Commentary

Oseltamivir and zanamivir are competitive inhibitors for the neuraminidase enzyme for the influenza virus. They block the surface receptor enzyme and prevent release of virus from the host cell, thus limiting propagation of the infection. These medications can be given as prophylaxis after exposure to influenza or can be given therapeutically for a suspected or confirmed infection. Oseltamivir is recommended for treatment of suspected or confirmed influenza infection in the special population of pregnant women, as the risk for complications of influenza is increased in this group.

Safety evidence

However, there are limited data on the safety and efficacy of the neuraminidase inhibitors in pregnancy. With respect to safety, there have been seven publications in the literature addressing the risk for major birth defects following treatment or prophylaxis with one or both of these products, with the majority of the published data relating to oseltamivir exposure.

In a review by Tanaka et al. in 2009, 90 pregnancies treated therapeutically with oseltamivir in the first trimester were reported to two teratogen information services in Japan; one major birth defect (1.1%) was reported (CMAJ. 2009 Jul 7;181[1-2]:55-8). A year later, Greer et al. published a retrospective chart review at a Texas hospital between 2003 and 2008. During that period, 137 pregnancies that involved a pharmacy record of dispensing of oseltamivir were identified. Of these, 18 were dispensed in the first trimester, and none were linked to a major birth defect outcome (Obstet Gynecol. 2010 Apr;115[4]:711-6).

A 2011 record linkage study in Sweden identified 86 pregnant women for whom oseltamivir (n=81) or zanamivir had been prescribed. Of these, four were linked to a major birth defect in the infant; however, only one of the four prescriptions had been filled in the first trimester (Pharmacoepidemiol Drug Saf. 2011 Oct;20[10]:1030-4). In 2013, Saito et al. reported on a case series gathered from 157 obstetric facilities in Japan. Among 156 infants born to women exposed to oseltamivir in the first trimester, 2 (1.3%) were reported to have a major congenital anomaly; there were no congenital malformations reported in the 15 first-trimester exposures to zanamivir (Am J Obstet Gynecol. 2013 Aug;209[2[:130.e1-9).

In 2014, a teratogen information service in the United Kingdom reported on eight first-trimester exposures to oseltamivir and 37 to zanamivir, with no major birth defects noted in either group (BJOG. 2014 Jun;121[7]:901-6). Additionally, a French prescription database study identified 49 pregnancies thought to be exposed to oseltamivir in the first trimester with one reported congenital anomaly (BJOG. 2014 Jun;121[7]:895-900).

Finally, the manufacturer of oseltamivir published a summary of pregnancies from global pharmacovigilance data accumulated through spontaneous reports and other studies between 2000 and 2012 (Pharmacoepidemiol Drug Saf. 2014 Oct;23[10]:1035-42). Outcomes were available for 1,875 infants. Among these, 81 (4.3%) had major birth defects. However, following case review, the authors indicated that only 11 of the defects (occurring in 9 infants) were biologically plausible based on the timing of the exposure to oseltamivir.

Efficacy examined

With respect to efficacy, two small studies have addressed the pharmacokinetics of oseltamivir in pregnancy to determine if the recommended dosages for nonpregnant individuals are appropriate for pregnancy.

In the earlier of the two studies, Greer et al. looked at the pharmacokinetics of oseltamivir in 30 pregnant women, 10 in each of the three trimesters, who were taking 75 mg of the drug either once or twice daily. Maternal samples were drawn before and after the first dose of oseltamivir. They found little evidence of differences across the three trimesters and concluded that the parent drug values were in the pharmacologic range for clinical efficacy (Am J Obstet Gynecol. 2011 Jun;204[6 Suppl 1]:S89-93).

In contrast, Pillai et al. enrolled a small sample of women being treated with oseltamivir; they evaluated pharmacokinetics for the active metabolite of oseltamivir following 48 or more hours of treatment in 29 pregnant and 35 nonpregnant women (Br J Clin Pharmacol. 2015 Nov;80[5]:1042-50). Significantly lower levels of the active metabolite were noted in the pregnant women, compared with nonpregnant women. The authors suggested that the physiologic changes of pregnancy, correlated with increased renal clearance, produced an approximate 30% lower exposure to the drug in the pregnant state. While they were not able to relate this to maternal or infant outcomes, this finding suggested that further work is needed to determine if dosing recommendations should be adjusted in pregnancy.

The current recommendation is that pregnant women or women within 2 weeks post partum be given oseltamivir for treatment of suspected or confirmed influenza regardless of trimester of pregnancy. The limited safety data that are currently available have not suggested an increased risk for major birth defects following treatment with this product. However, the data are sparse for oseltamivir and even more so for zanamivir. Larger studies focused on these treatments are needed.

Dr. Chambers is professor of pediatrics and director of clinical research at Rady Children’s Hospital, and associate director of the Clinical and Translational Research Institute at the University of California, San Diego. She is director of MotherToBaby California, past president of the Organization of Teratology Information Specialists, and past president of the Teratology Society. She reported having no financial disclosures relevant to this column, but has received research funding Roche-Genentech and GlaxoSmithKline unrelated to antiviral medications. Email her at [email protected].

Oseltamivir and zanamivir are competitive inhibitors for the neuraminidase enzyme for the influenza virus. They block the surface receptor enzyme and prevent release of virus from the host cell, thus limiting propagation of the infection. These medications can be given as prophylaxis after exposure to influenza or can be given therapeutically for a suspected or confirmed infection. Oseltamivir is recommended for treatment of suspected or confirmed influenza infection in the special population of pregnant women, as the risk for complications of influenza is increased in this group.

Safety evidence

However, there are limited data on the safety and efficacy of the neuraminidase inhibitors in pregnancy. With respect to safety, there have been seven publications in the literature addressing the risk for major birth defects following treatment or prophylaxis with one or both of these products, with the majority of the published data relating to oseltamivir exposure.

In a review by Tanaka et al. in 2009, 90 pregnancies treated therapeutically with oseltamivir in the first trimester were reported to two teratogen information services in Japan; one major birth defect (1.1%) was reported (CMAJ. 2009 Jul 7;181[1-2]:55-8). A year later, Greer et al. published a retrospective chart review at a Texas hospital between 2003 and 2008. During that period, 137 pregnancies that involved a pharmacy record of dispensing of oseltamivir were identified. Of these, 18 were dispensed in the first trimester, and none were linked to a major birth defect outcome (Obstet Gynecol. 2010 Apr;115[4]:711-6).

A 2011 record linkage study in Sweden identified 86 pregnant women for whom oseltamivir (n=81) or zanamivir had been prescribed. Of these, four were linked to a major birth defect in the infant; however, only one of the four prescriptions had been filled in the first trimester (Pharmacoepidemiol Drug Saf. 2011 Oct;20[10]:1030-4). In 2013, Saito et al. reported on a case series gathered from 157 obstetric facilities in Japan. Among 156 infants born to women exposed to oseltamivir in the first trimester, 2 (1.3%) were reported to have a major congenital anomaly; there were no congenital malformations reported in the 15 first-trimester exposures to zanamivir (Am J Obstet Gynecol. 2013 Aug;209[2[:130.e1-9).

In 2014, a teratogen information service in the United Kingdom reported on eight first-trimester exposures to oseltamivir and 37 to zanamivir, with no major birth defects noted in either group (BJOG. 2014 Jun;121[7]:901-6). Additionally, a French prescription database study identified 49 pregnancies thought to be exposed to oseltamivir in the first trimester with one reported congenital anomaly (BJOG. 2014 Jun;121[7]:895-900).

Finally, the manufacturer of oseltamivir published a summary of pregnancies from global pharmacovigilance data accumulated through spontaneous reports and other studies between 2000 and 2012 (Pharmacoepidemiol Drug Saf. 2014 Oct;23[10]:1035-42). Outcomes were available for 1,875 infants. Among these, 81 (4.3%) had major birth defects. However, following case review, the authors indicated that only 11 of the defects (occurring in 9 infants) were biologically plausible based on the timing of the exposure to oseltamivir.

Efficacy examined

With respect to efficacy, two small studies have addressed the pharmacokinetics of oseltamivir in pregnancy to determine if the recommended dosages for nonpregnant individuals are appropriate for pregnancy.

In the earlier of the two studies, Greer et al. looked at the pharmacokinetics of oseltamivir in 30 pregnant women, 10 in each of the three trimesters, who were taking 75 mg of the drug either once or twice daily. Maternal samples were drawn before and after the first dose of oseltamivir. They found little evidence of differences across the three trimesters and concluded that the parent drug values were in the pharmacologic range for clinical efficacy (Am J Obstet Gynecol. 2011 Jun;204[6 Suppl 1]:S89-93).

In contrast, Pillai et al. enrolled a small sample of women being treated with oseltamivir; they evaluated pharmacokinetics for the active metabolite of oseltamivir following 48 or more hours of treatment in 29 pregnant and 35 nonpregnant women (Br J Clin Pharmacol. 2015 Nov;80[5]:1042-50). Significantly lower levels of the active metabolite were noted in the pregnant women, compared with nonpregnant women. The authors suggested that the physiologic changes of pregnancy, correlated with increased renal clearance, produced an approximate 30% lower exposure to the drug in the pregnant state. While they were not able to relate this to maternal or infant outcomes, this finding suggested that further work is needed to determine if dosing recommendations should be adjusted in pregnancy.

The current recommendation is that pregnant women or women within 2 weeks post partum be given oseltamivir for treatment of suspected or confirmed influenza regardless of trimester of pregnancy. The limited safety data that are currently available have not suggested an increased risk for major birth defects following treatment with this product. However, the data are sparse for oseltamivir and even more so for zanamivir. Larger studies focused on these treatments are needed.

Dr. Chambers is professor of pediatrics and director of clinical research at Rady Children’s Hospital, and associate director of the Clinical and Translational Research Institute at the University of California, San Diego. She is director of MotherToBaby California, past president of the Organization of Teratology Information Specialists, and past president of the Teratology Society. She reported having no financial disclosures relevant to this column, but has received research funding Roche-Genentech and GlaxoSmithKline unrelated to antiviral medications. Email her at [email protected].

Oseltamivir and zanamivir are competitive inhibitors for the neuraminidase enzyme for the influenza virus. They block the surface receptor enzyme and prevent release of virus from the host cell, thus limiting propagation of the infection. These medications can be given as prophylaxis after exposure to influenza or can be given therapeutically for a suspected or confirmed infection. Oseltamivir is recommended for treatment of suspected or confirmed influenza infection in the special population of pregnant women, as the risk for complications of influenza is increased in this group.

Safety evidence

However, there are limited data on the safety and efficacy of the neuraminidase inhibitors in pregnancy. With respect to safety, there have been seven publications in the literature addressing the risk for major birth defects following treatment or prophylaxis with one or both of these products, with the majority of the published data relating to oseltamivir exposure.

In a review by Tanaka et al. in 2009, 90 pregnancies treated therapeutically with oseltamivir in the first trimester were reported to two teratogen information services in Japan; one major birth defect (1.1%) was reported (CMAJ. 2009 Jul 7;181[1-2]:55-8). A year later, Greer et al. published a retrospective chart review at a Texas hospital between 2003 and 2008. During that period, 137 pregnancies that involved a pharmacy record of dispensing of oseltamivir were identified. Of these, 18 were dispensed in the first trimester, and none were linked to a major birth defect outcome (Obstet Gynecol. 2010 Apr;115[4]:711-6).

A 2011 record linkage study in Sweden identified 86 pregnant women for whom oseltamivir (n=81) or zanamivir had been prescribed. Of these, four were linked to a major birth defect in the infant; however, only one of the four prescriptions had been filled in the first trimester (Pharmacoepidemiol Drug Saf. 2011 Oct;20[10]:1030-4). In 2013, Saito et al. reported on a case series gathered from 157 obstetric facilities in Japan. Among 156 infants born to women exposed to oseltamivir in the first trimester, 2 (1.3%) were reported to have a major congenital anomaly; there were no congenital malformations reported in the 15 first-trimester exposures to zanamivir (Am J Obstet Gynecol. 2013 Aug;209[2[:130.e1-9).

In 2014, a teratogen information service in the United Kingdom reported on eight first-trimester exposures to oseltamivir and 37 to zanamivir, with no major birth defects noted in either group (BJOG. 2014 Jun;121[7]:901-6). Additionally, a French prescription database study identified 49 pregnancies thought to be exposed to oseltamivir in the first trimester with one reported congenital anomaly (BJOG. 2014 Jun;121[7]:895-900).

