The Food and Drug Administration is warning health care professionals not to prescribe oral ketoconazole for patients with fungal infections of the skin and nails, because of "the risks of serious liver damage, adrenal gland problems, and harmful interactions with other medicines that outweigh its benefit in treating these conditions."

The advisory, issued on May 19, points out that oral ketoconazole (Nizoral) is no longer approved for treating nail or skin fungal infections. Topical forms of ketoconazole have not been associated with liver damage, adrenal problems, or drug interactions, the advisory adds.

"Health care professionals should use ketoconazole tablets only to treat serious fungal infections when no other antifungal therapies are available," according to the FDA. "Skin and nail fungal infections in otherwise healthy persons are not life-threatening, and so the risks associated with oral ketoconazole outweigh the benefits. Other treatment options are available over-the-counter and by prescription, but are also associated with risks that should be weighed against their benefits."

The advisory updates one issued in July 2013 when the drug's label was changed to reflect these safety concerns, including dropping the nail and skin infections from the approved indications. Since then, the FDA has received one report of a patient who died of liver failure associated with oral ketoconazole used to treat nail fungus. Furthermore, a survey of office-based physicians found that in the 18 months ending in June 2015, "skin and nail fungal infections were the only diagnoses cited for the use of oral ketoconazole."

Serious adverse events associated with oral ketoconazole should be reported to the FDA's MedWatch program online or call 800-332-1088.

The Food and Drug Administration is warning health care professionals not to prescribe oral ketoconazole for patients with fungal infections of the skin and nails, because of "the risks of serious liver damage, adrenal gland problems, and harmful interactions with other medicines that outweigh its benefit in treating these conditions."

The advisory, issued on May 19, points out that oral ketoconazole (Nizoral) is no longer approved for treating nail or skin fungal infections. Topical forms of ketoconazole have not been associated with liver damage, adrenal problems, or drug interactions, the advisory adds.

"Health care professionals should use ketoconazole tablets only to treat serious fungal infections when no other antifungal therapies are available," according to the FDA. "Skin and nail fungal infections in otherwise healthy persons are not life-threatening, and so the risks associated with oral ketoconazole outweigh the benefits. Other treatment options are available over-the-counter and by prescription, but are also associated with risks that should be weighed against their benefits."

The advisory updates one issued in July 2013 when the drug's label was changed to reflect these safety concerns, including dropping the nail and skin infections from the approved indications. Since then, the FDA has received one report of a patient who died of liver failure associated with oral ketoconazole used to treat nail fungus. Furthermore, a survey of office-based physicians found that in the 18 months ending in June 2015, "skin and nail fungal infections were the only diagnoses cited for the use of oral ketoconazole."

Serious adverse events associated with oral ketoconazole should be reported to the FDA's MedWatch program online or call 800-332-1088.

The Food and Drug Administration is warning health care professionals not to prescribe oral ketoconazole for patients with fungal infections of the skin and nails, because of "the risks of serious liver damage, adrenal gland problems, and harmful interactions with other medicines that outweigh its benefit in treating these conditions."

The advisory, issued on May 19, points out that oral ketoconazole (Nizoral) is no longer approved for treating nail or skin fungal infections. Topical forms of ketoconazole have not been associated with liver damage, adrenal problems, or drug interactions, the advisory adds.

"Health care professionals should use ketoconazole tablets only to treat serious fungal infections when no other antifungal therapies are available," according to the FDA. "Skin and nail fungal infections in otherwise healthy persons are not life-threatening, and so the risks associated with oral ketoconazole outweigh the benefits. Other treatment options are available over-the-counter and by prescription, but are also associated with risks that should be weighed against their benefits."

The advisory updates one issued in July 2013 when the drug's label was changed to reflect these safety concerns, including dropping the nail and skin infections from the approved indications. Since then, the FDA has received one report of a patient who died of liver failure associated with oral ketoconazole used to treat nail fungus. Furthermore, a survey of office-based physicians found that in the 18 months ending in June 2015, "skin and nail fungal infections were the only diagnoses cited for the use of oral ketoconazole."

Serious adverse events associated with oral ketoconazole should be reported to the FDA's MedWatch program online or call 800-332-1088.

Young adults who received a combined hepatitis A and B vaccination at age 12-15 years maintained immunity after 15 years, making a booster shot unnecessary, according to Dr. Jiri Beran of the Vaccination and Travel Medicine Centre, Hradec Kralove, Czech Republic, and associates.

Study participants received either a 2-dose adult formulation or a 3-dose pediatric formulation. Of the 162 participants included in the 15-year follow-up, all were seropositive for anti–hepatitis A vaccine antibodies, 81.1% of those who received the two-dose vaccination had anti–hepatitis B antibodies, and 81.8% of those who received the three-dose vaccination had anti–hepatitis B antibodies.

©luiscar/Thinkstockphotos

In a subsequent hepatitis B vaccine challenge, all of 8 participants who received the two-dose vaccination and 10 of 11 participants who received the three-dose vaccination developed an anamnastic response. No side effects inconsistent with previous experience were observed.

“The present study confirms that the combined hepatitis A and B vaccine is equally immunogenic and safe in adolescents when administered as the standard three-dose pediatric regimen or as two doses of the adult strength vacciwne,” the investigators said.

Find the full study in Vaccine (doi: 10.1016/j.vaccine.2016.04.033).

[email protected]

Young adults who received a combined hepatitis A and B vaccination at age 12-15 years maintained immunity after 15 years, making a booster shot unnecessary, according to Dr. Jiri Beran of the Vaccination and Travel Medicine Centre, Hradec Kralove, Czech Republic, and associates.

Study participants received either a 2-dose adult formulation or a 3-dose pediatric formulation. Of the 162 participants included in the 15-year follow-up, all were seropositive for anti–hepatitis A vaccine antibodies, 81.1% of those who received the two-dose vaccination had anti–hepatitis B antibodies, and 81.8% of those who received the three-dose vaccination had anti–hepatitis B antibodies.

©luiscar/Thinkstockphotos

In a subsequent hepatitis B vaccine challenge, all of 8 participants who received the two-dose vaccination and 10 of 11 participants who received the three-dose vaccination developed an anamnastic response. No side effects inconsistent with previous experience were observed.

“The present study confirms that the combined hepatitis A and B vaccine is equally immunogenic and safe in adolescents when administered as the standard three-dose pediatric regimen or as two doses of the adult strength vacciwne,” the investigators said.

Find the full study in Vaccine (doi: 10.1016/j.vaccine.2016.04.033).

[email protected]

Young adults who received a combined hepatitis A and B vaccination at age 12-15 years maintained immunity after 15 years, making a booster shot unnecessary, according to Dr. Jiri Beran of the Vaccination and Travel Medicine Centre, Hradec Kralove, Czech Republic, and associates.

Study participants received either a 2-dose adult formulation or a 3-dose pediatric formulation. Of the 162 participants included in the 15-year follow-up, all were seropositive for anti–hepatitis A vaccine antibodies, 81.1% of those who received the two-dose vaccination had anti–hepatitis B antibodies, and 81.8% of those who received the three-dose vaccination had anti–hepatitis B antibodies.

©luiscar/Thinkstockphotos

In a subsequent hepatitis B vaccine challenge, all of 8 participants who received the two-dose vaccination and 10 of 11 participants who received the three-dose vaccination developed an anamnastic response. No side effects inconsistent with previous experience were observed.

“The present study confirms that the combined hepatitis A and B vaccine is equally immunogenic and safe in adolescents when administered as the standard three-dose pediatric regimen or as two doses of the adult strength vacciwne,” the investigators said.

Find the full study in Vaccine (doi: 10.1016/j.vaccine.2016.04.033).

[email protected]

Pediatric doses of hepatitis B vaccine can provide long-term protection against hepatitis B up to 15-16 years, and also can produce strong immune memory, according to Dr. Olivier Van Der Meeren of GlaxoSmithKline Vaccines, Wavre, Belgium, and his associates.

The researchers looked at 303 healthy adolescents who had received three doses of monovalent pediatric hepatitis B vaccine (containing 10 mcg hepatitis B surface antigen, HBsAg) in infancy. Of the 293 patients analyzed, 71% were seropositive (anti-HBs antibodies greater than or equal to 6.2 mIU/mL) before the challenge dose and 65% remained seroprotected (anti-HBs antibodies greater than or equal to 10 mIU/mL) after challenge. One month after the challenge dose, the percentage of seroprotected subjects increased to 99%, and 91% of those patients had anti-HBs antibody concentrations greater than or equal to 100 mIU/mL.

