Commentary

Many of my patients ask, “Why do you have fortune cookies on your desk?” Then, I offer them one. I considered having other treats, but decided on fortune cookies because of

Comfort. The cookie is a small treat for those who want one.

Diet. You don’t have to eat the cookie to enjoy it; you can still read the fortune. For patients who have an eating disorder, the cookie allows us to naturally transition the conversation to issues they are experiencing.

Cultural competency. I treat patients of many backgrounds. Some have never seen a fortune cookie (remember to warn them there is a fortune inside!). Others know the fortune cookie is not a Chinese invention, as it is popu­larly thought to be.¹

Impulsivity. Do patients grab a cookie immediately, wait for one to be offered, or ask for one?

At this point, I ask patients to tell me their fortune. This allows me to assess:

Fine motor skills. Do they have a hand tremor or weakness, or a problem with involuntary movement? How well do they open the individually wrapped cookie?

Problem solving. On the slip of paper in the cookie, fortunes are printed on one side; on the other side are lucky numbers and a Chinese phrase. Some patients fail to turn the slip of paper over; they look it and say, “There are only numbers on this piece of paper.”

Eyesight. Can they see without glasses? Did they bring their glasses? (By extension, I can gauge whether they need, and use, glasses when reaching for a pill bottle in the medicine cabinet.)

Literacy. Can they read their fortune aloud?

Last, I ask what the fortune means and how it might apply to them. This helps me understand their:

Mindset. Having them explain how the fortune applies to them can be helpful to understanding their thinking.

Thought process. I am looking for how they think: Abstractly? Concretely? How well do they ar­ticulate and explain the meaning of the fortune?

Many of my patients ask, “Why do you have fortune cookies on your desk?” Then, I offer them one. I considered having other treats, but decided on fortune cookies because of

Comfort. The cookie is a small treat for those who want one.

Diet. You don’t have to eat the cookie to enjoy it; you can still read the fortune. For patients who have an eating disorder, the cookie allows us to naturally transition the conversation to issues they are experiencing.

Cultural competency. I treat patients of many backgrounds. Some have never seen a fortune cookie (remember to warn them there is a fortune inside!). Others know the fortune cookie is not a Chinese invention, as it is popu­larly thought to be.¹

Impulsivity. Do patients grab a cookie immediately, wait for one to be offered, or ask for one?

At this point, I ask patients to tell me their fortune. This allows me to assess:

Fine motor skills. Do they have a hand tremor or weakness, or a problem with involuntary movement? How well do they open the individually wrapped cookie?

Problem solving. On the slip of paper in the cookie, fortunes are printed on one side; on the other side are lucky numbers and a Chinese phrase. Some patients fail to turn the slip of paper over; they look it and say, “There are only numbers on this piece of paper.”

Eyesight. Can they see without glasses? Did they bring their glasses? (By extension, I can gauge whether they need, and use, glasses when reaching for a pill bottle in the medicine cabinet.)

Literacy. Can they read their fortune aloud?

Last, I ask what the fortune means and how it might apply to them. This helps me understand their:

Mindset. Having them explain how the fortune applies to them can be helpful to understanding their thinking.

Thought process. I am looking for how they think: Abstractly? Concretely? How well do they ar­ticulate and explain the meaning of the fortune?

Many of my patients ask, “Why do you have fortune cookies on your desk?” Then, I offer them one. I considered having other treats, but decided on fortune cookies because of

Comfort. The cookie is a small treat for those who want one.

Diet. You don’t have to eat the cookie to enjoy it; you can still read the fortune. For patients who have an eating disorder, the cookie allows us to naturally transition the conversation to issues they are experiencing.

Cultural competency. I treat patients of many backgrounds. Some have never seen a fortune cookie (remember to warn them there is a fortune inside!). Others know the fortune cookie is not a Chinese invention, as it is popu­larly thought to be.¹

Impulsivity. Do patients grab a cookie immediately, wait for one to be offered, or ask for one?

At this point, I ask patients to tell me their fortune. This allows me to assess:

Fine motor skills. Do they have a hand tremor or weakness, or a problem with involuntary movement? How well do they open the individually wrapped cookie?

Problem solving. On the slip of paper in the cookie, fortunes are printed on one side; on the other side are lucky numbers and a Chinese phrase. Some patients fail to turn the slip of paper over; they look it and say, “There are only numbers on this piece of paper.”

Eyesight. Can they see without glasses? Did they bring their glasses? (By extension, I can gauge whether they need, and use, glasses when reaching for a pill bottle in the medicine cabinet.)

Literacy. Can they read their fortune aloud?

Last, I ask what the fortune means and how it might apply to them. This helps me understand their:

Mindset. Having them explain how the fortune applies to them can be helpful to understanding their thinking.

Thought process. I am looking for how they think: Abstractly? Concretely? How well do they ar­ticulate and explain the meaning of the fortune?

Pain was introduced as the “fifth vital sign” in the 1990s, ranking it as important a measure as blood pressure, heart and respiratory rate, and temperature.¹ The American Pain Society promoted this notion to increase awareness of pain treatment among health care professionals. Emphasizing its importance, the Veterans Health Administration in 1999 launched the “Pain as the 5th Vital Sign” initiative, which mandated a pain intensity rating at all clinical encounters.²

Interestingly, the Joint Commission standards never stated that pain needed to be treated as a vital sign. But many organizations started to require documentation of routine pain screening for all patients. Health care providers were instructed to inquire about pain and to treat it as an essential element of health history.

These changes were quite controversial. The additional measure, while important, competed with other priority screening needs, including diabetes, cancer, and hypertension. There was—and continues to be—quite the debate on whether pain actually can be measured and what impact that information has on the quality of care.

I do not intend to enter that debate here. Instead, I want to discuss what continues to be a conundrum for me: the paradox of pain management.

For many patients, especially those in acute or emergency care settings, the presenting complaint is pain. I would submit that for many the expectation is for pain to be immediately and permanently relieved. But is this a realistic goal?

I recall a lecture on pain management I attended years ago; at that time, the approach involved early identification and prompt, aggressive treatment. When asked “How much medication and for how long?” the lecturer used diabetes as a treatment model, stating, “You would increase insulin until the blood glucose was controlled—don’t be afraid to increase pain medication until the pain is controlled.” In the early days of pain management, that was the accepted norm. The possibility that a “zero” on the pain scale was unattainable for some patients was not considered.

Yet seemingly overnight, once pain was decreed a vital sign, health care providers were mandated to measure it and faced with the responsibility to treat it. This resulted in a vague 0-10 pain scale and providers who were inadequately educated on how to begin pain management. Unlike with diabetes or hypertension, there was no protocol, algorithm, or standard upon which to base a plan of care. Moreover, there was a lack of differentiation between pain that was a short-lived nuisance and pain that interfered with quality of life.

Faced with growing concern for undertreated pain in the US, however, many of us strove to achieve a balance of sufficient yet appropriate treatment. We struggled to determine how to relieve the pain our patients experienced without creating other problems, such as undesirable side effects, misuse, or addiction. That ­predicament, paired with the ever-increasing direct-to-consumer advertisements about pain relief and the insistence by (some, not all) patients that nonnarcotic pain medication is ineffective, bred the crisis of opioid overuse and addiction we now face.

But just as I chose not to debate the impact of pain measurement on quality of care, I also choose not to debate the existence of the opioid crisis. What I want to emphasize is that all policy changes have consequences. I reach out to you, my colleagues, for innovative ideas to strike the delicate balance of appropriate use of narcotics. How do we address the needs of patients whose pain is more than just an inconvenience and for whom daily use of a narcotic allows them to function—while also avoiding the pitfalls that we are now regularly warned about?

I have no doubt that each of us knows at least one person—a patient, a family member, a neighbor—for whom pain is a daily occurrence. But we must put that in perspective; not all pain is a barrier to physical and emotional functioning. Data suggest that a “33% to 50% decrease in pain intensity is meaningful from a patient’s perspective and represents a reasonable standard of intervention efficacy.”³ For those who deal with chronic pain, even a slight improvement is progress.

So, while the American Medical Association and the American Pain Society bicker about whether pain is the “fifth vital sign,” we must find a better means to resolve the discord in our society.⁴ Banning all opioid use is not the answer, but neither is considering narcotics the default treatment for pain.

We must remind our patients, our policymakers, and ourselves that identifying and assessing pain is not equated with writing an opioid or narcotic prescription. Nor will removing those medications from our formulary mitigate the crisis. We need to communicate a clear, consistent message that pain is real, that some pain is a fact of life, and that we will help our patients.

However, it is incumbent upon us to adopt a systematic yet personalized plan of care that is effective, cost conscious, culturally and developmentally appropriate, and safe—and that plan may or may not include prescribing narcotics. We have much work ahead of us in order to minimize the potential for misuse of these medications without impeding patients’ access to necessary health care.

Please share your thoughts on this conundrum by writing to [email protected].

Pain was introduced as the “fifth vital sign” in the 1990s, ranking it as important a measure as blood pressure, heart and respiratory rate, and temperature.¹ The American Pain Society promoted this notion to increase awareness of pain treatment among health care professionals. Emphasizing its importance, the Veterans Health Administration in 1999 launched the “Pain as the 5th Vital Sign” initiative, which mandated a pain intensity rating at all clinical encounters.²

Interestingly, the Joint Commission standards never stated that pain needed to be treated as a vital sign. But many organizations started to require documentation of routine pain screening for all patients. Health care providers were instructed to inquire about pain and to treat it as an essential element of health history.

These changes were quite controversial. The additional measure, while important, competed with other priority screening needs, including diabetes, cancer, and hypertension. There was—and continues to be—quite the debate on whether pain actually can be measured and what impact that information has on the quality of care.

I do not intend to enter that debate here. Instead, I want to discuss what continues to be a conundrum for me: the paradox of pain management.

For many patients, especially those in acute or emergency care settings, the presenting complaint is pain. I would submit that for many the expectation is for pain to be immediately and permanently relieved. But is this a realistic goal?

I recall a lecture on pain management I attended years ago; at that time, the approach involved early identification and prompt, aggressive treatment. When asked “How much medication and for how long?” the lecturer used diabetes as a treatment model, stating, “You would increase insulin until the blood glucose was controlled—don’t be afraid to increase pain medication until the pain is controlled.” In the early days of pain management, that was the accepted norm. The possibility that a “zero” on the pain scale was unattainable for some patients was not considered.

Yet seemingly overnight, once pain was decreed a vital sign, health care providers were mandated to measure it and faced with the responsibility to treat it. This resulted in a vague 0-10 pain scale and providers who were inadequately educated on how to begin pain management. Unlike with diabetes or hypertension, there was no protocol, algorithm, or standard upon which to base a plan of care. Moreover, there was a lack of differentiation between pain that was a short-lived nuisance and pain that interfered with quality of life.

Faced with growing concern for undertreated pain in the US, however, many of us strove to achieve a balance of sufficient yet appropriate treatment. We struggled to determine how to relieve the pain our patients experienced without creating other problems, such as undesirable side effects, misuse, or addiction. That ­predicament, paired with the ever-increasing direct-to-consumer advertisements about pain relief and the insistence by (some, not all) patients that nonnarcotic pain medication is ineffective, bred the crisis of opioid overuse and addiction we now face.

