Pediatrics

ORLANDO – Fertility preservation techniques pioneered in young cancer patients may someday allow some women with Turner syndrome to give birth to their own children, without relying on donated eggs.

Spontaneous conception and live birth are exceedingly rare among women with the genetic disorder. Until very recently, adoption was the only practical way for most to grow a family. In the last decade, however, fertility specialists in Europe and the United States have had good success with in vitro fertilization using donated eggs. Now, those clinicians are aiming for a higher goal: babies born from a patient’s own eggs, cryopreserved either individually or within whole ovarian tissue.

These are not pipe dreams, according to experts interviewed for this story. Autologous oocyte freezing is well established in healthy women and is now coming of age in cancer patients, with recent reports of live births. Ovarian tissue freezing and reimplantation is a much newer technique, also pioneered in cancer patients. To date, more than 70 live births have occurred from ovarian cortical tissue conservation and later transplantation in adults. Last December brought the first report of a live birth to a childhood cancer survivor who had prepubertal ovarian tissue frozen before chemotherapy. And a 2015 report detailed the case of a girl with primary ovarian failure secondary to sickle cell anemia treatment. At 25, she gave birth to a healthy child conceived from ovarian tissue removed when she was 14 years old.

Not all clinicians so enthusiastically embrace this future, however. A new set of consensus guidelines for the management of girls and women with Turner syndrome is in the works and will recommend a more conservative clinical approach, according to Nelly Mauras, MD, chief of endocrinology, diabetes, and metabolism at the Nemours Children’s Health System in Jacksonville, Fla.

A group of academic and patient advocacy stakeholders is cooperatively honing the document based on a meeting last summer in Cincinnati. These groups include the European Society of Endocrinology, the Endocrine Society, the U.S. Pediatric Endocrine Society, the European Society for Pediatric Endocrinology, Cardiology, and Reproductive Endocrinology, as well as Turner syndrome patient advocacy groups.

Dr. Mauras said the guideline will be “less discouraging” than the existing one issued in 2012 by the American Society of Reproductive Medicine. In its 2012 guidelines, the society identified Turner syndrome as a relative contraindication to pregnancy and an absolute contraindication in those with documented cardiac anomalies. However, greater experience has since been accrued in reproductive techniques of oocyte donation in Turner, with better outcomes.

The upcoming guidelines, however, will still recommend strongly against ovarian stimulation for fertility preservation for girls younger than 12, Dr. Mauras said, and will not recommend ovarian tissue conservation. “We just do not have the safety data and pregnancy outcomes that we need to give strong recommendations for these treatments,” she said. “These are still considered experimental treatments for girls with Turner syndrome.”

Turner syndrome, caused by a deletion of one X chromosome, throws a unique curve into the game – very early ovarian failure. Those with a complete deletion (45,X) begin losing their primordial ovarian follicles even before birth. Most will never experience spontaneous puberty; even if they do, their egg reserve is virtually gone soon after. Ovarian reserve may not be completely lost in girls with mosaicism, however, who have the X deletion in only a portion of their cells (46,XX/45,X). Some will enter puberty, and about 5% may even conceive spontaneously in younger years. But of the majority of Turner girls eventually experience complete ovarian failure.

This means that fertility preservation can’t be a wait-and-see issue, according to Kutluk Oktay, MD, PhD, a fertility specialist on the leading edge of this issue in the United States.

“We have to be proactive,” said Dr. Oktay, professor of obstetrics and gynecology at New York Medical College, Valhalla. “If we wait until girls are 12 or 13 to address this, a majority will have totally depleted their ovarian reserve by then. They will have no option other than an egg donor or adoption. We are suggesting that they should be screened as soon as they are diagnosed, and if they and their parents wish it, something should be done before it’s too late.”

Dr. Oktay is also the founder of fertilitypreservation.org, which specializes in advanced fertility treatments for cancer patients. He is one of a handful of physicians in the United States who advocate early oocyte harvesting in peripubertal girls and ovarian tissue harvesting in prepubertal girls with Turner syndrome. Last year, in conjunction with the Turner Syndrome Foundation, he and his colleagues published a set of guidelines for preserving fertility in these patients.

The paper recommends fertility assessment pathways for pre- and postpubertal girls. For both groups, Dr. Oktay employs serial assessments of ovarian reserve by monitoring several hormones, including follicle-stimulating hormone, luteinizing hormone, and antimüllerian hormone (AMH). Produced by primordial follicles, AMH declines as egg reserve declines over a lifetime, and is considered an accurate marker of ovarian reserve. When a girl experiences two consecutive AMH declines, egg depletion is probably accelerating. “This is the time to consider fertility preservation,” he said.

If a girl is peri- or postpubertal, the choice would probably be ovarian stimulation with the goal of retrieving mature oocytes. For prepubertal girls, the best choice is probably ovarian tissue cryopreservation. But because the egg reserve may already be spotty inside the ovary, he recommended freezing it en bloc, rather than preserving just cortical sections.

Because these techniques are only beginning to be used in young Turner patients, neither has been tested yet to see if it would result in a pregnancy. However, Dr. Oktay said, more than 80 babies have been born to women with other disorders who had ovaries frozen as adults. And European women with Turner syndrome have been successfully bearing children with donated oocytes for years.

“I don’t differentiate Europe from the U.S.,” he said. “We have no reason to believe Turner syndrome girls would be any different here than they are there.”

Pregnancy rates by egg donation in Turner syndrome patients are about half that typically seen in an otherwise healthy infertile woman, according to numerous sources; with a take-home baby rate of about 18%. There are numerous reasons for this. The miscarriage rate in Turner patients is about 44%. Women with Turner tend to have smaller uteri, with thinner endometrium, mostly because of the lack of estrogen.

But with careful management, those who do conceive can safely deliver a healthy baby, said Outi Hovatta, MD, a Finnish fertility specialist who has done extensive work in the area. “In Europe, we have been doing this quite liberally for years, and haven’t had a bad experience,” she said in an interview.

A 2013 review summarized both the success and the risks of these pregnancies. It examined obstetric and neonatal outcomes among 106 women with Turner syndrome who gave birth via egg donation from 1992 to 2011 in Sweden, Finland, and Denmark.

Most (70%) had a single embryo transferred, as virtually all guidelines recommend. Women with Turner are prone to cardiac and aortic defects that can worsen under the strain of pregnancy, or even present for the first time during gestation. Aortic dissection is a real threat; up to a third of patients with Turner experience it during adulthood, and it’s a major cause of death among them. In the Nordic series, 10 women (9%) had a known cardiac anomaly.

The multiple birth rate was 7%. More than a third (35%) developed a hypertensive disorder, including preeclampsia (20%). Four women had potentially life-threatening complications, including one with aortic dissection, one who developed mild regurgitation of the tricuspid and mitral valve, one with a mechanical heart valve who developed HELLP syndrome (hemolysis, elevated liver enzymes, low platelets), and one who underwent a postpartum hysterectomy because of severe hemorrhaging.

The infants, nevertheless, did well. The preterm birth rate was 8%, with 9% of the singleton infants having a low birth weight. About 4% had a major birth defect. Of the 131 born, three died (2.3%), including a set of extremely preterm twins.

Close follow-up and cross-specialty cooperation are what make these positive outcomes possible, said Dr. Hovatta, who is now a professor emeritus at the Karolinska Institute, Sweden.

“We do everything we can to exclude things that could cause bad outcomes.” That includes extremely rigorous cardiac testing before pregnancy and continuous monitoring during it. “If a woman has any sign of cardiac anomaly, she is advised not to become pregnant. If she shows any signs of aortic dilation, we follow her extremely carefully with experienced cardiologists.”