Finally, the manufacturer of oseltamivir published a summary of pregnancies from global pharmacovigilance data accumulated through spontaneous reports and other studies between 2000 and 2012 (Pharmacoepidemiol Drug Saf. 2014 Oct;23[10]:1035-42). Outcomes were available for 1,875 infants. Among these, 81 (4.3%) had major birth defects. However, following case review, the authors indicated that only 11 of the defects (occurring in 9 infants) were biologically plausible based on the timing of the exposure to oseltamivir.

Efficacy examined

With respect to efficacy, two small studies have addressed the pharmacokinetics of oseltamivir in pregnancy to determine if the recommended dosages for nonpregnant individuals are appropriate for pregnancy.

In the earlier of the two studies, Greer et al. looked at the pharmacokinetics of oseltamivir in 30 pregnant women, 10 in each of the three trimesters, who were taking 75 mg of the drug either once or twice daily. Maternal samples were drawn before and after the first dose of oseltamivir. They found little evidence of differences across the three trimesters and concluded that the parent drug values were in the pharmacologic range for clinical efficacy (Am J Obstet Gynecol. 2011 Jun;204[6 Suppl 1]:S89-93).

In contrast, Pillai et al. enrolled a small sample of women being treated with oseltamivir; they evaluated pharmacokinetics for the active metabolite of oseltamivir following 48 or more hours of treatment in 29 pregnant and 35 nonpregnant women (Br J Clin Pharmacol. 2015 Nov;80[5]:1042-50). Significantly lower levels of the active metabolite were noted in the pregnant women, compared with nonpregnant women. The authors suggested that the physiologic changes of pregnancy, correlated with increased renal clearance, produced an approximate 30% lower exposure to the drug in the pregnant state. While they were not able to relate this to maternal or infant outcomes, this finding suggested that further work is needed to determine if dosing recommendations should be adjusted in pregnancy.

The current recommendation is that pregnant women or women within 2 weeks post partum be given oseltamivir for treatment of suspected or confirmed influenza regardless of trimester of pregnancy. The limited safety data that are currently available have not suggested an increased risk for major birth defects following treatment with this product. However, the data are sparse for oseltamivir and even more so for zanamivir. Larger studies focused on these treatments are needed.

Dr. Chambers is professor of pediatrics and director of clinical research at Rady Children’s Hospital, and associate director of the Clinical and Translational Research Institute at the University of California, San Diego. She is director of MotherToBaby California, past president of the Organization of Teratology Information Specialists, and past president of the Teratology Society. She reported having no financial disclosures relevant to this column, but has received research funding Roche-Genentech and GlaxoSmithKline unrelated to antiviral medications. Email her at [email protected].

The National Football League (NFL) had its highest concussion tally last year: 182 such injuries reported¹ in the 2014-2015 regular season. The true rate of concussion in the NFL is likely higher, as a result of multiple factors (fear of “letting the team [or the coach] down,” fear of retaliation from team owners,² etc.).

To simply call a head injury a “concussion” is a disservice to players and their family: Any blow to the head, severe or otherwise, has the potential to cause microvascular disruption in the brain; repeated blows to the head undoubtedly cause further damage.

In reality, a “concussion” is a mild traumatic brain injury (mTBI). With repeated blows, an mTBI can lead to chronic traumatic encephalopathy (CTE). In 2015, eighty-seven of 91 brains from autopsied former NFL players displayed some stage of CTE.³

Pathophysiology and presentation
CTE comprises 4 histological stages; Stage 4 is the most advanced. Alzheimer’s disease (AD) and CTE display similarities, which suggests a separate classification of CTE-AD; the presence of amyloid β plaques correlates with (1) more severe hyperphosphorylated tau (pTau) pathology and (2) advanced stages of the disease and clinical presentations. Death tends to occur 10 years earlier in CTE-AD than in AD, suggesting that repetitive mTBI might change the deposition and accumulation of amyloid β plaques, and even accelerate the aging process in the brain.⁴

Symptoms. The case series by Omalu et al⁴ (which inspired the 2015 motion picture Concussion) and the case series presented by McKee et al⁵ described severe psychiatric symptoms associated with CTE:

• decreased speed of information processing
• increase in religiosity
• lack of insight
• poor judgment
• involvement in illegal activities
• substance abuse
• indiscretion
• verbal and physical abuse
• problems with interpersonal relationships
• isolation
• restlessness and hyperactivity
• somatic complaints.

The 2 groups of researchers also noted hopelessness, social phobia, anxiety, agitation, mania, labile mood, insomnia, explosivity, and suicidal ideation, attempt, and completion.^4,5

By Stage 4, all affected patients are symptomatic. Cognitive impairment is severe; many are described as having “severe memory loss with dementia,”⁵ “profound” inattention and loss of concentration,⁵ and dysarthria. Paranoia may develop. Mood symptoms can be severe: Approximately 31% of subjects studied have contemplated suicide; of those, 26% had “suicidal tendencies” and 14% completed suicide.⁵

Two distinct types of CTE progression are apparent:

• patients who display cognitive deficits first; they progress to dementia but live longer
• patients who display mood and behavioral symptoms first; they tend to be younger, more violent, depressed, and explosive.⁶

CTE cannot be diagnosed with imaging. There are, however, a few positron emission tomography (PET) ligands for pTau that show promise:

• [F-18]FDDNP, which consistently identifies pTau deposits in brains in which CTE is clinically suspected, in the same distribution of pTau neurofibrillary tangles on autopsy.
• [11C]DPA-713, which detected TBI-related inflammation of neurons in 9 former NFL players in whom CTE was suspected based on the clinical presentation.
• PiB amyloid ligand, under investigation for use in PET neuroimaging.⁷

Casualties
In January 2016 alone, at least 3 former NFL players were found to have CTE posthumously.

Earl Morrall. Former quarterback who had a 21-year NFL career. Official cause of death in 2014 at age 79 was recorded as “complications of Parkinson’s disease.” In 2016, Stage-4 CTE was discovered on autopsy.⁸

Ken Stabler. Former quarterback for several NFL teams over 15 seasons. Died of colon cancer at age 69 in 2015. On autopsy, was found to have Stage-3 CTE.⁹

Tyler Sash. Former University of Iowa and New York Giants football player. Died in September 2015 at age 27 of an apparent drug overdose; post­humously, determined to have Stage-2 CTE. His family reported memory loss, minor fits of rage, confusion, inattention, lack of focus, and chronic pain.

Sash’s mother said, “My son knew something was wrong, but he couldn’t express it. He was such a good person, and it’s sad that he struggled so with this—not knowing where to go with it. Now it makes sense.”¹⁰ Sash played 16 years of football in all, sustaining at least 5 concussions. (“If you’ve played football, you know there are often other incidents [of head trauma],” Sash’s father said.¹⁰)

Cultural and medical mindsets about contact sports
In the United States, children as young as age 5, with a low weight limit of 35 pounds, routinely are introduced to football.¹¹ Reports of 5 high school players dying from football-related injury in the 2014 season, and 3 deaths in the 2015 season, led a St. Louis, Missouri, area school district to defund their football program entirely. The district’s 2015 homecoming game was a soccer match; students and parents seemed to embrace the change.¹²

On its face, soccer seems a good alternative to football. When children are instructed to “head” the ball, however, concern arises about CTE: Mild CTE changes have been reported in 2 young soccer players, and late-stage CTE changes were seen in a retired soccer player with dementia.¹³

Perhaps most disturbing is that players who develop symptoms of CTE, or are at risk, are unlikely to seek psychiatric help. We, as psychiatric clinicians, must be diligent about questioning young patients about their extracurricular activities. It is not enough to simply ask about a history of head trauma: Ask patients about any blow to the head, and don’t limit your questioning to whether they sustained a “concussion” during practice or play.

When speaking with adult and geriatric patients, ask about a history of playing interscholastic or collegiate contact sports, such as football, hockey, and soccer.

Is the solution to better shield the head?
That is not a solution: Helmets and other protective headgear appear to be insufficient to protect the brain from traumatic injury. Perhaps keeping children from engaging in violent sports that put them at high risk of CTE later is the preventive approach that merits the most attention.

The National Football League (NFL) had its highest concussion tally last year: 182 such injuries reported¹ in the 2014-2015 regular season. The true rate of concussion in the NFL is likely higher, as a result of multiple factors (fear of “letting the team [or the coach] down,” fear of retaliation from team owners,² etc.).

To simply call a head injury a “concussion” is a disservice to players and their family: Any blow to the head, severe or otherwise, has the potential to cause microvascular disruption in the brain; repeated blows to the head undoubtedly cause further damage.

In reality, a “concussion” is a mild traumatic brain injury (mTBI). With repeated blows, an mTBI can lead to chronic traumatic encephalopathy (CTE). In 2015, eighty-seven of 91 brains from autopsied former NFL players displayed some stage of CTE.³

Pathophysiology and presentation
CTE comprises 4 histological stages; Stage 4 is the most advanced. Alzheimer’s disease (AD) and CTE display similarities, which suggests a separate classification of CTE-AD; the presence of amyloid β plaques correlates with (1) more severe hyperphosphorylated tau (pTau) pathology and (2) advanced stages of the disease and clinical presentations. Death tends to occur 10 years earlier in CTE-AD than in AD, suggesting that repetitive mTBI might change the deposition and accumulation of amyloid β plaques, and even accelerate the aging process in the brain.⁴

Symptoms. The case series by Omalu et al⁴ (which inspired the 2015 motion picture Concussion) and the case series presented by McKee et al⁵ described severe psychiatric symptoms associated with CTE:

• decreased speed of information processing
• increase in religiosity
• lack of insight
• poor judgment
• involvement in illegal activities
• substance abuse
• indiscretion
• verbal and physical abuse
• problems with interpersonal relationships
• isolation
• restlessness and hyperactivity
• somatic complaints.

The 2 groups of researchers also noted hopelessness, social phobia, anxiety, agitation, mania, labile mood, insomnia, explosivity, and suicidal ideation, attempt, and completion.^4,5

By Stage 4, all affected patients are symptomatic. Cognitive impairment is severe; many are described as having “severe memory loss with dementia,”⁵ “profound” inattention and loss of concentration,⁵ and dysarthria. Paranoia may develop. Mood symptoms can be severe: Approximately 31% of subjects studied have contemplated suicide; of those, 26% had “suicidal tendencies” and 14% completed suicide.⁵

Two distinct types of CTE progression are apparent:

• patients who display cognitive deficits first; they progress to dementia but live longer
• patients who display mood and behavioral symptoms first; they tend to be younger, more violent, depressed, and explosive.⁶

CTE cannot be diagnosed with imaging. There are, however, a few positron emission tomography (PET) ligands for pTau that show promise:

• [F-18]FDDNP, which consistently identifies pTau deposits in brains in which CTE is clinically suspected, in the same distribution of pTau neurofibrillary tangles on autopsy.
• [11C]DPA-713, which detected TBI-related inflammation of neurons in 9 former NFL players in whom CTE was suspected based on the clinical presentation.
• PiB amyloid ligand, under investigation for use in PET neuroimaging.⁷

Casualties
In January 2016 alone, at least 3 former NFL players were found to have CTE posthumously.

Earl Morrall. Former quarterback who had a 21-year NFL career. Official cause of death in 2014 at age 79 was recorded as “complications of Parkinson’s disease.” In 2016, Stage-4 CTE was discovered on autopsy.⁸

Ken Stabler. Former quarterback for several NFL teams over 15 seasons. Died of colon cancer at age 69 in 2015. On autopsy, was found to have Stage-3 CTE.⁹

Tyler Sash. Former University of Iowa and New York Giants football player. Died in September 2015 at age 27 of an apparent drug overdose; post­humously, determined to have Stage-2 CTE. His family reported memory loss, minor fits of rage, confusion, inattention, lack of focus, and chronic pain.