But just as I chose not to debate the impact of pain measurement on quality of care, I also choose not to debate the existence of the opioid crisis. What I want to emphasize is that all policy changes have consequences. I reach out to you, my colleagues, for innovative ideas to strike the delicate balance of appropriate use of narcotics. How do we address the needs of patients whose pain is more than just an inconvenience and for whom daily use of a narcotic allows them to function—while also avoiding the pitfalls that we are now regularly warned about?

I have no doubt that each of us knows at least one person—a patient, a family member, a neighbor—for whom pain is a daily occurrence. But we must put that in perspective; not all pain is a barrier to physical and emotional functioning. Data suggest that a “33% to 50% decrease in pain intensity is meaningful from a patient’s perspective and represents a reasonable standard of intervention efficacy.”³ For those who deal with chronic pain, even a slight improvement is progress.

So, while the American Medical Association and the American Pain Society bicker about whether pain is the “fifth vital sign,” we must find a better means to resolve the discord in our society.⁴ Banning all opioid use is not the answer, but neither is considering narcotics the default treatment for pain.

We must remind our patients, our policymakers, and ourselves that identifying and assessing pain is not equated with writing an opioid or narcotic prescription. Nor will removing those medications from our formulary mitigate the crisis. We need to communicate a clear, consistent message that pain is real, that some pain is a fact of life, and that we will help our patients.

However, it is incumbent upon us to adopt a systematic yet personalized plan of care that is effective, cost conscious, culturally and developmentally appropriate, and safe—and that plan may or may not include prescribing narcotics. We have much work ahead of us in order to minimize the potential for misuse of these medications without impeding patients’ access to necessary health care.

Please share your thoughts on this conundrum by writing to [email protected].

Pain was introduced as the “fifth vital sign” in the 1990s, ranking it as important a measure as blood pressure, heart and respiratory rate, and temperature.¹ The American Pain Society promoted this notion to increase awareness of pain treatment among health care professionals. Emphasizing its importance, the Veterans Health Administration in 1999 launched the “Pain as the 5th Vital Sign” initiative, which mandated a pain intensity rating at all clinical encounters.²

Interestingly, the Joint Commission standards never stated that pain needed to be treated as a vital sign. But many organizations started to require documentation of routine pain screening for all patients. Health care providers were instructed to inquire about pain and to treat it as an essential element of health history.

These changes were quite controversial. The additional measure, while important, competed with other priority screening needs, including diabetes, cancer, and hypertension. There was—and continues to be—quite the debate on whether pain actually can be measured and what impact that information has on the quality of care.

I do not intend to enter that debate here. Instead, I want to discuss what continues to be a conundrum for me: the paradox of pain management.

For many patients, especially those in acute or emergency care settings, the presenting complaint is pain. I would submit that for many the expectation is for pain to be immediately and permanently relieved. But is this a realistic goal?

I recall a lecture on pain management I attended years ago; at that time, the approach involved early identification and prompt, aggressive treatment. When asked “How much medication and for how long?” the lecturer used diabetes as a treatment model, stating, “You would increase insulin until the blood glucose was controlled—don’t be afraid to increase pain medication until the pain is controlled.” In the early days of pain management, that was the accepted norm. The possibility that a “zero” on the pain scale was unattainable for some patients was not considered.

Yet seemingly overnight, once pain was decreed a vital sign, health care providers were mandated to measure it and faced with the responsibility to treat it. This resulted in a vague 0-10 pain scale and providers who were inadequately educated on how to begin pain management. Unlike with diabetes or hypertension, there was no protocol, algorithm, or standard upon which to base a plan of care. Moreover, there was a lack of differentiation between pain that was a short-lived nuisance and pain that interfered with quality of life.

Faced with growing concern for undertreated pain in the US, however, many of us strove to achieve a balance of sufficient yet appropriate treatment. We struggled to determine how to relieve the pain our patients experienced without creating other problems, such as undesirable side effects, misuse, or addiction. That ­predicament, paired with the ever-increasing direct-to-consumer advertisements about pain relief and the insistence by (some, not all) patients that nonnarcotic pain medication is ineffective, bred the crisis of opioid overuse and addiction we now face.

But just as I chose not to debate the impact of pain measurement on quality of care, I also choose not to debate the existence of the opioid crisis. What I want to emphasize is that all policy changes have consequences. I reach out to you, my colleagues, for innovative ideas to strike the delicate balance of appropriate use of narcotics. How do we address the needs of patients whose pain is more than just an inconvenience and for whom daily use of a narcotic allows them to function—while also avoiding the pitfalls that we are now regularly warned about?

I have no doubt that each of us knows at least one person—a patient, a family member, a neighbor—for whom pain is a daily occurrence. But we must put that in perspective; not all pain is a barrier to physical and emotional functioning. Data suggest that a “33% to 50% decrease in pain intensity is meaningful from a patient’s perspective and represents a reasonable standard of intervention efficacy.”³ For those who deal with chronic pain, even a slight improvement is progress.

So, while the American Medical Association and the American Pain Society bicker about whether pain is the “fifth vital sign,” we must find a better means to resolve the discord in our society.⁴ Banning all opioid use is not the answer, but neither is considering narcotics the default treatment for pain.

We must remind our patients, our policymakers, and ourselves that identifying and assessing pain is not equated with writing an opioid or narcotic prescription. Nor will removing those medications from our formulary mitigate the crisis. We need to communicate a clear, consistent message that pain is real, that some pain is a fact of life, and that we will help our patients.

However, it is incumbent upon us to adopt a systematic yet personalized plan of care that is effective, cost conscious, culturally and developmentally appropriate, and safe—and that plan may or may not include prescribing narcotics. We have much work ahead of us in order to minimize the potential for misuse of these medications without impeding patients’ access to necessary health care.

Please share your thoughts on this conundrum by writing to [email protected].

The American Academy of Pediatrics released a new set of recommendations for the appropriate amount of screen time for children and adolescents in October 2016.

Among other changes, the AAP now recommends no screen time (except for video chatting) for infants and children up to 18 months old. For 18- to 24-month-olds, the AAP discourages screen time, recommending that parents introduce only selected “high-quality” programming and cowatch with their children. Likewise, for children up to 5 years old, the AAP urges parents to limit all screen time to 1 hour/day, half of its previous recommendation, and again recommends that parents cowatch with their children and use only reliable providers of quality content, such as the Public Broadcasting Service (PBS). For older children, the AAP does not set specific time limits, but recommends that parents collaborate with the children on a media plan that limits screen time so that it does not interfere with other important activities, including homework, social time, exercise, and sleep.

BunnyHollywood/iStockphoto.com

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 Wellesley Hospital, also in Boston. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

The American Academy of Pediatrics released a new set of recommendations for the appropriate amount of screen time for children and adolescents in October 2016.

Among other changes, the AAP now recommends no screen time (except for video chatting) for infants and children up to 18 months old. For 18- to 24-month-olds, the AAP discourages screen time, recommending that parents introduce only selected “high-quality” programming and cowatch with their children. Likewise, for children up to 5 years old, the AAP urges parents to limit all screen time to 1 hour/day, half of its previous recommendation, and again recommends that parents cowatch with their children and use only reliable providers of quality content, such as the Public Broadcasting Service (PBS). For older children, the AAP does not set specific time limits, but recommends that parents collaborate with the children on a media plan that limits screen time so that it does not interfere with other important activities, including homework, social time, exercise, and sleep.

BunnyHollywood/iStockphoto.com

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 Wellesley Hospital, also in Boston. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

The American Academy of Pediatrics released a new set of recommendations for the appropriate amount of screen time for children and adolescents in October 2016.

Among other changes, the AAP now recommends no screen time (except for video chatting) for infants and children up to 18 months old. For 18- to 24-month-olds, the AAP discourages screen time, recommending that parents introduce only selected “high-quality” programming and cowatch with their children. Likewise, for children up to 5 years old, the AAP urges parents to limit all screen time to 1 hour/day, half of its previous recommendation, and again recommends that parents cowatch with their children and use only reliable providers of quality content, such as the Public Broadcasting Service (PBS). For older children, the AAP does not set specific time limits, but recommends that parents collaborate with the children on a media plan that limits screen time so that it does not interfere with other important activities, including homework, social time, exercise, and sleep.

BunnyHollywood/iStockphoto.com

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 Wellesley Hospital, also in Boston. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

The Centers for Disease Control and Prevention released results from the first nationally representative study on health risk behaviors of gay, lesbian, and bisexual (GLB) high school students in August 2016.

These data were collected through the Youth Risk Behavior Survey (YRBS) questionnaire. The YRBS questionnaire was developed in 1990 as a way to monitor health-related behaviors that contribute to the leading causes of mortality and morbidity in youth and young adults. Areas covered by the survey include behaviors related to unintentional injuries and violence, tobacco use, alcohol and other drug use, sexual behaviors, dietary behaviors, and physical activity. Data are collected every 2 years through national, state, territorial, tribal government, and local school-based surveys of representative samples of 9th-12th grade students.

Selected questionnaire results

Sexual identity

• 88.8% of students identified as heterosexual.

• 6.0% identified as bisexual.

• 3.2% were not sure.

• 2.0% identified as gay or lesbian.

Sexual behaviors

• 48% had had sexual contact with the opposite sex only.

• 4.6% had sexual contact with both sexes.

• 1.7% had had sexual contact with the same sex only.

• 45.7% had no sexual contact.

Mental health

Percent of students who reported making a suicide plan in the 12 months preceding the survey:

• 11.9% of heterosexual students.

• 27.9% of students not sure of sexual identity.

• 38.2% of gay, lesbian, bisexual (GLB) students.

Percent of students who attempted suicide in the 12 months preceding the survey:

• 6.4% of heterosexual students.

• 13.7% of students not sure of sexual identity.

• 29.4% of GLB students.

Sexual Behaviors

First sex before the age of 13:

• 3.4% of heterosexual students.

• 8.8% of students not sure of their sexual identity.

• 7.3% of GLB students.

Drank alcohol or used drugs before last sex:

• 20.0% of heterosexual students.

• 44.5% of students not sure of their sexual identity.

• 22.4% of GLB students.

Tested for HIV:

• 9.3% of heterosexual students.

• 12.8% of students not sure of their sexual identity.

• 18.2% of GLB students.

Substance use

Currently smoking cigarettes daily:

• 1.9% of heterosexual students.

• 7.0% of students not sure of their sexual identity.

• 4.0% of GLB students.

Current alcohol use:

• 32.1% of heterosexual students.

• 34.6% of students not sure of their sexual identity.

• 40.5% of GLB students.

Current marijuana use:

• 20.7% of heterosexual students.

• 26.0% of students not sure of their sexual identity.

• 32.0% of GLB students.

Used hallucinogenic drugs (such as LSD, acid, PCP, angel dust, mescaline, or mushrooms):

• 5.5% of heterosexual students.

• 15.7% of students not sure of their sexual identity.

• 11.5% of GLB students.

Ever used heroin:

• 1.3% of heterosexual students.

• 9.3% of students not sure of their sexual identity.

• 6.0% of GLB students.

Ever took prescription drugs without a doctor’s prescription:

15.5% of heterosexual students.

24.3% of students not sure of their sexual identity.

27.5% of GLB students.

Physical Activity

Did not participate in at least 60 minutes of physical activity on at least 1 day in past week:

• 12.6% of heterosexual students.

• 27.0% of students not sure of their sexual identity.

• 25.7% of GLB students.