Like Dr. Oktay, Dr. Hovatta and her European colleagues make fertility preservation an early topic of conversation. Unlike in the United States, where many girls aren’t diagnosed with the disorder until they fail to enter puberty, almost all Turner girls in Europe are identified very early in childhood. They receive early growth hormone treatment, and there is frequent consultation with interdisciplinary specialists. Fertility is spoken of early and often.

Early oocyte retrieval is common, Dr. Hovatta said. “Yes, it’s possible to wait until puberty, but for so many girls, most of the eggs have disappeared by then, so we typically don’t wait. We start looking at that option around 11 years, which is the same time we think about cryopreserving ovarian tissue.”

However, she added, as in the United States, the outcomes of these procedures are still unknown. But the existing data in other populations, the ability to carefully shepherd women through a successful pregnancy, and the willingness of families to provide the option all support further exploring them. Dr. Hovatta was at the Cincinnati gathering last summer and said she did not agree with the conservative tone she heard. Dr. Oktay also does not agree.

“This evidence we have so far is good evidence,” he said. “Look, where we are right now with Turner girls is where we were 15 years ago with cancer patients. People thought, ‘They have cancer. They should just be worrying about surviving cancer, not about their fertility.’ Now fertility counseling is a very important part of cancer care. We have all these tools available to us for cancer patients who don’t want to lose their fertility. This accumulated experience that has already been applied in other medical conditions … why not use that for Turner syndrome? This is my point: With all the data out there about the potential benefits and the ways to manage the risks, we shouldn’t have to tell girls, ‘Well, you have to become menopausal, and maybe you can adopt someday.’ That doesn’t sit well with parents any more. We want these girls to thrive. Not just to survive, but to have as close to a normal quality of life as possible.”
 

msullivan@frontlinemedcom.com

ORLANDO – Fertility preservation techniques pioneered in young cancer patients may someday allow some women with Turner syndrome to give birth to their own children, without relying on donated eggs.

Spontaneous conception and live birth are exceedingly rare among women with the genetic disorder. Until very recently, adoption was the only practical way for most to grow a family. In the last decade, however, fertility specialists in Europe and the United States have had good success with in vitro fertilization using donated eggs. Now, those clinicians are aiming for a higher goal: babies born from a patient’s own eggs, cryopreserved either individually or within whole ovarian tissue.

These are not pipe dreams, according to experts interviewed for this story. Autologous oocyte freezing is well established in healthy women and is now coming of age in cancer patients, with recent reports of live births. Ovarian tissue freezing and reimplantation is a much newer technique, also pioneered in cancer patients. To date, more than 70 live births have occurred from ovarian cortical tissue conservation and later transplantation in adults. Last December brought the first report of a live birth to a childhood cancer survivor who had prepubertal ovarian tissue frozen before chemotherapy. And a 2015 report detailed the case of a girl with primary ovarian failure secondary to sickle cell anemia treatment. At 25, she gave birth to a healthy child conceived from ovarian tissue removed when she was 14 years old.

Not all clinicians so enthusiastically embrace this future, however. A new set of consensus guidelines for the management of girls and women with Turner syndrome is in the works and will recommend a more conservative clinical approach, according to Nelly Mauras, MD, chief of endocrinology, diabetes, and metabolism at the Nemours Children’s Health System in Jacksonville, Fla.

A group of academic and patient advocacy stakeholders is cooperatively honing the document based on a meeting last summer in Cincinnati. These groups include the European Society of Endocrinology, the Endocrine Society, the U.S. Pediatric Endocrine Society, the European Society for Pediatric Endocrinology, Cardiology, and Reproductive Endocrinology, as well as Turner syndrome patient advocacy groups.

Dr. Mauras said the guideline will be “less discouraging” than the existing one issued in 2012 by the American Society of Reproductive Medicine. In its 2012 guidelines, the society identified Turner syndrome as a relative contraindication to pregnancy and an absolute contraindication in those with documented cardiac anomalies. However, greater experience has since been accrued in reproductive techniques of oocyte donation in Turner, with better outcomes.

The upcoming guidelines, however, will still recommend strongly against ovarian stimulation for fertility preservation for girls younger than 12, Dr. Mauras said, and will not recommend ovarian tissue conservation. “We just do not have the safety data and pregnancy outcomes that we need to give strong recommendations for these treatments,” she said. “These are still considered experimental treatments for girls with Turner syndrome.”

Turner syndrome, caused by a deletion of one X chromosome, throws a unique curve into the game – very early ovarian failure. Those with a complete deletion (45,X) begin losing their primordial ovarian follicles even before birth. Most will never experience spontaneous puberty; even if they do, their egg reserve is virtually gone soon after. Ovarian reserve may not be completely lost in girls with mosaicism, however, who have the X deletion in only a portion of their cells (46,XX/45,X). Some will enter puberty, and about 5% may even conceive spontaneously in younger years. But of the majority of Turner girls eventually experience complete ovarian failure.

This means that fertility preservation can’t be a wait-and-see issue, according to Kutluk Oktay, MD, PhD, a fertility specialist on the leading edge of this issue in the United States.

“We have to be proactive,” said Dr. Oktay, professor of obstetrics and gynecology at New York Medical College, Valhalla. “If we wait until girls are 12 or 13 to address this, a majority will have totally depleted their ovarian reserve by then. They will have no option other than an egg donor or adoption. We are suggesting that they should be screened as soon as they are diagnosed, and if they and their parents wish it, something should be done before it’s too late.”

Dr. Oktay is also the founder of fertilitypreservation.org, which specializes in advanced fertility treatments for cancer patients. He is one of a handful of physicians in the United States who advocate early oocyte harvesting in peripubertal girls and ovarian tissue harvesting in prepubertal girls with Turner syndrome. Last year, in conjunction with the Turner Syndrome Foundation, he and his colleagues published a set of guidelines for preserving fertility in these patients.

The paper recommends fertility assessment pathways for pre- and postpubertal girls. For both groups, Dr. Oktay employs serial assessments of ovarian reserve by monitoring several hormones, including follicle-stimulating hormone, luteinizing hormone, and antimüllerian hormone (AMH). Produced by primordial follicles, AMH declines as egg reserve declines over a lifetime, and is considered an accurate marker of ovarian reserve. When a girl experiences two consecutive AMH declines, egg depletion is probably accelerating. “This is the time to consider fertility preservation,” he said.

If a girl is peri- or postpubertal, the choice would probably be ovarian stimulation with the goal of retrieving mature oocytes. For prepubertal girls, the best choice is probably ovarian tissue cryopreservation. But because the egg reserve may already be spotty inside the ovary, he recommended freezing it en bloc, rather than preserving just cortical sections.

Because these techniques are only beginning to be used in young Turner patients, neither has been tested yet to see if it would result in a pregnancy. However, Dr. Oktay said, more than 80 babies have been born to women with other disorders who had ovaries frozen as adults. And European women with Turner syndrome have been successfully bearing children with donated oocytes for years.

“I don’t differentiate Europe from the U.S.,” he said. “We have no reason to believe Turner syndrome girls would be any different here than they are there.”

Pregnancy rates by egg donation in Turner syndrome patients are about half that typically seen in an otherwise healthy infertile woman, according to numerous sources; with a take-home baby rate of about 18%. There are numerous reasons for this. The miscarriage rate in Turner patients is about 44%. Women with Turner tend to have smaller uteri, with thinner endometrium, mostly because of the lack of estrogen.

But with careful management, those who do conceive can safely deliver a healthy baby, said Outi Hovatta, MD, a Finnish fertility specialist who has done extensive work in the area. “In Europe, we have been doing this quite liberally for years, and haven’t had a bad experience,” she said in an interview.