CDC/Dr. Erskine Palmer

The study also looked at safety and reactogenicity. The researchers stated that it was well tolerated, with pain and fatigue the most frequently reported adverse effects.

“Despite declining levels of circulating anti-HBs antibodies, the vast majority of subjects in our study were able to mount a rapid and robust anamnestic response after a challenge dose (more than 150-fold increase in GMC [geometric mean concentration]) regardless of their pre-challenge serostatus,” the researchers concluded. “This confirms that maintaining anti-HBs antibody concentrations greater than 10 mIU/mL may not be essential for protection against clinically significant breakthrough hepatitis B infection.”

Find the study in Vaccine (doi:10.1016/j.vaccine.2016.04.013).

[email protected]

Pediatric doses of hepatitis B vaccine can provide long-term protection against hepatitis B up to 15-16 years, and also can produce strong immune memory, according to Dr. Olivier Van Der Meeren of GlaxoSmithKline Vaccines, Wavre, Belgium, and his associates.

The researchers looked at 303 healthy adolescents who had received three doses of monovalent pediatric hepatitis B vaccine (containing 10 mcg hepatitis B surface antigen, HBsAg) in infancy. Of the 293 patients analyzed, 71% were seropositive (anti-HBs antibodies greater than or equal to 6.2 mIU/mL) before the challenge dose and 65% remained seroprotected (anti-HBs antibodies greater than or equal to 10 mIU/mL) after challenge. One month after the challenge dose, the percentage of seroprotected subjects increased to 99%, and 91% of those patients had anti-HBs antibody concentrations greater than or equal to 100 mIU/mL.

CDC/Dr. Erskine Palmer

The study also looked at safety and reactogenicity. The researchers stated that it was well tolerated, with pain and fatigue the most frequently reported adverse effects.

“Despite declining levels of circulating anti-HBs antibodies, the vast majority of subjects in our study were able to mount a rapid and robust anamnestic response after a challenge dose (more than 150-fold increase in GMC [geometric mean concentration]) regardless of their pre-challenge serostatus,” the researchers concluded. “This confirms that maintaining anti-HBs antibody concentrations greater than 10 mIU/mL may not be essential for protection against clinically significant breakthrough hepatitis B infection.”

Find the study in Vaccine (doi:10.1016/j.vaccine.2016.04.013).

[email protected]

Pediatric doses of hepatitis B vaccine can provide long-term protection against hepatitis B up to 15-16 years, and also can produce strong immune memory, according to Dr. Olivier Van Der Meeren of GlaxoSmithKline Vaccines, Wavre, Belgium, and his associates.

The researchers looked at 303 healthy adolescents who had received three doses of monovalent pediatric hepatitis B vaccine (containing 10 mcg hepatitis B surface antigen, HBsAg) in infancy. Of the 293 patients analyzed, 71% were seropositive (anti-HBs antibodies greater than or equal to 6.2 mIU/mL) before the challenge dose and 65% remained seroprotected (anti-HBs antibodies greater than or equal to 10 mIU/mL) after challenge. One month after the challenge dose, the percentage of seroprotected subjects increased to 99%, and 91% of those patients had anti-HBs antibody concentrations greater than or equal to 100 mIU/mL.

CDC/Dr. Erskine Palmer

The study also looked at safety and reactogenicity. The researchers stated that it was well tolerated, with pain and fatigue the most frequently reported adverse effects.

“Despite declining levels of circulating anti-HBs antibodies, the vast majority of subjects in our study were able to mount a rapid and robust anamnestic response after a challenge dose (more than 150-fold increase in GMC [geometric mean concentration]) regardless of their pre-challenge serostatus,” the researchers concluded. “This confirms that maintaining anti-HBs antibody concentrations greater than 10 mIU/mL may not be essential for protection against clinically significant breakthrough hepatitis B infection.”

Find the study in Vaccine (doi:10.1016/j.vaccine.2016.04.013).

[email protected]

Learn more:

• forYou team, University of Missouri
• Trust Team, Carilion Clinic

Learn more:

• forYou team, University of Missouri
• Trust Team, Carilion Clinic

Learn more:

• forYou team, University of Missouri
• Trust Team, Carilion Clinic

Among patients with type 2 diabetes, those with foot ulcers show cognitive impairment across all domains when compared with those without, according to a report published in Diabetes Care.

In what they described as one of the first studies to examine cognitive function in people with diabetic foot ulcers, researchers found that these patients “remember less, have decreased ability to concentrate, and more difficulty with learning, less inhibition, slower cognitive and psychomotor responses, and less verbal fluency” than patients with diabetes that does not include foot involvement.

©Balkonsky/ThinkStockPhotos

Although this study had a cross-sectional design that precluded drawing conclusions about causality, an analysis that estimated the participants’ premorbid and postmorbid cognitive abilities suggested that people with diabetic foot ulcers had experienced a recent significant cognitive decline, while those without foot ulcers had not, said Rachel Natovich, Ph.D., of the department of public health, Ben-Gurion University of the Negev, Be’er Sheva (Israel) and the Endocrinology Institute, Sheba Medical Center, Ramat Gan (Israel) and her associates. These findings indicate that patients with diabetic foot ulcers – the very patients who face the greatest self-treatment challenges – are the ones who have the weakest cognitive resources to do so, they noted.

The investigators examined this issue after noting that recent consensus guidelines require patients with diabetic foot ulcers to take on even more self-management than is already required for the diabetes. This demands “applying complex cognitive abilities in learning, understanding, and remembering new information; planning and initiating self-care practices; adopting behavioral changes that involve psychomotor abilities; and maintaining these behaviors while controlling and repressing impulses.” So Dr. Natovich and her associates assessed whether the cognitive profile of patients who have diabetic foot problems differs from that of patients who don’t, using a case-control study design.

The 194 study participants were aged 45-75 years. The 99 subjects who had at least one diabetic foot ulcer (cases) were matched for age and duration of diabetes with 95 subjects who did not (controls). All underwent a comprehensive battery of neuropsychological tests assessing general intelligence, short- and long-term memory, attention and concentration, psychomotor efficiency, reaction time, executive function, nonverbal IQ, visual-motor speed, coordination, capacity for learning, verbal production, semantic memory, and language. All were also assessed for depression via the Patient Health Questionnaire.

After scores were standardized according to the expected performance by age and education level, patients with diabetic foot ulcers showed significantly lower scores in all the domains tested, compared with the patients without foot ulcers. This difference persisted after the data were adjusted to account for possible confounding factors such as smoking status, hemoglobin A_1c level, presence or absence of depressive symptoms, and presence or absence of macrovascular disease (Diab Care. 2016 May. doi:10.2337/dc15-2838).

The estimated premorbid cognitive function was similar between the two study groups, but current cognitive function declined significantly in the patients with foot ulcers while remaining relatively constant in the patients without foot ulcers. Prospective studies are needed to explore the timing of cognitive decline and the possibility of causation, Dr. Natovich and her associates said.

The study results “highlight the importance of focusing on cognitive functioning, a less-studied area in diabetic foot research,” they added.

“We feel that it is important to screen the cognitive status of these patients regularly and to take cognitive abilities into consideration in treatment-planning recommendations and follow-up.”

Among patients with type 2 diabetes, those with foot ulcers show cognitive impairment across all domains when compared with those without, according to a report published in Diabetes Care.

In what they described as one of the first studies to examine cognitive function in people with diabetic foot ulcers, researchers found that these patients “remember less, have decreased ability to concentrate, and more difficulty with learning, less inhibition, slower cognitive and psychomotor responses, and less verbal fluency” than patients with diabetes that does not include foot involvement.

©Balkonsky/ThinkStockPhotos

Although this study had a cross-sectional design that precluded drawing conclusions about causality, an analysis that estimated the participants’ premorbid and postmorbid cognitive abilities suggested that people with diabetic foot ulcers had experienced a recent significant cognitive decline, while those without foot ulcers had not, said Rachel Natovich, Ph.D., of the department of public health, Ben-Gurion University of the Negev, Be’er Sheva (Israel) and the Endocrinology Institute, Sheba Medical Center, Ramat Gan (Israel) and her associates. These findings indicate that patients with diabetic foot ulcers – the very patients who face the greatest self-treatment challenges – are the ones who have the weakest cognitive resources to do so, they noted.