Dr. Chelvakumar is an attending physician in the division of adolescent medicine at Nationwide Children’s Hospital and an assistant professor of clinical pediatrics at the Ohio State University, both in Columbus.

The Centers for Disease Control and Prevention released results from the first nationally representative study on health risk behaviors of gay, lesbian, and bisexual (GLB) high school students in August 2016.

These data were collected through the Youth Risk Behavior Survey (YRBS) questionnaire. The YRBS questionnaire was developed in 1990 as a way to monitor health-related behaviors that contribute to the leading causes of mortality and morbidity in youth and young adults. Areas covered by the survey include behaviors related to unintentional injuries and violence, tobacco use, alcohol and other drug use, sexual behaviors, dietary behaviors, and physical activity. Data are collected every 2 years through national, state, territorial, tribal government, and local school-based surveys of representative samples of 9th-12th grade students.

Selected questionnaire results

Sexual identity

• 88.8% of students identified as heterosexual.

• 6.0% identified as bisexual.

• 3.2% were not sure.

• 2.0% identified as gay or lesbian.

Sexual behaviors

• 48% had had sexual contact with the opposite sex only.

• 4.6% had sexual contact with both sexes.

• 1.7% had had sexual contact with the same sex only.

• 45.7% had no sexual contact.

Mental health

Percent of students who reported making a suicide plan in the 12 months preceding the survey:

• 11.9% of heterosexual students.

• 27.9% of students not sure of sexual identity.

• 38.2% of gay, lesbian, bisexual (GLB) students.

Percent of students who attempted suicide in the 12 months preceding the survey:

• 6.4% of heterosexual students.

• 13.7% of students not sure of sexual identity.

• 29.4% of GLB students.

Sexual Behaviors

First sex before the age of 13:

• 3.4% of heterosexual students.

• 8.8% of students not sure of their sexual identity.

• 7.3% of GLB students.

Drank alcohol or used drugs before last sex:

• 20.0% of heterosexual students.

• 44.5% of students not sure of their sexual identity.

• 22.4% of GLB students.

Tested for HIV:

• 9.3% of heterosexual students.

• 12.8% of students not sure of their sexual identity.

• 18.2% of GLB students.

Substance use

Currently smoking cigarettes daily:

• 1.9% of heterosexual students.

• 7.0% of students not sure of their sexual identity.

• 4.0% of GLB students.

Current alcohol use:

• 32.1% of heterosexual students.

• 34.6% of students not sure of their sexual identity.

• 40.5% of GLB students.

Current marijuana use:

• 20.7% of heterosexual students.

• 26.0% of students not sure of their sexual identity.

• 32.0% of GLB students.

Used hallucinogenic drugs (such as LSD, acid, PCP, angel dust, mescaline, or mushrooms):

• 5.5% of heterosexual students.

• 15.7% of students not sure of their sexual identity.

• 11.5% of GLB students.

Ever used heroin:

• 1.3% of heterosexual students.

• 9.3% of students not sure of their sexual identity.

• 6.0% of GLB students.

Ever took prescription drugs without a doctor’s prescription:

15.5% of heterosexual students.

24.3% of students not sure of their sexual identity.

27.5% of GLB students.

Physical Activity

Did not participate in at least 60 minutes of physical activity on at least 1 day in past week:

• 12.6% of heterosexual students.

• 27.0% of students not sure of their sexual identity.

• 25.7% of GLB students.

Dr. Chelvakumar is an attending physician in the division of adolescent medicine at Nationwide Children’s Hospital and an assistant professor of clinical pediatrics at the Ohio State University, both in Columbus.

The Centers for Disease Control and Prevention released results from the first nationally representative study on health risk behaviors of gay, lesbian, and bisexual (GLB) high school students in August 2016.

These data were collected through the Youth Risk Behavior Survey (YRBS) questionnaire. The YRBS questionnaire was developed in 1990 as a way to monitor health-related behaviors that contribute to the leading causes of mortality and morbidity in youth and young adults. Areas covered by the survey include behaviors related to unintentional injuries and violence, tobacco use, alcohol and other drug use, sexual behaviors, dietary behaviors, and physical activity. Data are collected every 2 years through national, state, territorial, tribal government, and local school-based surveys of representative samples of 9th-12th grade students.

Selected questionnaire results

Sexual identity

• 88.8% of students identified as heterosexual.

• 6.0% identified as bisexual.

• 3.2% were not sure.

• 2.0% identified as gay or lesbian.

Sexual behaviors

• 48% had had sexual contact with the opposite sex only.

• 4.6% had sexual contact with both sexes.

• 1.7% had had sexual contact with the same sex only.

• 45.7% had no sexual contact.

Mental health

Percent of students who reported making a suicide plan in the 12 months preceding the survey:

• 11.9% of heterosexual students.

• 27.9% of students not sure of sexual identity.

• 38.2% of gay, lesbian, bisexual (GLB) students.

Percent of students who attempted suicide in the 12 months preceding the survey:

• 6.4% of heterosexual students.

• 13.7% of students not sure of sexual identity.

• 29.4% of GLB students.

Sexual Behaviors

First sex before the age of 13:

• 3.4% of heterosexual students.

• 8.8% of students not sure of their sexual identity.

• 7.3% of GLB students.

Drank alcohol or used drugs before last sex:

• 20.0% of heterosexual students.

• 44.5% of students not sure of their sexual identity.

• 22.4% of GLB students.

Tested for HIV:

• 9.3% of heterosexual students.

• 12.8% of students not sure of their sexual identity.

• 18.2% of GLB students.

Substance use

Currently smoking cigarettes daily:

• 1.9% of heterosexual students.

• 7.0% of students not sure of their sexual identity.

• 4.0% of GLB students.

Current alcohol use:

• 32.1% of heterosexual students.

• 34.6% of students not sure of their sexual identity.

• 40.5% of GLB students.

Current marijuana use:

• 20.7% of heterosexual students.

• 26.0% of students not sure of their sexual identity.

• 32.0% of GLB students.

Used hallucinogenic drugs (such as LSD, acid, PCP, angel dust, mescaline, or mushrooms):

• 5.5% of heterosexual students.

• 15.7% of students not sure of their sexual identity.

• 11.5% of GLB students.

Ever used heroin:

• 1.3% of heterosexual students.

• 9.3% of students not sure of their sexual identity.

• 6.0% of GLB students.

Ever took prescription drugs without a doctor’s prescription:

15.5% of heterosexual students.

24.3% of students not sure of their sexual identity.

27.5% of GLB students.

Physical Activity

Did not participate in at least 60 minutes of physical activity on at least 1 day in past week:

• 12.6% of heterosexual students.

• 27.0% of students not sure of their sexual identity.

• 25.7% of GLB students.

Dr. Chelvakumar is an attending physician in the division of adolescent medicine at Nationwide Children’s Hospital and an assistant professor of clinical pediatrics at the Ohio State University, both in Columbus.

“SHOULD RISK-REDUCING GYNECOLOGIC SURGERY FOR BRCA MUTATION CARRIERS INCLUDE HYSTERECTOMY?”

ANDREW M. KAUNITZ, MD (WEB EXCLUSIVE, AUGUST 28, 2016)

Hysterectomy warranted?

I am wondering if Dr. Kaunitz really is recommending performing 270 hysterectomies to prevent one endometrial cancer? Is this justified given the risks from the hysterectomy itself, the economics of the disease, or any significant reductions in endometrial cancer mortality?

David O. Holtz, MD
Paoli, Pennsylvania

Dr. Kaunitz responds

I appreciate Dr. Holtz’s interest in my commentary on the role of hysterectomy as part of risk-reducing surgery in BRCA mutation carriers. Women who are mutation carriers are at increased risk for serous or serous-like endometrial cancers. Further, hysterectomy offers specific advantages for young mutation carriers for whom menopausal hormone therapy is often indicated after risk-reducing salpingo-oophorectomy. Accordingly, I would indeed encourage such women to consider hysterectomy as part of risk-reducing gynecologic surgery if such surgery can be accomplished via minimally invasive techniques.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

“SHOULD RISK-REDUCING GYNECOLOGIC SURGERY FOR BRCA MUTATION CARRIERS INCLUDE HYSTERECTOMY?”

ANDREW M. KAUNITZ, MD (WEB EXCLUSIVE, AUGUST 28, 2016)

Hysterectomy warranted?

I am wondering if Dr. Kaunitz really is recommending performing 270 hysterectomies to prevent one endometrial cancer? Is this justified given the risks from the hysterectomy itself, the economics of the disease, or any significant reductions in endometrial cancer mortality?

David O. Holtz, MD
Paoli, Pennsylvania

Dr. Kaunitz responds

I appreciate Dr. Holtz’s interest in my commentary on the role of hysterectomy as part of risk-reducing surgery in BRCA mutation carriers. Women who are mutation carriers are at increased risk for serous or serous-like endometrial cancers. Further, hysterectomy offers specific advantages for young mutation carriers for whom menopausal hormone therapy is often indicated after risk-reducing salpingo-oophorectomy. Accordingly, I would indeed encourage such women to consider hysterectomy as part of risk-reducing gynecologic surgery if such surgery can be accomplished via minimally invasive techniques.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

“SHOULD RISK-REDUCING GYNECOLOGIC SURGERY FOR BRCA MUTATION CARRIERS INCLUDE HYSTERECTOMY?”

ANDREW M. KAUNITZ, MD (WEB EXCLUSIVE, AUGUST 28, 2016)

Hysterectomy warranted?

I am wondering if Dr. Kaunitz really is recommending performing 270 hysterectomies to prevent one endometrial cancer? Is this justified given the risks from the hysterectomy itself, the economics of the disease, or any significant reductions in endometrial cancer mortality?

David O. Holtz, MD
Paoli, Pennsylvania

Dr. Kaunitz responds

I appreciate Dr. Holtz’s interest in my commentary on the role of hysterectomy as part of risk-reducing surgery in BRCA mutation carriers. Women who are mutation carriers are at increased risk for serous or serous-like endometrial cancers. Further, hysterectomy offers specific advantages for young mutation carriers for whom menopausal hormone therapy is often indicated after risk-reducing salpingo-oophorectomy. Accordingly, I would indeed encourage such women to consider hysterectomy as part of risk-reducing gynecologic surgery if such surgery can be accomplished via minimally invasive techniques.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Bone disease in patients with kidney disease is indeed a tricky interplay, as the article by Nyman et al (J Fam Pract. 2016;65:606-612) aptly states in its title.

The author made incorrect statements on page 607 regarding hyperphosphatemia and hypocalcemia and the escalation of fracture risk. (Editor’s Note: See erratum.)

In addition, on page 610, the article mentions that 1,25-(OH)₂ vitamin D may help prevent hypertension, myocardial infarction, and stroke in patients without chronic kidney disease. This is not supported by the literature and even the reference cited states that fact.

Roy N. Morcos, MD, FAAFP
Boardman, OH

Thank you, Dr. Morcos, for your careful read of our article.

Despite the lack of evidence, some providers are still prescribing native vitamin D for their patients with chronic kidney disease for reasons unrelated to parathyroid hormone suppression.Regarding the discussion of 1,25-(OH)₂ vitamin D, we are in agreement. In fact, the last sentence of our paragraph reads: “There are no data, however, confirming that 25(OH)D supplementation mitigates these outcomes.” We were simply calling attention to the fact that despite the lack of evidence, some providers are still prescribing native vitamin D for their patients with chronic kidney disease for reasons unrelated to parathyroid hormone suppression.