A 2013 review summarized both the success and the risks of these pregnancies. It examined obstetric and neonatal outcomes among 106 women with Turner syndrome who gave birth via egg donation from 1992 to 2011 in Sweden, Finland, and Denmark.

Most (70%) had a single embryo transferred, as virtually all guidelines recommend. Women with Turner are prone to cardiac and aortic defects that can worsen under the strain of pregnancy, or even present for the first time during gestation. Aortic dissection is a real threat; up to a third of patients with Turner experience it during adulthood, and it’s a major cause of death among them. In the Nordic series, 10 women (9%) had a known cardiac anomaly.

The multiple birth rate was 7%. More than a third (35%) developed a hypertensive disorder, including preeclampsia (20%). Four women had potentially life-threatening complications, including one with aortic dissection, one who developed mild regurgitation of the tricuspid and mitral valve, one with a mechanical heart valve who developed HELLP syndrome (hemolysis, elevated liver enzymes, low platelets), and one who underwent a postpartum hysterectomy because of severe hemorrhaging.

The infants, nevertheless, did well. The preterm birth rate was 8%, with 9% of the singleton infants having a low birth weight. About 4% had a major birth defect. Of the 131 born, three died (2.3%), including a set of extremely preterm twins.

Close follow-up and cross-specialty cooperation are what make these positive outcomes possible, said Dr. Hovatta, who is now a professor emeritus at the Karolinska Institute, Sweden.

“We do everything we can to exclude things that could cause bad outcomes.” That includes extremely rigorous cardiac testing before pregnancy and continuous monitoring during it. “If a woman has any sign of cardiac anomaly, she is advised not to become pregnant. If she shows any signs of aortic dilation, we follow her extremely carefully with experienced cardiologists.”

Like Dr. Oktay, Dr. Hovatta and her European colleagues make fertility preservation an early topic of conversation. Unlike in the United States, where many girls aren’t diagnosed with the disorder until they fail to enter puberty, almost all Turner girls in Europe are identified very early in childhood. They receive early growth hormone treatment, and there is frequent consultation with interdisciplinary specialists. Fertility is spoken of early and often.

Early oocyte retrieval is common, Dr. Hovatta said. “Yes, it’s possible to wait until puberty, but for so many girls, most of the eggs have disappeared by then, so we typically don’t wait. We start looking at that option around 11 years, which is the same time we think about cryopreserving ovarian tissue.”

However, she added, as in the United States, the outcomes of these procedures are still unknown. But the existing data in other populations, the ability to carefully shepherd women through a successful pregnancy, and the willingness of families to provide the option all support further exploring them. Dr. Hovatta was at the Cincinnati gathering last summer and said she did not agree with the conservative tone she heard. Dr. Oktay also does not agree.

“This evidence we have so far is good evidence,” he said. “Look, where we are right now with Turner girls is where we were 15 years ago with cancer patients. People thought, ‘They have cancer. They should just be worrying about surviving cancer, not about their fertility.’ Now fertility counseling is a very important part of cancer care. We have all these tools available to us for cancer patients who don’t want to lose their fertility. This accumulated experience that has already been applied in other medical conditions … why not use that for Turner syndrome? This is my point: With all the data out there about the potential benefits and the ways to manage the risks, we shouldn’t have to tell girls, ‘Well, you have to become menopausal, and maybe you can adopt someday.’ That doesn’t sit well with parents any more. We want these girls to thrive. Not just to survive, but to have as close to a normal quality of life as possible.”
 

msullivan@frontlinemedcom.com

ORLANDO – Fertility preservation techniques pioneered in young cancer patients may someday allow some women with Turner syndrome to give birth to their own children, without relying on donated eggs.

Spontaneous conception and live birth are exceedingly rare among women with the genetic disorder. Until very recently, adoption was the only practical way for most to grow a family. In the last decade, however, fertility specialists in Europe and the United States have had good success with in vitro fertilization using donated eggs. Now, those clinicians are aiming for a higher goal: babies born from a patient’s own eggs, cryopreserved either individually or within whole ovarian tissue.

These are not pipe dreams, according to experts interviewed for this story. Autologous oocyte freezing is well established in healthy women and is now coming of age in cancer patients, with recent reports of live births. Ovarian tissue freezing and reimplantation is a much newer technique, also pioneered in cancer patients. To date, more than 70 live births have occurred from ovarian cortical tissue conservation and later transplantation in adults. Last December brought the first report of a live birth to a childhood cancer survivor who had prepubertal ovarian tissue frozen before chemotherapy. And a 2015 report detailed the case of a girl with primary ovarian failure secondary to sickle cell anemia treatment. At 25, she gave birth to a healthy child conceived from ovarian tissue removed when she was 14 years old.

Not all clinicians so enthusiastically embrace this future, however. A new set of consensus guidelines for the management of girls and women with Turner syndrome is in the works and will recommend a more conservative clinical approach, according to Nelly Mauras, MD, chief of endocrinology, diabetes, and metabolism at the Nemours Children’s Health System in Jacksonville, Fla.

A group of academic and patient advocacy stakeholders is cooperatively honing the document based on a meeting last summer in Cincinnati. These groups include the European Society of Endocrinology, the Endocrine Society, the U.S. Pediatric Endocrine Society, the European Society for Pediatric Endocrinology, Cardiology, and Reproductive Endocrinology, as well as Turner syndrome patient advocacy groups.

Dr. Mauras said the guideline will be “less discouraging” than the existing one issued in 2012 by the American Society of Reproductive Medicine. In its 2012 guidelines, the society identified Turner syndrome as a relative contraindication to pregnancy and an absolute contraindication in those with documented cardiac anomalies. However, greater experience has since been accrued in reproductive techniques of oocyte donation in Turner, with better outcomes.

The upcoming guidelines, however, will still recommend strongly against ovarian stimulation for fertility preservation for girls younger than 12, Dr. Mauras said, and will not recommend ovarian tissue conservation. “We just do not have the safety data and pregnancy outcomes that we need to give strong recommendations for these treatments,” she said. “These are still considered experimental treatments for girls with Turner syndrome.”

Turner syndrome, caused by a deletion of one X chromosome, throws a unique curve into the game – very early ovarian failure. Those with a complete deletion (45,X) begin losing their primordial ovarian follicles even before birth. Most will never experience spontaneous puberty; even if they do, their egg reserve is virtually gone soon after. Ovarian reserve may not be completely lost in girls with mosaicism, however, who have the X deletion in only a portion of their cells (46,XX/45,X). Some will enter puberty, and about 5% may even conceive spontaneously in younger years. But of the majority of Turner girls eventually experience complete ovarian failure.

This means that fertility preservation can’t be a wait-and-see issue, according to Kutluk Oktay, MD, PhD, a fertility specialist on the leading edge of this issue in the United States.

“We have to be proactive,” said Dr. Oktay, professor of obstetrics and gynecology at New York Medical College, Valhalla. “If we wait until girls are 12 or 13 to address this, a majority will have totally depleted their ovarian reserve by then. They will have no option other than an egg donor or adoption. We are suggesting that they should be screened as soon as they are diagnosed, and if they and their parents wish it, something should be done before it’s too late.”

Dr. Oktay is also the founder of fertilitypreservation.org, which specializes in advanced fertility treatments for cancer patients. He is one of a handful of physicians in the United States who advocate early oocyte harvesting in peripubertal girls and ovarian tissue harvesting in prepubertal girls with Turner syndrome. Last year, in conjunction with the Turner Syndrome Foundation, he and his colleagues published a set of guidelines for preserving fertility in these patients.