The investigators examined this issue after noting that recent consensus guidelines require patients with diabetic foot ulcers to take on even more self-management than is already required for the diabetes. This demands “applying complex cognitive abilities in learning, understanding, and remembering new information; planning and initiating self-care practices; adopting behavioral changes that involve psychomotor abilities; and maintaining these behaviors while controlling and repressing impulses.” So Dr. Natovich and her associates assessed whether the cognitive profile of patients who have diabetic foot problems differs from that of patients who don’t, using a case-control study design.

The 194 study participants were aged 45-75 years. The 99 subjects who had at least one diabetic foot ulcer (cases) were matched for age and duration of diabetes with 95 subjects who did not (controls). All underwent a comprehensive battery of neuropsychological tests assessing general intelligence, short- and long-term memory, attention and concentration, psychomotor efficiency, reaction time, executive function, nonverbal IQ, visual-motor speed, coordination, capacity for learning, verbal production, semantic memory, and language. All were also assessed for depression via the Patient Health Questionnaire.

After scores were standardized according to the expected performance by age and education level, patients with diabetic foot ulcers showed significantly lower scores in all the domains tested, compared with the patients without foot ulcers. This difference persisted after the data were adjusted to account for possible confounding factors such as smoking status, hemoglobin A_1c level, presence or absence of depressive symptoms, and presence or absence of macrovascular disease (Diab Care. 2016 May. doi:10.2337/dc15-2838).

The estimated premorbid cognitive function was similar between the two study groups, but current cognitive function declined significantly in the patients with foot ulcers while remaining relatively constant in the patients without foot ulcers. Prospective studies are needed to explore the timing of cognitive decline and the possibility of causation, Dr. Natovich and her associates said.

The study results “highlight the importance of focusing on cognitive functioning, a less-studied area in diabetic foot research,” they added.

“We feel that it is important to screen the cognitive status of these patients regularly and to take cognitive abilities into consideration in treatment-planning recommendations and follow-up.”

Among patients with type 2 diabetes, those with foot ulcers show cognitive impairment across all domains when compared with those without, according to a report published in Diabetes Care.

In what they described as one of the first studies to examine cognitive function in people with diabetic foot ulcers, researchers found that these patients “remember less, have decreased ability to concentrate, and more difficulty with learning, less inhibition, slower cognitive and psychomotor responses, and less verbal fluency” than patients with diabetes that does not include foot involvement.

©Balkonsky/ThinkStockPhotos

Although this study had a cross-sectional design that precluded drawing conclusions about causality, an analysis that estimated the participants’ premorbid and postmorbid cognitive abilities suggested that people with diabetic foot ulcers had experienced a recent significant cognitive decline, while those without foot ulcers had not, said Rachel Natovich, Ph.D., of the department of public health, Ben-Gurion University of the Negev, Be’er Sheva (Israel) and the Endocrinology Institute, Sheba Medical Center, Ramat Gan (Israel) and her associates. These findings indicate that patients with diabetic foot ulcers – the very patients who face the greatest self-treatment challenges – are the ones who have the weakest cognitive resources to do so, they noted.

The investigators examined this issue after noting that recent consensus guidelines require patients with diabetic foot ulcers to take on even more self-management than is already required for the diabetes. This demands “applying complex cognitive abilities in learning, understanding, and remembering new information; planning and initiating self-care practices; adopting behavioral changes that involve psychomotor abilities; and maintaining these behaviors while controlling and repressing impulses.” So Dr. Natovich and her associates assessed whether the cognitive profile of patients who have diabetic foot problems differs from that of patients who don’t, using a case-control study design.

The 194 study participants were aged 45-75 years. The 99 subjects who had at least one diabetic foot ulcer (cases) were matched for age and duration of diabetes with 95 subjects who did not (controls). All underwent a comprehensive battery of neuropsychological tests assessing general intelligence, short- and long-term memory, attention and concentration, psychomotor efficiency, reaction time, executive function, nonverbal IQ, visual-motor speed, coordination, capacity for learning, verbal production, semantic memory, and language. All were also assessed for depression via the Patient Health Questionnaire.

After scores were standardized according to the expected performance by age and education level, patients with diabetic foot ulcers showed significantly lower scores in all the domains tested, compared with the patients without foot ulcers. This difference persisted after the data were adjusted to account for possible confounding factors such as smoking status, hemoglobin A_1c level, presence or absence of depressive symptoms, and presence or absence of macrovascular disease (Diab Care. 2016 May. doi:10.2337/dc15-2838).

The estimated premorbid cognitive function was similar between the two study groups, but current cognitive function declined significantly in the patients with foot ulcers while remaining relatively constant in the patients without foot ulcers. Prospective studies are needed to explore the timing of cognitive decline and the possibility of causation, Dr. Natovich and her associates said.

The study results “highlight the importance of focusing on cognitive functioning, a less-studied area in diabetic foot research,” they added.

“We feel that it is important to screen the cognitive status of these patients regularly and to take cognitive abilities into consideration in treatment-planning recommendations and follow-up.”

Tasked with tackling the literature on the subject and debating the question of whether or not it is best to electively induce labor in women with low-risk pregnancies at 39 weeks (vs at 41 weeks after expectant management), Errol Norwitz, MD, PhD, Chairman of the Department of Obstetrics and Gynecology and Professor at Tufts University School of Medicine in Boston, Massachusetts, and Charles Lockwood, MD, Senior Vice President at the University of South Florida (USF) and Dean of the USF Health Morsani College of Medicine in Tampa came to the same conclusion: Elective induction of labor (eIOL) at 39 weeks is superior to expectant management when it comes to fetal outcomes.

In addition, they both agreed that complication rates to the mother (ie, number of cesarean deliveries [CDs]) would not be increased, and possibly even reduced, with eIOL at 39 weeks versus 41 weeks. Dr. Norwitz postulated that, with IOL there is no increase in CD rate in multiparous women and nulliparous women with a favorable cervical exam but that there likely could be an increase in the CD rate for nulliparous women with an unfavorable cervical exam.

The finding that eIOL at 39 weeks is better than at 41 weeks for the infant is likely due to a bigger baby size past 39 weeks (with more traumatic deliveries) and higher rates of postmaturity complications, said Dr. Lockwood. And for the mother, eIOL at 39 weeks can reduce risks—of preeclampsia, abruption, sepsis, and others—the presenters pointed out.

Arriving at their conclusions: The dataDr. Norwitz explained the challenge before them in this unusual “debate.” “In ObGyn we all read the same literature but we often come away with very different takes as to what the implications are and how we incorporate this into our management algorithms. Instead of taking a pro/con approach, with one assigned to ‘yes’ and the other assigned to ‘no,’ and selectively picking out the literature to support our positions, what we did was we each went away, read the literature, synthesized it, and tried to answer this question for ourselves.”

Dr. Norwitz, who is widely published and known for his research on the causes and prevention of preeclampsia and preterm labor, examined and presented the published literature for benefit and harms to the fetus and mother in continuing pregnancy past 39 weeks.

Dr. Lockwood also examined the literature, including a large population cohort of about 1.27 million women that examined CD rates, perinatal mortality, and neonatal and maternal outcomes of eIOL at 39 weeks versus expectant management.¹ He presented, however, that the best evidence to compare the question at hand would be a randomized clinical trial comparing specifically eIOL at 39 weeks versus expectant management, with IOL at 41 weeks. To be powered to detect a difference in perinatal and maternal mortality, this trial would need to include 2.2 to 12.6 million women, he maintained. “When empirical evidence doesn’t exist, the only alternative is some kind of other modeling,” he said. Therefore, he and a team of researchers conducted a Monte Carlo microsimulation modeling decision analysis, taking into account “all outcomes and all preferences that we possibly could cull from the literature.”

Which women actually could benefit from eIOL at 39 weeks?Women with high-risk pregnancies were not included in this debate or considered. Dr. Norwitz clearly defined his case patient at the outset as a 22-year-old G1 at 39 0/7 weeks who has had an uncomplicated pregnancy but is now complaining of decreased fetal movement and tells you that she is worried because her sister lost her baby at 40 weeks to stillbirth. She specifically asks, “Doctor, why can’t you induce my labor now?” 

What counseling a patient about the risks/benefits of eIOL at 39 weeks would requireTwo fundamentals would need to be ensured. The first: precise gestational dating. Dr. Norwitz pointed out that menstrual history can be inaccurate, especially in women with irregular cycles, who are taking hormonal contraception, or who have intermenstrual bleeding. “Early dating ultrasound is the best way to date pregnancies and probably should be done routinely,” although it is not currently standard of care in the United States, he said.