Sash’s mother said, “My son knew something was wrong, but he couldn’t express it. He was such a good person, and it’s sad that he struggled so with this—not knowing where to go with it. Now it makes sense.”¹⁰ Sash played 16 years of football in all, sustaining at least 5 concussions. (“If you’ve played football, you know there are often other incidents [of head trauma],” Sash’s father said.¹⁰)

Cultural and medical mindsets about contact sports
In the United States, children as young as age 5, with a low weight limit of 35 pounds, routinely are introduced to football.¹¹ Reports of 5 high school players dying from football-related injury in the 2014 season, and 3 deaths in the 2015 season, led a St. Louis, Missouri, area school district to defund their football program entirely. The district’s 2015 homecoming game was a soccer match; students and parents seemed to embrace the change.¹²

On its face, soccer seems a good alternative to football. When children are instructed to “head” the ball, however, concern arises about CTE: Mild CTE changes have been reported in 2 young soccer players, and late-stage CTE changes were seen in a retired soccer player with dementia.¹³

Perhaps most disturbing is that players who develop symptoms of CTE, or are at risk, are unlikely to seek psychiatric help. We, as psychiatric clinicians, must be diligent about questioning young patients about their extracurricular activities. It is not enough to simply ask about a history of head trauma: Ask patients about any blow to the head, and don’t limit your questioning to whether they sustained a “concussion” during practice or play.

When speaking with adult and geriatric patients, ask about a history of playing interscholastic or collegiate contact sports, such as football, hockey, and soccer.

Is the solution to better shield the head?
That is not a solution: Helmets and other protective headgear appear to be insufficient to protect the brain from traumatic injury. Perhaps keeping children from engaging in violent sports that put them at high risk of CTE later is the preventive approach that merits the most attention.

The National Football League (NFL) had its highest concussion tally last year: 182 such injuries reported¹ in the 2014-2015 regular season. The true rate of concussion in the NFL is likely higher, as a result of multiple factors (fear of “letting the team [or the coach] down,” fear of retaliation from team owners,² etc.).

To simply call a head injury a “concussion” is a disservice to players and their family: Any blow to the head, severe or otherwise, has the potential to cause microvascular disruption in the brain; repeated blows to the head undoubtedly cause further damage.

In reality, a “concussion” is a mild traumatic brain injury (mTBI). With repeated blows, an mTBI can lead to chronic traumatic encephalopathy (CTE). In 2015, eighty-seven of 91 brains from autopsied former NFL players displayed some stage of CTE.³

Pathophysiology and presentation
CTE comprises 4 histological stages; Stage 4 is the most advanced. Alzheimer’s disease (AD) and CTE display similarities, which suggests a separate classification of CTE-AD; the presence of amyloid β plaques correlates with (1) more severe hyperphosphorylated tau (pTau) pathology and (2) advanced stages of the disease and clinical presentations. Death tends to occur 10 years earlier in CTE-AD than in AD, suggesting that repetitive mTBI might change the deposition and accumulation of amyloid β plaques, and even accelerate the aging process in the brain.⁴

Symptoms. The case series by Omalu et al⁴ (which inspired the 2015 motion picture Concussion) and the case series presented by McKee et al⁵ described severe psychiatric symptoms associated with CTE:

• decreased speed of information processing
• increase in religiosity
• lack of insight
• poor judgment
• involvement in illegal activities
• substance abuse
• indiscretion
• verbal and physical abuse
• problems with interpersonal relationships
• isolation
• restlessness and hyperactivity
• somatic complaints.

The 2 groups of researchers also noted hopelessness, social phobia, anxiety, agitation, mania, labile mood, insomnia, explosivity, and suicidal ideation, attempt, and completion.^4,5

By Stage 4, all affected patients are symptomatic. Cognitive impairment is severe; many are described as having “severe memory loss with dementia,”⁵ “profound” inattention and loss of concentration,⁵ and dysarthria. Paranoia may develop. Mood symptoms can be severe: Approximately 31% of subjects studied have contemplated suicide; of those, 26% had “suicidal tendencies” and 14% completed suicide.⁵

Two distinct types of CTE progression are apparent:

• patients who display cognitive deficits first; they progress to dementia but live longer
• patients who display mood and behavioral symptoms first; they tend to be younger, more violent, depressed, and explosive.⁶

CTE cannot be diagnosed with imaging. There are, however, a few positron emission tomography (PET) ligands for pTau that show promise:

• [F-18]FDDNP, which consistently identifies pTau deposits in brains in which CTE is clinically suspected, in the same distribution of pTau neurofibrillary tangles on autopsy.
• [11C]DPA-713, which detected TBI-related inflammation of neurons in 9 former NFL players in whom CTE was suspected based on the clinical presentation.
• PiB amyloid ligand, under investigation for use in PET neuroimaging.⁷

Casualties
In January 2016 alone, at least 3 former NFL players were found to have CTE posthumously.

Earl Morrall. Former quarterback who had a 21-year NFL career. Official cause of death in 2014 at age 79 was recorded as “complications of Parkinson’s disease.” In 2016, Stage-4 CTE was discovered on autopsy.⁸

Ken Stabler. Former quarterback for several NFL teams over 15 seasons. Died of colon cancer at age 69 in 2015. On autopsy, was found to have Stage-3 CTE.⁹

Tyler Sash. Former University of Iowa and New York Giants football player. Died in September 2015 at age 27 of an apparent drug overdose; post­humously, determined to have Stage-2 CTE. His family reported memory loss, minor fits of rage, confusion, inattention, lack of focus, and chronic pain.

Sash’s mother said, “My son knew something was wrong, but he couldn’t express it. He was such a good person, and it’s sad that he struggled so with this—not knowing where to go with it. Now it makes sense.”¹⁰ Sash played 16 years of football in all, sustaining at least 5 concussions. (“If you’ve played football, you know there are often other incidents [of head trauma],” Sash’s father said.¹⁰)

Cultural and medical mindsets about contact sports
In the United States, children as young as age 5, with a low weight limit of 35 pounds, routinely are introduced to football.¹¹ Reports of 5 high school players dying from football-related injury in the 2014 season, and 3 deaths in the 2015 season, led a St. Louis, Missouri, area school district to defund their football program entirely. The district’s 2015 homecoming game was a soccer match; students and parents seemed to embrace the change.¹²

On its face, soccer seems a good alternative to football. When children are instructed to “head” the ball, however, concern arises about CTE: Mild CTE changes have been reported in 2 young soccer players, and late-stage CTE changes were seen in a retired soccer player with dementia.¹³

Perhaps most disturbing is that players who develop symptoms of CTE, or are at risk, are unlikely to seek psychiatric help. We, as psychiatric clinicians, must be diligent about questioning young patients about their extracurricular activities. It is not enough to simply ask about a history of head trauma: Ask patients about any blow to the head, and don’t limit your questioning to whether they sustained a “concussion” during practice or play.

When speaking with adult and geriatric patients, ask about a history of playing interscholastic or collegiate contact sports, such as football, hockey, and soccer.

Is the solution to better shield the head?
That is not a solution: Helmets and other protective headgear appear to be insufficient to protect the brain from traumatic injury. Perhaps keeping children from engaging in violent sports that put them at high risk of CTE later is the preventive approach that merits the most attention.

On July 9, 2015, the Centers for Medicare and Medicaid Services announced the Comprehensive Care for Joint Replacement model, which aims to improve coordination of the whole episode of care for total hip and knee replacement.¹ At stake is the fact that hip and knee replacements are the most common inpatient procedures among Medicare beneficiaries, costing over $7 billion in 2014¹ and projected to grow to $50 billion by 2030.² Under Medicare’s new initiative, hospitals and physicians are held accountable for the quality and cost of care delivered from the time of surgery through 90 days after discharge. For the first time in the history of our profession, large-scale reimbursement is based on outcomes and value rather than fee-for-service. As a result, a hospital can either earn a reward or be held liable for added expenses related to events such as prolonged hospitalization, readmissions, and complications.

How can we optimize outcomes for total joint arthroplasty (TJA) patients in this era of Medicare (r)evolution? A good outcome starts with good patient selection. Numerous studies have been published on patient-related risk factors for postoperative TJA complications including obesity, congestive heart failure, lung disease, and depression.^3,4 The risks and benefits of TJA should be carefully weighed in high-risk patients and surgery delayed until appropriate medical optimization has been achieved. Following the famous saying, “Good surgeons know how to operate, better surgeons know when to operate, and the best surgeons know when not to operate,” one cannot overemphasize the need for an objective assessment of the likelihood of patient outcome weighed against patient risk factors.

Moderating patient expectation is another crucial component given the changing demographics of our country. Patients seeking TJA today are younger, more obese, and better educated; live longer; and have higher expectations.⁵ Unrealistic expectations can have a profound impact on surgical outcomes, leading to frustration, dissatisfaction, and unnecessary resource utilization. For example, despite alleviating pain and restoring function in a severely degenerative joint, TJA does not necessarily translate to weight loss. There is currently conflicting evidence on this topic,^6-8 and the expectation of weight loss after TJA cannot be supported. There is also a paucity of data regarding return to athletic activity after TJA and the effect of athletic activity on TJA survivorship.⁹ Communication and transparency are needed to moderate unrealistic expectations before surgery, outlining clear and achievable goals.

Clinical pathways for TJA have seen tremendous improvements in the past decade with the advent of multimodal analgesia, rapid recovery programs, use of spinal and regional anesthesia, and evidence-based guidelines for prevention of venous thromboembolic disease. Adequate pain control is critical to recovery. In a prospective, randomized controlled trial, Lamplot and colleagues¹⁰ showed that the use of multimodal analgesia correlated with improved pain scores, decreased narcotic usage, faster functional recovery, and higher patient satisfaction after total knee arthroplasty (TKA). In another study, Quack and colleagues¹¹ performed a systematic review of the literature on fast-track rehabilitation and found that it reduced both inpatient length of stay and costs after TKA. With respect to anesthetic choice, Pugely and colleagues¹² reviewed a national database of 14,052 cases of primary TKA and found that patients with multiple comorbidities were at higher risk of complications after general anesthesia when compared with spinal anesthesia. We should continue to invest in safer and more effective modalities for pain control and functional recovery.

Last but not least, in today’s era of Medicare’s Comprehensive Care for Joint Replacement, the role of low-volume orthopedic surgeons performing TJA deserves special mention. Over the next few years, we could likely see a decline in the role of low-volume surgeons in favor of high-volume surgeons. While most orthopedic surgeons are comfortable doing primary TJA, failed cases and complications are frequently referred to larger centers, which may create frustration among patients owing to fragmentation of care. The economic pressures related to bundled payments could further influence this transition. Given the lack of a widespread, long-standing national joint registry, the incidence of failed TJA performed by low-volume orthopedic surgeons compared with high-volume orthopedic surgeons is unknown. However, multiple studies have shown surgeon volume to be associated with lower rates of complication, mortality, readmission, reoperation, and discharge to postacute facilities.^13-16 As hospitals assume further financial risk, considerable data on physician performance will undoubtedly be gathered and leveraged. Time and data will determine the value of this transition of care.

Today, more than ever, we are challenged to provide efficient, high-quality, patient-centered care. As our nation grapples with reforming a broken health care system, initiatives like the Comprehensive Care for Joint Replacement will continue to emerge in the future. Orthopedic surgeons are the gatekeepers of the system and therefore hold significant responsibility to patients and society. Ensuring good outcomes should be a top priority not just from a financial standpoint, but as a moral obligation. We shall continue to be leaders in the face of challenges, using innovation and integrity to produce the best results and advance our profession.

On July 9, 2015, the Centers for Medicare and Medicaid Services announced the Comprehensive Care for Joint Replacement model, which aims to improve coordination of the whole episode of care for total hip and knee replacement.¹ At stake is the fact that hip and knee replacements are the most common inpatient procedures among Medicare beneficiaries, costing over $7 billion in 2014¹ and projected to grow to $50 billion by 2030.² Under Medicare’s new initiative, hospitals and physicians are held accountable for the quality and cost of care delivered from the time of surgery through 90 days after discharge. For the first time in the history of our profession, large-scale reimbursement is based on outcomes and value rather than fee-for-service. As a result, a hospital can either earn a reward or be held liable for added expenses related to events such as prolonged hospitalization, readmissions, and complications.

How can we optimize outcomes for total joint arthroplasty (TJA) patients in this era of Medicare (r)evolution? A good outcome starts with good patient selection. Numerous studies have been published on patient-related risk factors for postoperative TJA complications including obesity, congestive heart failure, lung disease, and depression.^3,4 The risks and benefits of TJA should be carefully weighed in high-risk patients and surgery delayed until appropriate medical optimization has been achieved. Following the famous saying, “Good surgeons know how to operate, better surgeons know when to operate, and the best surgeons know when not to operate,” one cannot overemphasize the need for an objective assessment of the likelihood of patient outcome weighed against patient risk factors.

