was not referring to the primary process we experienced during this election cycle.

From a neuropsychiatric perspective, the limbic system has kicked the cortex in the metaphorical derrière in this election campaign.

Unabashed display of character flaws, personal shortcomings, and biases prove that anyone can run for president in a democracy, and that some voters will display a flight of reason and vote for a flawed candidate.

Even an inept demagogue can be misperceived as a savior by followers. Some voters could use a few sessions of insight-oriented therapy or cognitive-behavioral therapy for their unrealistic expectations.

It is dizzying, mentally, to watch candidates’ verbal acrobatics as they try to pass several litmus tests to satisfy disparate demands of sundry constituencies and mendaciously flip-flop on many issues—ignoring the fact that everything they have said was recorded or videotaped. Intellectual transvestism is a political sin, and sinners abound.

Oh, for a Jenner, Pasteur, or Sabin to discover vaccines for the intellect
Writing this editorial has been therapeutic. It feels good to ventilate about this bizarre election process that has the nation in its grip. I would feel much better if neuroscientists would develop and license vaccines that would broadly inoculate candidates against demagoguery, dishonesty, and pandering and voters against mind-boggling gullibility.

That would make elections so boring. But also so on-label….

Granulosa cell tumors arise from ovarian sex cords and make up an estimated 1% of all ovarian cancer cases but comprise more than 70% of all sex cord stromal tumors.

Granulosa cell tumors (GCTs) can be divided into adult and juvenile types. Adult GCTs are much more common, representing 95% of all GCTs. Women diagnosed with adult GCTs are typically younger as compared with those with epithelial ovarian cancer. The average age of diagnosis for adult GCTs is 50 years, and for women with juvenile GCTs, the average age at diagnosis is 20 years.

Granulosa cell tumors have been shown to be more common in nonwhite women, those with a high body mass index, and a family history of breast or ovarian cancer.¹

Adult GCTs can be associated with Peutz-Jeghers and Potter syndromes. Juvenile GCTs are exceedingly rare but can also be associated with mesodermal dysplastic syndromes characterized by the presence of enchondromatosis and hemangioma formation, such as Ollier disease or Maffucci syndrome.

Adult granulosa cell tumors are large, hormonally active tumors; typically secreting estrogen and associated with symptoms of hyperestrogenism. In one study, 55% of women with GCTs were reported to have hyperestrogenic findings such as breast tenderness, virulism, abnormal or postmenopausal bleeding, and hyperplasia, and those with juvenile GCTs may present with precocious puberty.^2,3

In pregnancy, hormonal symptoms are temporized, thus the most common presentation is acute rupture. Initial evaluation of women with adult GCTs will reveal a palpable unilateral pelvic mass typically larger than 10cm. Juvenile and adult GCTs are unilateral in 95% of cases.⁴

In women presenting with a large adnexal mass, the appropriate initial clinical evaluation includes radiographic and laboratory studies. Endovaginal ultrasound typically reveals a large adnexal mass with heterogeneous solid and cystic components, areas of hemorrhage or necrosis and increased vascularity on Doppler. Juvenile GCTs have a more distinct appearance of solid growth with focal areas of follicular formation.

Laboratory findings suggestive of GCT include elevated inhibin-A, inhibin-B, anti-Mullerian hormone (AMH), and CA-125. Inhibin-B is the most commonly used tumor marker for the clinical monitoring of adult GCTs, but AMH may be the most specific.⁵ Lastly, an endometrial biopsy should be considered in all patients with abnormal uterine bleeding and in all postmenopausal women with an adnexal mass and an endometrial stripe greater than 5mm.⁶

Surgical staging for adult GCTs is the standard of care. For women who do not desire fertility, this includes total hysterectomy, bilateral salpingo-oophorectomy and removal of all gross disease. Comprehensive nodal dissection is not indicated except when necessary for complete cytoreduction. In contrast to epithelial ovarian cancer, approximately 80% of women with adult GCTs are diagnosed with stage I disease. For stage IA disease, treatment with surgery alone is sufficient, yet in women with stage II-IV disease or with tumors that are ruptured intraoperatively, platinum-based chemotherapy is recommended. The most common regimen is bleomycin, etoposide, and cisplatin, though there is increasing experience with an outpatient regimen of paclitaxel and carboplatin.

The gross appearance of both adult and juvenile GCTs are of a large, tan-yellow tumor with cystic, solid, and hemorrhagic components. Microscopically, juvenile GCTs are more distinct than that of adult GCTs. Whereas adult GCTs comprise diffuse cords or trabeculae and small follicles termed Call-Exner bodies of rounded cells with scant cytoplasm and pale “coffee-bean” nuclei, juvenile GCTs have nuclei that are rounded, hyperchromatic with moderate to abundant eosinophilic or vacuolated cytoplasm.

The prognosis of GCTs is largely dependent on the stage at diagnosis and presence of residual disease after debulking. Negative prognostic factors for recurrence include tumor size, rupture, atypia and increased mitotic activity.

There are distinct clinical, radiographic, and laboratory characteristics that may raise the suspicion of the practicing gynecologist for a GCT. In such cases, expedient referral for surgical exploration to a gynecologic oncologist is warranted. If the tumor is encountered inadvertently, intraoperative consultation from a gynecologic oncologist should be requested. If a gynecologic oncologist is not available, it is paramount to optimize surgical exposure to clearly document any abnormal pelvic or intra-abdominal findings, take care to prevent surgical spillage, and preserve fertility if indicated.