The paper recommends fertility assessment pathways for pre- and postpubertal girls. For both groups, Dr. Oktay employs serial assessments of ovarian reserve by monitoring several hormones, including follicle-stimulating hormone, luteinizing hormone, and antimüllerian hormone (AMH). Produced by primordial follicles, AMH declines as egg reserve declines over a lifetime, and is considered an accurate marker of ovarian reserve. When a girl experiences two consecutive AMH declines, egg depletion is probably accelerating. “This is the time to consider fertility preservation,” he said.

If a girl is peri- or postpubertal, the choice would probably be ovarian stimulation with the goal of retrieving mature oocytes. For prepubertal girls, the best choice is probably ovarian tissue cryopreservation. But because the egg reserve may already be spotty inside the ovary, he recommended freezing it en bloc, rather than preserving just cortical sections.

Because these techniques are only beginning to be used in young Turner patients, neither has been tested yet to see if it would result in a pregnancy. However, Dr. Oktay said, more than 80 babies have been born to women with other disorders who had ovaries frozen as adults. And European women with Turner syndrome have been successfully bearing children with donated oocytes for years.

“I don’t differentiate Europe from the U.S.,” he said. “We have no reason to believe Turner syndrome girls would be any different here than they are there.”

Pregnancy rates by egg donation in Turner syndrome patients are about half that typically seen in an otherwise healthy infertile woman, according to numerous sources; with a take-home baby rate of about 18%. There are numerous reasons for this. The miscarriage rate in Turner patients is about 44%. Women with Turner tend to have smaller uteri, with thinner endometrium, mostly because of the lack of estrogen.

But with careful management, those who do conceive can safely deliver a healthy baby, said Outi Hovatta, MD, a Finnish fertility specialist who has done extensive work in the area. “In Europe, we have been doing this quite liberally for years, and haven’t had a bad experience,” she said in an interview.

A 2013 review summarized both the success and the risks of these pregnancies. It examined obstetric and neonatal outcomes among 106 women with Turner syndrome who gave birth via egg donation from 1992 to 2011 in Sweden, Finland, and Denmark.

Most (70%) had a single embryo transferred, as virtually all guidelines recommend. Women with Turner are prone to cardiac and aortic defects that can worsen under the strain of pregnancy, or even present for the first time during gestation. Aortic dissection is a real threat; up to a third of patients with Turner experience it during adulthood, and it’s a major cause of death among them. In the Nordic series, 10 women (9%) had a known cardiac anomaly.

The multiple birth rate was 7%. More than a third (35%) developed a hypertensive disorder, including preeclampsia (20%). Four women had potentially life-threatening complications, including one with aortic dissection, one who developed mild regurgitation of the tricuspid and mitral valve, one with a mechanical heart valve who developed HELLP syndrome (hemolysis, elevated liver enzymes, low platelets), and one who underwent a postpartum hysterectomy because of severe hemorrhaging.

The infants, nevertheless, did well. The preterm birth rate was 8%, with 9% of the singleton infants having a low birth weight. About 4% had a major birth defect. Of the 131 born, three died (2.3%), including a set of extremely preterm twins.

Close follow-up and cross-specialty cooperation are what make these positive outcomes possible, said Dr. Hovatta, who is now a professor emeritus at the Karolinska Institute, Sweden.

“We do everything we can to exclude things that could cause bad outcomes.” That includes extremely rigorous cardiac testing before pregnancy and continuous monitoring during it. “If a woman has any sign of cardiac anomaly, she is advised not to become pregnant. If she shows any signs of aortic dilation, we follow her extremely carefully with experienced cardiologists.”

Like Dr. Oktay, Dr. Hovatta and her European colleagues make fertility preservation an early topic of conversation. Unlike in the United States, where many girls aren’t diagnosed with the disorder until they fail to enter puberty, almost all Turner girls in Europe are identified very early in childhood. They receive early growth hormone treatment, and there is frequent consultation with interdisciplinary specialists. Fertility is spoken of early and often.

Early oocyte retrieval is common, Dr. Hovatta said. “Yes, it’s possible to wait until puberty, but for so many girls, most of the eggs have disappeared by then, so we typically don’t wait. We start looking at that option around 11 years, which is the same time we think about cryopreserving ovarian tissue.”

However, she added, as in the United States, the outcomes of these procedures are still unknown. But the existing data in other populations, the ability to carefully shepherd women through a successful pregnancy, and the willingness of families to provide the option all support further exploring them. Dr. Hovatta was at the Cincinnati gathering last summer and said she did not agree with the conservative tone she heard. Dr. Oktay also does not agree.

“This evidence we have so far is good evidence,” he said. “Look, where we are right now with Turner girls is where we were 15 years ago with cancer patients. People thought, ‘They have cancer. They should just be worrying about surviving cancer, not about their fertility.’ Now fertility counseling is a very important part of cancer care. We have all these tools available to us for cancer patients who don’t want to lose their fertility. This accumulated experience that has already been applied in other medical conditions … why not use that for Turner syndrome? This is my point: With all the data out there about the potential benefits and the ways to manage the risks, we shouldn’t have to tell girls, ‘Well, you have to become menopausal, and maybe you can adopt someday.’ That doesn’t sit well with parents any more. We want these girls to thrive. Not just to survive, but to have as close to a normal quality of life as possible.”
 

msullivan@frontlinemedcom.com

BOSTON – Adjunctive treatment with cannabidiol significantly reduced convulsive seizure frequency in Dravet syndrome patients in a randomized, double-blind, placebo-controlled trial.

Over a 14-week treatment period, including 2 weeks of titration and 12 weeks of maintenance, convulsive seizure frequency in 61 treated children and adolescents decreased from a median of 12.4 to 5.9 per month (median reduction of 39%), compared with a decrease from a median of 14.9 to 14.1 per month (median reduction of 13%) in 59 patients who received placebo, J. Helen Cross, MD, reported at the annual meeting of the American Academy of Neurology.

The proportion of patients with at least a 50% reduction in convulsive seizures was 42.6% with cannabidiol vs. 27.1% with placebo (odds ratio, 2.0), but this difference did not reach statistical significance, said Dr. Cross of the University College London Great Ormond Street Institute of Child Health and the Great Ormond Street Hospital for Children NHS Trust, London.

In a video interview, Dr. Cross discussed the findings and the importance of improving seizure control in patients with Dravet syndrome, a rare infantile-onset developmental and epileptic encephalopathy with very poor prognosis for long-term seizure control and neurodevelopmental outcomes.

Participants in the study (GWPCARE1) had a mean age of 10 years, but nearly a third were younger than 6 years. All had Dravet syndrome and drug-resistant seizures; the median number of antiepilepsy drugs previously tried was four, and the median number being used was three. Those randomized to the treatment group received cannabidiol oral solution up to 20 mg/kg per day.

Adverse events were common, occurring in 93.4% and 74.6% of treatment group and placebo group patients, respectively. But adverse events reported in the treatment group were mild or moderate in 84% of patients, and treatment was generally well tolerated.

“These are very complex patients with a high seizure burden... and therefore, to have another medication that looks as if it can be of benefit is really very exciting for this population,” Dr. Cross said, noting that cannabidiol was also shown in other studies presented at the AAN meeting (GWPCARE3 and GWPCARE4) to reduce seizure frequency in patients with Lennox-Gastaut syndrome.

GW Research sponsored the study. Dr. Cross is a member of the advisory boards for Eisai, GW Pharmaceuticals, Shire, and Zogenix.

sworcester@frontlinemedcom.com

BOSTON – Adjunctive treatment with cannabidiol significantly reduced convulsive seizure frequency in Dravet syndrome patients in a randomized, double-blind, placebo-controlled trial.