Karly Pippitt, MD,
on behalf of co-authors Heather Nyman, PharmD, BCPS;
Alisyn Hansen, PharmD, BCACP, CDE;
Karen Gunning, PharmD, BCPS, BCACP, FCCP
Salt Lake City, UT

Bone disease in patients with kidney disease is indeed a tricky interplay, as the article by Nyman et al (J Fam Pract. 2016;65:606-612) aptly states in its title.

The author made incorrect statements on page 607 regarding hyperphosphatemia and hypocalcemia and the escalation of fracture risk. (Editor’s Note: See erratum.)

In addition, on page 610, the article mentions that 1,25-(OH)₂ vitamin D may help prevent hypertension, myocardial infarction, and stroke in patients without chronic kidney disease. This is not supported by the literature and even the reference cited states that fact.

Roy N. Morcos, MD, FAAFP
Boardman, OH

Thank you, Dr. Morcos, for your careful read of our article.

Despite the lack of evidence, some providers are still prescribing native vitamin D for their patients with chronic kidney disease for reasons unrelated to parathyroid hormone suppression.Regarding the discussion of 1,25-(OH)₂ vitamin D, we are in agreement. In fact, the last sentence of our paragraph reads: “There are no data, however, confirming that 25(OH)D supplementation mitigates these outcomes.” We were simply calling attention to the fact that despite the lack of evidence, some providers are still prescribing native vitamin D for their patients with chronic kidney disease for reasons unrelated to parathyroid hormone suppression.

Karly Pippitt, MD,
on behalf of co-authors Heather Nyman, PharmD, BCPS;
Alisyn Hansen, PharmD, BCACP, CDE;
Karen Gunning, PharmD, BCPS, BCACP, FCCP
Salt Lake City, UT

Bone disease in patients with kidney disease is indeed a tricky interplay, as the article by Nyman et al (J Fam Pract. 2016;65:606-612) aptly states in its title.

The author made incorrect statements on page 607 regarding hyperphosphatemia and hypocalcemia and the escalation of fracture risk. (Editor’s Note: See erratum.)

In addition, on page 610, the article mentions that 1,25-(OH)₂ vitamin D may help prevent hypertension, myocardial infarction, and stroke in patients without chronic kidney disease. This is not supported by the literature and even the reference cited states that fact.

Roy N. Morcos, MD, FAAFP
Boardman, OH

Thank you, Dr. Morcos, for your careful read of our article.

Despite the lack of evidence, some providers are still prescribing native vitamin D for their patients with chronic kidney disease for reasons unrelated to parathyroid hormone suppression.Regarding the discussion of 1,25-(OH)₂ vitamin D, we are in agreement. In fact, the last sentence of our paragraph reads: “There are no data, however, confirming that 25(OH)D supplementation mitigates these outcomes.” We were simply calling attention to the fact that despite the lack of evidence, some providers are still prescribing native vitamin D for their patients with chronic kidney disease for reasons unrelated to parathyroid hormone suppression.

Karly Pippitt, MD,
on behalf of co-authors Heather Nyman, PharmD, BCPS;
Alisyn Hansen, PharmD, BCACP, CDE;
Karen Gunning, PharmD, BCPS, BCACP, FCCP
Salt Lake City, UT

Each year the American Academy of Pediatrics National Conference and Exhibition fills a huge convention hall with the latest products that can improve health and generate practice revenue.

Some products are solutions to the minor annoyances of everyday practice. For instance, there are ear curettes equipped with their own LED light and a magnifying lens. There are countless creams to treat rashes. There are new automated devices for testing hearing, vision, and attention. And at the far extreme, there are products with the potential to revolutionize clinical care or to bankrupt it. The latest technology in that category is whole exome sequencing.

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis.

Each year the American Academy of Pediatrics National Conference and Exhibition fills a huge convention hall with the latest products that can improve health and generate practice revenue.

Some products are solutions to the minor annoyances of everyday practice. For instance, there are ear curettes equipped with their own LED light and a magnifying lens. There are countless creams to treat rashes. There are new automated devices for testing hearing, vision, and attention. And at the far extreme, there are products with the potential to revolutionize clinical care or to bankrupt it. The latest technology in that category is whole exome sequencing.

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis.

Each year the American Academy of Pediatrics National Conference and Exhibition fills a huge convention hall with the latest products that can improve health and generate practice revenue.

Some products are solutions to the minor annoyances of everyday practice. For instance, there are ear curettes equipped with their own LED light and a magnifying lens. There are countless creams to treat rashes. There are new automated devices for testing hearing, vision, and attention. And at the far extreme, there are products with the potential to revolutionize clinical care or to bankrupt it. The latest technology in that category is whole exome sequencing.

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis.

Editor’s note: As Ob.Gyn. News celebrates its 50th anniversary, we wanted to know how far the medical community has come in identifying and mitigating drug risks during pregnancy and in the postpartum period. In this article, our four expert columnists share their experiences trying to find and interpret critical pregnancy data, as well as how they weigh the potential risks and benefits for their patients.

The search for information

The biggest advance in the past 50 years is the availability of information, even though limited, relating to the effects of drugs in pregnancy and lactation. In the first few years of this period, it was a daunting task to obtain this information. I can recall spending hours in the hospital’s medical library going through huge volumes of Index Medicus to obtain references that the library could order for me. The appearance of Thomas H. Shepard’s first edition (Catalog of Teratogenic Agents) in 1973 was a step forward and in 1977, O.P. Heinonen and colleagues’ book (Birth Defects and Drugs in Pregnancy) was helpful.

Purestock/Thinkstock

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, and Washington State University, Spokane. He is coauthor of “Drugs in Pregnancy and Lactation,” and coeditor of “Diseases, Complications, and Drug Therapy in Obstetrics.” He has no relevant financial disclosures.

Learning the lessons of the past

During the last 50 years, two of the most potent known human teratogens, thalidomide and isotretinoin, became available for prescription in the United States. Thanks to the efforts of Frances Kelsey, MD, PhD, at the FDA, the initial application for approval of thalidomide in the United States was denied in the early 1960s. Subsequently, based on evidence from other countries where thalidomide was marketed that the drug can cause a pattern of serious birth defects, a very strict pregnancy prevention program was implemented when the drug was finally approved in the United States in 2006.

Dr. Chambers is a professor of pediatrics and director of clinical research at Rady Children’s Hospital, San Diego, and associate director of the Clinical and Translational Research Institute at the University of California, San Diego. She is director of MotherToBaby California, a past president of the Organization of Teratology Information Specialists, and past president of the Teratology Society. She has no relevant financial disclosures.

Moving toward personalized medicine

Nowhere is a lack of actionable data more pronounced than in the impact of mental health drugs in pregnancy.

As Dr. Briggs and Dr. Chambers have outlined, the quality of data regarding the reproductive safety of medications across the therapeutic spectrum has historically been fair at best. The methodology and the rigor has been sparse and to a large extent, in psychiatry, we were only able to look for signals of concern. Prior to the late 1980s and early 1990s, there was little to guide clinicians on the safety of even very commonly used psychiatric medications during pregnancy. The health implications for women of reproductive age are extraordinary and yet that urgency was not matched by the level of investigation until more recently.

Dr. Cohen is the director of the Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications.

Perception of risk

Every year, numerous new medicines are approved by the FDA without data in pregnancy. Animal studies may show a problem that doesn’t appear in humans, or as was the case with thalidomide, the problem may not be apparent in animals and show up later in humans. There are many drugs that are safe in pregnancy, but women are understandably afraid of the potential impact on fetal development.

While my colleagues have presented the advances we’ve made in understanding the actual risks of medications during the prenatal period, it’s also important to focus on the perception of risk and to recognize that the reality and the perception can be vastly different.

Dr. Koren is a professor of physiology/pharmacology at Western University, London, Ont., and a professor of medicine at Tel Aviv University. He is the founder of the Motherisk Program. He reported being a paid consultant for Duchesnay and Novartis.

Editor’s note: As Ob.Gyn. News celebrates its 50th anniversary, we wanted to know how far the medical community has come in identifying and mitigating drug risks during pregnancy and in the postpartum period. In this article, our four expert columnists share their experiences trying to find and interpret critical pregnancy data, as well as how they weigh the potential risks and benefits for their patients.

The search for information

The biggest advance in the past 50 years is the availability of information, even though limited, relating to the effects of drugs in pregnancy and lactation. In the first few years of this period, it was a daunting task to obtain this information. I can recall spending hours in the hospital’s medical library going through huge volumes of Index Medicus to obtain references that the library could order for me. The appearance of Thomas H. Shepard’s first edition (Catalog of Teratogenic Agents) in 1973 was a step forward and in 1977, O.P. Heinonen and colleagues’ book (Birth Defects and Drugs in Pregnancy) was helpful.

Purestock/Thinkstock

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, and Washington State University, Spokane. He is coauthor of “Drugs in Pregnancy and Lactation,” and coeditor of “Diseases, Complications, and Drug Therapy in Obstetrics.” He has no relevant financial disclosures.

Learning the lessons of the past

During the last 50 years, two of the most potent known human teratogens, thalidomide and isotretinoin, became available for prescription in the United States. Thanks to the efforts of Frances Kelsey, MD, PhD, at the FDA, the initial application for approval of thalidomide in the United States was denied in the early 1960s. Subsequently, based on evidence from other countries where thalidomide was marketed that the drug can cause a pattern of serious birth defects, a very strict pregnancy prevention program was implemented when the drug was finally approved in the United States in 2006.

Dr. Chambers is a professor of pediatrics and director of clinical research at Rady Children’s Hospital, San Diego, and associate director of the Clinical and Translational Research Institute at the University of California, San Diego. She is director of MotherToBaby California, a past president of the Organization of Teratology Information Specialists, and past president of the Teratology Society. She has no relevant financial disclosures.

Moving toward personalized medicine

Nowhere is a lack of actionable data more pronounced than in the impact of mental health drugs in pregnancy.

As Dr. Briggs and Dr. Chambers have outlined, the quality of data regarding the reproductive safety of medications across the therapeutic spectrum has historically been fair at best. The methodology and the rigor has been sparse and to a large extent, in psychiatry, we were only able to look for signals of concern. Prior to the late 1980s and early 1990s, there was little to guide clinicians on the safety of even very commonly used psychiatric medications during pregnancy. The health implications for women of reproductive age are extraordinary and yet that urgency was not matched by the level of investigation until more recently.

Dr. Cohen is the director of the Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications.

Perception of risk

Every year, numerous new medicines are approved by the FDA without data in pregnancy. Animal studies may show a problem that doesn’t appear in humans, or as was the case with thalidomide, the problem may not be apparent in animals and show up later in humans. There are many drugs that are safe in pregnancy, but women are understandably afraid of the potential impact on fetal development.

While my colleagues have presented the advances we’ve made in understanding the actual risks of medications during the prenatal period, it’s also important to focus on the perception of risk and to recognize that the reality and the perception can be vastly different.

Dr. Koren is a professor of physiology/pharmacology at Western University, London, Ont., and a professor of medicine at Tel Aviv University. He is the founder of the Motherisk Program. He reported being a paid consultant for Duchesnay and Novartis.