If referred appropriately and completely resected, the 5-year overall survival of stage IA disease can be upward of 90%. Recurrences are stage dependent with an average time to recurrence of just under 5 years. When recurrences occur, they tend to happen in the pelvis. All women with a history of GCT will require surveillance and monitoring.

References

1. Gynecol Oncol. 2005 May;97(2):519-23.

2. “Rare and Uncommon Gynecological Cancers: A Clinical Guide” (Heidelberg: Springer, 2011): Reed N.

3. Obstet Gynecol. 1980 Feb;55(2):231-8.

4. “Principles and Practice of Gynecologic Oncology” (Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2013): Barakat R.

5. Indian J Surg Oncol. 2013 Mar;4(1):37-47.

6. “Uncommon Gynecologic Cancers” (Indianapolis: Wiley-Blackwell, 2014): Del Carmen M.

Dr. Gehrig is professor and director of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Castellano is a resident physician in the obstetrics and gynecology program at the university. They reported having no relevant financial disclosures. To comment, email them at [email protected].

Granulosa cell tumors arise from ovarian sex cords and make up an estimated 1% of all ovarian cancer cases but comprise more than 70% of all sex cord stromal tumors.

Granulosa cell tumors (GCTs) can be divided into adult and juvenile types. Adult GCTs are much more common, representing 95% of all GCTs. Women diagnosed with adult GCTs are typically younger as compared with those with epithelial ovarian cancer. The average age of diagnosis for adult GCTs is 50 years, and for women with juvenile GCTs, the average age at diagnosis is 20 years.

Granulosa cell tumors have been shown to be more common in nonwhite women, those with a high body mass index, and a family history of breast or ovarian cancer.¹

Adult GCTs can be associated with Peutz-Jeghers and Potter syndromes. Juvenile GCTs are exceedingly rare but can also be associated with mesodermal dysplastic syndromes characterized by the presence of enchondromatosis and hemangioma formation, such as Ollier disease or Maffucci syndrome.

Adult granulosa cell tumors are large, hormonally active tumors; typically secreting estrogen and associated with symptoms of hyperestrogenism. In one study, 55% of women with GCTs were reported to have hyperestrogenic findings such as breast tenderness, virulism, abnormal or postmenopausal bleeding, and hyperplasia, and those with juvenile GCTs may present with precocious puberty.^2,3

In pregnancy, hormonal symptoms are temporized, thus the most common presentation is acute rupture. Initial evaluation of women with adult GCTs will reveal a palpable unilateral pelvic mass typically larger than 10cm. Juvenile and adult GCTs are unilateral in 95% of cases.⁴

In women presenting with a large adnexal mass, the appropriate initial clinical evaluation includes radiographic and laboratory studies. Endovaginal ultrasound typically reveals a large adnexal mass with heterogeneous solid and cystic components, areas of hemorrhage or necrosis and increased vascularity on Doppler. Juvenile GCTs have a more distinct appearance of solid growth with focal areas of follicular formation.

Laboratory findings suggestive of GCT include elevated inhibin-A, inhibin-B, anti-Mullerian hormone (AMH), and CA-125. Inhibin-B is the most commonly used tumor marker for the clinical monitoring of adult GCTs, but AMH may be the most specific.⁵ Lastly, an endometrial biopsy should be considered in all patients with abnormal uterine bleeding and in all postmenopausal women with an adnexal mass and an endometrial stripe greater than 5mm.⁶

Surgical staging for adult GCTs is the standard of care. For women who do not desire fertility, this includes total hysterectomy, bilateral salpingo-oophorectomy and removal of all gross disease. Comprehensive nodal dissection is not indicated except when necessary for complete cytoreduction. In contrast to epithelial ovarian cancer, approximately 80% of women with adult GCTs are diagnosed with stage I disease. For stage IA disease, treatment with surgery alone is sufficient, yet in women with stage II-IV disease or with tumors that are ruptured intraoperatively, platinum-based chemotherapy is recommended. The most common regimen is bleomycin, etoposide, and cisplatin, though there is increasing experience with an outpatient regimen of paclitaxel and carboplatin.

The gross appearance of both adult and juvenile GCTs are of a large, tan-yellow tumor with cystic, solid, and hemorrhagic components. Microscopically, juvenile GCTs are more distinct than that of adult GCTs. Whereas adult GCTs comprise diffuse cords or trabeculae and small follicles termed Call-Exner bodies of rounded cells with scant cytoplasm and pale “coffee-bean” nuclei, juvenile GCTs have nuclei that are rounded, hyperchromatic with moderate to abundant eosinophilic or vacuolated cytoplasm.

The prognosis of GCTs is largely dependent on the stage at diagnosis and presence of residual disease after debulking. Negative prognostic factors for recurrence include tumor size, rupture, atypia and increased mitotic activity.

There are distinct clinical, radiographic, and laboratory characteristics that may raise the suspicion of the practicing gynecologist for a GCT. In such cases, expedient referral for surgical exploration to a gynecologic oncologist is warranted. If the tumor is encountered inadvertently, intraoperative consultation from a gynecologic oncologist should be requested. If a gynecologic oncologist is not available, it is paramount to optimize surgical exposure to clearly document any abnormal pelvic or intra-abdominal findings, take care to prevent surgical spillage, and preserve fertility if indicated.

If referred appropriately and completely resected, the 5-year overall survival of stage IA disease can be upward of 90%. Recurrences are stage dependent with an average time to recurrence of just under 5 years. When recurrences occur, they tend to happen in the pelvis. All women with a history of GCT will require surveillance and monitoring.