Over a 14-week treatment period, including 2 weeks of titration and 12 weeks of maintenance, convulsive seizure frequency in 61 treated children and adolescents decreased from a median of 12.4 to 5.9 per month (median reduction of 39%), compared with a decrease from a median of 14.9 to 14.1 per month (median reduction of 13%) in 59 patients who received placebo, J. Helen Cross, MD, reported at the annual meeting of the American Academy of Neurology.

The proportion of patients with at least a 50% reduction in convulsive seizures was 42.6% with cannabidiol vs. 27.1% with placebo (odds ratio, 2.0), but this difference did not reach statistical significance, said Dr. Cross of the University College London Great Ormond Street Institute of Child Health and the Great Ormond Street Hospital for Children NHS Trust, London.

In a video interview, Dr. Cross discussed the findings and the importance of improving seizure control in patients with Dravet syndrome, a rare infantile-onset developmental and epileptic encephalopathy with very poor prognosis for long-term seizure control and neurodevelopmental outcomes.

Participants in the study (GWPCARE1) had a mean age of 10 years, but nearly a third were younger than 6 years. All had Dravet syndrome and drug-resistant seizures; the median number of antiepilepsy drugs previously tried was four, and the median number being used was three. Those randomized to the treatment group received cannabidiol oral solution up to 20 mg/kg per day.

Adverse events were common, occurring in 93.4% and 74.6% of treatment group and placebo group patients, respectively. But adverse events reported in the treatment group were mild or moderate in 84% of patients, and treatment was generally well tolerated.

“These are very complex patients with a high seizure burden... and therefore, to have another medication that looks as if it can be of benefit is really very exciting for this population,” Dr. Cross said, noting that cannabidiol was also shown in other studies presented at the AAN meeting (GWPCARE3 and GWPCARE4) to reduce seizure frequency in patients with Lennox-Gastaut syndrome.

GW Research sponsored the study. Dr. Cross is a member of the advisory boards for Eisai, GW Pharmaceuticals, Shire, and Zogenix.

sworcester@frontlinemedcom.com

BOSTON – Adjunctive treatment with cannabidiol significantly reduced convulsive seizure frequency in Dravet syndrome patients in a randomized, double-blind, placebo-controlled trial.

Over a 14-week treatment period, including 2 weeks of titration and 12 weeks of maintenance, convulsive seizure frequency in 61 treated children and adolescents decreased from a median of 12.4 to 5.9 per month (median reduction of 39%), compared with a decrease from a median of 14.9 to 14.1 per month (median reduction of 13%) in 59 patients who received placebo, J. Helen Cross, MD, reported at the annual meeting of the American Academy of Neurology.

The proportion of patients with at least a 50% reduction in convulsive seizures was 42.6% with cannabidiol vs. 27.1% with placebo (odds ratio, 2.0), but this difference did not reach statistical significance, said Dr. Cross of the University College London Great Ormond Street Institute of Child Health and the Great Ormond Street Hospital for Children NHS Trust, London.

In a video interview, Dr. Cross discussed the findings and the importance of improving seizure control in patients with Dravet syndrome, a rare infantile-onset developmental and epileptic encephalopathy with very poor prognosis for long-term seizure control and neurodevelopmental outcomes.

Participants in the study (GWPCARE1) had a mean age of 10 years, but nearly a third were younger than 6 years. All had Dravet syndrome and drug-resistant seizures; the median number of antiepilepsy drugs previously tried was four, and the median number being used was three. Those randomized to the treatment group received cannabidiol oral solution up to 20 mg/kg per day.

Adverse events were common, occurring in 93.4% and 74.6% of treatment group and placebo group patients, respectively. But adverse events reported in the treatment group were mild or moderate in 84% of patients, and treatment was generally well tolerated.

“These are very complex patients with a high seizure burden... and therefore, to have another medication that looks as if it can be of benefit is really very exciting for this population,” Dr. Cross said, noting that cannabidiol was also shown in other studies presented at the AAN meeting (GWPCARE3 and GWPCARE4) to reduce seizure frequency in patients with Lennox-Gastaut syndrome.

GW Research sponsored the study. Dr. Cross is a member of the advisory boards for Eisai, GW Pharmaceuticals, Shire, and Zogenix.

sworcester@frontlinemedcom.com

BOSTON – Children with multiple sclerosis (MS) and related conditions are as much as 10 times more likely than the general population to need to be hospitalized for various psychiatric conditions, a study showed.

“The true prevalence of morbidity is almost certainly higher than suggested by our data,” said study lead author Julia Pakpoor, BM BCh, who presented data from her research at the annual meeting of the American Academy of Neurology.

While several studies have examined links between MS and mental illness in adults, there’s been little research into the topic in children. The number of children with the disease is far from tiny, however. According to the National MS Society, an estimated 8,000-10,000 children have the condition in the United States.

SIphotography/Thinkstock

cnnews@frontlinemedcom.com

BOSTON – Children with multiple sclerosis (MS) and related conditions are as much as 10 times more likely than the general population to need to be hospitalized for various psychiatric conditions, a study showed.

“The true prevalence of morbidity is almost certainly higher than suggested by our data,” said study lead author Julia Pakpoor, BM BCh, who presented data from her research at the annual meeting of the American Academy of Neurology.

While several studies have examined links between MS and mental illness in adults, there’s been little research into the topic in children. The number of children with the disease is far from tiny, however. According to the National MS Society, an estimated 8,000-10,000 children have the condition in the United States.

SIphotography/Thinkstock

cnnews@frontlinemedcom.com

BOSTON – Children with multiple sclerosis (MS) and related conditions are as much as 10 times more likely than the general population to need to be hospitalized for various psychiatric conditions, a study showed.

“The true prevalence of morbidity is almost certainly higher than suggested by our data,” said study lead author Julia Pakpoor, BM BCh, who presented data from her research at the annual meeting of the American Academy of Neurology.

While several studies have examined links between MS and mental illness in adults, there’s been little research into the topic in children. The number of children with the disease is far from tiny, however. According to the National MS Society, an estimated 8,000-10,000 children have the condition in the United States.

SIphotography/Thinkstock

cnnews@frontlinemedcom.com

How many times do you come out of the exam room after seeing a patient in follow-up and heave a sigh because the parents did not give their child the medicine as you prescribed it?

Without adherence to the medication plan, a lot of suboptimal outcomes can and do occur. A urinary tract infection may come back partially treated, requiring a more extensive work-up. A strep infection may spread to family members. Inflammatory bowel disease may require bowel resection. Asthma may simmer with long-term inflammation and pulmonary compromise as well as concurrent activity limitations. Often children with asthma are given less than 50% of prescribed controller medicines. In one pediatric study, medication adherence was not even asked about in 66% of cases. In adults, 20%-30% of prescriptions are never filled.

As physicians, we are carefully schooled in making complex diagnoses, sorting out and prioritizing the laboratory work-up, and memorizing the latest and most effective treatment regimens. What is rarely taught, however, is how to conduct the conversation needed to optimize subsequent adherence to the medication plan.

Problem-solving counseling is an evidence-based method to improve medication adherence. This is a semistructured form of cognitive-behavioral intervention designed to engage the responsible person (parent or child) in shared decision making about whether and how to take medication, and which one to take. After all, for good or for bad, it is really their choice!

1. Problem definition. This step involves developing a clear and specific definition of the problem. Educating families about a medical condition has to start with asking what they already know. This often includes sagas of bad outcomes in relatives. Ask: Who do you know with asthma? How was it for them? The family needs to know symptoms, simple pathophysiology (such as inflammation you can’t see or feel), course, and prognosis. They also need to know where their child’s condition falls on the continuum. And they need to understand the essential prevention aspect of controllers in what appears to be an asymptomatic child. Failure to communicate this is a common reason for nonadherence in asthma.