The second fundamental: a true induction of labor process, not one that involves “stopping at 5 PM,” said Dr. Lockwood.

“Although Dr. Lockwood’s 5-PM statement was made tongue-in-cheek,” said Dr. Norwitz after the debate, “he certainly was implying that a genuine effort should be made to effect a vaginal delivery—that is, giving the most effective cervical ripening agents, allowing enough time to pass, and defining clearly the criteria for failed IOL. You shouldn’t just throw the towel in at 5 PM because you want to go home.”

Cost implicationsElectively inducing labor in all women with low-risk pregnancies at 39 weeks is a strategy with unknown cost implications, and the cost difference between this strategy and expectant management up to 41 weeks is not known.

“We need to be sure that we understand the cost implications of these strategies, which of course would need to be balanced against the potential perinatal and maternal morbidity and fetal death,” said Dr. Lockwood.

The meaning of “elective”Dr. Norwitz also made the point postdebate that the American College of Obstetricians and Gynecologists (ACOG) does not support elective IOL prior to 39 weeks’ gestation. “The key term here is ‘elective,’" he said, "which refers to a delivery without a clear medical or obstetric indication. ACOG does support delivery prior to 39 weeks’ gestation, there just needs to be an appropriate indication.”

Tasked with tackling the literature on the subject and debating the question of whether or not it is best to electively induce labor in women with low-risk pregnancies at 39 weeks (vs at 41 weeks after expectant management), Errol Norwitz, MD, PhD, Chairman of the Department of Obstetrics and Gynecology and Professor at Tufts University School of Medicine in Boston, Massachusetts, and Charles Lockwood, MD, Senior Vice President at the University of South Florida (USF) and Dean of the USF Health Morsani College of Medicine in Tampa came to the same conclusion: Elective induction of labor (eIOL) at 39 weeks is superior to expectant management when it comes to fetal outcomes.

In addition, they both agreed that complication rates to the mother (ie, number of cesarean deliveries [CDs]) would not be increased, and possibly even reduced, with eIOL at 39 weeks versus 41 weeks. Dr. Norwitz postulated that, with IOL there is no increase in CD rate in multiparous women and nulliparous women with a favorable cervical exam but that there likely could be an increase in the CD rate for nulliparous women with an unfavorable cervical exam.

The finding that eIOL at 39 weeks is better than at 41 weeks for the infant is likely due to a bigger baby size past 39 weeks (with more traumatic deliveries) and higher rates of postmaturity complications, said Dr. Lockwood. And for the mother, eIOL at 39 weeks can reduce risks—of preeclampsia, abruption, sepsis, and others—the presenters pointed out.

Arriving at their conclusions: The dataDr. Norwitz explained the challenge before them in this unusual “debate.” “In ObGyn we all read the same literature but we often come away with very different takes as to what the implications are and how we incorporate this into our management algorithms. Instead of taking a pro/con approach, with one assigned to ‘yes’ and the other assigned to ‘no,’ and selectively picking out the literature to support our positions, what we did was we each went away, read the literature, synthesized it, and tried to answer this question for ourselves.”

Dr. Norwitz, who is widely published and known for his research on the causes and prevention of preeclampsia and preterm labor, examined and presented the published literature for benefit and harms to the fetus and mother in continuing pregnancy past 39 weeks.

Dr. Lockwood also examined the literature, including a large population cohort of about 1.27 million women that examined CD rates, perinatal mortality, and neonatal and maternal outcomes of eIOL at 39 weeks versus expectant management.¹ He presented, however, that the best evidence to compare the question at hand would be a randomized clinical trial comparing specifically eIOL at 39 weeks versus expectant management, with IOL at 41 weeks. To be powered to detect a difference in perinatal and maternal mortality, this trial would need to include 2.2 to 12.6 million women, he maintained. “When empirical evidence doesn’t exist, the only alternative is some kind of other modeling,” he said. Therefore, he and a team of researchers conducted a Monte Carlo microsimulation modeling decision analysis, taking into account “all outcomes and all preferences that we possibly could cull from the literature.”

Which women actually could benefit from eIOL at 39 weeks?Women with high-risk pregnancies were not included in this debate or considered. Dr. Norwitz clearly defined his case patient at the outset as a 22-year-old G1 at 39 0/7 weeks who has had an uncomplicated pregnancy but is now complaining of decreased fetal movement and tells you that she is worried because her sister lost her baby at 40 weeks to stillbirth. She specifically asks, “Doctor, why can’t you induce my labor now?” 

What counseling a patient about the risks/benefits of eIOL at 39 weeks would requireTwo fundamentals would need to be ensured. The first: precise gestational dating. Dr. Norwitz pointed out that menstrual history can be inaccurate, especially in women with irregular cycles, who are taking hormonal contraception, or who have intermenstrual bleeding. “Early dating ultrasound is the best way to date pregnancies and probably should be done routinely,” although it is not currently standard of care in the United States, he said.

The second fundamental: a true induction of labor process, not one that involves “stopping at 5 PM,” said Dr. Lockwood.

“Although Dr. Lockwood’s 5-PM statement was made tongue-in-cheek,” said Dr. Norwitz after the debate, “he certainly was implying that a genuine effort should be made to effect a vaginal delivery—that is, giving the most effective cervical ripening agents, allowing enough time to pass, and defining clearly the criteria for failed IOL. You shouldn’t just throw the towel in at 5 PM because you want to go home.”

Cost implicationsElectively inducing labor in all women with low-risk pregnancies at 39 weeks is a strategy with unknown cost implications, and the cost difference between this strategy and expectant management up to 41 weeks is not known.

“We need to be sure that we understand the cost implications of these strategies, which of course would need to be balanced against the potential perinatal and maternal morbidity and fetal death,” said Dr. Lockwood.

The meaning of “elective”Dr. Norwitz also made the point postdebate that the American College of Obstetricians and Gynecologists (ACOG) does not support elective IOL prior to 39 weeks’ gestation. “The key term here is ‘elective,’" he said, "which refers to a delivery without a clear medical or obstetric indication. ACOG does support delivery prior to 39 weeks’ gestation, there just needs to be an appropriate indication.”

Tasked with tackling the literature on the subject and debating the question of whether or not it is best to electively induce labor in women with low-risk pregnancies at 39 weeks (vs at 41 weeks after expectant management), Errol Norwitz, MD, PhD, Chairman of the Department of Obstetrics and Gynecology and Professor at Tufts University School of Medicine in Boston, Massachusetts, and Charles Lockwood, MD, Senior Vice President at the University of South Florida (USF) and Dean of the USF Health Morsani College of Medicine in Tampa came to the same conclusion: Elective induction of labor (eIOL) at 39 weeks is superior to expectant management when it comes to fetal outcomes.

In addition, they both agreed that complication rates to the mother (ie, number of cesarean deliveries [CDs]) would not be increased, and possibly even reduced, with eIOL at 39 weeks versus 41 weeks. Dr. Norwitz postulated that, with IOL there is no increase in CD rate in multiparous women and nulliparous women with a favorable cervical exam but that there likely could be an increase in the CD rate for nulliparous women with an unfavorable cervical exam.

The finding that eIOL at 39 weeks is better than at 41 weeks for the infant is likely due to a bigger baby size past 39 weeks (with more traumatic deliveries) and higher rates of postmaturity complications, said Dr. Lockwood. And for the mother, eIOL at 39 weeks can reduce risks—of preeclampsia, abruption, sepsis, and others—the presenters pointed out.

Arriving at their conclusions: The dataDr. Norwitz explained the challenge before them in this unusual “debate.” “In ObGyn we all read the same literature but we often come away with very different takes as to what the implications are and how we incorporate this into our management algorithms. Instead of taking a pro/con approach, with one assigned to ‘yes’ and the other assigned to ‘no,’ and selectively picking out the literature to support our positions, what we did was we each went away, read the literature, synthesized it, and tried to answer this question for ourselves.”

Dr. Norwitz, who is widely published and known for his research on the causes and prevention of preeclampsia and preterm labor, examined and presented the published literature for benefit and harms to the fetus and mother in continuing pregnancy past 39 weeks.