References

1. Gynecol Oncol. 2005 May;97(2):519-23.

2. “Rare and Uncommon Gynecological Cancers: A Clinical Guide” (Heidelberg: Springer, 2011): Reed N.

3. Obstet Gynecol. 1980 Feb;55(2):231-8.

4. “Principles and Practice of Gynecologic Oncology” (Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2013): Barakat R.

5. Indian J Surg Oncol. 2013 Mar;4(1):37-47.

6. “Uncommon Gynecologic Cancers” (Indianapolis: Wiley-Blackwell, 2014): Del Carmen M.

Dr. Gehrig is professor and director of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Castellano is a resident physician in the obstetrics and gynecology program at the university. They reported having no relevant financial disclosures. To comment, email them at [email protected].

Granulosa cell tumors arise from ovarian sex cords and make up an estimated 1% of all ovarian cancer cases but comprise more than 70% of all sex cord stromal tumors.

Granulosa cell tumors (GCTs) can be divided into adult and juvenile types. Adult GCTs are much more common, representing 95% of all GCTs. Women diagnosed with adult GCTs are typically younger as compared with those with epithelial ovarian cancer. The average age of diagnosis for adult GCTs is 50 years, and for women with juvenile GCTs, the average age at diagnosis is 20 years.

Granulosa cell tumors have been shown to be more common in nonwhite women, those with a high body mass index, and a family history of breast or ovarian cancer.¹

Adult GCTs can be associated with Peutz-Jeghers and Potter syndromes. Juvenile GCTs are exceedingly rare but can also be associated with mesodermal dysplastic syndromes characterized by the presence of enchondromatosis and hemangioma formation, such as Ollier disease or Maffucci syndrome.

Adult granulosa cell tumors are large, hormonally active tumors; typically secreting estrogen and associated with symptoms of hyperestrogenism. In one study, 55% of women with GCTs were reported to have hyperestrogenic findings such as breast tenderness, virulism, abnormal or postmenopausal bleeding, and hyperplasia, and those with juvenile GCTs may present with precocious puberty.^2,3

In pregnancy, hormonal symptoms are temporized, thus the most common presentation is acute rupture. Initial evaluation of women with adult GCTs will reveal a palpable unilateral pelvic mass typically larger than 10cm. Juvenile and adult GCTs are unilateral in 95% of cases.⁴

In women presenting with a large adnexal mass, the appropriate initial clinical evaluation includes radiographic and laboratory studies. Endovaginal ultrasound typically reveals a large adnexal mass with heterogeneous solid and cystic components, areas of hemorrhage or necrosis and increased vascularity on Doppler. Juvenile GCTs have a more distinct appearance of solid growth with focal areas of follicular formation.

Laboratory findings suggestive of GCT include elevated inhibin-A, inhibin-B, anti-Mullerian hormone (AMH), and CA-125. Inhibin-B is the most commonly used tumor marker for the clinical monitoring of adult GCTs, but AMH may be the most specific.⁵ Lastly, an endometrial biopsy should be considered in all patients with abnormal uterine bleeding and in all postmenopausal women with an adnexal mass and an endometrial stripe greater than 5mm.⁶

Surgical staging for adult GCTs is the standard of care. For women who do not desire fertility, this includes total hysterectomy, bilateral salpingo-oophorectomy and removal of all gross disease. Comprehensive nodal dissection is not indicated except when necessary for complete cytoreduction. In contrast to epithelial ovarian cancer, approximately 80% of women with adult GCTs are diagnosed with stage I disease. For stage IA disease, treatment with surgery alone is sufficient, yet in women with stage II-IV disease or with tumors that are ruptured intraoperatively, platinum-based chemotherapy is recommended. The most common regimen is bleomycin, etoposide, and cisplatin, though there is increasing experience with an outpatient regimen of paclitaxel and carboplatin.

The gross appearance of both adult and juvenile GCTs are of a large, tan-yellow tumor with cystic, solid, and hemorrhagic components. Microscopically, juvenile GCTs are more distinct than that of adult GCTs. Whereas adult GCTs comprise diffuse cords or trabeculae and small follicles termed Call-Exner bodies of rounded cells with scant cytoplasm and pale “coffee-bean” nuclei, juvenile GCTs have nuclei that are rounded, hyperchromatic with moderate to abundant eosinophilic or vacuolated cytoplasm.

The prognosis of GCTs is largely dependent on the stage at diagnosis and presence of residual disease after debulking. Negative prognostic factors for recurrence include tumor size, rupture, atypia and increased mitotic activity.

There are distinct clinical, radiographic, and laboratory characteristics that may raise the suspicion of the practicing gynecologist for a GCT. In such cases, expedient referral for surgical exploration to a gynecologic oncologist is warranted. If the tumor is encountered inadvertently, intraoperative consultation from a gynecologic oncologist should be requested. If a gynecologic oncologist is not available, it is paramount to optimize surgical exposure to clearly document any abnormal pelvic or intra-abdominal findings, take care to prevent surgical spillage, and preserve fertility if indicated.

If referred appropriately and completely resected, the 5-year overall survival of stage IA disease can be upward of 90%. Recurrences are stage dependent with an average time to recurrence of just under 5 years. When recurrences occur, they tend to happen in the pelvis. All women with a history of GCT will require surveillance and monitoring.

References

1. Gynecol Oncol. 2005 May;97(2):519-23.

2. “Rare and Uncommon Gynecological Cancers: A Clinical Guide” (Heidelberg: Springer, 2011): Reed N.

3. Obstet Gynecol. 1980 Feb;55(2):231-8.

4. “Principles and Practice of Gynecologic Oncology” (Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2013): Barakat R.