2. Generation of alternatives. This involves brainstorming to identify multiple and creative solutions. This step will reveal past experiences as well as things the family learned on the Internet that may be true and relevant, or true but irrelevant, or false. Ask: What have you heard about treatments for asthma? What do you think would be best for your child? Generic handouts with a sampling of medicines, advantages and disadvantages, side effects, and costs of the main choices have been shown to be helpful guides that enhance adherence through empowering the family in their choice and reassuring family members that you have been thorough. It can be a balancing act to describe possible side effects without scaring the family into shutting down and being unable to make any choice at all. However, failure to discuss common effects they may notice – such as a racing heart from rescue medications – but that you think of as trivial, may also lead to nonadherence. A way to communicate about perceived side effects and manage them has to be part of an effective plan. Planning a phone or email check-in can make a big difference.

3. Decision making. This step involves evaluating all the solutions to identify the most effective and feasible option. Once the family understands the problem and the alternatives, it is crucial for you, as the physician, to not only ask their preference but be ready to suggest what you think would be best. While not wanting to be patronized, families want your opinion. I like to have family members close their eyes and visualize carrying out the selected routine. This is a good hypnotic technique for future remembering, but you also may discover important facts by this simple exercise, such as that the child gets up alone for school, making morning dosing unreliable. Shared decision making is not a way to abdicate your expert opinion, just to incorporate family preferences and factors.

4. Solution implementation. This step involves carrying out the plan. There is no substitute for a real life trial! There may be surprising issues: Autistic children may be afraid of a nebulizer machine. Sensitive children may refuse the flavor of some inhalers.

5. Solution verification. Evaluate the effectiveness of the solution and modify the plan as necessary. Follow-up contact is crucial, especially at the start of a new chronic medication plan. When families know that the plan can be changed if things do not go well or they change their minds, they will be less fearful of giving it a try and more honest about barriers they perceive or encounter rather than simply showing up at the next visit with the child’s condition out of control.

Although using problem-solving counseling may sound complicated, it is intended to be focused and brief, and has been shown to be feasibly done in the clinic by primary care providers, without lengthening the visit. CHADIS even has teleprompter text specific to parent-reported barriers to help you.

Even when family members understand and agrees to a medication plan during the visit, there are a variety of reasons they may not adhere to it. They may forget to give the medicine, be unable to afford it once prescribed, experience unpleasant side effects, encounter resistance from the child, or get unanticipated push back from family members. All of these issues can be addressed if you know that they happen. You just have to ask! Recommending smartphone reminders or reminder apps (such as Medisafe), using GoodRx to find cheaper sources, suggesting candy as a chaser, recommending behavior strategies for feisty kids, and providing written materials (or a phone call) for reluctant relatives are strategies you can prepare in advance to have in your quiver and are well worth your time.

If it weren’t enough to address adherence to optimize outcomes, asthma management and control will likely be a Clinical Quality Measure, determining how we will be paid starting this year. Now you have a tool to do it!
 

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to Frontline Medical News.

How many times do you come out of the exam room after seeing a patient in follow-up and heave a sigh because the parents did not give their child the medicine as you prescribed it?

Without adherence to the medication plan, a lot of suboptimal outcomes can and do occur. A urinary tract infection may come back partially treated, requiring a more extensive work-up. A strep infection may spread to family members. Inflammatory bowel disease may require bowel resection. Asthma may simmer with long-term inflammation and pulmonary compromise as well as concurrent activity limitations. Often children with asthma are given less than 50% of prescribed controller medicines. In one pediatric study, medication adherence was not even asked about in 66% of cases. In adults, 20%-30% of prescriptions are never filled.

As physicians, we are carefully schooled in making complex diagnoses, sorting out and prioritizing the laboratory work-up, and memorizing the latest and most effective treatment regimens. What is rarely taught, however, is how to conduct the conversation needed to optimize subsequent adherence to the medication plan.

Problem-solving counseling is an evidence-based method to improve medication adherence. This is a semistructured form of cognitive-behavioral intervention designed to engage the responsible person (parent or child) in shared decision making about whether and how to take medication, and which one to take. After all, for good or for bad, it is really their choice!

1. Problem definition. This step involves developing a clear and specific definition of the problem. Educating families about a medical condition has to start with asking what they already know. This often includes sagas of bad outcomes in relatives. Ask: Who do you know with asthma? How was it for them? The family needs to know symptoms, simple pathophysiology (such as inflammation you can’t see or feel), course, and prognosis. They also need to know where their child’s condition falls on the continuum. And they need to understand the essential prevention aspect of controllers in what appears to be an asymptomatic child. Failure to communicate this is a common reason for nonadherence in asthma.

2. Generation of alternatives. This involves brainstorming to identify multiple and creative solutions. This step will reveal past experiences as well as things the family learned on the Internet that may be true and relevant, or true but irrelevant, or false. Ask: What have you heard about treatments for asthma? What do you think would be best for your child? Generic handouts with a sampling of medicines, advantages and disadvantages, side effects, and costs of the main choices have been shown to be helpful guides that enhance adherence through empowering the family in their choice and reassuring family members that you have been thorough. It can be a balancing act to describe possible side effects without scaring the family into shutting down and being unable to make any choice at all. However, failure to discuss common effects they may notice – such as a racing heart from rescue medications – but that you think of as trivial, may also lead to nonadherence. A way to communicate about perceived side effects and manage them has to be part of an effective plan. Planning a phone or email check-in can make a big difference.

3. Decision making. This step involves evaluating all the solutions to identify the most effective and feasible option. Once the family understands the problem and the alternatives, it is crucial for you, as the physician, to not only ask their preference but be ready to suggest what you think would be best. While not wanting to be patronized, families want your opinion. I like to have family members close their eyes and visualize carrying out the selected routine. This is a good hypnotic technique for future remembering, but you also may discover important facts by this simple exercise, such as that the child gets up alone for school, making morning dosing unreliable. Shared decision making is not a way to abdicate your expert opinion, just to incorporate family preferences and factors.

4. Solution implementation. This step involves carrying out the plan. There is no substitute for a real life trial! There may be surprising issues: Autistic children may be afraid of a nebulizer machine. Sensitive children may refuse the flavor of some inhalers.

5. Solution verification. Evaluate the effectiveness of the solution and modify the plan as necessary. Follow-up contact is crucial, especially at the start of a new chronic medication plan. When families know that the plan can be changed if things do not go well or they change their minds, they will be less fearful of giving it a try and more honest about barriers they perceive or encounter rather than simply showing up at the next visit with the child’s condition out of control.

Although using problem-solving counseling may sound complicated, it is intended to be focused and brief, and has been shown to be feasibly done in the clinic by primary care providers, without lengthening the visit. CHADIS even has teleprompter text specific to parent-reported barriers to help you.

Even when family members understand and agrees to a medication plan during the visit, there are a variety of reasons they may not adhere to it. They may forget to give the medicine, be unable to afford it once prescribed, experience unpleasant side effects, encounter resistance from the child, or get unanticipated push back from family members. All of these issues can be addressed if you know that they happen. You just have to ask! Recommending smartphone reminders or reminder apps (such as Medisafe), using GoodRx to find cheaper sources, suggesting candy as a chaser, recommending behavior strategies for feisty kids, and providing written materials (or a phone call) for reluctant relatives are strategies you can prepare in advance to have in your quiver and are well worth your time.

If it weren’t enough to address adherence to optimize outcomes, asthma management and control will likely be a Clinical Quality Measure, determining how we will be paid starting this year. Now you have a tool to do it!
 

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to Frontline Medical News.