Dr. Lockwood also examined the literature, including a large population cohort of about 1.27 million women that examined CD rates, perinatal mortality, and neonatal and maternal outcomes of eIOL at 39 weeks versus expectant management.¹ He presented, however, that the best evidence to compare the question at hand would be a randomized clinical trial comparing specifically eIOL at 39 weeks versus expectant management, with IOL at 41 weeks. To be powered to detect a difference in perinatal and maternal mortality, this trial would need to include 2.2 to 12.6 million women, he maintained. “When empirical evidence doesn’t exist, the only alternative is some kind of other modeling,” he said. Therefore, he and a team of researchers conducted a Monte Carlo microsimulation modeling decision analysis, taking into account “all outcomes and all preferences that we possibly could cull from the literature.”

Which women actually could benefit from eIOL at 39 weeks?Women with high-risk pregnancies were not included in this debate or considered. Dr. Norwitz clearly defined his case patient at the outset as a 22-year-old G1 at 39 0/7 weeks who has had an uncomplicated pregnancy but is now complaining of decreased fetal movement and tells you that she is worried because her sister lost her baby at 40 weeks to stillbirth. She specifically asks, “Doctor, why can’t you induce my labor now?” 

What counseling a patient about the risks/benefits of eIOL at 39 weeks would requireTwo fundamentals would need to be ensured. The first: precise gestational dating. Dr. Norwitz pointed out that menstrual history can be inaccurate, especially in women with irregular cycles, who are taking hormonal contraception, or who have intermenstrual bleeding. “Early dating ultrasound is the best way to date pregnancies and probably should be done routinely,” although it is not currently standard of care in the United States, he said.

The second fundamental: a true induction of labor process, not one that involves “stopping at 5 PM,” said Dr. Lockwood.

“Although Dr. Lockwood’s 5-PM statement was made tongue-in-cheek,” said Dr. Norwitz after the debate, “he certainly was implying that a genuine effort should be made to effect a vaginal delivery—that is, giving the most effective cervical ripening agents, allowing enough time to pass, and defining clearly the criteria for failed IOL. You shouldn’t just throw the towel in at 5 PM because you want to go home.”

Cost implicationsElectively inducing labor in all women with low-risk pregnancies at 39 weeks is a strategy with unknown cost implications, and the cost difference between this strategy and expectant management up to 41 weeks is not known.

“We need to be sure that we understand the cost implications of these strategies, which of course would need to be balanced against the potential perinatal and maternal morbidity and fetal death,” said Dr. Lockwood.

The meaning of “elective”Dr. Norwitz also made the point postdebate that the American College of Obstetricians and Gynecologists (ACOG) does not support elective IOL prior to 39 weeks’ gestation. “The key term here is ‘elective,’" he said, "which refers to a delivery without a clear medical or obstetric indication. ACOG does support delivery prior to 39 weeks’ gestation, there just needs to be an appropriate indication.”

Vascular surgery fellow case logs reflect an increase in endovascular interventions, but general surgery residents may be missing out on training opportunities, according to a study of national case data.

In addition, general surgery residents saw a decrease in open vascular surgery cases, which was not reflected among the vascular surgery fellows, according to Dr. Rose C. Pedersen and colleagues in the department of surgery, Kaiser Permanente Los Angeles Medical Center. The report was published online in Annals of Vascular Surgery (doi: 10.1016/j.avsg.2016.02.008).

The paper was originally presented at the 2105 annual meeting of the Southern California Vascular Society. The study reports findings of a review of the Accreditation Council for Graduate Medical Education national case log reports from 2001 to 2012.

During that period, the number of general surgery residents increased from 1,021 to 1,098, while the number of vascular surgery fellows increased from 96 to 121. The total number of vascular cases logged by the vascular fellows significantly increased by 161%, from an average of 298 cases to 762 cases over the time period assessed. During that same period, vascular cases done by general surgery residents significantly decreased by 40%, from an average of 186 to 116 cases.

In terms of open cases. vascular fellows saw a significant 43% decrease in open abdominal aortic aneurysm (AAA) cases, going from 26 to 15, and a slight but significant increase in carotid endarterectomy cases logged (44 to 49). Hemodialysis access and major amputations also both increased significantly. A decreases in open surgery for peripheral obstructive disease was small and not significant.

General surgery residents saw decreases in all open surgery areas over the time period: AAA cases fell significantly by 78% (9 cases to 2 cases); carotid endarterectomies decreased significantly from 23 to 12 cases; and surgery for peripheral obstructive disease fell significantly from 21 to 8). Hemodialysis access cases and major amputations both decreased as well, but not significantly.

Endovascular cases increased from 2001 to 2012 for both vascular fellows and general surgery residents. Vascular fellows saw endovascular AAA repair significantly increase from an average of 17 to 46 cases, while those for general surgery residents rosed from roughly 1 to 3 cases. Similarly, endovascular interventions for peripheral obstructive disease significantly increased for vascular fellows from 17 to 85, and from 1.3 to 4 for general surgery residents.

“The contemporary management of abdominal aortic aneurysmal diseases and peripheral obstructive diseases has been particularly changed by endovascular therapies that have been adopted into the training experience of vascular surgery fellows, but not those of general surgery residents. Open surgery experience has decreased overall for general surgery residents in all major categories, a change not seen in vascular fellows,” the researchers concluded.

The authors reported no relevant disclosures.

[email protected]

Vascular surgery fellow case logs reflect an increase in endovascular interventions, but general surgery residents may be missing out on training opportunities, according to a study of national case data.

In addition, general surgery residents saw a decrease in open vascular surgery cases, which was not reflected among the vascular surgery fellows, according to Dr. Rose C. Pedersen and colleagues in the department of surgery, Kaiser Permanente Los Angeles Medical Center. The report was published online in Annals of Vascular Surgery (doi: 10.1016/j.avsg.2016.02.008).

The paper was originally presented at the 2105 annual meeting of the Southern California Vascular Society. The study reports findings of a review of the Accreditation Council for Graduate Medical Education national case log reports from 2001 to 2012.

During that period, the number of general surgery residents increased from 1,021 to 1,098, while the number of vascular surgery fellows increased from 96 to 121. The total number of vascular cases logged by the vascular fellows significantly increased by 161%, from an average of 298 cases to 762 cases over the time period assessed. During that same period, vascular cases done by general surgery residents significantly decreased by 40%, from an average of 186 to 116 cases.

In terms of open cases. vascular fellows saw a significant 43% decrease in open abdominal aortic aneurysm (AAA) cases, going from 26 to 15, and a slight but significant increase in carotid endarterectomy cases logged (44 to 49). Hemodialysis access and major amputations also both increased significantly. A decreases in open surgery for peripheral obstructive disease was small and not significant.

General surgery residents saw decreases in all open surgery areas over the time period: AAA cases fell significantly by 78% (9 cases to 2 cases); carotid endarterectomies decreased significantly from 23 to 12 cases; and surgery for peripheral obstructive disease fell significantly from 21 to 8). Hemodialysis access cases and major amputations both decreased as well, but not significantly.

Endovascular cases increased from 2001 to 2012 for both vascular fellows and general surgery residents. Vascular fellows saw endovascular AAA repair significantly increase from an average of 17 to 46 cases, while those for general surgery residents rosed from roughly 1 to 3 cases. Similarly, endovascular interventions for peripheral obstructive disease significantly increased for vascular fellows from 17 to 85, and from 1.3 to 4 for general surgery residents.

“The contemporary management of abdominal aortic aneurysmal diseases and peripheral obstructive diseases has been particularly changed by endovascular therapies that have been adopted into the training experience of vascular surgery fellows, but not those of general surgery residents. Open surgery experience has decreased overall for general surgery residents in all major categories, a change not seen in vascular fellows,” the researchers concluded.

The authors reported no relevant disclosures.

[email protected]

Vascular surgery fellow case logs reflect an increase in endovascular interventions, but general surgery residents may be missing out on training opportunities, according to a study of national case data.

In addition, general surgery residents saw a decrease in open vascular surgery cases, which was not reflected among the vascular surgery fellows, according to Dr. Rose C. Pedersen and colleagues in the department of surgery, Kaiser Permanente Los Angeles Medical Center. The report was published online in Annals of Vascular Surgery (doi: 10.1016/j.avsg.2016.02.008).

The paper was originally presented at the 2105 annual meeting of the Southern California Vascular Society. The study reports findings of a review of the Accreditation Council for Graduate Medical Education national case log reports from 2001 to 2012.

During that period, the number of general surgery residents increased from 1,021 to 1,098, while the number of vascular surgery fellows increased from 96 to 121. The total number of vascular cases logged by the vascular fellows significantly increased by 161%, from an average of 298 cases to 762 cases over the time period assessed. During that same period, vascular cases done by general surgery residents significantly decreased by 40%, from an average of 186 to 116 cases.