5. Indian J Surg Oncol. 2013 Mar;4(1):37-47.

6. “Uncommon Gynecologic Cancers” (Indianapolis: Wiley-Blackwell, 2014): Del Carmen M.

Dr. Gehrig is professor and director of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Castellano is a resident physician in the obstetrics and gynecology program at the university. They reported having no relevant financial disclosures. To comment, email them at [email protected].

To the Editor: In their review,¹ Thomas et al noted that the benefits of intensive blood pressure lowering seen in the SPRINT study² were not observed in the Action to Control Cardiovascular Risk in Diabetes-Blood pressure (ACCORD BP) trial³ or in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial.⁴ In addition to the reasons discussed in their review, the discrepancy may be due to the surprisingly low rate of statin use in the patients enrolled in SPRINT. Even though 61% of the patients in SPRINT had a 10-year Framingham risk score greater than 15%, only 44% of the patients were on statin therapy. In comparison, rates of statin use in ACCORD BP and SPS3 were 65% and 83%, respectively.

A possible interaction between statin use and intensive blood pressure lowering is consistent with previous data on angiotensin-converting enzyme (ACE) inhibitor use in high-risk populations.

The Heart Outcomes Prevention Evaluation (HOPE) trial,⁵ in which only 29% of patients received lipid-lowering therapy, found that ACE inhibitor use was associated with a significant reduction in a composite cardiovascular outcome, whereas the Prevention of Events With Angiotensin-Converting Enzyme Inhibitor Therapy (PEACE) trial,⁶ in which 70% of patients were on lipid-lowering therapy, did not show a benefit for ACE inhibitor therapy. In addition, there are many drug interactions between statins and calcium channel blockers, potentially limiting options for simultaneous aggressive treatment of lipid levels and blood pressure.

In summary, aggressive use of statins may confer sufficient cardiovascular protection when aggressive antihypertensive therapy provides little or no incremental benefit. Hopefully, further analyses of these trials will shed light on this important question.

To the Editor: In their review,¹ Thomas et al noted that the benefits of intensive blood pressure lowering seen in the SPRINT study² were not observed in the Action to Control Cardiovascular Risk in Diabetes-Blood pressure (ACCORD BP) trial³ or in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial.⁴ In addition to the reasons discussed in their review, the discrepancy may be due to the surprisingly low rate of statin use in the patients enrolled in SPRINT. Even though 61% of the patients in SPRINT had a 10-year Framingham risk score greater than 15%, only 44% of the patients were on statin therapy. In comparison, rates of statin use in ACCORD BP and SPS3 were 65% and 83%, respectively.

A possible interaction between statin use and intensive blood pressure lowering is consistent with previous data on angiotensin-converting enzyme (ACE) inhibitor use in high-risk populations.

The Heart Outcomes Prevention Evaluation (HOPE) trial,⁵ in which only 29% of patients received lipid-lowering therapy, found that ACE inhibitor use was associated with a significant reduction in a composite cardiovascular outcome, whereas the Prevention of Events With Angiotensin-Converting Enzyme Inhibitor Therapy (PEACE) trial,⁶ in which 70% of patients were on lipid-lowering therapy, did not show a benefit for ACE inhibitor therapy. In addition, there are many drug interactions between statins and calcium channel blockers, potentially limiting options for simultaneous aggressive treatment of lipid levels and blood pressure.

In summary, aggressive use of statins may confer sufficient cardiovascular protection when aggressive antihypertensive therapy provides little or no incremental benefit. Hopefully, further analyses of these trials will shed light on this important question.

To the Editor: In their review,¹ Thomas et al noted that the benefits of intensive blood pressure lowering seen in the SPRINT study² were not observed in the Action to Control Cardiovascular Risk in Diabetes-Blood pressure (ACCORD BP) trial³ or in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial.⁴ In addition to the reasons discussed in their review, the discrepancy may be due to the surprisingly low rate of statin use in the patients enrolled in SPRINT. Even though 61% of the patients in SPRINT had a 10-year Framingham risk score greater than 15%, only 44% of the patients were on statin therapy. In comparison, rates of statin use in ACCORD BP and SPS3 were 65% and 83%, respectively.

A possible interaction between statin use and intensive blood pressure lowering is consistent with previous data on angiotensin-converting enzyme (ACE) inhibitor use in high-risk populations.

The Heart Outcomes Prevention Evaluation (HOPE) trial,⁵ in which only 29% of patients received lipid-lowering therapy, found that ACE inhibitor use was associated with a significant reduction in a composite cardiovascular outcome, whereas the Prevention of Events With Angiotensin-Converting Enzyme Inhibitor Therapy (PEACE) trial,⁶ in which 70% of patients were on lipid-lowering therapy, did not show a benefit for ACE inhibitor therapy. In addition, there are many drug interactions between statins and calcium channel blockers, potentially limiting options for simultaneous aggressive treatment of lipid levels and blood pressure.

In summary, aggressive use of statins may confer sufficient cardiovascular protection when aggressive antihypertensive therapy provides little or no incremental benefit. Hopefully, further analyses of these trials will shed light on this important question.

A retrospective study of nearly 1.5 million patients over the course of 44 years showed no evidence to support the claim that neurodegenerative disorders can be transmitted between individuals through blood transfusions.

“Given that the neurodegenerative diseases on the dementia spectrum are relatively common, the misfolded proteins in affected persons have a wide tissue distribution, and the diseases may have a protracted prediagnostic course, potential transmission through transfusion could have important public health implications,” explained study authors led by Gustaf Edgren, MD, PhD, of the Karolinska Institute in Stockholm.