Editor’s note: As Ob.Gyn. News celebrates its 50th anniversary, we wanted to know how far the medical community has come in identifying and mitigating drug risks during pregnancy and in the postpartum period. In this article, our four expert columnists share their experiences trying to find and interpret critical pregnancy data, as well as how they weigh the potential risks and benefits for their patients.

The search for information

The biggest advance in the past 50 years is the availability of information, even though limited, relating to the effects of drugs in pregnancy and lactation. In the first few years of this period, it was a daunting task to obtain this information. I can recall spending hours in the hospital’s medical library going through huge volumes of Index Medicus to obtain references that the library could order for me. The appearance of Thomas H. Shepard’s first edition (Catalog of Teratogenic Agents) in 1973 was a step forward and in 1977, O.P. Heinonen and colleagues’ book (Birth Defects and Drugs in Pregnancy) was helpful.

Purestock/Thinkstock

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, and Washington State University, Spokane. He is coauthor of “Drugs in Pregnancy and Lactation,” and coeditor of “Diseases, Complications, and Drug Therapy in Obstetrics.” He has no relevant financial disclosures.

Learning the lessons of the past

During the last 50 years, two of the most potent known human teratogens, thalidomide and isotretinoin, became available for prescription in the United States. Thanks to the efforts of Frances Kelsey, MD, PhD, at the FDA, the initial application for approval of thalidomide in the United States was denied in the early 1960s. Subsequently, based on evidence from other countries where thalidomide was marketed that the drug can cause a pattern of serious birth defects, a very strict pregnancy prevention program was implemented when the drug was finally approved in the United States in 2006.

Dr. Chambers is a professor of pediatrics and director of clinical research at Rady Children’s Hospital, San Diego, and associate director of the Clinical and Translational Research Institute at the University of California, San Diego. She is director of MotherToBaby California, a past president of the Organization of Teratology Information Specialists, and past president of the Teratology Society. She has no relevant financial disclosures.

Moving toward personalized medicine

Nowhere is a lack of actionable data more pronounced than in the impact of mental health drugs in pregnancy.

As Dr. Briggs and Dr. Chambers have outlined, the quality of data regarding the reproductive safety of medications across the therapeutic spectrum has historically been fair at best. The methodology and the rigor has been sparse and to a large extent, in psychiatry, we were only able to look for signals of concern. Prior to the late 1980s and early 1990s, there was little to guide clinicians on the safety of even very commonly used psychiatric medications during pregnancy. The health implications for women of reproductive age are extraordinary and yet that urgency was not matched by the level of investigation until more recently.

Dr. Cohen is the director of the Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications.

Perception of risk

Every year, numerous new medicines are approved by the FDA without data in pregnancy. Animal studies may show a problem that doesn’t appear in humans, or as was the case with thalidomide, the problem may not be apparent in animals and show up later in humans. There are many drugs that are safe in pregnancy, but women are understandably afraid of the potential impact on fetal development.

While my colleagues have presented the advances we’ve made in understanding the actual risks of medications during the prenatal period, it’s also important to focus on the perception of risk and to recognize that the reality and the perception can be vastly different.

Dr. Koren is a professor of physiology/pharmacology at Western University, London, Ont., and a professor of medicine at Tel Aviv University. He is the founder of the Motherisk Program. He reported being a paid consultant for Duchesnay and Novartis.

Suicide is a staggering, tragic, and growing cause of death in the United States. One out of every 62 Americans will die from suicide, based on the national lifetime prevalence rate.¹ More than 42,000 Americans died from suicide in 2014, making suicide the second leading cause of death in individuals age 15 to 34, the fourth leading cause among those age 35 to 54, and the tenth leading cause of death in the country overall.² The incidence of suicide in the general population of the United States increased by 24% between 1999 and 2014.³ This tragedy obviously is not solving itself.

The proposal

U.S. Centers for Disease Control and Prevention (CDC) publishes statistics about the number of suicides, as well as demographic information, collected from coroners and medical examiners across the country. However, these sources do not provide a biological sample that could be used to gather data concerning DNA, RNA, and other potential blood markers, including those reflecting inflammatory and epigenetic processes. However, such biological samples are commonly collected by the U.S. medicolegal death investigation system. In 2003, this system investigated 450,000 unnatural and/or unexplained deaths (ie, approximately 20% of the 2.4 million deaths in the United States that year).⁴

Each unnatural or unexplained death is examined, often extensively, by a coroner or medical examiner. This examination system costs more than $600 million annually. Yet the data that are collected are handled on a case-by-case and often county-by-county basis, rather than in aggregate. The essence of the proposal presented here is to take the information and biological samples collected in this process and put them into a National Suicide Database (NSD), which then can serve as a resource for scientists to increase our understanding of the genetic, epigenetic, and other factors underlying death due to suicide. This increased understanding will result in the development more effective tools to detect to those at risk for suicide (ie, risk factor tests), to monitor treatment, and to develop new treatments based on a better understanding of the underlying pathophysiology and pathogenesis of suicide. These tools will reduce:

• the number of lives lost to suicide
• the pain and suffering of loved ones
• lost productivity to society, especially when one considers that suicide disproportionately affects individuals during the most productive period of their lives (ie, age 15 to 54).

The NSD will be organized as a government–private partnership, with the government represented by the National Institutes of Health (NIH) and/or the CDC. The goal will be to take the information that is currently being collected by the nation’s medicolegal death investigation system, including the biological samples, systematize it, enter it into a common database, and make it available to qualified researchers across the country. The administrative arm of the system will be responsible for ensuring systematic data collection, storage in a searchable and integrated database housed within the NIH and/or the CDC, and vetting researchers who will have access to the data, including those with expertise in genomics, molecular biology, suicide, epidemiology, and data-mining. (Currently, the CDC’s National Violent Death Reporting System, which is a state-based surveillance system, pools data on violent deaths from multiple sources into a usable, anonymous database. These sources include state and local medical examiners, coroners, law enforcement, crime labs, and vital statistics records, but they do not include any biological material even though it is collected [personal correspondence with the CDC, July 2016].)

Because information on suicides currently are handled primarily on a county-by-county basis, data concerning these deaths are not facilitating a better understanding of the causes and strategies for preventing suicide. Correcting this situation is the goal of this proposal, as modeled by the National Cancer Institute’s War on Cancer, which has transformed the treatment and the outcomes of cancer. If this proposal is enacted, the same type of transformation will occur and result in a reduction in the suicide rate and better outcomes for the psychiatric illnesses that underlie most instances of suicide.

The proposed NSD will address a major and common problem for researchers in this area—small sample sizes. When considered from the perspective of the size of samples feasible for most independent research teams to collect and study, suicide on an annual basis is rare—however, that is not the case when the incidence of suicide in the nation as a whole is considered. In contrast to the data concerning suicides that individual research teams can collect, the proposed genomic database will grow by approximately 40,000 individuals every year, until a meaningful reduction in deaths due to suicide is achieved.

From a research perspective, suicide, although tragic, is one of the few binary outcomes in psychiatry—that is, life or death. Although there may be >1 genetic and/or epigenetic contributor to suicide, within a relatively short period of time, the proposed database will amass—and continue to amass on an ongoing basis—data from a large population of suicide victims. Researchers then can compare the findings from this database with the normative human genome, looking for variants that are over-represented in the population of those who have died by suicide.

Environmental factors undoubtedly also contribute to the risk of suicide, given that the incidence of suicide increases with age, particularly among white males, and with the addition of psychiatric and medical comorbidities. Inflammatory processes also have been implicated in the pathophysiology of a number of psychiatric disorders, including major depression, which is the primary psychiatric risk factor for suicide. Therefore, consideration should be given to collecting whole blood samples if the time between death and autopsy is within an appropriate limit to obtain interpretable data concerning RNA (ie, gene expression) and even biomarkers of inflammatory and other processes at the time of the suicide. This approach has been used by Niculescu et al^5,6 for whole blood gene expression. The rationale for using samples of whole blood is that this strategy could be more easily adapted to clinical practice in contrast to using samples from the target organ (ie, brain) or cerebrospinal fluid.

Roadblocks to progress. In the absence of this proposed NSD, progress in this area has been stymied despite concerted governmental efforts (Box^7-10). One reason for the lack of progress has been that governmental efforts have focused on a public health model rather than also including a basic science model aimed at exploring the biological mechanisms underlying the risk of death from suicide. In the current decentralized system, individual researchers and even teams of researchers cannot easily collect data from a sufficiently large population of suicide victims to make inroads in gaining the needed understanding.

Because of the relatively small samples that individual research teams can collect in a reasonable period of time (ie, in terms of grant cycles), many investigators have studied suicide attempts as a surrogate for suicide itself, undoubtedly because suicide attempts are more numerous than suicides themselves, making it easier to collect data. However, there is evidence that these 2 populations—suicide attempters vs those who die by suicide—only partially overlap.

First, the frequency of suicide attempts is 10 to 20 times higher than actual suicides. Second, suicide attempters are 3 times more likely to be female whereas those who die by suicide are 4 times more likely to be male. Third, most individuals who die by suicide do so on their first or second attempt, whereas individuals who have made ≥4 attempts have an increased risk of future attempts rather than for completed suicide compared with the general population. Fourth, certain psychiatric illnesses are more often associated with death by suicide (particularly major depressive disorder, bipolar disorder, and schizophrenia in the first 5 years of an illness) whereas multiple suicide attempts are more often associated with other psychiatric diagnoses such as antisocial and borderline personality disorders.

Finally, in a study in men with a psychiatric disorder, Niculescu et al⁵ started with 412 candidate genes and found that 208 were associated with suicidal ideation but not suicide itself, whereas 76 genes were associated with both suicidal ideation and completion. Taken together, this evidence suggests that findings concerning suicide attempters, especially those who have made multiple (ie, >3) attempts, might not be extrapolatable to the population of actual suicides.

Is there evidence that this proposal could work?

Yes, research supports the potential utility of the proposed NSD, and this section highlights some of the major findings from these studies, although this review is not intended to be exhaustive.

First, considerable evidence exists for a biological basis for the risk of death due to suicide. The concordance rates for suicide are 10 times higher in monozygotic (“identical”) vs dizygotic (“fraternal”) twins (24.1% vs 2.8%) and 2 to 5 times higher in relatives of those who die by suicide than in the general population. Heritability estimates of fatal suicides and nonfatal suicide attempts in biological relatives of adoptees who die from suicide range from 17% to 45%.¹¹

Second, studies using information from small samples that was arduously collected by individual research groups have yielded important positive data. Most recently, in 2015, a multidisciplinary group led by Niculescu et al⁵ at Indiana University and other institutions described a test that could predict suicidality in men. This test was developed on the basis of a within-participant discovery approach to identify genes that change in expression between states of no suicidal ideation and high suicidal ideation, which was combined with clinical information assessed by 2 scales, the Convergent Functional Information for Suicidality and the Simplified Affective State Scale. Gene expression was measured in whole blood collected postmortem unless the method of suicide involved a medication overdose that could affect gene expression. These researchers identified 76 genes that likely were involved in suicidal ideation and suicide.

This report had a number of limitations.⁵ All of the individuals in these studies were being treated for psychiatric illness, were being closely followed by the investigators, and all were male. In addition, as noted above, suicides by overdose were eliminated from the analysis.