Moderating patient expectation is another crucial component given the changing demographics of our country. Patients seeking TJA today are younger, more obese, and better educated; live longer; and have higher expectations.⁵ Unrealistic expectations can have a profound impact on surgical outcomes, leading to frustration, dissatisfaction, and unnecessary resource utilization. For example, despite alleviating pain and restoring function in a severely degenerative joint, TJA does not necessarily translate to weight loss. There is currently conflicting evidence on this topic,^6-8 and the expectation of weight loss after TJA cannot be supported. There is also a paucity of data regarding return to athletic activity after TJA and the effect of athletic activity on TJA survivorship.⁹ Communication and transparency are needed to moderate unrealistic expectations before surgery, outlining clear and achievable goals.

Clinical pathways for TJA have seen tremendous improvements in the past decade with the advent of multimodal analgesia, rapid recovery programs, use of spinal and regional anesthesia, and evidence-based guidelines for prevention of venous thromboembolic disease. Adequate pain control is critical to recovery. In a prospective, randomized controlled trial, Lamplot and colleagues¹⁰ showed that the use of multimodal analgesia correlated with improved pain scores, decreased narcotic usage, faster functional recovery, and higher patient satisfaction after total knee arthroplasty (TKA). In another study, Quack and colleagues¹¹ performed a systematic review of the literature on fast-track rehabilitation and found that it reduced both inpatient length of stay and costs after TKA. With respect to anesthetic choice, Pugely and colleagues¹² reviewed a national database of 14,052 cases of primary TKA and found that patients with multiple comorbidities were at higher risk of complications after general anesthesia when compared with spinal anesthesia. We should continue to invest in safer and more effective modalities for pain control and functional recovery.

Last but not least, in today’s era of Medicare’s Comprehensive Care for Joint Replacement, the role of low-volume orthopedic surgeons performing TJA deserves special mention. Over the next few years, we could likely see a decline in the role of low-volume surgeons in favor of high-volume surgeons. While most orthopedic surgeons are comfortable doing primary TJA, failed cases and complications are frequently referred to larger centers, which may create frustration among patients owing to fragmentation of care. The economic pressures related to bundled payments could further influence this transition. Given the lack of a widespread, long-standing national joint registry, the incidence of failed TJA performed by low-volume orthopedic surgeons compared with high-volume orthopedic surgeons is unknown. However, multiple studies have shown surgeon volume to be associated with lower rates of complication, mortality, readmission, reoperation, and discharge to postacute facilities.^13-16 As hospitals assume further financial risk, considerable data on physician performance will undoubtedly be gathered and leveraged. Time and data will determine the value of this transition of care.

Today, more than ever, we are challenged to provide efficient, high-quality, patient-centered care. As our nation grapples with reforming a broken health care system, initiatives like the Comprehensive Care for Joint Replacement will continue to emerge in the future. Orthopedic surgeons are the gatekeepers of the system and therefore hold significant responsibility to patients and society. Ensuring good outcomes should be a top priority not just from a financial standpoint, but as a moral obligation. We shall continue to be leaders in the face of challenges, using innovation and integrity to produce the best results and advance our profession.

On July 9, 2015, the Centers for Medicare and Medicaid Services announced the Comprehensive Care for Joint Replacement model, which aims to improve coordination of the whole episode of care for total hip and knee replacement.¹ At stake is the fact that hip and knee replacements are the most common inpatient procedures among Medicare beneficiaries, costing over $7 billion in 2014¹ and projected to grow to $50 billion by 2030.² Under Medicare’s new initiative, hospitals and physicians are held accountable for the quality and cost of care delivered from the time of surgery through 90 days after discharge. For the first time in the history of our profession, large-scale reimbursement is based on outcomes and value rather than fee-for-service. As a result, a hospital can either earn a reward or be held liable for added expenses related to events such as prolonged hospitalization, readmissions, and complications.

How can we optimize outcomes for total joint arthroplasty (TJA) patients in this era of Medicare (r)evolution? A good outcome starts with good patient selection. Numerous studies have been published on patient-related risk factors for postoperative TJA complications including obesity, congestive heart failure, lung disease, and depression.^3,4 The risks and benefits of TJA should be carefully weighed in high-risk patients and surgery delayed until appropriate medical optimization has been achieved. Following the famous saying, “Good surgeons know how to operate, better surgeons know when to operate, and the best surgeons know when not to operate,” one cannot overemphasize the need for an objective assessment of the likelihood of patient outcome weighed against patient risk factors.

Moderating patient expectation is another crucial component given the changing demographics of our country. Patients seeking TJA today are younger, more obese, and better educated; live longer; and have higher expectations.⁵ Unrealistic expectations can have a profound impact on surgical outcomes, leading to frustration, dissatisfaction, and unnecessary resource utilization. For example, despite alleviating pain and restoring function in a severely degenerative joint, TJA does not necessarily translate to weight loss. There is currently conflicting evidence on this topic,^6-8 and the expectation of weight loss after TJA cannot be supported. There is also a paucity of data regarding return to athletic activity after TJA and the effect of athletic activity on TJA survivorship.⁹ Communication and transparency are needed to moderate unrealistic expectations before surgery, outlining clear and achievable goals.

Clinical pathways for TJA have seen tremendous improvements in the past decade with the advent of multimodal analgesia, rapid recovery programs, use of spinal and regional anesthesia, and evidence-based guidelines for prevention of venous thromboembolic disease. Adequate pain control is critical to recovery. In a prospective, randomized controlled trial, Lamplot and colleagues¹⁰ showed that the use of multimodal analgesia correlated with improved pain scores, decreased narcotic usage, faster functional recovery, and higher patient satisfaction after total knee arthroplasty (TKA). In another study, Quack and colleagues¹¹ performed a systematic review of the literature on fast-track rehabilitation and found that it reduced both inpatient length of stay and costs after TKA. With respect to anesthetic choice, Pugely and colleagues¹² reviewed a national database of 14,052 cases of primary TKA and found that patients with multiple comorbidities were at higher risk of complications after general anesthesia when compared with spinal anesthesia. We should continue to invest in safer and more effective modalities for pain control and functional recovery.

Last but not least, in today’s era of Medicare’s Comprehensive Care for Joint Replacement, the role of low-volume orthopedic surgeons performing TJA deserves special mention. Over the next few years, we could likely see a decline in the role of low-volume surgeons in favor of high-volume surgeons. While most orthopedic surgeons are comfortable doing primary TJA, failed cases and complications are frequently referred to larger centers, which may create frustration among patients owing to fragmentation of care. The economic pressures related to bundled payments could further influence this transition. Given the lack of a widespread, long-standing national joint registry, the incidence of failed TJA performed by low-volume orthopedic surgeons compared with high-volume orthopedic surgeons is unknown. However, multiple studies have shown surgeon volume to be associated with lower rates of complication, mortality, readmission, reoperation, and discharge to postacute facilities.^13-16 As hospitals assume further financial risk, considerable data on physician performance will undoubtedly be gathered and leveraged. Time and data will determine the value of this transition of care.

Today, more than ever, we are challenged to provide efficient, high-quality, patient-centered care. As our nation grapples with reforming a broken health care system, initiatives like the Comprehensive Care for Joint Replacement will continue to emerge in the future. Orthopedic surgeons are the gatekeepers of the system and therefore hold significant responsibility to patients and society. Ensuring good outcomes should be a top priority not just from a financial standpoint, but as a moral obligation. We shall continue to be leaders in the face of challenges, using innovation and integrity to produce the best results and advance our profession.

As the busy days of a long, gray winter drag on and an early season of Lent has begun, this column flows from reflections on life, death, and the promise of a new season of spring and green trees, hopefully coming soon – no matter what that groundhog saw.

Clinical ethics consultation often involves end of life (EOL) care. When I recall patients from my career, many memories are of patients who died. I trained with an intensivist who said he felt he was under less stress than the general pediatricians. While his patients were sicker, if one of his patients died, it was not unexpected. The presumption was that in the ICU everything possible had been done. General pediatricians rarely have a patient who dies. When they do, everyone, including the pediatrician, will ponder over whether something might have been caught earlier or something could have been done differently. But the most difficult problems in pediatric EOL care involve deciding when to stop aggressive care and let nature take its course.

I think the natural tendency for scholars is to approach difficult decisions by seeking more information. The delusion (which scholars can usually elucidate in great postmodern detail as long as it doesn’t apply to our own behavior) is that extensive information and deep reflection will lead to the best, most accurate, immutable, and nonambivalent declaration of goals, desires, values, and intents. To even make this delusion plausible, a sci-fi writer had to create a nonhuman species of Vulcans. But medical ethicists routinely apply this paradigm to existentially frightening EOL matters in a medical world full of prognostic uncertainty. Ethicists have recommended that this method of decision making be adopted by a population with low health literacy and a predilection to using Tinder.

For the internists, EOL care is mostly about specifying which modalities to use and which to limit. Over time, it became evident that a single check box, labeled Do Not Resuscitate yes/no, was insufficient to capture patient preferences. I recall once seeing a draft document with 49 boxes. It was clearly unwieldy. Most states that have adopted a POLST (Physician Orders for Life-Sustaining Treatment) paradigm have settled for forms with five to seven options. I think that if it were possible to capture advance directives better than that, eharmony.com, with its plethora of questions, would have already created an app for it. In adult medicine, we always can lament that the conversation about EOL care was too brief, but in my experience raising expectations of a more comprehensive discussion usually lowers the likelihood of people ever undertaking even an abbreviated conversation. In ethics, if you raise the bar high enough, people seem to walk under it.

Pediatrics at the EOL tends to focus discussion more on the goals of care, the likely outcomes, and the quality of life. These perspectives are then sometimes mapped, with poor reliability, onto the POLST paradigm designed for adults. Parents are usually at the bedside often enough to recognize their child’s suffering during aggressive care. Surrogate decision makers for adult EOL care occasionally lack that insight.

While advance directive documents are helpful, I don’t think there is a substitute for a physician motivated by empathy and a caring, involved surrogate decision maker at bedside. Providing information is not the key focus. The process should emphasize building trusting relationships, clear understanding, and reasonable expectations. I am reminded in those situations of an ancient quote: Medical care is “to cure sometimes, to relieve often, and to comfort always.”

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Dr. Powell said he had no relevant financial disclosures or conflicts of interest. E-mail him at [email protected].

As the busy days of a long, gray winter drag on and an early season of Lent has begun, this column flows from reflections on life, death, and the promise of a new season of spring and green trees, hopefully coming soon – no matter what that groundhog saw.

Clinical ethics consultation often involves end of life (EOL) care. When I recall patients from my career, many memories are of patients who died. I trained with an intensivist who said he felt he was under less stress than the general pediatricians. While his patients were sicker, if one of his patients died, it was not unexpected. The presumption was that in the ICU everything possible had been done. General pediatricians rarely have a patient who dies. When they do, everyone, including the pediatrician, will ponder over whether something might have been caught earlier or something could have been done differently. But the most difficult problems in pediatric EOL care involve deciding when to stop aggressive care and let nature take its course.

I think the natural tendency for scholars is to approach difficult decisions by seeking more information. The delusion (which scholars can usually elucidate in great postmodern detail as long as it doesn’t apply to our own behavior) is that extensive information and deep reflection will lead to the best, most accurate, immutable, and nonambivalent declaration of goals, desires, values, and intents. To even make this delusion plausible, a sci-fi writer had to create a nonhuman species of Vulcans. But medical ethicists routinely apply this paradigm to existentially frightening EOL matters in a medical world full of prognostic uncertainty. Ethicists have recommended that this method of decision making be adopted by a population with low health literacy and a predilection to using Tinder.

For the internists, EOL care is mostly about specifying which modalities to use and which to limit. Over time, it became evident that a single check box, labeled Do Not Resuscitate yes/no, was insufficient to capture patient preferences. I recall once seeing a draft document with 49 boxes. It was clearly unwieldy. Most states that have adopted a POLST (Physician Orders for Life-Sustaining Treatment) paradigm have settled for forms with five to seven options. I think that if it were possible to capture advance directives better than that, eharmony.com, with its plethora of questions, would have already created an app for it. In adult medicine, we always can lament that the conversation about EOL care was too brief, but in my experience raising expectations of a more comprehensive discussion usually lowers the likelihood of people ever undertaking even an abbreviated conversation. In ethics, if you raise the bar high enough, people seem to walk under it.