©Hemera/Thinkstock.com

The retrospective cohort study analyzed data on 1,465,845 patients listed in nationwide transfusion registers, all of whom had undergone transfusions between 1968 and 2012 in Sweden, or during 1981-2012 in Denmark. The investigators looked for transfusions in which the donor had a diagnosis – either before or after the transfusion – of Alzheimer’s disease, Parkinson’s disease, or amyotrophic lateral sclerosis, and compared them with transfusions involving two healthy control groups. Creutzfeldt-Jakob disease was not included in the analysis (Ann Intern Med. 2016 Jun 28. doi: 10.7326/M15-2421).

All transfusion recipients were followed from 180 days after the transfusion date in order to minimize the risk of including a patient who had a neurodegenerative disorder that was present but not registered at the time of the transfusion. Follow-ups lasted until either the first diagnosis of a neurodegenerative disorder, death, emigration, or the end of the trial period on Dec. 31, 2012.

If a donor had received a diagnosis of a neurodegenerative disorder within 20 years of the transfusion, all recipients from said donor were considered to be exposed. “The maximum latency of 20 years was used as a compromise between allowing a long preclinical phase – during which donors may still be infectious – and avoiding classifying clearly healthy donors as potentially infectious,” the authors wrote.

Only 42,254 (2.9%) of subjects were deemed to be exposed to a neurodegenerative disorder based on their blood transfusion donor. However, there was no evidence of any increased risk of dementia of any type from exposure to blood from affected donors in any of the recipients over the course of the follow-up period (hazard ratio, 1.04; 95% confidence interval, 0.99-1.09), and similar results were obtained individually for Alzheimer’s disease and Parkinson’s disease. As a control measure, the investigators also tested for hepatitis C transmission before and after transfusions, and were “as expected, readily able to detect transmission of viral hepatitis,” despite finding no traces of neurodegenerative conditions.

“Despite accumulating scientific support for horizontal transmissibility of a range of disorders in the neurodegenerative spectrum through various methods of inoculation in animal models and of variant Creutzfeldt-Jakob disease from human and animal model data, this study provides evidence against blood transfusion as an important route of transmission of neurodegenerative diseases between humans,” the authors concluded.

The authors also added that “given that the study was based on the entire computerized blood banking history in two countries with several decades of follow-up, more comprehensive data are unlikely to be available in the foreseeable future.”

Funding for the study was provided by the Swedish Research Council, the Swedish Heart-Lung Foundation, the Swedish Society for Medical Research, and the Danish Council for Independent Research. One coauthor reported receiving a grant from the Danish Council for Independent Research, and another reported receiving grants from the Swedish Research Council and the Swedish Heart-Lung Foundation during the conduct of the study. No other authors reported any relevant financial disclosures.

[email protected]

A retrospective study of nearly 1.5 million patients over the course of 44 years showed no evidence to support the claim that neurodegenerative disorders can be transmitted between individuals through blood transfusions.

“Given that the neurodegenerative diseases on the dementia spectrum are relatively common, the misfolded proteins in affected persons have a wide tissue distribution, and the diseases may have a protracted prediagnostic course, potential transmission through transfusion could have important public health implications,” explained study authors led by Gustaf Edgren, MD, PhD, of the Karolinska Institute in Stockholm.

©Hemera/Thinkstock.com

The retrospective cohort study analyzed data on 1,465,845 patients listed in nationwide transfusion registers, all of whom had undergone transfusions between 1968 and 2012 in Sweden, or during 1981-2012 in Denmark. The investigators looked for transfusions in which the donor had a diagnosis – either before or after the transfusion – of Alzheimer’s disease, Parkinson’s disease, or amyotrophic lateral sclerosis, and compared them with transfusions involving two healthy control groups. Creutzfeldt-Jakob disease was not included in the analysis (Ann Intern Med. 2016 Jun 28. doi: 10.7326/M15-2421).

All transfusion recipients were followed from 180 days after the transfusion date in order to minimize the risk of including a patient who had a neurodegenerative disorder that was present but not registered at the time of the transfusion. Follow-ups lasted until either the first diagnosis of a neurodegenerative disorder, death, emigration, or the end of the trial period on Dec. 31, 2012.

If a donor had received a diagnosis of a neurodegenerative disorder within 20 years of the transfusion, all recipients from said donor were considered to be exposed. “The maximum latency of 20 years was used as a compromise between allowing a long preclinical phase – during which donors may still be infectious – and avoiding classifying clearly healthy donors as potentially infectious,” the authors wrote.

Only 42,254 (2.9%) of subjects were deemed to be exposed to a neurodegenerative disorder based on their blood transfusion donor. However, there was no evidence of any increased risk of dementia of any type from exposure to blood from affected donors in any of the recipients over the course of the follow-up period (hazard ratio, 1.04; 95% confidence interval, 0.99-1.09), and similar results were obtained individually for Alzheimer’s disease and Parkinson’s disease. As a control measure, the investigators also tested for hepatitis C transmission before and after transfusions, and were “as expected, readily able to detect transmission of viral hepatitis,” despite finding no traces of neurodegenerative conditions.

“Despite accumulating scientific support for horizontal transmissibility of a range of disorders in the neurodegenerative spectrum through various methods of inoculation in animal models and of variant Creutzfeldt-Jakob disease from human and animal model data, this study provides evidence against blood transfusion as an important route of transmission of neurodegenerative diseases between humans,” the authors concluded.

The authors also added that “given that the study was based on the entire computerized blood banking history in two countries with several decades of follow-up, more comprehensive data are unlikely to be available in the foreseeable future.”