In a subsequent study published in 2016, the Niculescu group⁶ extended their work to women and identified 50 genes contributing to suicide risk in women. Underscoring the need for larger samples, only 3 of the top contributing genes were seen in both men and women, suggesting that there are likely significant sex differences in the biology of suicide completion. This important work needs to be replicated and extended.

In addition to these remarkable advances made in genetic understanding of the risk of suicide, recent research also has demonstrated a role for epigenetic and inflammatory processes as contributors to suicide risk.^12-15

There are likely many contributors, including genetic, epigenetic, and environmental factors such as inflammatory processes, that increase the risk of suicide. The goal of this article is not to provide an exhaustive or integrative review of research in this area but rather to argue for the establishment of a national initiative to study all of these factors and to begin that process by establishing the NSD.

What will be the foreseeable outcome of this initiative?

The establishment of the NSD is expected to lead to better identification of those who are genetically at increased risk of suicide as well as biological factors (eg, inflammatory or other processes) and environmental factors (eg, drug abuse), which can turn that genetic risk into reality. Using research results made possible by the implementation of this proposal, objective testing can be developed to monitor risk more effectively than is currently possible using clinical assessment alone.

Furthermore, this work also can provide targets for developing new treatments. For example, there is convergence between the work of Niculescu et al,^5,6 who identified genetic biomarkers for mechanistic target of rapamycin (mTOR) signaling as a risk factor in individuals who died by suicide and the work of Li et al and other researchers,^16-18 whose findings have implicated mTOR-dependent synapse formation as a mechanism underlying the rapid (ie, within hours to a couple of days) antidepressant effects of N-methyl-d-aspartate antagonists, such as ketamine, CP-101,606, and esketamine. In fact, the authors of a study presented earlier this year reported that esketamine—an active enantiomer of ketamine—rapidly reduced suicidal ideation as well as other depressive symptoms in individuals admitted to the hospital for suicidal ideation.¹⁹ (mTOR is a serine/threonine protein kinase that regulates a number of biological processes in addition to synaptogenesis, including cell growth, cell proliferation, cell motility, cell survival, protein synthesis, and autophagy.^20,21)

In aggregate, establishment of this proposed database will facilitate identification of biological (and therefore pharmaceutical) mechanisms beyond those involving biogenic amines, which have been the exclusive biological targets for antidepressants for the past 50 years.²² The likely consequences of the findings generated from research made possible by the proposed NSD will open completely new vistas for helping people at risk for suicide and psychiatric illnesses.

What foreseeable obstacles will need to be addressed?

Of course, obstacles and problems will arise but these will not exceed those encountered by the War on Cancer and they can similarly be overcome with sufficient public support and cooperation. Potential obstacles include:

• need for incremental funding
• obtaining the cooperation of the offices of each county medical examiner or coroner in a process that includes uniform systematic data collection
• determining the situations (eg, time after death and means of death) that will allow for meaningful collection of data such as RNA and inflammatory biomarkers
• establishing how data and particularly biological samples will be transported and stored
• issues related to privacy of health information particularly for relatives of suicide victims
• ensuring the reliability, validity, and comparability of the data received from different medical examiners and coroners.

With regard to the last issue, because stigma is associated with death by suicide, some true suicides could be missed, which would compromise sensitivity but simultaneously increase specificity. Other obstacles or problems may arise; however, I am certain that all such issues are surmountable and that the resulting NSD will be much better than what we have now and will propel our understanding of the biological underpinnings of the loss of life to suicide. (The author proposed a similar but even more ambitious plan 25 years ago,²³ but he believes that this is an idea whose time has come.)

Acknowledgments

The author thanks Wayne C. Drevets, MD, Alexander Niculescu, MD, PhD, John Oldman, MD, and John Savitz, PhD, David Sheehan, MD, and Matthew Macaluso, DO for their review and suggestions concerning this proposal/manuscript, and Kaylee Hervey, MPH, from the Sedgwick County Health Department, Wichita, Kansas, for her input. The author also thanks Ruth Ross, as always, for her excellent editing and general assistance.

Suicide is a staggering, tragic, and growing cause of death in the United States. One out of every 62 Americans will die from suicide, based on the national lifetime prevalence rate.¹ More than 42,000 Americans died from suicide in 2014, making suicide the second leading cause of death in individuals age 15 to 34, the fourth leading cause among those age 35 to 54, and the tenth leading cause of death in the country overall.² The incidence of suicide in the general population of the United States increased by 24% between 1999 and 2014.³ This tragedy obviously is not solving itself.

The proposal

U.S. Centers for Disease Control and Prevention (CDC) publishes statistics about the number of suicides, as well as demographic information, collected from coroners and medical examiners across the country. However, these sources do not provide a biological sample that could be used to gather data concerning DNA, RNA, and other potential blood markers, including those reflecting inflammatory and epigenetic processes. However, such biological samples are commonly collected by the U.S. medicolegal death investigation system. In 2003, this system investigated 450,000 unnatural and/or unexplained deaths (ie, approximately 20% of the 2.4 million deaths in the United States that year).⁴

Each unnatural or unexplained death is examined, often extensively, by a coroner or medical examiner. This examination system costs more than $600 million annually. Yet the data that are collected are handled on a case-by-case and often county-by-county basis, rather than in aggregate. The essence of the proposal presented here is to take the information and biological samples collected in this process and put them into a National Suicide Database (NSD), which then can serve as a resource for scientists to increase our understanding of the genetic, epigenetic, and other factors underlying death due to suicide. This increased understanding will result in the development more effective tools to detect to those at risk for suicide (ie, risk factor tests), to monitor treatment, and to develop new treatments based on a better understanding of the underlying pathophysiology and pathogenesis of suicide. These tools will reduce:

• the number of lives lost to suicide
• the pain and suffering of loved ones
• lost productivity to society, especially when one considers that suicide disproportionately affects individuals during the most productive period of their lives (ie, age 15 to 54).

The NSD will be organized as a government–private partnership, with the government represented by the National Institutes of Health (NIH) and/or the CDC. The goal will be to take the information that is currently being collected by the nation’s medicolegal death investigation system, including the biological samples, systematize it, enter it into a common database, and make it available to qualified researchers across the country. The administrative arm of the system will be responsible for ensuring systematic data collection, storage in a searchable and integrated database housed within the NIH and/or the CDC, and vetting researchers who will have access to the data, including those with expertise in genomics, molecular biology, suicide, epidemiology, and data-mining. (Currently, the CDC’s National Violent Death Reporting System, which is a state-based surveillance system, pools data on violent deaths from multiple sources into a usable, anonymous database. These sources include state and local medical examiners, coroners, law enforcement, crime labs, and vital statistics records, but they do not include any biological material even though it is collected [personal correspondence with the CDC, July 2016].)

Because information on suicides currently are handled primarily on a county-by-county basis, data concerning these deaths are not facilitating a better understanding of the causes and strategies for preventing suicide. Correcting this situation is the goal of this proposal, as modeled by the National Cancer Institute’s War on Cancer, which has transformed the treatment and the outcomes of cancer. If this proposal is enacted, the same type of transformation will occur and result in a reduction in the suicide rate and better outcomes for the psychiatric illnesses that underlie most instances of suicide.

The proposed NSD will address a major and common problem for researchers in this area—small sample sizes. When considered from the perspective of the size of samples feasible for most independent research teams to collect and study, suicide on an annual basis is rare—however, that is not the case when the incidence of suicide in the nation as a whole is considered. In contrast to the data concerning suicides that individual research teams can collect, the proposed genomic database will grow by approximately 40,000 individuals every year, until a meaningful reduction in deaths due to suicide is achieved.

From a research perspective, suicide, although tragic, is one of the few binary outcomes in psychiatry—that is, life or death. Although there may be >1 genetic and/or epigenetic contributor to suicide, within a relatively short period of time, the proposed database will amass—and continue to amass on an ongoing basis—data from a large population of suicide victims. Researchers then can compare the findings from this database with the normative human genome, looking for variants that are over-represented in the population of those who have died by suicide.

Environmental factors undoubtedly also contribute to the risk of suicide, given that the incidence of suicide increases with age, particularly among white males, and with the addition of psychiatric and medical comorbidities. Inflammatory processes also have been implicated in the pathophysiology of a number of psychiatric disorders, including major depression, which is the primary psychiatric risk factor for suicide. Therefore, consideration should be given to collecting whole blood samples if the time between death and autopsy is within an appropriate limit to obtain interpretable data concerning RNA (ie, gene expression) and even biomarkers of inflammatory and other processes at the time of the suicide. This approach has been used by Niculescu et al^5,6 for whole blood gene expression. The rationale for using samples of whole blood is that this strategy could be more easily adapted to clinical practice in contrast to using samples from the target organ (ie, brain) or cerebrospinal fluid.

Roadblocks to progress. In the absence of this proposed NSD, progress in this area has been stymied despite concerted governmental efforts (Box^7-10). One reason for the lack of progress has been that governmental efforts have focused on a public health model rather than also including a basic science model aimed at exploring the biological mechanisms underlying the risk of death from suicide. In the current decentralized system, individual researchers and even teams of researchers cannot easily collect data from a sufficiently large population of suicide victims to make inroads in gaining the needed understanding.

Because of the relatively small samples that individual research teams can collect in a reasonable period of time (ie, in terms of grant cycles), many investigators have studied suicide attempts as a surrogate for suicide itself, undoubtedly because suicide attempts are more numerous than suicides themselves, making it easier to collect data. However, there is evidence that these 2 populations—suicide attempters vs those who die by suicide—only partially overlap.

First, the frequency of suicide attempts is 10 to 20 times higher than actual suicides. Second, suicide attempters are 3 times more likely to be female whereas those who die by suicide are 4 times more likely to be male. Third, most individuals who die by suicide do so on their first or second attempt, whereas individuals who have made ≥4 attempts have an increased risk of future attempts rather than for completed suicide compared with the general population. Fourth, certain psychiatric illnesses are more often associated with death by suicide (particularly major depressive disorder, bipolar disorder, and schizophrenia in the first 5 years of an illness) whereas multiple suicide attempts are more often associated with other psychiatric diagnoses such as antisocial and borderline personality disorders.

Finally, in a study in men with a psychiatric disorder, Niculescu et al⁵ started with 412 candidate genes and found that 208 were associated with suicidal ideation but not suicide itself, whereas 76 genes were associated with both suicidal ideation and completion. Taken together, this evidence suggests that findings concerning suicide attempters, especially those who have made multiple (ie, >3) attempts, might not be extrapolatable to the population of actual suicides.

Is there evidence that this proposal could work?

Yes, research supports the potential utility of the proposed NSD, and this section highlights some of the major findings from these studies, although this review is not intended to be exhaustive.

First, considerable evidence exists for a biological basis for the risk of death due to suicide. The concordance rates for suicide are 10 times higher in monozygotic (“identical”) vs dizygotic (“fraternal”) twins (24.1% vs 2.8%) and 2 to 5 times higher in relatives of those who die by suicide than in the general population. Heritability estimates of fatal suicides and nonfatal suicide attempts in biological relatives of adoptees who die from suicide range from 17% to 45%.¹¹

Second, studies using information from small samples that was arduously collected by individual research groups have yielded important positive data. Most recently, in 2015, a multidisciplinary group led by Niculescu et al⁵ at Indiana University and other institutions described a test that could predict suicidality in men. This test was developed on the basis of a within-participant discovery approach to identify genes that change in expression between states of no suicidal ideation and high suicidal ideation, which was combined with clinical information assessed by 2 scales, the Convergent Functional Information for Suicidality and the Simplified Affective State Scale. Gene expression was measured in whole blood collected postmortem unless the method of suicide involved a medication overdose that could affect gene expression. These researchers identified 76 genes that likely were involved in suicidal ideation and suicide.