In terms of open cases. vascular fellows saw a significant 43% decrease in open abdominal aortic aneurysm (AAA) cases, going from 26 to 15, and a slight but significant increase in carotid endarterectomy cases logged (44 to 49). Hemodialysis access and major amputations also both increased significantly. A decreases in open surgery for peripheral obstructive disease was small and not significant.

General surgery residents saw decreases in all open surgery areas over the time period: AAA cases fell significantly by 78% (9 cases to 2 cases); carotid endarterectomies decreased significantly from 23 to 12 cases; and surgery for peripheral obstructive disease fell significantly from 21 to 8). Hemodialysis access cases and major amputations both decreased as well, but not significantly.

Endovascular cases increased from 2001 to 2012 for both vascular fellows and general surgery residents. Vascular fellows saw endovascular AAA repair significantly increase from an average of 17 to 46 cases, while those for general surgery residents rosed from roughly 1 to 3 cases. Similarly, endovascular interventions for peripheral obstructive disease significantly increased for vascular fellows from 17 to 85, and from 1.3 to 4 for general surgery residents.

“The contemporary management of abdominal aortic aneurysmal diseases and peripheral obstructive diseases has been particularly changed by endovascular therapies that have been adopted into the training experience of vascular surgery fellows, but not those of general surgery residents. Open surgery experience has decreased overall for general surgery residents in all major categories, a change not seen in vascular fellows,” the researchers concluded.

The authors reported no relevant disclosures.

[email protected]

With summer almost upon us, and the weather warming in many parts of the country, we have received questions from colleagues about the best over-the-counter insect repellants to advise their pregnant patients to use.

The preferred insect repellent for skin coverate is DEET (N,N-diethyl-meta-toluamide) (TABLE). Oil of lemon/eucalyptus/para-menthane-diol and IR3535 are also acceptable repellents to use on the skin that are safe for use in pregnancy. In addition, patients should be instructed to spray permethrin on their clothing or buy clothing (boots, pants, socks) that has been pretreated with permethrin.^1,2

With summer almost upon us, and the weather warming in many parts of the country, we have received questions from colleagues about the best over-the-counter insect repellants to advise their pregnant patients to use.

The preferred insect repellent for skin coverate is DEET (N,N-diethyl-meta-toluamide) (TABLE). Oil of lemon/eucalyptus/para-menthane-diol and IR3535 are also acceptable repellents to use on the skin that are safe for use in pregnancy. In addition, patients should be instructed to spray permethrin on their clothing or buy clothing (boots, pants, socks) that has been pretreated with permethrin.^1,2

With summer almost upon us, and the weather warming in many parts of the country, we have received questions from colleagues about the best over-the-counter insect repellants to advise their pregnant patients to use.

The preferred insect repellent for skin coverate is DEET (N,N-diethyl-meta-toluamide) (TABLE). Oil of lemon/eucalyptus/para-menthane-diol and IR3535 are also acceptable repellents to use on the skin that are safe for use in pregnancy. In addition, patients should be instructed to spray permethrin on their clothing or buy clothing (boots, pants, socks) that has been pretreated with permethrin.^1,2

Pediatric patients diagnosed with pheochromocytomas (PHEO) or paragangliomas (PGL) were nearly three times as likely to also carry a diagnosis of attention deficit hyperactivity disorder (ADHD), compared to pediatric patients without PHEO or PGL, investigators reported.

In addition, in 33% of the patients with PHEO and PGL, ADHD symptoms were resolved following surgical removal of the tumor.

PHEO and PGL are rare tumors of the adrenal gland. About 10% of PHEO and PGL cases occur in patients younger than 18 years. PHEOs form inside the adrenal gland in the adrenal medulla while PGLs form outside the adrenal gland. Both tumors cause excess secretion of epinephrine and norepinephrine resulting in high blood pressure, headaches, weight loss, excess sweating, anxiety, and depression. These tumors are most often surgically removed or treated with medication. Chemotherapy and radiation therapy have not been as effective in treating PHEO or PGL.

ADHD is a neurodevelopment disorder characterized by a pattern of inattention and hyperactivity or impulsivity. ADHD is associated with catecholamine dysregulation; the function of catecholamine receptors is impaired by either excess or deficient stimulation. ADHD has a prevalence of 7.2% in children aged 4-18.

©mik38/thinkstockphotos.com

In addition to the overlap in symptoms, “the stimulants used to treat ADHD may exacerbate the symptoms of the PHEO/PGL and potentially lead to a hypertensive crisis ... Amphetamines, the most widely used ADHD medication class, lead to release of stored catecholamines from vesicles, block reuptake of norepinephrine and dopamine, and block catecholamine degradation,” wrote Dr. M. Batsis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and her associates (Horm Metab Res. 2016 May 12. doi: 10.1055/s-0042-106725).

“I noticed that a lot of patients with the same story as follows: [parents] went to their pediatrician when their child started having feelings of anxiety or their heart was racing. And these symptoms were attributed to ADHD, and the child was started on medications. It wasn’t until later symptoms – an abdominal mass or a hypertensive crisis – that the patient was ultimately found out to have a pheochromocytoma,” Dr. Maya Lodish, a pediatric endocrinologist and coauthor of the paper, said in an interview.

“In hindsight, it just was not picked up. ADHD medications in no way affect tumor growth. The substances that these tumors release are stimulants. Endocrine tumors release catecholamine which are naturally occurring hormones we release under stress. When you add on top of that a stimulant medication [to treat ADHD] that may causes the nervous system to go into overdrive,” she said.

Due to the rarity of PHEO and PGL, their association with ADHD has not been well characterized. The purpose of this study was to therefore better assess the relationship between ADHD and PHEO/PGL development.

Investigators recruited 43 pediatric patients aged 6-17 who had been diagnosed with PHEO or PGL. Twenty-one percent (n = 9) of patients with PHEO/PGL carried a diagnosis of ADHD, compared to 7.2% in the general population (P = .0328).

Prior to the surgical removal of the tumors, eight of the nine patients had elevated levels of norepinephrine (n = 7), dopamine (n = 3), epinephrine (n = 1), metanephrine (n = 5) and/or normetanephrine (n = 7). In the remaining patient, levels were not measured.

Following the surgical removal of the tumors, three of the nine patients experienced both a resolution of their ADHD-related symptoms and a drop or normalization of their catecholamine and metanephrine levels. Two of those three patients showed no clinical signs of recurrent tumors while the third is under evaluation for a small pelvic lesion.

“These tumors are very rare and the vast majority of patients with ADHD are not affected by them, but they do occur. There are other organic conditions with the same symptoms – drug abuse, medications, Graves disease. If the child has symptoms attributed to ADHD and high blood pressure or family history of endocrine tumors then it is important to have a full organic workup to measure other causes of hypertension prior to starting stimulant medication,” Dr. Lodish said.

“My observation is that, and a lot of articles out there would agree, diagnoses of ADHD are on the rise and the prescribing of ADHD medication is also on the rise. I hope this is a bit of a wake-up call to practitioners that what’s common is common but there are some rare [conditions] to be aware of and so don’t have a knee jerk reaction to prescribing a medication for symptoms believed to be attributed to ADHD,” she said.

The Division of Intramural Research at the Eunice Kennedy Shriver National Institute of Child Health and Human Development supported the study. The investigators had no disclosures to report.

[email protected]

On Twitter @JessCraig_OP

Pediatric patients diagnosed with pheochromocytomas (PHEO) or paragangliomas (PGL) were nearly three times as likely to also carry a diagnosis of attention deficit hyperactivity disorder (ADHD), compared to pediatric patients without PHEO or PGL, investigators reported.

In addition, in 33% of the patients with PHEO and PGL, ADHD symptoms were resolved following surgical removal of the tumor.

PHEO and PGL are rare tumors of the adrenal gland. About 10% of PHEO and PGL cases occur in patients younger than 18 years. PHEOs form inside the adrenal gland in the adrenal medulla while PGLs form outside the adrenal gland. Both tumors cause excess secretion of epinephrine and norepinephrine resulting in high blood pressure, headaches, weight loss, excess sweating, anxiety, and depression. These tumors are most often surgically removed or treated with medication. Chemotherapy and radiation therapy have not been as effective in treating PHEO or PGL.

ADHD is a neurodevelopment disorder characterized by a pattern of inattention and hyperactivity or impulsivity. ADHD is associated with catecholamine dysregulation; the function of catecholamine receptors is impaired by either excess or deficient stimulation. ADHD has a prevalence of 7.2% in children aged 4-18.