Funding for the study was provided by the Swedish Research Council, the Swedish Heart-Lung Foundation, the Swedish Society for Medical Research, and the Danish Council for Independent Research. One coauthor reported receiving a grant from the Danish Council for Independent Research, and another reported receiving grants from the Swedish Research Council and the Swedish Heart-Lung Foundation during the conduct of the study. No other authors reported any relevant financial disclosures.

[email protected]

A retrospective study of nearly 1.5 million patients over the course of 44 years showed no evidence to support the claim that neurodegenerative disorders can be transmitted between individuals through blood transfusions.

“Given that the neurodegenerative diseases on the dementia spectrum are relatively common, the misfolded proteins in affected persons have a wide tissue distribution, and the diseases may have a protracted prediagnostic course, potential transmission through transfusion could have important public health implications,” explained study authors led by Gustaf Edgren, MD, PhD, of the Karolinska Institute in Stockholm.

©Hemera/Thinkstock.com

The retrospective cohort study analyzed data on 1,465,845 patients listed in nationwide transfusion registers, all of whom had undergone transfusions between 1968 and 2012 in Sweden, or during 1981-2012 in Denmark. The investigators looked for transfusions in which the donor had a diagnosis – either before or after the transfusion – of Alzheimer’s disease, Parkinson’s disease, or amyotrophic lateral sclerosis, and compared them with transfusions involving two healthy control groups. Creutzfeldt-Jakob disease was not included in the analysis (Ann Intern Med. 2016 Jun 28. doi: 10.7326/M15-2421).

All transfusion recipients were followed from 180 days after the transfusion date in order to minimize the risk of including a patient who had a neurodegenerative disorder that was present but not registered at the time of the transfusion. Follow-ups lasted until either the first diagnosis of a neurodegenerative disorder, death, emigration, or the end of the trial period on Dec. 31, 2012.

If a donor had received a diagnosis of a neurodegenerative disorder within 20 years of the transfusion, all recipients from said donor were considered to be exposed. “The maximum latency of 20 years was used as a compromise between allowing a long preclinical phase – during which donors may still be infectious – and avoiding classifying clearly healthy donors as potentially infectious,” the authors wrote.

Only 42,254 (2.9%) of subjects were deemed to be exposed to a neurodegenerative disorder based on their blood transfusion donor. However, there was no evidence of any increased risk of dementia of any type from exposure to blood from affected donors in any of the recipients over the course of the follow-up period (hazard ratio, 1.04; 95% confidence interval, 0.99-1.09), and similar results were obtained individually for Alzheimer’s disease and Parkinson’s disease. As a control measure, the investigators also tested for hepatitis C transmission before and after transfusions, and were “as expected, readily able to detect transmission of viral hepatitis,” despite finding no traces of neurodegenerative conditions.

“Despite accumulating scientific support for horizontal transmissibility of a range of disorders in the neurodegenerative spectrum through various methods of inoculation in animal models and of variant Creutzfeldt-Jakob disease from human and animal model data, this study provides evidence against blood transfusion as an important route of transmission of neurodegenerative diseases between humans,” the authors concluded.

The authors also added that “given that the study was based on the entire computerized blood banking history in two countries with several decades of follow-up, more comprehensive data are unlikely to be available in the foreseeable future.”

Funding for the study was provided by the Swedish Research Council, the Swedish Heart-Lung Foundation, the Swedish Society for Medical Research, and the Danish Council for Independent Research. One coauthor reported receiving a grant from the Danish Council for Independent Research, and another reported receiving grants from the Swedish Research Council and the Swedish Heart-Lung Foundation during the conduct of the study. No other authors reported any relevant financial disclosures.

[email protected]

Clinical question: Which medications are most safe and effective at managing type 2 diabetes?

Background: Patients and practitioners need an updated review of the evidence to select the optimal medication for type 2 diabetes management.

Study design: Systematic review.

Synopsis: The authors reviewed 179 trials and 25 observational studies. When comparing metformin to sulfonylureas, metformin was associated with less cardiovascular mortality.

However, when trying to make comparisons based on all-cause mortality or microvascular complications, the evidence is limited. Improvements in hemoglobin A1c levels are similar when comparing different monotherapy options, and low blood sugar was most common with sulfonylureas. The short duration of many trials limits the ability to provide better data on long-term outcomes.

Bottom line: Metformin remains the first-line agent for type 2 diabetes management.

Citation: Maruthur NM, Tseng E, Hutfless S, et al. Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes: a systemic review and meta-analysis. Ann Intern Med. 2016;164(1):740-751.

Short Take

Patients Discharge Readiness May Not Be Adequately Assessed and/or Addressed During Hospitalization

Prospective observational study found unresolved barriers to discharge were common in at least 90% of patients. Patients frequently cited issues including unresolved pain, lack of understanding around discharge plans, and ability to provide self-care.

Citation: Harrison JD, Greysen RS, Jacolbia R, Nguyen A, Auerbach AD. Not ready, not set…discharge: patient-reported barriers to discharge readiness at an academic medical center [published online ahead of print April 15, 2016]. J Hosp Med. doi:10.1002/jhm.2591.

Clinical question: Which medications are most safe and effective at managing type 2 diabetes?

Background: Patients and practitioners need an updated review of the evidence to select the optimal medication for type 2 diabetes management.

Study design: Systematic review.

Synopsis: The authors reviewed 179 trials and 25 observational studies. When comparing metformin to sulfonylureas, metformin was associated with less cardiovascular mortality.