This report had a number of limitations.⁵ All of the individuals in these studies were being treated for psychiatric illness, were being closely followed by the investigators, and all were male. In addition, as noted above, suicides by overdose were eliminated from the analysis.

In a subsequent study published in 2016, the Niculescu group⁶ extended their work to women and identified 50 genes contributing to suicide risk in women. Underscoring the need for larger samples, only 3 of the top contributing genes were seen in both men and women, suggesting that there are likely significant sex differences in the biology of suicide completion. This important work needs to be replicated and extended.

In addition to these remarkable advances made in genetic understanding of the risk of suicide, recent research also has demonstrated a role for epigenetic and inflammatory processes as contributors to suicide risk.^12-15

There are likely many contributors, including genetic, epigenetic, and environmental factors such as inflammatory processes, that increase the risk of suicide. The goal of this article is not to provide an exhaustive or integrative review of research in this area but rather to argue for the establishment of a national initiative to study all of these factors and to begin that process by establishing the NSD.

What will be the foreseeable outcome of this initiative?

The establishment of the NSD is expected to lead to better identification of those who are genetically at increased risk of suicide as well as biological factors (eg, inflammatory or other processes) and environmental factors (eg, drug abuse), which can turn that genetic risk into reality. Using research results made possible by the implementation of this proposal, objective testing can be developed to monitor risk more effectively than is currently possible using clinical assessment alone.

Furthermore, this work also can provide targets for developing new treatments. For example, there is convergence between the work of Niculescu et al,^5,6 who identified genetic biomarkers for mechanistic target of rapamycin (mTOR) signaling as a risk factor in individuals who died by suicide and the work of Li et al and other researchers,^16-18 whose findings have implicated mTOR-dependent synapse formation as a mechanism underlying the rapid (ie, within hours to a couple of days) antidepressant effects of N-methyl-d-aspartate antagonists, such as ketamine, CP-101,606, and esketamine. In fact, the authors of a study presented earlier this year reported that esketamine—an active enantiomer of ketamine—rapidly reduced suicidal ideation as well as other depressive symptoms in individuals admitted to the hospital for suicidal ideation.¹⁹ (mTOR is a serine/threonine protein kinase that regulates a number of biological processes in addition to synaptogenesis, including cell growth, cell proliferation, cell motility, cell survival, protein synthesis, and autophagy.^20,21)

In aggregate, establishment of this proposed database will facilitate identification of biological (and therefore pharmaceutical) mechanisms beyond those involving biogenic amines, which have been the exclusive biological targets for antidepressants for the past 50 years.²² The likely consequences of the findings generated from research made possible by the proposed NSD will open completely new vistas for helping people at risk for suicide and psychiatric illnesses.

What foreseeable obstacles will need to be addressed?

Of course, obstacles and problems will arise but these will not exceed those encountered by the War on Cancer and they can similarly be overcome with sufficient public support and cooperation. Potential obstacles include:

• need for incremental funding
• obtaining the cooperation of the offices of each county medical examiner or coroner in a process that includes uniform systematic data collection
• determining the situations (eg, time after death and means of death) that will allow for meaningful collection of data such as RNA and inflammatory biomarkers
• establishing how data and particularly biological samples will be transported and stored
• issues related to privacy of health information particularly for relatives of suicide victims
• ensuring the reliability, validity, and comparability of the data received from different medical examiners and coroners.

With regard to the last issue, because stigma is associated with death by suicide, some true suicides could be missed, which would compromise sensitivity but simultaneously increase specificity. Other obstacles or problems may arise; however, I am certain that all such issues are surmountable and that the resulting NSD will be much better than what we have now and will propel our understanding of the biological underpinnings of the loss of life to suicide. (The author proposed a similar but even more ambitious plan 25 years ago,²³ but he believes that this is an idea whose time has come.)

Acknowledgments

The author thanks Wayne C. Drevets, MD, Alexander Niculescu, MD, PhD, John Oldman, MD, and John Savitz, PhD, David Sheehan, MD, and Matthew Macaluso, DO for their review and suggestions concerning this proposal/manuscript, and Kaylee Hervey, MPH, from the Sedgwick County Health Department, Wichita, Kansas, for her input. The author also thanks Ruth Ross, as always, for her excellent editing and general assistance.

Suicide is a staggering, tragic, and growing cause of death in the United States. One out of every 62 Americans will die from suicide, based on the national lifetime prevalence rate.¹ More than 42,000 Americans died from suicide in 2014, making suicide the second leading cause of death in individuals age 15 to 34, the fourth leading cause among those age 35 to 54, and the tenth leading cause of death in the country overall.² The incidence of suicide in the general population of the United States increased by 24% between 1999 and 2014.³ This tragedy obviously is not solving itself.

The proposal

U.S. Centers for Disease Control and Prevention (CDC) publishes statistics about the number of suicides, as well as demographic information, collected from coroners and medical examiners across the country. However, these sources do not provide a biological sample that could be used to gather data concerning DNA, RNA, and other potential blood markers, including those reflecting inflammatory and epigenetic processes. However, such biological samples are commonly collected by the U.S. medicolegal death investigation system. In 2003, this system investigated 450,000 unnatural and/or unexplained deaths (ie, approximately 20% of the 2.4 million deaths in the United States that year).⁴

Each unnatural or unexplained death is examined, often extensively, by a coroner or medical examiner. This examination system costs more than $600 million annually. Yet the data that are collected are handled on a case-by-case and often county-by-county basis, rather than in aggregate. The essence of the proposal presented here is to take the information and biological samples collected in this process and put them into a National Suicide Database (NSD), which then can serve as a resource for scientists to increase our understanding of the genetic, epigenetic, and other factors underlying death due to suicide. This increased understanding will result in the development more effective tools to detect to those at risk for suicide (ie, risk factor tests), to monitor treatment, and to develop new treatments based on a better understanding of the underlying pathophysiology and pathogenesis of suicide. These tools will reduce:

• the number of lives lost to suicide
• the pain and suffering of loved ones
• lost productivity to society, especially when one considers that suicide disproportionately affects individuals during the most productive period of their lives (ie, age 15 to 54).

The NSD will be organized as a government–private partnership, with the government represented by the National Institutes of Health (NIH) and/or the CDC. The goal will be to take the information that is currently being collected by the nation’s medicolegal death investigation system, including the biological samples, systematize it, enter it into a common database, and make it available to qualified researchers across the country. The administrative arm of the system will be responsible for ensuring systematic data collection, storage in a searchable and integrated database housed within the NIH and/or the CDC, and vetting researchers who will have access to the data, including those with expertise in genomics, molecular biology, suicide, epidemiology, and data-mining. (Currently, the CDC’s National Violent Death Reporting System, which is a state-based surveillance system, pools data on violent deaths from multiple sources into a usable, anonymous database. These sources include state and local medical examiners, coroners, law enforcement, crime labs, and vital statistics records, but they do not include any biological material even though it is collected [personal correspondence with the CDC, July 2016].)

Because information on suicides currently are handled primarily on a county-by-county basis, data concerning these deaths are not facilitating a better understanding of the causes and strategies for preventing suicide. Correcting this situation is the goal of this proposal, as modeled by the National Cancer Institute’s War on Cancer, which has transformed the treatment and the outcomes of cancer. If this proposal is enacted, the same type of transformation will occur and result in a reduction in the suicide rate and better outcomes for the psychiatric illnesses that underlie most instances of suicide.

The proposed NSD will address a major and common problem for researchers in this area—small sample sizes. When considered from the perspective of the size of samples feasible for most independent research teams to collect and study, suicide on an annual basis is rare—however, that is not the case when the incidence of suicide in the nation as a whole is considered. In contrast to the data concerning suicides that individual research teams can collect, the proposed genomic database will grow by approximately 40,000 individuals every year, until a meaningful reduction in deaths due to suicide is achieved.

From a research perspective, suicide, although tragic, is one of the few binary outcomes in psychiatry—that is, life or death. Although there may be >1 genetic and/or epigenetic contributor to suicide, within a relatively short period of time, the proposed database will amass—and continue to amass on an ongoing basis—data from a large population of suicide victims. Researchers then can compare the findings from this database with the normative human genome, looking for variants that are over-represented in the population of those who have died by suicide.

Environmental factors undoubtedly also contribute to the risk of suicide, given that the incidence of suicide increases with age, particularly among white males, and with the addition of psychiatric and medical comorbidities. Inflammatory processes also have been implicated in the pathophysiology of a number of psychiatric disorders, including major depression, which is the primary psychiatric risk factor for suicide. Therefore, consideration should be given to collecting whole blood samples if the time between death and autopsy is within an appropriate limit to obtain interpretable data concerning RNA (ie, gene expression) and even biomarkers of inflammatory and other processes at the time of the suicide. This approach has been used by Niculescu et al^5,6 for whole blood gene expression. The rationale for using samples of whole blood is that this strategy could be more easily adapted to clinical practice in contrast to using samples from the target organ (ie, brain) or cerebrospinal fluid.

Roadblocks to progress. In the absence of this proposed NSD, progress in this area has been stymied despite concerted governmental efforts (Box^7-10). One reason for the lack of progress has been that governmental efforts have focused on a public health model rather than also including a basic science model aimed at exploring the biological mechanisms underlying the risk of death from suicide. In the current decentralized system, individual researchers and even teams of researchers cannot easily collect data from a sufficiently large population of suicide victims to make inroads in gaining the needed understanding.

Because of the relatively small samples that individual research teams can collect in a reasonable period of time (ie, in terms of grant cycles), many investigators have studied suicide attempts as a surrogate for suicide itself, undoubtedly because suicide attempts are more numerous than suicides themselves, making it easier to collect data. However, there is evidence that these 2 populations—suicide attempters vs those who die by suicide—only partially overlap.

First, the frequency of suicide attempts is 10 to 20 times higher than actual suicides. Second, suicide attempters are 3 times more likely to be female whereas those who die by suicide are 4 times more likely to be male. Third, most individuals who die by suicide do so on their first or second attempt, whereas individuals who have made ≥4 attempts have an increased risk of future attempts rather than for completed suicide compared with the general population. Fourth, certain psychiatric illnesses are more often associated with death by suicide (particularly major depressive disorder, bipolar disorder, and schizophrenia in the first 5 years of an illness) whereas multiple suicide attempts are more often associated with other psychiatric diagnoses such as antisocial and borderline personality disorders.

Finally, in a study in men with a psychiatric disorder, Niculescu et al⁵ started with 412 candidate genes and found that 208 were associated with suicidal ideation but not suicide itself, whereas 76 genes were associated with both suicidal ideation and completion. Taken together, this evidence suggests that findings concerning suicide attempters, especially those who have made multiple (ie, >3) attempts, might not be extrapolatable to the population of actual suicides.

Is there evidence that this proposal could work?

Yes, research supports the potential utility of the proposed NSD, and this section highlights some of the major findings from these studies, although this review is not intended to be exhaustive.