Pediatrics at the EOL tends to focus discussion more on the goals of care, the likely outcomes, and the quality of life. These perspectives are then sometimes mapped, with poor reliability, onto the POLST paradigm designed for adults. Parents are usually at the bedside often enough to recognize their child’s suffering during aggressive care. Surrogate decision makers for adult EOL care occasionally lack that insight.

While advance directive documents are helpful, I don’t think there is a substitute for a physician motivated by empathy and a caring, involved surrogate decision maker at bedside. Providing information is not the key focus. The process should emphasize building trusting relationships, clear understanding, and reasonable expectations. I am reminded in those situations of an ancient quote: Medical care is “to cure sometimes, to relieve often, and to comfort always.”

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Dr. Powell said he had no relevant financial disclosures or conflicts of interest. E-mail him at [email protected].

As the busy days of a long, gray winter drag on and an early season of Lent has begun, this column flows from reflections on life, death, and the promise of a new season of spring and green trees, hopefully coming soon – no matter what that groundhog saw.

Clinical ethics consultation often involves end of life (EOL) care. When I recall patients from my career, many memories are of patients who died. I trained with an intensivist who said he felt he was under less stress than the general pediatricians. While his patients were sicker, if one of his patients died, it was not unexpected. The presumption was that in the ICU everything possible had been done. General pediatricians rarely have a patient who dies. When they do, everyone, including the pediatrician, will ponder over whether something might have been caught earlier or something could have been done differently. But the most difficult problems in pediatric EOL care involve deciding when to stop aggressive care and let nature take its course.

I think the natural tendency for scholars is to approach difficult decisions by seeking more information. The delusion (which scholars can usually elucidate in great postmodern detail as long as it doesn’t apply to our own behavior) is that extensive information and deep reflection will lead to the best, most accurate, immutable, and nonambivalent declaration of goals, desires, values, and intents. To even make this delusion plausible, a sci-fi writer had to create a nonhuman species of Vulcans. But medical ethicists routinely apply this paradigm to existentially frightening EOL matters in a medical world full of prognostic uncertainty. Ethicists have recommended that this method of decision making be adopted by a population with low health literacy and a predilection to using Tinder.

For the internists, EOL care is mostly about specifying which modalities to use and which to limit. Over time, it became evident that a single check box, labeled Do Not Resuscitate yes/no, was insufficient to capture patient preferences. I recall once seeing a draft document with 49 boxes. It was clearly unwieldy. Most states that have adopted a POLST (Physician Orders for Life-Sustaining Treatment) paradigm have settled for forms with five to seven options. I think that if it were possible to capture advance directives better than that, eharmony.com, with its plethora of questions, would have already created an app for it. In adult medicine, we always can lament that the conversation about EOL care was too brief, but in my experience raising expectations of a more comprehensive discussion usually lowers the likelihood of people ever undertaking even an abbreviated conversation. In ethics, if you raise the bar high enough, people seem to walk under it.

Pediatrics at the EOL tends to focus discussion more on the goals of care, the likely outcomes, and the quality of life. These perspectives are then sometimes mapped, with poor reliability, onto the POLST paradigm designed for adults. Parents are usually at the bedside often enough to recognize their child’s suffering during aggressive care. Surrogate decision makers for adult EOL care occasionally lack that insight.

While advance directive documents are helpful, I don’t think there is a substitute for a physician motivated by empathy and a caring, involved surrogate decision maker at bedside. Providing information is not the key focus. The process should emphasize building trusting relationships, clear understanding, and reasonable expectations. I am reminded in those situations of an ancient quote: Medical care is “to cure sometimes, to relieve often, and to comfort always.”

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Dr. Powell said he had no relevant financial disclosures or conflicts of interest. E-mail him at [email protected].

Many lesbian, gay, bisexual, and transgender (LGBT) youth face misconceptions about their sexual or gender identity. This is especially true when it comes to sex and relationships. Unfortunately, many clinicians believe these myths, and they can have devastating consequences on the health of LGBT youth.

Here are some common myths about sex and relationships in LGBT youth, and how you, as a provider, can combat them with knowledge and compassion:

Myth No. 1: Bisexual youth are promiscuous. This is a stereotype that even plagues bisexual adults. There is a persistent misconception that just because bisexuals are attracted to both sexes, they are naturally promiscuous. In fact, most bisexuals describe themselves as monogamous.¹

Myth No. 2: Youth who are transgender are lesbian/gay/bisexual before transition and are straight after transition. According to the National Transgender Discrimination Survey, regardless of where they are in the transition process, 23% of transgender people identify as heterosexual, 23% identify as gay or lesbian, 25% identify as bisexual, 23% label themselves as queer, 4% describe themselves as asexual and 2% wrote in other answers.²

Myth No. 3: Gay and lesbian teens only have sex or romantic relationships with the same sex. According to the Youth Risk Behavior Survey, although 22% of lesbian and gay teens say they have sex with the same sex only, about 9% say that they have sex with both sexes.³ This shows that sexual identity does not predict sexual behavior and has important implications for the following myths.

Myth No. 4: Lesbian and bisexual girls don’t experience intimate partner violence. Because the majority of those who perpetrate intimate partner violence are men, it is tempting to assume that lesbian and bisexual teenage girls don’t experience abuse in their relationships.

Unfortunately, one study shows that 42% of lesbian and bisexual girls experienced intimate partner violence in the past, compared with 16% of heterosexual girls.⁴ However, this study and others do not tell us whether they have experienced abuse in their relationships with girls or with boys.

Myth No. 5: Lesbian girls can’t get gonorrhea or chlamydia or pelvic inflammatory disease (PID). About 2% of young lesbians report ever having any sexually transmitted infection (STI). A small percentage of young lesbians report having chlamydia, and this is associated with PID. It is true, however, that gonorrhea is rare among lesbians,⁵ but don’t forget that young lesbian women may have had sex with men.

Interestingly, the prevalence of bacterial vaginosis, a condition characterized by overgrowth of vaginal anaerobic bacteria, is higher in young women who have sex with women.⁶ Possible sources of transmission include digital-to-vaginal contact, oral sex, or sex toys.

Myth No. 6: Young women who have sex with women can’t get pregnant, so you don’t have to worry about birth control. Don’t forget that heterosexuals use birth control for other reasons than preventing pregnancy. Some women use birth control to help regulate periods, to ease cramping, or to treat acne. Lesbians and bisexual girls are at the same risk for these problems as are heterosexual girls, so don’t assume that they’re not interested in birth control just because they are not concerned about getting pregnant.

Also, as previously mentioned, lesbian girls may be having sex with boys, so conversations about birth control should be driven by who they are having sex with, not by how they identify.

Myth No. 7: Gay boys can’t get girls pregnant. Lesbian girls can’t get pregnant. A study by the Toronto Teen Sex Survey found that 28% of sexual minority youth report involvement in pregnancy, compared with 7% of heterosexual youth.⁷

Now many who are reading this may be scratching their heads. If someone finds the same sex attractive, then why are they engaging in heterosexual sex? Some studies suggest that engaging in heterosexual sex is a way to hide their true sexual orientation,⁸ because we live in a heterosexist and homophobic environment. After all, what better way to prove that you’re heterosexual? Another study suggests that intentionally getting pregnant or getting someone pregnant is the quickest way to parenthood, and becoming a parent can compensate for one’s identity as a sexual minority.⁹

So how do you overcome these persistent myths? The most important thing to do is not assume. Identity and behaviors are not the same. Always be specific when you’re asking questions about sex and relationships in LGBT youth.

The Centers for Disease Control and Prevention (CDC) recommends the following when obtaining a sexual history:

• Ask, “Are your sexual partner’s male, female, or both?”

• Ask, “When you do have sex with your partner, what do you do?” Here, you have to be very specific. Younger teenagers tend to be concrete thinkers, so don’t just ask “Are you sexually active?” Instead, try asking, “Have you ever had a penis in your mouth, vagina, or anus?” or “Do you use sex toys?”

• In terms of protection from STIs, you might ask, “Do you use condoms or a dental dam?”

• Ask, “Have you ever had an STI, and if so, how was it treated?”

• Ask, “What do you use for birth control?” either hormonal or barrier methods.

In addition to above questions, I would also ask about intimate partner violence. Often, health care providers may ask if their patient has been hit, punch, slapped, or kicked by their partners. But intimate partner violence can go beyond physical violence. It also involves emotional manipulation or birth control sabotage. Sometimes, it is better to ask if a patient has been forced to do something sexual with her partners when she didn’t want to. The patient may deny it, however, even though you highly suspect it. So it is better to remember to build a rapport, and when the patient is ready to get out of an abusive relationship, he or she will come to you for help.

Some clinicians have told me that they have a hard time asking sexual histories in LGBT youth because they’re afraid of offending them, especially when it comes to asking about sex with the opposite sex. This is a valid concern and an area of ongoing research, but I think that by making things normative, just like with any behavior, teens and young adults are more likely to disclose critical pieces of information. It is a good idea, then, to start off with “Because of homophobia, many LGBT youth may engage in heterosexual sex. Tell me, have you ever…”

By not assuming and asking specific questions, LGBT youth are more likely to tell their health care provider important information. With that information, health care providers can prevent many adverse health outcomes like teen pregnancy, STIs, and intimate partner violence. It also will give health care providers an opportunity to address the rampant stigma and discrimination that plagues this vulnerable population.

Here are some resources on sex and relationships in LGBT youth:

• The CDC 2015 STI Guidelines have a special section on STIs in men who have sex with men, women who have sex with women, and transgender men and women.

• Bedsider.org is an excellent website about birth control options and STI prevention for all sexual orientations and gender identities.

• Futures Without Violence provides resources for health care professionals to manage and prevent intimate partner violence.

References

1. J Bisex. 2000;1(1):31-68.

2. National Transgender Discrimination Survey: Full Report. 2012.

3. MMWR Surveill Summ. 2011 Jun 10;60(7):1-133.

4. J Youth Adolesc. 2015 Jan;44(1):211-24.

5. Perspect Sex Reprod Health. 2008 Dec;40(4):212-7.

6. Sex Transm Dis. 2010 May;37(5):335-9.

7. Sexpress: The Toronto teen survey report. 2009.

8. Fletcher RC. Social context and social support: Exploring the lived experiences of LGBTQ youth who have been pregnant. [Master’s Project]: School of Public Health, University of Minnesota; 2011.

9. Can J Hum Sex. 2008;17(3):123-139.

Dr. Montano is an adolescent medicine fellow at Children’s Hospital of Pittsburgh of UPMC and a postdoctoral fellow in the department of pediatrics at the University of Pittsburgh. He has no relevant financial disclosures.

Many lesbian, gay, bisexual, and transgender (LGBT) youth face misconceptions about their sexual or gender identity. This is especially true when it comes to sex and relationships. Unfortunately, many clinicians believe these myths, and they can have devastating consequences on the health of LGBT youth.

Here are some common myths about sex and relationships in LGBT youth, and how you, as a provider, can combat them with knowledge and compassion:

Myth No. 1: Bisexual youth are promiscuous. This is a stereotype that even plagues bisexual adults. There is a persistent misconception that just because bisexuals are attracted to both sexes, they are naturally promiscuous. In fact, most bisexuals describe themselves as monogamous.¹

Myth No. 2: Youth who are transgender are lesbian/gay/bisexual before transition and are straight after transition. According to the National Transgender Discrimination Survey, regardless of where they are in the transition process, 23% of transgender people identify as heterosexual, 23% identify as gay or lesbian, 25% identify as bisexual, 23% label themselves as queer, 4% describe themselves as asexual and 2% wrote in other answers.²

Myth No. 3: Gay and lesbian teens only have sex or romantic relationships with the same sex. According to the Youth Risk Behavior Survey, although 22% of lesbian and gay teens say they have sex with the same sex only, about 9% say that they have sex with both sexes.³ This shows that sexual identity does not predict sexual behavior and has important implications for the following myths.

Myth No. 4: Lesbian and bisexual girls don’t experience intimate partner violence. Because the majority of those who perpetrate intimate partner violence are men, it is tempting to assume that lesbian and bisexual teenage girls don’t experience abuse in their relationships.