©mik38/thinkstockphotos.com

In addition to the overlap in symptoms, “the stimulants used to treat ADHD may exacerbate the symptoms of the PHEO/PGL and potentially lead to a hypertensive crisis ... Amphetamines, the most widely used ADHD medication class, lead to release of stored catecholamines from vesicles, block reuptake of norepinephrine and dopamine, and block catecholamine degradation,” wrote Dr. M. Batsis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and her associates (Horm Metab Res. 2016 May 12. doi: 10.1055/s-0042-106725).

“I noticed that a lot of patients with the same story as follows: [parents] went to their pediatrician when their child started having feelings of anxiety or their heart was racing. And these symptoms were attributed to ADHD, and the child was started on medications. It wasn’t until later symptoms – an abdominal mass or a hypertensive crisis – that the patient was ultimately found out to have a pheochromocytoma,” Dr. Maya Lodish, a pediatric endocrinologist and coauthor of the paper, said in an interview.

“In hindsight, it just was not picked up. ADHD medications in no way affect tumor growth. The substances that these tumors release are stimulants. Endocrine tumors release catecholamine which are naturally occurring hormones we release under stress. When you add on top of that a stimulant medication [to treat ADHD] that may causes the nervous system to go into overdrive,” she said.

Due to the rarity of PHEO and PGL, their association with ADHD has not been well characterized. The purpose of this study was to therefore better assess the relationship between ADHD and PHEO/PGL development.

Investigators recruited 43 pediatric patients aged 6-17 who had been diagnosed with PHEO or PGL. Twenty-one percent (n = 9) of patients with PHEO/PGL carried a diagnosis of ADHD, compared to 7.2% in the general population (P = .0328).

Prior to the surgical removal of the tumors, eight of the nine patients had elevated levels of norepinephrine (n = 7), dopamine (n = 3), epinephrine (n = 1), metanephrine (n = 5) and/or normetanephrine (n = 7). In the remaining patient, levels were not measured.

Following the surgical removal of the tumors, three of the nine patients experienced both a resolution of their ADHD-related symptoms and a drop or normalization of their catecholamine and metanephrine levels. Two of those three patients showed no clinical signs of recurrent tumors while the third is under evaluation for a small pelvic lesion.

“These tumors are very rare and the vast majority of patients with ADHD are not affected by them, but they do occur. There are other organic conditions with the same symptoms – drug abuse, medications, Graves disease. If the child has symptoms attributed to ADHD and high blood pressure or family history of endocrine tumors then it is important to have a full organic workup to measure other causes of hypertension prior to starting stimulant medication,” Dr. Lodish said.

“My observation is that, and a lot of articles out there would agree, diagnoses of ADHD are on the rise and the prescribing of ADHD medication is also on the rise. I hope this is a bit of a wake-up call to practitioners that what’s common is common but there are some rare [conditions] to be aware of and so don’t have a knee jerk reaction to prescribing a medication for symptoms believed to be attributed to ADHD,” she said.

The Division of Intramural Research at the Eunice Kennedy Shriver National Institute of Child Health and Human Development supported the study. The investigators had no disclosures to report.

[email protected]

On Twitter @JessCraig_OP

Pediatric patients diagnosed with pheochromocytomas (PHEO) or paragangliomas (PGL) were nearly three times as likely to also carry a diagnosis of attention deficit hyperactivity disorder (ADHD), compared to pediatric patients without PHEO or PGL, investigators reported.

In addition, in 33% of the patients with PHEO and PGL, ADHD symptoms were resolved following surgical removal of the tumor.

PHEO and PGL are rare tumors of the adrenal gland. About 10% of PHEO and PGL cases occur in patients younger than 18 years. PHEOs form inside the adrenal gland in the adrenal medulla while PGLs form outside the adrenal gland. Both tumors cause excess secretion of epinephrine and norepinephrine resulting in high blood pressure, headaches, weight loss, excess sweating, anxiety, and depression. These tumors are most often surgically removed or treated with medication. Chemotherapy and radiation therapy have not been as effective in treating PHEO or PGL.

ADHD is a neurodevelopment disorder characterized by a pattern of inattention and hyperactivity or impulsivity. ADHD is associated with catecholamine dysregulation; the function of catecholamine receptors is impaired by either excess or deficient stimulation. ADHD has a prevalence of 7.2% in children aged 4-18.

©mik38/thinkstockphotos.com

In addition to the overlap in symptoms, “the stimulants used to treat ADHD may exacerbate the symptoms of the PHEO/PGL and potentially lead to a hypertensive crisis ... Amphetamines, the most widely used ADHD medication class, lead to release of stored catecholamines from vesicles, block reuptake of norepinephrine and dopamine, and block catecholamine degradation,” wrote Dr. M. Batsis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and her associates (Horm Metab Res. 2016 May 12. doi: 10.1055/s-0042-106725).

“I noticed that a lot of patients with the same story as follows: [parents] went to their pediatrician when their child started having feelings of anxiety or their heart was racing. And these symptoms were attributed to ADHD, and the child was started on medications. It wasn’t until later symptoms – an abdominal mass or a hypertensive crisis – that the patient was ultimately found out to have a pheochromocytoma,” Dr. Maya Lodish, a pediatric endocrinologist and coauthor of the paper, said in an interview.

“In hindsight, it just was not picked up. ADHD medications in no way affect tumor growth. The substances that these tumors release are stimulants. Endocrine tumors release catecholamine which are naturally occurring hormones we release under stress. When you add on top of that a stimulant medication [to treat ADHD] that may causes the nervous system to go into overdrive,” she said.

Due to the rarity of PHEO and PGL, their association with ADHD has not been well characterized. The purpose of this study was to therefore better assess the relationship between ADHD and PHEO/PGL development.

Investigators recruited 43 pediatric patients aged 6-17 who had been diagnosed with PHEO or PGL. Twenty-one percent (n = 9) of patients with PHEO/PGL carried a diagnosis of ADHD, compared to 7.2% in the general population (P = .0328).

Prior to the surgical removal of the tumors, eight of the nine patients had elevated levels of norepinephrine (n = 7), dopamine (n = 3), epinephrine (n = 1), metanephrine (n = 5) and/or normetanephrine (n = 7). In the remaining patient, levels were not measured.

Following the surgical removal of the tumors, three of the nine patients experienced both a resolution of their ADHD-related symptoms and a drop or normalization of their catecholamine and metanephrine levels. Two of those three patients showed no clinical signs of recurrent tumors while the third is under evaluation for a small pelvic lesion.

“These tumors are very rare and the vast majority of patients with ADHD are not affected by them, but they do occur. There are other organic conditions with the same symptoms – drug abuse, medications, Graves disease. If the child has symptoms attributed to ADHD and high blood pressure or family history of endocrine tumors then it is important to have a full organic workup to measure other causes of hypertension prior to starting stimulant medication,” Dr. Lodish said.

“My observation is that, and a lot of articles out there would agree, diagnoses of ADHD are on the rise and the prescribing of ADHD medication is also on the rise. I hope this is a bit of a wake-up call to practitioners that what’s common is common but there are some rare [conditions] to be aware of and so don’t have a knee jerk reaction to prescribing a medication for symptoms believed to be attributed to ADHD,” she said.

The Division of Intramural Research at the Eunice Kennedy Shriver National Institute of Child Health and Human Development supported the study. The investigators had no disclosures to report.

[email protected]

On Twitter @JessCraig_OP

LOS ANGELES – Fungi might play a far larger role in asthma and chronic sinusitis than previously thought, according to investigators at Baylor College of Medicine in Houston.

With the help of a special culturing technique to wash antifungal elements out of sputum samples, six or more fungal colony-forming units grew out of the sputum of 112 of 134 patients (83.5%) at the Houston Veterans Affairs Medical Center; about a third of the patients had asthma, a third had chronic sinusitis, and a third had both. Although Aspergillus and Candida species were common, more than 30 fungal species were identified. Only a handful of patients had positive results on IgE testing.

Of 62 patients treated with standard-dose voriconazole or terbinafine, sometimes for more than a year, 54 (87%) reported symptomatic benefit including 31 (50%) with decreased sputum production, 24 (39%) with improved breathing, 20 (32%) with less cough, and nine (14.5%) with less rescue inhaler use.

At Baylor, prescribing antifungals for patients with recalcitrant asthma and chronic sinusitis “has evolved into something we pretty much do all the time now regardless of sensitivity results. I’m pretty certain we are the only institution that does this,” said allergy and immunology fellow Dr. Evan Li.