However, when trying to make comparisons based on all-cause mortality or microvascular complications, the evidence is limited. Improvements in hemoglobin A1c levels are similar when comparing different monotherapy options, and low blood sugar was most common with sulfonylureas. The short duration of many trials limits the ability to provide better data on long-term outcomes.

Bottom line: Metformin remains the first-line agent for type 2 diabetes management.

Citation: Maruthur NM, Tseng E, Hutfless S, et al. Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes: a systemic review and meta-analysis. Ann Intern Med. 2016;164(1):740-751.

Short Take

Patients Discharge Readiness May Not Be Adequately Assessed and/or Addressed During Hospitalization

Prospective observational study found unresolved barriers to discharge were common in at least 90% of patients. Patients frequently cited issues including unresolved pain, lack of understanding around discharge plans, and ability to provide self-care.

Citation: Harrison JD, Greysen RS, Jacolbia R, Nguyen A, Auerbach AD. Not ready, not set…discharge: patient-reported barriers to discharge readiness at an academic medical center [published online ahead of print April 15, 2016]. J Hosp Med. doi:10.1002/jhm.2591.

Clinical question: Which medications are most safe and effective at managing type 2 diabetes?

Background: Patients and practitioners need an updated review of the evidence to select the optimal medication for type 2 diabetes management.

Study design: Systematic review.

Synopsis: The authors reviewed 179 trials and 25 observational studies. When comparing metformin to sulfonylureas, metformin was associated with less cardiovascular mortality.

However, when trying to make comparisons based on all-cause mortality or microvascular complications, the evidence is limited. Improvements in hemoglobin A1c levels are similar when comparing different monotherapy options, and low blood sugar was most common with sulfonylureas. The short duration of many trials limits the ability to provide better data on long-term outcomes.

Bottom line: Metformin remains the first-line agent for type 2 diabetes management.

Citation: Maruthur NM, Tseng E, Hutfless S, et al. Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes: a systemic review and meta-analysis. Ann Intern Med. 2016;164(1):740-751.

Short Take

Patients Discharge Readiness May Not Be Adequately Assessed and/or Addressed During Hospitalization

Prospective observational study found unresolved barriers to discharge were common in at least 90% of patients. Patients frequently cited issues including unresolved pain, lack of understanding around discharge plans, and ability to provide self-care.

Citation: Harrison JD, Greysen RS, Jacolbia R, Nguyen A, Auerbach AD. Not ready, not set…discharge: patient-reported barriers to discharge readiness at an academic medical center [published online ahead of print April 15, 2016]. J Hosp Med. doi:10.1002/jhm.2591.

Clinical question: What is the prognosis of patients who have a TIA or minor stroke?

Background: Prior studies had estimated the risk in the three months following a TIA or minor stroke of having a stroke or acute coronary syndrome (ACS) as 12% to 20%, but this may not reflect the risk of modern patients receiving the current standards of care.

Study design: Prospective observational registry of patients with recent TIA or minor stroke.

Setting: International, including 21 countries.

Synopsis: Adults with recent TIA or minor stroke were included in this multi-center, international registry, and one-year outcomes were reported. At one year, the Kaplan-Meier estimated event rate for the combined outcome of stroke, ACS, or death from cardiovascular causes was 6.2%. The risk of the cardiovascular events was found to be lower than previously reported, suggesting an improvement in outcomes with current interventions. Elevated ABCD2 score, infarction seen on brain imaging, and large-artery atherosclerosis were each associated with higher risk.

Bottom line: Elevated ABCD2 score, brain imaging findings, and large-artery atherosclerosis suggest increased risk for recurrent stroke.

Citation: Amarenco P, Lavallée PC, Labreuche J, et al. One-year risk of stroke after transient ischemic attack or minor stroke. N Engl J Med. 2016;374(16):1533-1542.

Clinical question: What is the prognosis of patients who have a TIA or minor stroke?

Background: Prior studies had estimated the risk in the three months following a TIA or minor stroke of having a stroke or acute coronary syndrome (ACS) as 12% to 20%, but this may not reflect the risk of modern patients receiving the current standards of care.

Study design: Prospective observational registry of patients with recent TIA or minor stroke.

Setting: International, including 21 countries.

Synopsis: Adults with recent TIA or minor stroke were included in this multi-center, international registry, and one-year outcomes were reported. At one year, the Kaplan-Meier estimated event rate for the combined outcome of stroke, ACS, or death from cardiovascular causes was 6.2%. The risk of the cardiovascular events was found to be lower than previously reported, suggesting an improvement in outcomes with current interventions. Elevated ABCD2 score, infarction seen on brain imaging, and large-artery atherosclerosis were each associated with higher risk.

Bottom line: Elevated ABCD2 score, brain imaging findings, and large-artery atherosclerosis suggest increased risk for recurrent stroke.

Citation: Amarenco P, Lavallée PC, Labreuche J, et al. One-year risk of stroke after transient ischemic attack or minor stroke. N Engl J Med. 2016;374(16):1533-1542.

Clinical question: What is the prognosis of patients who have a TIA or minor stroke?

Background: Prior studies had estimated the risk in the three months following a TIA or minor stroke of having a stroke or acute coronary syndrome (ACS) as 12% to 20%, but this may not reflect the risk of modern patients receiving the current standards of care.

Study design: Prospective observational registry of patients with recent TIA or minor stroke.

Setting: International, including 21 countries.