Unfortunately, one study shows that 42% of lesbian and bisexual girls experienced intimate partner violence in the past, compared with 16% of heterosexual girls.⁴ However, this study and others do not tell us whether they have experienced abuse in their relationships with girls or with boys.

Myth No. 5: Lesbian girls can’t get gonorrhea or chlamydia or pelvic inflammatory disease (PID). About 2% of young lesbians report ever having any sexually transmitted infection (STI). A small percentage of young lesbians report having chlamydia, and this is associated with PID. It is true, however, that gonorrhea is rare among lesbians,⁵ but don’t forget that young lesbian women may have had sex with men.

Interestingly, the prevalence of bacterial vaginosis, a condition characterized by overgrowth of vaginal anaerobic bacteria, is higher in young women who have sex with women.⁶ Possible sources of transmission include digital-to-vaginal contact, oral sex, or sex toys.

Myth No. 6: Young women who have sex with women can’t get pregnant, so you don’t have to worry about birth control. Don’t forget that heterosexuals use birth control for other reasons than preventing pregnancy. Some women use birth control to help regulate periods, to ease cramping, or to treat acne. Lesbians and bisexual girls are at the same risk for these problems as are heterosexual girls, so don’t assume that they’re not interested in birth control just because they are not concerned about getting pregnant.

Also, as previously mentioned, lesbian girls may be having sex with boys, so conversations about birth control should be driven by who they are having sex with, not by how they identify.

Myth No. 7: Gay boys can’t get girls pregnant. Lesbian girls can’t get pregnant. A study by the Toronto Teen Sex Survey found that 28% of sexual minority youth report involvement in pregnancy, compared with 7% of heterosexual youth.⁷

Now many who are reading this may be scratching their heads. If someone finds the same sex attractive, then why are they engaging in heterosexual sex? Some studies suggest that engaging in heterosexual sex is a way to hide their true sexual orientation,⁸ because we live in a heterosexist and homophobic environment. After all, what better way to prove that you’re heterosexual? Another study suggests that intentionally getting pregnant or getting someone pregnant is the quickest way to parenthood, and becoming a parent can compensate for one’s identity as a sexual minority.⁹

So how do you overcome these persistent myths? The most important thing to do is not assume. Identity and behaviors are not the same. Always be specific when you’re asking questions about sex and relationships in LGBT youth.

The Centers for Disease Control and Prevention (CDC) recommends the following when obtaining a sexual history:

• Ask, “Are your sexual partner’s male, female, or both?”

• Ask, “When you do have sex with your partner, what do you do?” Here, you have to be very specific. Younger teenagers tend to be concrete thinkers, so don’t just ask “Are you sexually active?” Instead, try asking, “Have you ever had a penis in your mouth, vagina, or anus?” or “Do you use sex toys?”

• In terms of protection from STIs, you might ask, “Do you use condoms or a dental dam?”

• Ask, “Have you ever had an STI, and if so, how was it treated?”

• Ask, “What do you use for birth control?” either hormonal or barrier methods.

In addition to above questions, I would also ask about intimate partner violence. Often, health care providers may ask if their patient has been hit, punch, slapped, or kicked by their partners. But intimate partner violence can go beyond physical violence. It also involves emotional manipulation or birth control sabotage. Sometimes, it is better to ask if a patient has been forced to do something sexual with her partners when she didn’t want to. The patient may deny it, however, even though you highly suspect it. So it is better to remember to build a rapport, and when the patient is ready to get out of an abusive relationship, he or she will come to you for help.

Some clinicians have told me that they have a hard time asking sexual histories in LGBT youth because they’re afraid of offending them, especially when it comes to asking about sex with the opposite sex. This is a valid concern and an area of ongoing research, but I think that by making things normative, just like with any behavior, teens and young adults are more likely to disclose critical pieces of information. It is a good idea, then, to start off with “Because of homophobia, many LGBT youth may engage in heterosexual sex. Tell me, have you ever…”

By not assuming and asking specific questions, LGBT youth are more likely to tell their health care provider important information. With that information, health care providers can prevent many adverse health outcomes like teen pregnancy, STIs, and intimate partner violence. It also will give health care providers an opportunity to address the rampant stigma and discrimination that plagues this vulnerable population.

Here are some resources on sex and relationships in LGBT youth:

• The CDC 2015 STI Guidelines have a special section on STIs in men who have sex with men, women who have sex with women, and transgender men and women.

• Bedsider.org is an excellent website about birth control options and STI prevention for all sexual orientations and gender identities.

• Futures Without Violence provides resources for health care professionals to manage and prevent intimate partner violence.

References

1. J Bisex. 2000;1(1):31-68.

2. National Transgender Discrimination Survey: Full Report. 2012.

3. MMWR Surveill Summ. 2011 Jun 10;60(7):1-133.

4. J Youth Adolesc. 2015 Jan;44(1):211-24.

5. Perspect Sex Reprod Health. 2008 Dec;40(4):212-7.

6. Sex Transm Dis. 2010 May;37(5):335-9.

7. Sexpress: The Toronto teen survey report. 2009.

8. Fletcher RC. Social context and social support: Exploring the lived experiences of LGBTQ youth who have been pregnant. [Master’s Project]: School of Public Health, University of Minnesota; 2011.

9. Can J Hum Sex. 2008;17(3):123-139.

Dr. Montano is an adolescent medicine fellow at Children’s Hospital of Pittsburgh of UPMC and a postdoctoral fellow in the department of pediatrics at the University of Pittsburgh. He has no relevant financial disclosures.

Many lesbian, gay, bisexual, and transgender (LGBT) youth face misconceptions about their sexual or gender identity. This is especially true when it comes to sex and relationships. Unfortunately, many clinicians believe these myths, and they can have devastating consequences on the health of LGBT youth.

Here are some common myths about sex and relationships in LGBT youth, and how you, as a provider, can combat them with knowledge and compassion:

Myth No. 1: Bisexual youth are promiscuous. This is a stereotype that even plagues bisexual adults. There is a persistent misconception that just because bisexuals are attracted to both sexes, they are naturally promiscuous. In fact, most bisexuals describe themselves as monogamous.¹

Myth No. 2: Youth who are transgender are lesbian/gay/bisexual before transition and are straight after transition. According to the National Transgender Discrimination Survey, regardless of where they are in the transition process, 23% of transgender people identify as heterosexual, 23% identify as gay or lesbian, 25% identify as bisexual, 23% label themselves as queer, 4% describe themselves as asexual and 2% wrote in other answers.²

Myth No. 3: Gay and lesbian teens only have sex or romantic relationships with the same sex. According to the Youth Risk Behavior Survey, although 22% of lesbian and gay teens say they have sex with the same sex only, about 9% say that they have sex with both sexes.³ This shows that sexual identity does not predict sexual behavior and has important implications for the following myths.

Myth No. 4: Lesbian and bisexual girls don’t experience intimate partner violence. Because the majority of those who perpetrate intimate partner violence are men, it is tempting to assume that lesbian and bisexual teenage girls don’t experience abuse in their relationships.

Unfortunately, one study shows that 42% of lesbian and bisexual girls experienced intimate partner violence in the past, compared with 16% of heterosexual girls.⁴ However, this study and others do not tell us whether they have experienced abuse in their relationships with girls or with boys.

Myth No. 5: Lesbian girls can’t get gonorrhea or chlamydia or pelvic inflammatory disease (PID). About 2% of young lesbians report ever having any sexually transmitted infection (STI). A small percentage of young lesbians report having chlamydia, and this is associated with PID. It is true, however, that gonorrhea is rare among lesbians,⁵ but don’t forget that young lesbian women may have had sex with men.

Interestingly, the prevalence of bacterial vaginosis, a condition characterized by overgrowth of vaginal anaerobic bacteria, is higher in young women who have sex with women.⁶ Possible sources of transmission include digital-to-vaginal contact, oral sex, or sex toys.

Myth No. 6: Young women who have sex with women can’t get pregnant, so you don’t have to worry about birth control. Don’t forget that heterosexuals use birth control for other reasons than preventing pregnancy. Some women use birth control to help regulate periods, to ease cramping, or to treat acne. Lesbians and bisexual girls are at the same risk for these problems as are heterosexual girls, so don’t assume that they’re not interested in birth control just because they are not concerned about getting pregnant.

Also, as previously mentioned, lesbian girls may be having sex with boys, so conversations about birth control should be driven by who they are having sex with, not by how they identify.

Myth No. 7: Gay boys can’t get girls pregnant. Lesbian girls can’t get pregnant. A study by the Toronto Teen Sex Survey found that 28% of sexual minority youth report involvement in pregnancy, compared with 7% of heterosexual youth.⁷

Now many who are reading this may be scratching their heads. If someone finds the same sex attractive, then why are they engaging in heterosexual sex? Some studies suggest that engaging in heterosexual sex is a way to hide their true sexual orientation,⁸ because we live in a heterosexist and homophobic environment. After all, what better way to prove that you’re heterosexual? Another study suggests that intentionally getting pregnant or getting someone pregnant is the quickest way to parenthood, and becoming a parent can compensate for one’s identity as a sexual minority.⁹

So how do you overcome these persistent myths? The most important thing to do is not assume. Identity and behaviors are not the same. Always be specific when you’re asking questions about sex and relationships in LGBT youth.

The Centers for Disease Control and Prevention (CDC) recommends the following when obtaining a sexual history:

• Ask, “Are your sexual partner’s male, female, or both?”

• Ask, “When you do have sex with your partner, what do you do?” Here, you have to be very specific. Younger teenagers tend to be concrete thinkers, so don’t just ask “Are you sexually active?” Instead, try asking, “Have you ever had a penis in your mouth, vagina, or anus?” or “Do you use sex toys?”

• In terms of protection from STIs, you might ask, “Do you use condoms or a dental dam?”

• Ask, “Have you ever had an STI, and if so, how was it treated?”

• Ask, “What do you use for birth control?” either hormonal or barrier methods.

In addition to above questions, I would also ask about intimate partner violence. Often, health care providers may ask if their patient has been hit, punch, slapped, or kicked by their partners. But intimate partner violence can go beyond physical violence. It also involves emotional manipulation or birth control sabotage. Sometimes, it is better to ask if a patient has been forced to do something sexual with her partners when she didn’t want to. The patient may deny it, however, even though you highly suspect it. So it is better to remember to build a rapport, and when the patient is ready to get out of an abusive relationship, he or she will come to you for help.

Some clinicians have told me that they have a hard time asking sexual histories in LGBT youth because they’re afraid of offending them, especially when it comes to asking about sex with the opposite sex. This is a valid concern and an area of ongoing research, but I think that by making things normative, just like with any behavior, teens and young adults are more likely to disclose critical pieces of information. It is a good idea, then, to start off with “Because of homophobia, many LGBT youth may engage in heterosexual sex. Tell me, have you ever…”

By not assuming and asking specific questions, LGBT youth are more likely to tell their health care provider important information. With that information, health care providers can prevent many adverse health outcomes like teen pregnancy, STIs, and intimate partner violence. It also will give health care providers an opportunity to address the rampant stigma and discrimination that plagues this vulnerable population.

Here are some resources on sex and relationships in LGBT youth:

• The CDC 2015 STI Guidelines have a special section on STIs in men who have sex with men, women who have sex with women, and transgender men and women.

• Bedsider.org is an excellent website about birth control options and STI prevention for all sexual orientations and gender identities.

• Futures Without Violence provides resources for health care professionals to manage and prevent intimate partner violence.

References

1. J Bisex. 2000;1(1):31-68.

2. National Transgender Discrimination Survey: Full Report. 2012.

3. MMWR Surveill Summ. 2011 Jun 10;60(7):1-133.

4. J Youth Adolesc. 2015 Jan;44(1):211-24.

5. Perspect Sex Reprod Health. 2008 Dec;40(4):212-7.

6. Sex Transm Dis. 2010 May;37(5):335-9.

7. Sexpress: The Toronto teen survey report. 2009.

8. Fletcher RC. Social context and social support: Exploring the lived experiences of LGBTQ youth who have been pregnant. [Master’s Project]: School of Public Health, University of Minnesota; 2011.

9. Can J Hum Sex. 2008;17(3):123-139.

Dr. Montano is an adolescent medicine fellow at Children’s Hospital of Pittsburgh of UPMC and a postdoctoral fellow in the department of pediatrics at the University of Pittsburgh. He has no relevant financial disclosures.