First, considerable evidence exists for a biological basis for the risk of death due to suicide. The concordance rates for suicide are 10 times higher in monozygotic (“identical”) vs dizygotic (“fraternal”) twins (24.1% vs 2.8%) and 2 to 5 times higher in relatives of those who die by suicide than in the general population. Heritability estimates of fatal suicides and nonfatal suicide attempts in biological relatives of adoptees who die from suicide range from 17% to 45%.¹¹

Second, studies using information from small samples that was arduously collected by individual research groups have yielded important positive data. Most recently, in 2015, a multidisciplinary group led by Niculescu et al⁵ at Indiana University and other institutions described a test that could predict suicidality in men. This test was developed on the basis of a within-participant discovery approach to identify genes that change in expression between states of no suicidal ideation and high suicidal ideation, which was combined with clinical information assessed by 2 scales, the Convergent Functional Information for Suicidality and the Simplified Affective State Scale. Gene expression was measured in whole blood collected postmortem unless the method of suicide involved a medication overdose that could affect gene expression. These researchers identified 76 genes that likely were involved in suicidal ideation and suicide.

This report had a number of limitations.⁵ All of the individuals in these studies were being treated for psychiatric illness, were being closely followed by the investigators, and all were male. In addition, as noted above, suicides by overdose were eliminated from the analysis.

In a subsequent study published in 2016, the Niculescu group⁶ extended their work to women and identified 50 genes contributing to suicide risk in women. Underscoring the need for larger samples, only 3 of the top contributing genes were seen in both men and women, suggesting that there are likely significant sex differences in the biology of suicide completion. This important work needs to be replicated and extended.

In addition to these remarkable advances made in genetic understanding of the risk of suicide, recent research also has demonstrated a role for epigenetic and inflammatory processes as contributors to suicide risk.^12-15

There are likely many contributors, including genetic, epigenetic, and environmental factors such as inflammatory processes, that increase the risk of suicide. The goal of this article is not to provide an exhaustive or integrative review of research in this area but rather to argue for the establishment of a national initiative to study all of these factors and to begin that process by establishing the NSD.

What will be the foreseeable outcome of this initiative?

The establishment of the NSD is expected to lead to better identification of those who are genetically at increased risk of suicide as well as biological factors (eg, inflammatory or other processes) and environmental factors (eg, drug abuse), which can turn that genetic risk into reality. Using research results made possible by the implementation of this proposal, objective testing can be developed to monitor risk more effectively than is currently possible using clinical assessment alone.

Furthermore, this work also can provide targets for developing new treatments. For example, there is convergence between the work of Niculescu et al,^5,6 who identified genetic biomarkers for mechanistic target of rapamycin (mTOR) signaling as a risk factor in individuals who died by suicide and the work of Li et al and other researchers,^16-18 whose findings have implicated mTOR-dependent synapse formation as a mechanism underlying the rapid (ie, within hours to a couple of days) antidepressant effects of N-methyl-d-aspartate antagonists, such as ketamine, CP-101,606, and esketamine. In fact, the authors of a study presented earlier this year reported that esketamine—an active enantiomer of ketamine—rapidly reduced suicidal ideation as well as other depressive symptoms in individuals admitted to the hospital for suicidal ideation.¹⁹ (mTOR is a serine/threonine protein kinase that regulates a number of biological processes in addition to synaptogenesis, including cell growth, cell proliferation, cell motility, cell survival, protein synthesis, and autophagy.^20,21)

In aggregate, establishment of this proposed database will facilitate identification of biological (and therefore pharmaceutical) mechanisms beyond those involving biogenic amines, which have been the exclusive biological targets for antidepressants for the past 50 years.²² The likely consequences of the findings generated from research made possible by the proposed NSD will open completely new vistas for helping people at risk for suicide and psychiatric illnesses.

What foreseeable obstacles will need to be addressed?

Of course, obstacles and problems will arise but these will not exceed those encountered by the War on Cancer and they can similarly be overcome with sufficient public support and cooperation. Potential obstacles include:

• need for incremental funding
• obtaining the cooperation of the offices of each county medical examiner or coroner in a process that includes uniform systematic data collection
• determining the situations (eg, time after death and means of death) that will allow for meaningful collection of data such as RNA and inflammatory biomarkers
• establishing how data and particularly biological samples will be transported and stored
• issues related to privacy of health information particularly for relatives of suicide victims
• ensuring the reliability, validity, and comparability of the data received from different medical examiners and coroners.

With regard to the last issue, because stigma is associated with death by suicide, some true suicides could be missed, which would compromise sensitivity but simultaneously increase specificity. Other obstacles or problems may arise; however, I am certain that all such issues are surmountable and that the resulting NSD will be much better than what we have now and will propel our understanding of the biological underpinnings of the loss of life to suicide. (The author proposed a similar but even more ambitious plan 25 years ago,²³ but he believes that this is an idea whose time has come.)

Acknowledgments

The author thanks Wayne C. Drevets, MD, Alexander Niculescu, MD, PhD, John Oldman, MD, and John Savitz, PhD, David Sheehan, MD, and Matthew Macaluso, DO for their review and suggestions concerning this proposal/manuscript, and Kaylee Hervey, MPH, from the Sedgwick County Health Department, Wichita, Kansas, for her input. The author also thanks Ruth Ross, as always, for her excellent editing and general assistance.

The study¹ that served as the basis for the PURL entitled, “Ramipril for claudication?” (J Fam Pract. 2013;62:579-580), has been retracted from the Journal of the American Medical Association.² Therefore we, on behalf of all of the authors of the PURL, are retracting the PURL, as well.

According to JAMA’s retraction statement, the first author of the article admitted to data fabrication following an internal investigation.² The source article does not provide subgroup analysis to determine how much of an effect the fabricated data may have had on the final reported outcome. However, a separately reported (and also retracted) sub-analysis of this study indicates that 165/212 (77.8%) patients were enrolled from the site of the first author.³

The question remains: Does ramipril work for symptoms of claudication?

The question remains: Does ramipril work for symptoms of claudication? A completely separate group of researchers conducted a similar, but smaller, randomized clinical trial of ramipril in patients with intermittent claudication.⁴ In this study, 33 patients were randomized to ramipril or placebo for a 24-week trial. The ramipril group (n=14) improved maximum treadmill walking distance by an adjusted mean of 131 meters (m) (95% confidence interval [CI], 62-199; P=.001), improved treadmill intermittent claudication distance by 122 m (95% CI, 56-188; P=.001), and improved patient-reported walking distance by 159 m (95% CI, 66-313; P=.043).

The 2004 Heart Outcomes Prevention Evaluation (HOPE) study indicates that ramipril maintains a mortality benefit for patients with intermittent claudication.⁵ A subgroup of this study included 1725 patients with baseline peripheral artery disease who were randomized to ramipril at 10 mg, which yielded a relative risk (RR) of 0.75 (95% CI, 0.61-0.92) for the primary outcome (cardiovascular mortality, myocardial infarction, stroke). This alone validates the use of ramipril in patients with intermittent claudication. But with the retraction of the large randomized controlled trial, we are not sure how much it may improve walk distances. Further studies might better clarify if ramipril provides symptomatic benefit by reducing claudication symptoms, in addition to the known cardiovascular mortality benefit.

Luke Stephens, MD, MSPH
Park Ridge, IL

James J. Stevermer, MD, MSPH
Columbia, MO

The study¹ that served as the basis for the PURL entitled, “Ramipril for claudication?” (J Fam Pract. 2013;62:579-580), has been retracted from the Journal of the American Medical Association.² Therefore we, on behalf of all of the authors of the PURL, are retracting the PURL, as well.

According to JAMA’s retraction statement, the first author of the article admitted to data fabrication following an internal investigation.² The source article does not provide subgroup analysis to determine how much of an effect the fabricated data may have had on the final reported outcome. However, a separately reported (and also retracted) sub-analysis of this study indicates that 165/212 (77.8%) patients were enrolled from the site of the first author.³

The question remains: Does ramipril work for symptoms of claudication?

The question remains: Does ramipril work for symptoms of claudication? A completely separate group of researchers conducted a similar, but smaller, randomized clinical trial of ramipril in patients with intermittent claudication.⁴ In this study, 33 patients were randomized to ramipril or placebo for a 24-week trial. The ramipril group (n=14) improved maximum treadmill walking distance by an adjusted mean of 131 meters (m) (95% confidence interval [CI], 62-199; P=.001), improved treadmill intermittent claudication distance by 122 m (95% CI, 56-188; P=.001), and improved patient-reported walking distance by 159 m (95% CI, 66-313; P=.043).

The 2004 Heart Outcomes Prevention Evaluation (HOPE) study indicates that ramipril maintains a mortality benefit for patients with intermittent claudication.⁵ A subgroup of this study included 1725 patients with baseline peripheral artery disease who were randomized to ramipril at 10 mg, which yielded a relative risk (RR) of 0.75 (95% CI, 0.61-0.92) for the primary outcome (cardiovascular mortality, myocardial infarction, stroke). This alone validates the use of ramipril in patients with intermittent claudication. But with the retraction of the large randomized controlled trial, we are not sure how much it may improve walk distances. Further studies might better clarify if ramipril provides symptomatic benefit by reducing claudication symptoms, in addition to the known cardiovascular mortality benefit.

Luke Stephens, MD, MSPH
Park Ridge, IL

James J. Stevermer, MD, MSPH
Columbia, MO

The study¹ that served as the basis for the PURL entitled, “Ramipril for claudication?” (J Fam Pract. 2013;62:579-580), has been retracted from the Journal of the American Medical Association.² Therefore we, on behalf of all of the authors of the PURL, are retracting the PURL, as well.

According to JAMA’s retraction statement, the first author of the article admitted to data fabrication following an internal investigation.² The source article does not provide subgroup analysis to determine how much of an effect the fabricated data may have had on the final reported outcome. However, a separately reported (and also retracted) sub-analysis of this study indicates that 165/212 (77.8%) patients were enrolled from the site of the first author.³

The question remains: Does ramipril work for symptoms of claudication?

The question remains: Does ramipril work for symptoms of claudication? A completely separate group of researchers conducted a similar, but smaller, randomized clinical trial of ramipril in patients with intermittent claudication.⁴ In this study, 33 patients were randomized to ramipril or placebo for a 24-week trial. The ramipril group (n=14) improved maximum treadmill walking distance by an adjusted mean of 131 meters (m) (95% confidence interval [CI], 62-199; P=.001), improved treadmill intermittent claudication distance by 122 m (95% CI, 56-188; P=.001), and improved patient-reported walking distance by 159 m (95% CI, 66-313; P=.043).

The 2004 Heart Outcomes Prevention Evaluation (HOPE) study indicates that ramipril maintains a mortality benefit for patients with intermittent claudication.⁵ A subgroup of this study included 1725 patients with baseline peripheral artery disease who were randomized to ramipril at 10 mg, which yielded a relative risk (RR) of 0.75 (95% CI, 0.61-0.92) for the primary outcome (cardiovascular mortality, myocardial infarction, stroke). This alone validates the use of ramipril in patients with intermittent claudication. But with the retraction of the large randomized controlled trial, we are not sure how much it may improve walk distances. Further studies might better clarify if ramipril provides symptomatic benefit by reducing claudication symptoms, in addition to the known cardiovascular mortality benefit.

Luke Stephens, MD, MSPH
Park Ridge, IL

James J. Stevermer, MD, MSPH
Columbia, MO