How many times do you come out of the exam room after seeing a patient in follow-up and heave a sigh because the parents did not give their child the medicine as you prescribed it?

Without adherence to the medication plan, a lot of suboptimal outcomes can and do occur. A urinary tract infection may come back partially treated, requiring a more extensive work-up. A strep infection may spread to family members. Inflammatory bowel disease may require bowel resection. Asthma may simmer with long-term inflammation and pulmonary compromise as well as concurrent activity limitations. Often children with asthma are given less than 50% of prescribed controller medicines. In one pediatric study, medication adherence was not even asked about in 66% of cases. In adults, 20%-30% of prescriptions are never filled.

As physicians, we are carefully schooled in making complex diagnoses, sorting out and prioritizing the laboratory work-up, and memorizing the latest and most effective treatment regimens. What is rarely taught, however, is how to conduct the conversation needed to optimize subsequent adherence to the medication plan.

Problem-solving counseling is an evidence-based method to improve medication adherence. This is a semistructured form of cognitive-behavioral intervention designed to engage the responsible person (parent or child) in shared decision making about whether and how to take medication, and which one to take. After all, for good or for bad, it is really their choice!

1. Problem definition. This step involves developing a clear and specific definition of the problem. Educating families about a medical condition has to start with asking what they already know. This often includes sagas of bad outcomes in relatives. Ask: Who do you know with asthma? How was it for them? The family needs to know symptoms, simple pathophysiology (such as inflammation you can’t see or feel), course, and prognosis. They also need to know where their child’s condition falls on the continuum. And they need to understand the essential prevention aspect of controllers in what appears to be an asymptomatic child. Failure to communicate this is a common reason for nonadherence in asthma.

2. Generation of alternatives. This involves brainstorming to identify multiple and creative solutions. This step will reveal past experiences as well as things the family learned on the Internet that may be true and relevant, or true but irrelevant, or false. Ask: What have you heard about treatments for asthma? What do you think would be best for your child? Generic handouts with a sampling of medicines, advantages and disadvantages, side effects, and costs of the main choices have been shown to be helpful guides that enhance adherence through empowering the family in their choice and reassuring family members that you have been thorough. It can be a balancing act to describe possible side effects without scaring the family into shutting down and being unable to make any choice at all. However, failure to discuss common effects they may notice – such as a racing heart from rescue medications – but that you think of as trivial, may also lead to nonadherence. A way to communicate about perceived side effects and manage them has to be part of an effective plan. Planning a phone or email check-in can make a big difference.

3. Decision making. This step involves evaluating all the solutions to identify the most effective and feasible option. Once the family understands the problem and the alternatives, it is crucial for you, as the physician, to not only ask their preference but be ready to suggest what you think would be best. While not wanting to be patronized, families want your opinion. I like to have family members close their eyes and visualize carrying out the selected routine. This is a good hypnotic technique for future remembering, but you also may discover important facts by this simple exercise, such as that the child gets up alone for school, making morning dosing unreliable. Shared decision making is not a way to abdicate your expert opinion, just to incorporate family preferences and factors.

4. Solution implementation. This step involves carrying out the plan. There is no substitute for a real life trial! There may be surprising issues: Autistic children may be afraid of a nebulizer machine. Sensitive children may refuse the flavor of some inhalers.

5. Solution verification. Evaluate the effectiveness of the solution and modify the plan as necessary. Follow-up contact is crucial, especially at the start of a new chronic medication plan. When families know that the plan can be changed if things do not go well or they change their minds, they will be less fearful of giving it a try and more honest about barriers they perceive or encounter rather than simply showing up at the next visit with the child’s condition out of control.

Although using problem-solving counseling may sound complicated, it is intended to be focused and brief, and has been shown to be feasibly done in the clinic by primary care providers, without lengthening the visit. CHADIS even has teleprompter text specific to parent-reported barriers to help you.

Even when family members understand and agrees to a medication plan during the visit, there are a variety of reasons they may not adhere to it. They may forget to give the medicine, be unable to afford it once prescribed, experience unpleasant side effects, encounter resistance from the child, or get unanticipated push back from family members. All of these issues can be addressed if you know that they happen. You just have to ask! Recommending smartphone reminders or reminder apps (such as Medisafe), using GoodRx to find cheaper sources, suggesting candy as a chaser, recommending behavior strategies for feisty kids, and providing written materials (or a phone call) for reluctant relatives are strategies you can prepare in advance to have in your quiver and are well worth your time.

If it weren’t enough to address adherence to optimize outcomes, asthma management and control will likely be a Clinical Quality Measure, determining how we will be paid starting this year. Now you have a tool to do it!
 

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to Frontline Medical News.

There are several things you should know about necessary vaccinations, and sometimes potential supply problems, if your families will be traveling internationally.

Yellow fever and vaccine supply

Yellow fever is caused by a Flavivirus transmitted by the bite of an infected mosquito. It occurs in sub-Saharan Africa and in tropical areas in South America. Multiple factors determine a traveler’s risk for acquisition, including destination, season, duration of potential exposure, activities, and the local transmission rate. The majority of those infected are asymptomatic or have minimal clinical symptoms. The incubation period is 3-6 days, which is then followed by an influenza-like illness. Approximately 15% of infected individuals develop more serious symptoms including jaundice, hemorrhagic symptoms, shock, and, ultimately, multiorgan system failure with a fatality rate of 90%. There is no specific treatment.

Zika, dengue, and chikungunya

These three Flaviviruses all are transmitted by mosquitoes and can present with fever, rash, and headache. Their distribution is overlapping in several parts of the world. Most infected people are asymptomatic. If symptoms develop, they usually are self-limited. Disease prevention is by mosquito avoidance. There are no preventive vaccines.

Zika virus is the only one associated with a congenital syndrome. It is characterized by brain abnormalities with or without microcephaly, neural tube defects, and ocular abnormalities.

Guidelines for the evaluation and management of Zika virus–exposed infants were initially published in January, 2016, with the most recent update published in August 2016 (MMWR Morb Mortal Wkly Rep. 2016 Aug 26;65[33]:870-8).

Preliminary data from the U.S. Zika pregnancy registry of 442 completed pregnancies between Jan. 15 to Sept. 22, 2016, identified birth defects in 26 fetuses/ infants (6%). There were 21 infants with birth defects among 395 live births and 5 fetuses with birth defects among 47 pregnancy losses. Birth defects were reported for 16 of 271 (6%) asymptomatic and 10 of 167 (6%) symptomatic women. There were no birth defects in infants when exposure occurred after the first trimester. Of the 26 affected infants, 4 had microcephaly and no neuroimaging and 3 (12%) had no fetal or infant testing. Approximately 41% (82/442) of infants did not have Zika virus testing (JAMA. 2017 Jan 3;317[1]:59-68).

It is unclear why testing was not performed. One concern is that the pediatrician may not have been aware of the maternal Zika virus exposure or test results. It may behoove us to begin asking questions about parental international travel to provide optimal management for our patients. We also should be familiar with the current guidelines for evaluating any potentially exposed infants, which include postnatal neuroimaging, Zika virus testing, a comprehensive newborn examination including neurologic exam, and a standard newborn hearing screen prior to hospital discharge.

Regardless of maternal Zika virus test results, infants with any clinical findings suggestive of congenital Zika virus syndrome and possible maternal exposure based on epidemiologic link also should be tested. Zika virus travel alerts and the most up to date information can be found on the Centers for Disease Control and Prevention website (www. cdc.gov/Zika).

CDC/Molly Kurnit, M.P.H.