Lead poisoning is a well-established cause of serious and permanent neurological, cognitive, and behavioral problems, particularly in exposed children.

Children can be exposed to lead from ingesting paint chips in their homes, when old paint is scrapped from the exterior of houses or bridges, and through the water they drink. The damage caused by lead poisoning was first recognized in the United States in the early 20th century, although lead was added to gasoline and paint until the 1970’s. Since then, regulations for lead in consumer products have become increasingly strict, and the Centers for Disease Control and Prevention’s definition of a toxic lead level has shifted from 60 micrograms/deciliter (mcg/dL) in 1970 to 5 mcg/dL in 2012. In many communities, removing lead paint up to the height of a young child is a requirement whenever an older home is sold.

Unfortunately, these regulations did not protect the families in Flint, Michigan from being exposed to high levels of lead when a change in water supply and inadequate water treatment allowed lead to enter the system from decaying water pipes. It is worth reviewing what is known about the short- and long-term consequences of lead exposure, and what lies ahead for the children of Flint.

Lead is a naturally occurring element that is not metabolized, but rather absorbed, distributed to tissues, and excreted. Lead can be inhaled (with 100% absorption) and introduced through the GI tract (with about 70% absorption in children and 20% absorption in adults). GI absorption is enhanced by calcium or iron deficiency, both conditions that are relatively common, especially in poor children and can lead to pica (or eating of non-nutritious materials), further increasing the chances of lead exposure. Absorbed lead is distributed to blood (for 28-36 days), soft tissue, including the nervous system (40 days), and to bone (where it lasts for over 25 years). Blood that is retained in growing bones can be mobilized during periods of physiologic stress (such as illness, injury, or pregnancy), meaning children exposed to lead during a period of rapid bone growth are at long-term risk for acute lead poisoning from their endogenous reservoir without a new exposure. What lead is not retained by tissues is excreted by the kidneys, with adults retaining about 1% of absorbed lead, while children younger than 2 years retain over 30% of absorbed lead. So children, especially toddlers, have a greater likelihood to absorb lead from the GI tract and to retain lead in their tissues, both due to active mineralization of bone and the permeability of the blood brain barrier, primarily in children under 3 years old. This is why we are addressing what will happen to the children of Flint and not to all the residents of Flint.

Lead competitively inhibits interactions between cations and sulfhydryl groups, which are present in most human biochemical reactions. This leads to irreversible cell damage and often cell death, especially within the central nervous system. Lead exposure is associated with particular dysfunction within dopaminergic pathways within the brain, and has been associated in a dose-dependent fashion with decreased prefrontal gray matter volume. Lead poisoning also has hematologic consequences (anemia), renal consequences (interstitial nephritis), gastrointestinal symptoms (vomiting, constipation), and endocrine consequences (reversible inhibition of Vitamin D metabolism and permanently short stature). But the CNS consequences of lead exposure are particularly devastating, as they appear to have no threshold and are permanent. Their incidence is the driving force for the CDC’s lowering of the official toxic lead level and the public health efforts to screen children and educate parents about the risk of lead exposure.

So what do these serious consequences look like? People with severe lead intoxication (blood lead levels greater than 70 mcg/dL) typically present with signs of acute encephalopathy (headache, vomiting, seizures, or coma) and require intensive medical management including chelation therapy. More typically, exposed children have low but accumulating levels of lead and present with nonspecific symptoms, including lost appetite, fatigue, irritability, and insomnia, which gradually worsen.

Behavior

High levels of impulsivity, aggression, and impaired attention are the prototypical sequelae of lead poisoning (following recovery from the acute intoxication). Multiple studies have demonstrated these high levels of aggressive and impulsive behaviors in preschoolers who were exposed to lead, and these behaviors appear to continue into adolescence and adulthood. Indeed, one study found that compared with children with the lowest measurable blood lead levels (0.2-0.7 mcg/dL), those children who were in the next two quartiles had seven and twelve times the odds of meeting diagnostic criteria for conduct disorder.¹ There have even been studies which correlated atmospheric lead levels (when leaded gasoline was common) with crime rates 20 years later, which supported an association between childhood lead exposure and adult criminal activity.^2-4.

Multiple studies have demonstrated higher rates of inattention, distractibility, and impulsivity in lead-exposed children than would be expected given the prevalence of attention-deficit/hyperactivity disorder (ADHD) in the general population. The incidence of these symptoms goes up in a dose-dependent fashion and appears to have no threshold (so they occur at even the lowest measurable blood lead levels). In a 2006 study of nearly 5,000 children between ages 4-15 years, those with blood lead levels greater than 2 mcg/dL (still below the level the CDC deems toxic) were four times more likely to be carrying a diagnosis of ADHD and be on stimulant medication than their peers with blood lead levels less than 0.8mcg/dL.

Cognition

Closely related to impulse control and attention, the cognitive domains of intelligence and executive function are clearly damaged by lead exposure. Poor performance on tasks requiring focus, cognitive flexibility, and inhibition of automatic responses was directly associated with higher blood lead levels in a group of preschoolers with levels between 0 and 13 mcg/dL.⁵

IQ has been found to be so consistently diminished by increasing blood lead levels that it is used as an overall index of neurodevelopmental morbidity of lead exposure, leading to the CDC’s adoption of a lower standard definition of toxic lead levels. Even very low blood lead levels are associated with decrements in IQ: children with blood lead levels less than 7.5 mcg/dL lost an average of 3 IQ points for every 1 mcg/dL increase in blood lead levels.⁶ In a study of 57,000 elementary school students in 2009, Miranda et al. found that those who had a blood lead level of 4 mcg/dL at 3 years old were significantly more likely to be diagnosed with a learning disability in elementary school. Another study of 48,000 children who had a blood lead level of 5 mcg/dL were 30% more likely to fail third grade reading and math tests than their peers without measurable lead levels.

Speech and language

More recent studies have demonstrated that children with higher bone lead concentrations had poorer performance on several language-processing measures, suggesting that childhood lead exposure damages language processing and function as the young people grow. These deficits in language processing can make social development and self-regulation much more challenging in adolescence, and make school and work settings much more challenging. These findings also have implications for the utility of psychotherapy, a language-based treatment, for the other behavioral problems of lead exposure.

Motor skills

Several recent studies have assessed both fine and gross motor skills in lead-exposed children. Findings have demonstrated that balance, coordination, gross motor and fine motor skills all appear to be compromised in a dose-dependent fashion by childhood lead exposure. These findings suggest that not only are children at greater risk for accident and injury through childhood and into adulthood, a risk already increased by their compromised attention and impulse control. But they also are likely to be physically clumsy, compromising an opportunity to cultivate strengths or experience mastery when cognitive tasks may prove frustrating for them.

With deficits in such fundamental cognitive, motor, and behavioral processes, exposed children are clearly vulnerable to more than ADHD, conduct disorder, and learning disabilities. These struggles may lead to secondary vulnerabilities to anxiety or mood symptoms or substance abuse as these children grow into teenagers who face frustration at every turn. In addition to treatment for their deficits in attention and executive function, these children will ideally receive specialized supports in school and at home, to be able to master cognitive tasks, manage new social circumstances and make friends, discover their interests and talents, and generally stay on their best developmental trajectories. Lastly, the specific consequences of lead exposure will vary for any individual child, so parents will have to deal with the uncertainty of their child’s behavior and development over many years. Clearly, the children of Flint face a long road that has been substantially impacted by their lead exposure. The only good that can come from the exposure in Flint is to heighten efforts to ensure that it never happens again.

1. Environ Health Perspect. 2008 Jul;116(7):956-62.

2. Environ Res. 2000 May;83(1):1-22.

3. Environ Res. 2007 Jul;104(3):315-36.

4. Arch Pediatr Adolesc Med. 2001 May;155(5):579-82.

5. Dev Neuropsychol. 2004;26(1):513-40.

6. Environ Health Perspect. 2005 Jul;113(7):894-9.

Dr. Swick is an attending psychiatrist in the division of child psychiatry at Massachusetts General Hospital, Boston, and director of the Parenting at a Challenging Time (PACT) Program at the Vernon Cancer Center at Newton (Mass.) Wellesley Hospital. Dr. Jellinek is professor of psychiatry and of pediatrics at Harvard Medical School, Boston.

Lead poisoning is a well-established cause of serious and permanent neurological, cognitive, and behavioral problems, particularly in exposed children.

Children can be exposed to lead from ingesting paint chips in their homes, when old paint is scrapped from the exterior of houses or bridges, and through the water they drink. The damage caused by lead poisoning was first recognized in the United States in the early 20th century, although lead was added to gasoline and paint until the 1970’s. Since then, regulations for lead in consumer products have become increasingly strict, and the Centers for Disease Control and Prevention’s definition of a toxic lead level has shifted from 60 micrograms/deciliter (mcg/dL) in 1970 to 5 mcg/dL in 2012. In many communities, removing lead paint up to the height of a young child is a requirement whenever an older home is sold.

Unfortunately, these regulations did not protect the families in Flint, Michigan from being exposed to high levels of lead when a change in water supply and inadequate water treatment allowed lead to enter the system from decaying water pipes. It is worth reviewing what is known about the short- and long-term consequences of lead exposure, and what lies ahead for the children of Flint.

Lead is a naturally occurring element that is not metabolized, but rather absorbed, distributed to tissues, and excreted. Lead can be inhaled (with 100% absorption) and introduced through the GI tract (with about 70% absorption in children and 20% absorption in adults). GI absorption is enhanced by calcium or iron deficiency, both conditions that are relatively common, especially in poor children and can lead to pica (or eating of non-nutritious materials), further increasing the chances of lead exposure. Absorbed lead is distributed to blood (for 28-36 days), soft tissue, including the nervous system (40 days), and to bone (where it lasts for over 25 years). Blood that is retained in growing bones can be mobilized during periods of physiologic stress (such as illness, injury, or pregnancy), meaning children exposed to lead during a period of rapid bone growth are at long-term risk for acute lead poisoning from their endogenous reservoir without a new exposure. What lead is not retained by tissues is excreted by the kidneys, with adults retaining about 1% of absorbed lead, while children younger than 2 years retain over 30% of absorbed lead. So children, especially toddlers, have a greater likelihood to absorb lead from the GI tract and to retain lead in their tissues, both due to active mineralization of bone and the permeability of the blood brain barrier, primarily in children under 3 years old. This is why we are addressing what will happen to the children of Flint and not to all the residents of Flint.

Lead competitively inhibits interactions between cations and sulfhydryl groups, which are present in most human biochemical reactions. This leads to irreversible cell damage and often cell death, especially within the central nervous system. Lead exposure is associated with particular dysfunction within dopaminergic pathways within the brain, and has been associated in a dose-dependent fashion with decreased prefrontal gray matter volume. Lead poisoning also has hematologic consequences (anemia), renal consequences (interstitial nephritis), gastrointestinal symptoms (vomiting, constipation), and endocrine consequences (reversible inhibition of Vitamin D metabolism and permanently short stature). But the CNS consequences of lead exposure are particularly devastating, as they appear to have no threshold and are permanent. Their incidence is the driving force for the CDC’s lowering of the official toxic lead level and the public health efforts to screen children and educate parents about the risk of lead exposure.

So what do these serious consequences look like? People with severe lead intoxication (blood lead levels greater than 70 mcg/dL) typically present with signs of acute encephalopathy (headache, vomiting, seizures, or coma) and require intensive medical management including chelation therapy. More typically, exposed children have low but accumulating levels of lead and present with nonspecific symptoms, including lost appetite, fatigue, irritability, and insomnia, which gradually worsen.

Behavior

High levels of impulsivity, aggression, and impaired attention are the prototypical sequelae of lead poisoning (following recovery from the acute intoxication). Multiple studies have demonstrated these high levels of aggressive and impulsive behaviors in preschoolers who were exposed to lead, and these behaviors appear to continue into adolescence and adulthood. Indeed, one study found that compared with children with the lowest measurable blood lead levels (0.2-0.7 mcg/dL), those children who were in the next two quartiles had seven and twelve times the odds of meeting diagnostic criteria for conduct disorder.¹ There have even been studies which correlated atmospheric lead levels (when leaded gasoline was common) with crime rates 20 years later, which supported an association between childhood lead exposure and adult criminal activity.^2-4.