Synopsis: Adults with recent TIA or minor stroke were included in this multi-center, international registry, and one-year outcomes were reported. At one year, the Kaplan-Meier estimated event rate for the combined outcome of stroke, ACS, or death from cardiovascular causes was 6.2%. The risk of the cardiovascular events was found to be lower than previously reported, suggesting an improvement in outcomes with current interventions. Elevated ABCD2 score, infarction seen on brain imaging, and large-artery atherosclerosis were each associated with higher risk.

Bottom line: Elevated ABCD2 score, brain imaging findings, and large-artery atherosclerosis suggest increased risk for recurrent stroke.

Citation: Amarenco P, Lavallée PC, Labreuche J, et al. One-year risk of stroke after transient ischemic attack or minor stroke. N Engl J Med. 2016;374(16):1533-1542.

Micrograph showing CMV

Image by Ed Uthman

Research published in PLOS Pathogens suggests that emetine, a drug once used to treat amebiasis and induce vomiting in cases of poisoning, may also halt replication of cytomegalovirus (CMV).

Although there are drugs available to treat CMV, they can cause serious toxicity.

Furthermore, resistant strains of CMV can emerge, creating “a desperate need for other ways to control this virus,” according to Ravit Boger, MD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.

Dr Boger and her colleagues decided to search for drugs to treat CMV by screening 1280 pharmacologically active compounds already approved by the US Food and Drug Administration.

The researchers found a “hit” with emetine, a drug that was used in the past to treat amebiasis before other drugs took its place decades ago.

Results showed that emetine can inhibit CMV at much lower doses than those used for amebiasis, and less frequent doses might be effective for CMV inhibition as well.

In vitro and in vivo tests showed that very low doses of emetine significantly reduced viral replication—75 nm in vitro and 0.1 mg/kg in mice.

Furthermore, with a half-life of 35 hours, the drug exerted its effects over a sustained period, effectively inhibiting virus replication at 14 days after 3 doses.

Additional investigation revealed that emetine’s action against CMV was due to its effects on proteins that control the cell cycle.

Dr Boger cautioned that there is a long way to go before emetine or similar agents can be considered for the treatment of CMV.

“But if further research affirms its potential value, emetine might eventually be used in patients who don’t respond to approved anti-CMV drugs, alone or in combination with these,” she said.

Dr Boger and her colleagues also believe that gaining a better understanding of emetine’s activity in cells could lead to the discovery of new drugs that take advantage of the same or similar pathways.

Micrograph showing CMV

Image by Ed Uthman

Research published in PLOS Pathogens suggests that emetine, a drug once used to treat amebiasis and induce vomiting in cases of poisoning, may also halt replication of cytomegalovirus (CMV).

Although there are drugs available to treat CMV, they can cause serious toxicity.

Furthermore, resistant strains of CMV can emerge, creating “a desperate need for other ways to control this virus,” according to Ravit Boger, MD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.

Dr Boger and her colleagues decided to search for drugs to treat CMV by screening 1280 pharmacologically active compounds already approved by the US Food and Drug Administration.

The researchers found a “hit” with emetine, a drug that was used in the past to treat amebiasis before other drugs took its place decades ago.

Results showed that emetine can inhibit CMV at much lower doses than those used for amebiasis, and less frequent doses might be effective for CMV inhibition as well.

In vitro and in vivo tests showed that very low doses of emetine significantly reduced viral replication—75 nm in vitro and 0.1 mg/kg in mice.

Furthermore, with a half-life of 35 hours, the drug exerted its effects over a sustained period, effectively inhibiting virus replication at 14 days after 3 doses.

Additional investigation revealed that emetine’s action against CMV was due to its effects on proteins that control the cell cycle.

Dr Boger cautioned that there is a long way to go before emetine or similar agents can be considered for the treatment of CMV.

“But if further research affirms its potential value, emetine might eventually be used in patients who don’t respond to approved anti-CMV drugs, alone or in combination with these,” she said.

Dr Boger and her colleagues also believe that gaining a better understanding of emetine’s activity in cells could lead to the discovery of new drugs that take advantage of the same or similar pathways.

Micrograph showing CMV

Image by Ed Uthman

Research published in PLOS Pathogens suggests that emetine, a drug once used to treat amebiasis and induce vomiting in cases of poisoning, may also halt replication of cytomegalovirus (CMV).

Although there are drugs available to treat CMV, they can cause serious toxicity.

Furthermore, resistant strains of CMV can emerge, creating “a desperate need for other ways to control this virus,” according to Ravit Boger, MD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.

Dr Boger and her colleagues decided to search for drugs to treat CMV by screening 1280 pharmacologically active compounds already approved by the US Food and Drug Administration.

The researchers found a “hit” with emetine, a drug that was used in the past to treat amebiasis before other drugs took its place decades ago.

Results showed that emetine can inhibit CMV at much lower doses than those used for amebiasis, and less frequent doses might be effective for CMV inhibition as well.

In vitro and in vivo tests showed that very low doses of emetine significantly reduced viral replication—75 nm in vitro and 0.1 mg/kg in mice.

Furthermore, with a half-life of 35 hours, the drug exerted its effects over a sustained period, effectively inhibiting virus replication at 14 days after 3 doses.

Additional investigation revealed that emetine’s action against CMV was due to its effects on proteins that control the cell cycle.

Dr Boger cautioned that there is a long way to go before emetine or similar agents can be considered for the treatment of CMV.

“But if further research affirms its potential value, emetine might eventually be used in patients who don’t respond to approved anti-CMV drugs, alone or in combination with these,” she said.

Dr Boger and her colleagues also believe that gaining a better understanding of emetine’s activity in cells could lead to the discovery of new drugs that take advantage of the same or similar pathways.