“Fungi, we think, are important initiating factors in many cases of asthma. They set up chronic mucosal infection. Our [treatment] experience is extremely positive; it may be in the future that if you have significant asthma or sinusitis, you just go on an antifungal, but more research and clinical trials are needed,” said senior investigator Dr. David Corry, professor and chief of medical immunology, allergy, and rheumatology at Baylor.

“The standard culture techniques that have been used for 100 years are inadequate when it comes to culturing fungi from sputum, and why results almost invariably come back negative,” Dr. Corry said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The problem is that “almost everything in sputum” – eosinophils, macrophages, cytokines, and so on – “is designed to kill fungi.” Those elements have to be removed before plating. At Baylor, “we solubilize [sputum] with the reducing agent dithiothreitol, and vigorously stir the mixture to disperse the organisms and wash away the cellular elements and the other things.” The process leaves behind “a sandy material that’s basically fibrin clots mixed with a lot of fungal elements. You spread that on a plate, and it grows like wildfire,” he said.

“It’s easy to do, but time consuming. People are actually shipping their samples to us now from around the country, and we are happy to do those cultures,” Dr. Corry said. There’s no patent on the technique because “we want the community to use it. We want people to be helped,” he said.

Voriconazole seems to be the most effective option, and the team opts for it when possible, Dr. Corry noted. Terbinafine is the go-to drug for patients who can’t tolerate voriconazole. Fluconazole is sometimes added when monotherapy doesn’t seem to be doing the trick.

The work began as a search for household proteases. “One of our first discoveries was that” most are fungal. “The twist is that you are not inhaling the proteases, you are inhaling the fungus,” Dr. Corry said.

There have been both positive and negative results from the few prior investigations of antifungals for asthma. The team suspects that negative findings were a result of patients not being treated long enough, among other reasons.

The Baylor team is looking for funding for a prospective trial. The investigators hope to develop a protocol for diagnosis and treatment of fungal airway disease, but “there’s a lot of work that needs to get done,” Dr. Corry said.

The investigators had no relevant financial disclosures, and there was no outside funding for the work.

[email protected]

LOS ANGELES – Fungi might play a far larger role in asthma and chronic sinusitis than previously thought, according to investigators at Baylor College of Medicine in Houston.

With the help of a special culturing technique to wash antifungal elements out of sputum samples, six or more fungal colony-forming units grew out of the sputum of 112 of 134 patients (83.5%) at the Houston Veterans Affairs Medical Center; about a third of the patients had asthma, a third had chronic sinusitis, and a third had both. Although Aspergillus and Candida species were common, more than 30 fungal species were identified. Only a handful of patients had positive results on IgE testing.

Of 62 patients treated with standard-dose voriconazole or terbinafine, sometimes for more than a year, 54 (87%) reported symptomatic benefit including 31 (50%) with decreased sputum production, 24 (39%) with improved breathing, 20 (32%) with less cough, and nine (14.5%) with less rescue inhaler use.

At Baylor, prescribing antifungals for patients with recalcitrant asthma and chronic sinusitis “has evolved into something we pretty much do all the time now regardless of sensitivity results. I’m pretty certain we are the only institution that does this,” said allergy and immunology fellow Dr. Evan Li.

“Fungi, we think, are important initiating factors in many cases of asthma. They set up chronic mucosal infection. Our [treatment] experience is extremely positive; it may be in the future that if you have significant asthma or sinusitis, you just go on an antifungal, but more research and clinical trials are needed,” said senior investigator Dr. David Corry, professor and chief of medical immunology, allergy, and rheumatology at Baylor.

“The standard culture techniques that have been used for 100 years are inadequate when it comes to culturing fungi from sputum, and why results almost invariably come back negative,” Dr. Corry said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The problem is that “almost everything in sputum” – eosinophils, macrophages, cytokines, and so on – “is designed to kill fungi.” Those elements have to be removed before plating. At Baylor, “we solubilize [sputum] with the reducing agent dithiothreitol, and vigorously stir the mixture to disperse the organisms and wash away the cellular elements and the other things.” The process leaves behind “a sandy material that’s basically fibrin clots mixed with a lot of fungal elements. You spread that on a plate, and it grows like wildfire,” he said.

“It’s easy to do, but time consuming. People are actually shipping their samples to us now from around the country, and we are happy to do those cultures,” Dr. Corry said. There’s no patent on the technique because “we want the community to use it. We want people to be helped,” he said.

Voriconazole seems to be the most effective option, and the team opts for it when possible, Dr. Corry noted. Terbinafine is the go-to drug for patients who can’t tolerate voriconazole. Fluconazole is sometimes added when monotherapy doesn’t seem to be doing the trick.

The work began as a search for household proteases. “One of our first discoveries was that” most are fungal. “The twist is that you are not inhaling the proteases, you are inhaling the fungus,” Dr. Corry said.

There have been both positive and negative results from the few prior investigations of antifungals for asthma. The team suspects that negative findings were a result of patients not being treated long enough, among other reasons.

The Baylor team is looking for funding for a prospective trial. The investigators hope to develop a protocol for diagnosis and treatment of fungal airway disease, but “there’s a lot of work that needs to get done,” Dr. Corry said.

The investigators had no relevant financial disclosures, and there was no outside funding for the work.

[email protected]

LOS ANGELES – Fungi might play a far larger role in asthma and chronic sinusitis than previously thought, according to investigators at Baylor College of Medicine in Houston.

With the help of a special culturing technique to wash antifungal elements out of sputum samples, six or more fungal colony-forming units grew out of the sputum of 112 of 134 patients (83.5%) at the Houston Veterans Affairs Medical Center; about a third of the patients had asthma, a third had chronic sinusitis, and a third had both. Although Aspergillus and Candida species were common, more than 30 fungal species were identified. Only a handful of patients had positive results on IgE testing.

Of 62 patients treated with standard-dose voriconazole or terbinafine, sometimes for more than a year, 54 (87%) reported symptomatic benefit including 31 (50%) with decreased sputum production, 24 (39%) with improved breathing, 20 (32%) with less cough, and nine (14.5%) with less rescue inhaler use.

At Baylor, prescribing antifungals for patients with recalcitrant asthma and chronic sinusitis “has evolved into something we pretty much do all the time now regardless of sensitivity results. I’m pretty certain we are the only institution that does this,” said allergy and immunology fellow Dr. Evan Li.

“Fungi, we think, are important initiating factors in many cases of asthma. They set up chronic mucosal infection. Our [treatment] experience is extremely positive; it may be in the future that if you have significant asthma or sinusitis, you just go on an antifungal, but more research and clinical trials are needed,” said senior investigator Dr. David Corry, professor and chief of medical immunology, allergy, and rheumatology at Baylor.

“The standard culture techniques that have been used for 100 years are inadequate when it comes to culturing fungi from sputum, and why results almost invariably come back negative,” Dr. Corry said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The problem is that “almost everything in sputum” – eosinophils, macrophages, cytokines, and so on – “is designed to kill fungi.” Those elements have to be removed before plating. At Baylor, “we solubilize [sputum] with the reducing agent dithiothreitol, and vigorously stir the mixture to disperse the organisms and wash away the cellular elements and the other things.” The process leaves behind “a sandy material that’s basically fibrin clots mixed with a lot of fungal elements. You spread that on a plate, and it grows like wildfire,” he said.

“It’s easy to do, but time consuming. People are actually shipping their samples to us now from around the country, and we are happy to do those cultures,” Dr. Corry said. There’s no patent on the technique because “we want the community to use it. We want people to be helped,” he said.

Voriconazole seems to be the most effective option, and the team opts for it when possible, Dr. Corry noted. Terbinafine is the go-to drug for patients who can’t tolerate voriconazole. Fluconazole is sometimes added when monotherapy doesn’t seem to be doing the trick.

The work began as a search for household proteases. “One of our first discoveries was that” most are fungal. “The twist is that you are not inhaling the proteases, you are inhaling the fungus,” Dr. Corry said.

There have been both positive and negative results from the few prior investigations of antifungals for asthma. The team suspects that negative findings were a result of patients not being treated long enough, among other reasons.

The Baylor team is looking for funding for a prospective trial. The investigators hope to develop a protocol for diagnosis and treatment of fungal airway disease, but “there’s a lot of work that needs to get done,” Dr. Corry said.

The investigators had no relevant financial disclosures, and there was no outside funding for the work.

[email protected]