Multiple studies have demonstrated higher rates of inattention, distractibility, and impulsivity in lead-exposed children than would be expected given the prevalence of attention-deficit/hyperactivity disorder (ADHD) in the general population. The incidence of these symptoms goes up in a dose-dependent fashion and appears to have no threshold (so they occur at even the lowest measurable blood lead levels). In a 2006 study of nearly 5,000 children between ages 4-15 years, those with blood lead levels greater than 2 mcg/dL (still below the level the CDC deems toxic) were four times more likely to be carrying a diagnosis of ADHD and be on stimulant medication than their peers with blood lead levels less than 0.8mcg/dL.

Cognition

Closely related to impulse control and attention, the cognitive domains of intelligence and executive function are clearly damaged by lead exposure. Poor performance on tasks requiring focus, cognitive flexibility, and inhibition of automatic responses was directly associated with higher blood lead levels in a group of preschoolers with levels between 0 and 13 mcg/dL.⁵

IQ has been found to be so consistently diminished by increasing blood lead levels that it is used as an overall index of neurodevelopmental morbidity of lead exposure, leading to the CDC’s adoption of a lower standard definition of toxic lead levels. Even very low blood lead levels are associated with decrements in IQ: children with blood lead levels less than 7.5 mcg/dL lost an average of 3 IQ points for every 1 mcg/dL increase in blood lead levels.⁶ In a study of 57,000 elementary school students in 2009, Miranda et al. found that those who had a blood lead level of 4 mcg/dL at 3 years old were significantly more likely to be diagnosed with a learning disability in elementary school. Another study of 48,000 children who had a blood lead level of 5 mcg/dL were 30% more likely to fail third grade reading and math tests than their peers without measurable lead levels.

Speech and language

More recent studies have demonstrated that children with higher bone lead concentrations had poorer performance on several language-processing measures, suggesting that childhood lead exposure damages language processing and function as the young people grow. These deficits in language processing can make social development and self-regulation much more challenging in adolescence, and make school and work settings much more challenging. These findings also have implications for the utility of psychotherapy, a language-based treatment, for the other behavioral problems of lead exposure.

Motor skills

Several recent studies have assessed both fine and gross motor skills in lead-exposed children. Findings have demonstrated that balance, coordination, gross motor and fine motor skills all appear to be compromised in a dose-dependent fashion by childhood lead exposure. These findings suggest that not only are children at greater risk for accident and injury through childhood and into adulthood, a risk already increased by their compromised attention and impulse control. But they also are likely to be physically clumsy, compromising an opportunity to cultivate strengths or experience mastery when cognitive tasks may prove frustrating for them.

With deficits in such fundamental cognitive, motor, and behavioral processes, exposed children are clearly vulnerable to more than ADHD, conduct disorder, and learning disabilities. These struggles may lead to secondary vulnerabilities to anxiety or mood symptoms or substance abuse as these children grow into teenagers who face frustration at every turn. In addition to treatment for their deficits in attention and executive function, these children will ideally receive specialized supports in school and at home, to be able to master cognitive tasks, manage new social circumstances and make friends, discover their interests and talents, and generally stay on their best developmental trajectories. Lastly, the specific consequences of lead exposure will vary for any individual child, so parents will have to deal with the uncertainty of their child’s behavior and development over many years. Clearly, the children of Flint face a long road that has been substantially impacted by their lead exposure. The only good that can come from the exposure in Flint is to heighten efforts to ensure that it never happens again.

1. Environ Health Perspect. 2008 Jul;116(7):956-62.

2. Environ Res. 2000 May;83(1):1-22.

3. Environ Res. 2007 Jul;104(3):315-36.

4. Arch Pediatr Adolesc Med. 2001 May;155(5):579-82.

5. Dev Neuropsychol. 2004;26(1):513-40.

6. Environ Health Perspect. 2005 Jul;113(7):894-9.

Dr. Swick is an attending psychiatrist in the division of child psychiatry at Massachusetts General Hospital, Boston, and director of the Parenting at a Challenging Time (PACT) Program at the Vernon Cancer Center at Newton (Mass.) Wellesley Hospital. Dr. Jellinek is professor of psychiatry and of pediatrics at Harvard Medical School, Boston.

Lead poisoning is a well-established cause of serious and permanent neurological, cognitive, and behavioral problems, particularly in exposed children.

Children can be exposed to lead from ingesting paint chips in their homes, when old paint is scrapped from the exterior of houses or bridges, and through the water they drink. The damage caused by lead poisoning was first recognized in the United States in the early 20th century, although lead was added to gasoline and paint until the 1970’s. Since then, regulations for lead in consumer products have become increasingly strict, and the Centers for Disease Control and Prevention’s definition of a toxic lead level has shifted from 60 micrograms/deciliter (mcg/dL) in 1970 to 5 mcg/dL in 2012. In many communities, removing lead paint up to the height of a young child is a requirement whenever an older home is sold.

Unfortunately, these regulations did not protect the families in Flint, Michigan from being exposed to high levels of lead when a change in water supply and inadequate water treatment allowed lead to enter the system from decaying water pipes. It is worth reviewing what is known about the short- and long-term consequences of lead exposure, and what lies ahead for the children of Flint.

Lead is a naturally occurring element that is not metabolized, but rather absorbed, distributed to tissues, and excreted. Lead can be inhaled (with 100% absorption) and introduced through the GI tract (with about 70% absorption in children and 20% absorption in adults). GI absorption is enhanced by calcium or iron deficiency, both conditions that are relatively common, especially in poor children and can lead to pica (or eating of non-nutritious materials), further increasing the chances of lead exposure. Absorbed lead is distributed to blood (for 28-36 days), soft tissue, including the nervous system (40 days), and to bone (where it lasts for over 25 years). Blood that is retained in growing bones can be mobilized during periods of physiologic stress (such as illness, injury, or pregnancy), meaning children exposed to lead during a period of rapid bone growth are at long-term risk for acute lead poisoning from their endogenous reservoir without a new exposure. What lead is not retained by tissues is excreted by the kidneys, with adults retaining about 1% of absorbed lead, while children younger than 2 years retain over 30% of absorbed lead. So children, especially toddlers, have a greater likelihood to absorb lead from the GI tract and to retain lead in their tissues, both due to active mineralization of bone and the permeability of the blood brain barrier, primarily in children under 3 years old. This is why we are addressing what will happen to the children of Flint and not to all the residents of Flint.

Lead competitively inhibits interactions between cations and sulfhydryl groups, which are present in most human biochemical reactions. This leads to irreversible cell damage and often cell death, especially within the central nervous system. Lead exposure is associated with particular dysfunction within dopaminergic pathways within the brain, and has been associated in a dose-dependent fashion with decreased prefrontal gray matter volume. Lead poisoning also has hematologic consequences (anemia), renal consequences (interstitial nephritis), gastrointestinal symptoms (vomiting, constipation), and endocrine consequences (reversible inhibition of Vitamin D metabolism and permanently short stature). But the CNS consequences of lead exposure are particularly devastating, as they appear to have no threshold and are permanent. Their incidence is the driving force for the CDC’s lowering of the official toxic lead level and the public health efforts to screen children and educate parents about the risk of lead exposure.

So what do these serious consequences look like? People with severe lead intoxication (blood lead levels greater than 70 mcg/dL) typically present with signs of acute encephalopathy (headache, vomiting, seizures, or coma) and require intensive medical management including chelation therapy. More typically, exposed children have low but accumulating levels of lead and present with nonspecific symptoms, including lost appetite, fatigue, irritability, and insomnia, which gradually worsen.

Behavior

High levels of impulsivity, aggression, and impaired attention are the prototypical sequelae of lead poisoning (following recovery from the acute intoxication). Multiple studies have demonstrated these high levels of aggressive and impulsive behaviors in preschoolers who were exposed to lead, and these behaviors appear to continue into adolescence and adulthood. Indeed, one study found that compared with children with the lowest measurable blood lead levels (0.2-0.7 mcg/dL), those children who were in the next two quartiles had seven and twelve times the odds of meeting diagnostic criteria for conduct disorder.¹ There have even been studies which correlated atmospheric lead levels (when leaded gasoline was common) with crime rates 20 years later, which supported an association between childhood lead exposure and adult criminal activity.^2-4.

Multiple studies have demonstrated higher rates of inattention, distractibility, and impulsivity in lead-exposed children than would be expected given the prevalence of attention-deficit/hyperactivity disorder (ADHD) in the general population. The incidence of these symptoms goes up in a dose-dependent fashion and appears to have no threshold (so they occur at even the lowest measurable blood lead levels). In a 2006 study of nearly 5,000 children between ages 4-15 years, those with blood lead levels greater than 2 mcg/dL (still below the level the CDC deems toxic) were four times more likely to be carrying a diagnosis of ADHD and be on stimulant medication than their peers with blood lead levels less than 0.8mcg/dL.

Cognition

Closely related to impulse control and attention, the cognitive domains of intelligence and executive function are clearly damaged by lead exposure. Poor performance on tasks requiring focus, cognitive flexibility, and inhibition of automatic responses was directly associated with higher blood lead levels in a group of preschoolers with levels between 0 and 13 mcg/dL.⁵

IQ has been found to be so consistently diminished by increasing blood lead levels that it is used as an overall index of neurodevelopmental morbidity of lead exposure, leading to the CDC’s adoption of a lower standard definition of toxic lead levels. Even very low blood lead levels are associated with decrements in IQ: children with blood lead levels less than 7.5 mcg/dL lost an average of 3 IQ points for every 1 mcg/dL increase in blood lead levels.⁶ In a study of 57,000 elementary school students in 2009, Miranda et al. found that those who had a blood lead level of 4 mcg/dL at 3 years old were significantly more likely to be diagnosed with a learning disability in elementary school. Another study of 48,000 children who had a blood lead level of 5 mcg/dL were 30% more likely to fail third grade reading and math tests than their peers without measurable lead levels.

Speech and language

More recent studies have demonstrated that children with higher bone lead concentrations had poorer performance on several language-processing measures, suggesting that childhood lead exposure damages language processing and function as the young people grow. These deficits in language processing can make social development and self-regulation much more challenging in adolescence, and make school and work settings much more challenging. These findings also have implications for the utility of psychotherapy, a language-based treatment, for the other behavioral problems of lead exposure.

Motor skills

Several recent studies have assessed both fine and gross motor skills in lead-exposed children. Findings have demonstrated that balance, coordination, gross motor and fine motor skills all appear to be compromised in a dose-dependent fashion by childhood lead exposure. These findings suggest that not only are children at greater risk for accident and injury through childhood and into adulthood, a risk already increased by their compromised attention and impulse control. But they also are likely to be physically clumsy, compromising an opportunity to cultivate strengths or experience mastery when cognitive tasks may prove frustrating for them.

With deficits in such fundamental cognitive, motor, and behavioral processes, exposed children are clearly vulnerable to more than ADHD, conduct disorder, and learning disabilities. These struggles may lead to secondary vulnerabilities to anxiety or mood symptoms or substance abuse as these children grow into teenagers who face frustration at every turn. In addition to treatment for their deficits in attention and executive function, these children will ideally receive specialized supports in school and at home, to be able to master cognitive tasks, manage new social circumstances and make friends, discover their interests and talents, and generally stay on their best developmental trajectories. Lastly, the specific consequences of lead exposure will vary for any individual child, so parents will have to deal with the uncertainty of their child’s behavior and development over many years. Clearly, the children of Flint face a long road that has been substantially impacted by their lead exposure. The only good that can come from the exposure in Flint is to heighten efforts to ensure that it never happens again.

1. Environ Health Perspect. 2008 Jul;116(7):956-62.

2. Environ Res. 2000 May;83(1):1-22.

3. Environ Res. 2007 Jul;104(3):315-36.

4. Arch Pediatr Adolesc Med. 2001 May;155(5):579-82.

5. Dev Neuropsychol. 2004;26(1):513-40.

6. Environ Health Perspect. 2005 Jul;113(7):894-9.

Dr. Swick is an attending psychiatrist in the division of child psychiatry at Massachusetts General Hospital, Boston, and director of the Parenting at a Challenging Time (PACT) Program at the Vernon Cancer Center at Newton (Mass.) Wellesley Hospital. Dr. Jellinek is professor of psychiatry and of pediatrics at Harvard Medical School, Boston.