Measles

Although endemic measles was eliminated in the United States in 2000, it is still common in many countries in Europe, Africa, and the Pacific. Most cases in the United States occur in unvaccinated individuals, with 78 cases reported in 2016. As of March 25, 2017, 28 cases have been reported. At least 10 countries – including Belgium, France, Italy, Germany, Portugal, and Thailand – have reported outbreaks of measles since April 2017. As reminder, all children aged 6-11 months should receive one dose of MMR and those 12 months or older should receive two doses of MMR at least 28 days apart if international travel is planned. Adults born after 1956 also should have received two doses of MMR prior to international travel.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She reported having no relevant financial disclosures.

There are several things you should know about necessary vaccinations, and sometimes potential supply problems, if your families will be traveling internationally.

Yellow fever and vaccine supply

Yellow fever is caused by a Flavivirus transmitted by the bite of an infected mosquito. It occurs in sub-Saharan Africa and in tropical areas in South America. Multiple factors determine a traveler’s risk for acquisition, including destination, season, duration of potential exposure, activities, and the local transmission rate. The majority of those infected are asymptomatic or have minimal clinical symptoms. The incubation period is 3-6 days, which is then followed by an influenza-like illness. Approximately 15% of infected individuals develop more serious symptoms including jaundice, hemorrhagic symptoms, shock, and, ultimately, multiorgan system failure with a fatality rate of 90%. There is no specific treatment.

Zika, dengue, and chikungunya

These three Flaviviruses all are transmitted by mosquitoes and can present with fever, rash, and headache. Their distribution is overlapping in several parts of the world. Most infected people are asymptomatic. If symptoms develop, they usually are self-limited. Disease prevention is by mosquito avoidance. There are no preventive vaccines.

Zika virus is the only one associated with a congenital syndrome. It is characterized by brain abnormalities with or without microcephaly, neural tube defects, and ocular abnormalities.

Guidelines for the evaluation and management of Zika virus–exposed infants were initially published in January, 2016, with the most recent update published in August 2016 (MMWR Morb Mortal Wkly Rep. 2016 Aug 26;65[33]:870-8).

Preliminary data from the U.S. Zika pregnancy registry of 442 completed pregnancies between Jan. 15 to Sept. 22, 2016, identified birth defects in 26 fetuses/ infants (6%). There were 21 infants with birth defects among 395 live births and 5 fetuses with birth defects among 47 pregnancy losses. Birth defects were reported for 16 of 271 (6%) asymptomatic and 10 of 167 (6%) symptomatic women. There were no birth defects in infants when exposure occurred after the first trimester. Of the 26 affected infants, 4 had microcephaly and no neuroimaging and 3 (12%) had no fetal or infant testing. Approximately 41% (82/442) of infants did not have Zika virus testing (JAMA. 2017 Jan 3;317[1]:59-68).

It is unclear why testing was not performed. One concern is that the pediatrician may not have been aware of the maternal Zika virus exposure or test results. It may behoove us to begin asking questions about parental international travel to provide optimal management for our patients. We also should be familiar with the current guidelines for evaluating any potentially exposed infants, which include postnatal neuroimaging, Zika virus testing, a comprehensive newborn examination including neurologic exam, and a standard newborn hearing screen prior to hospital discharge.

Regardless of maternal Zika virus test results, infants with any clinical findings suggestive of congenital Zika virus syndrome and possible maternal exposure based on epidemiologic link also should be tested. Zika virus travel alerts and the most up to date information can be found on the Centers for Disease Control and Prevention website (www. cdc.gov/Zika).

CDC/Molly Kurnit, M.P.H.

Measles

Although endemic measles was eliminated in the United States in 2000, it is still common in many countries in Europe, Africa, and the Pacific. Most cases in the United States occur in unvaccinated individuals, with 78 cases reported in 2016. As of March 25, 2017, 28 cases have been reported. At least 10 countries – including Belgium, France, Italy, Germany, Portugal, and Thailand – have reported outbreaks of measles since April 2017. As reminder, all children aged 6-11 months should receive one dose of MMR and those 12 months or older should receive two doses of MMR at least 28 days apart if international travel is planned. Adults born after 1956 also should have received two doses of MMR prior to international travel.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She reported having no relevant financial disclosures.

There are several things you should know about necessary vaccinations, and sometimes potential supply problems, if your families will be traveling internationally.

Yellow fever and vaccine supply

Yellow fever is caused by a Flavivirus transmitted by the bite of an infected mosquito. It occurs in sub-Saharan Africa and in tropical areas in South America. Multiple factors determine a traveler’s risk for acquisition, including destination, season, duration of potential exposure, activities, and the local transmission rate. The majority of those infected are asymptomatic or have minimal clinical symptoms. The incubation period is 3-6 days, which is then followed by an influenza-like illness. Approximately 15% of infected individuals develop more serious symptoms including jaundice, hemorrhagic symptoms, shock, and, ultimately, multiorgan system failure with a fatality rate of 90%. There is no specific treatment.

Zika, dengue, and chikungunya

These three Flaviviruses all are transmitted by mosquitoes and can present with fever, rash, and headache. Their distribution is overlapping in several parts of the world. Most infected people are asymptomatic. If symptoms develop, they usually are self-limited. Disease prevention is by mosquito avoidance. There are no preventive vaccines.

Zika virus is the only one associated with a congenital syndrome. It is characterized by brain abnormalities with or without microcephaly, neural tube defects, and ocular abnormalities.

Guidelines for the evaluation and management of Zika virus–exposed infants were initially published in January, 2016, with the most recent update published in August 2016 (MMWR Morb Mortal Wkly Rep. 2016 Aug 26;65[33]:870-8).

Preliminary data from the U.S. Zika pregnancy registry of 442 completed pregnancies between Jan. 15 to Sept. 22, 2016, identified birth defects in 26 fetuses/ infants (6%). There were 21 infants with birth defects among 395 live births and 5 fetuses with birth defects among 47 pregnancy losses. Birth defects were reported for 16 of 271 (6%) asymptomatic and 10 of 167 (6%) symptomatic women. There were no birth defects in infants when exposure occurred after the first trimester. Of the 26 affected infants, 4 had microcephaly and no neuroimaging and 3 (12%) had no fetal or infant testing. Approximately 41% (82/442) of infants did not have Zika virus testing (JAMA. 2017 Jan 3;317[1]:59-68).

It is unclear why testing was not performed. One concern is that the pediatrician may not have been aware of the maternal Zika virus exposure or test results. It may behoove us to begin asking questions about parental international travel to provide optimal management for our patients. We also should be familiar with the current guidelines for evaluating any potentially exposed infants, which include postnatal neuroimaging, Zika virus testing, a comprehensive newborn examination including neurologic exam, and a standard newborn hearing screen prior to hospital discharge.

Regardless of maternal Zika virus test results, infants with any clinical findings suggestive of congenital Zika virus syndrome and possible maternal exposure based on epidemiologic link also should be tested. Zika virus travel alerts and the most up to date information can be found on the Centers for Disease Control and Prevention website (www. cdc.gov/Zika).

CDC/Molly Kurnit, M.P.H.

Measles

Although endemic measles was eliminated in the United States in 2000, it is still common in many countries in Europe, Africa, and the Pacific. Most cases in the United States occur in unvaccinated individuals, with 78 cases reported in 2016. As of March 25, 2017, 28 cases have been reported. At least 10 countries – including Belgium, France, Italy, Germany, Portugal, and Thailand – have reported outbreaks of measles since April 2017. As reminder, all children aged 6-11 months should receive one dose of MMR and those 12 months or older should receive two doses of MMR at least 28 days apart if international travel is planned. Adults born after 1956 also should have received two doses of MMR prior to international travel.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She reported having no relevant financial disclosures.

BOSTON – Some of the most influential clinical research reports coming out of the annual meeting of the American Academy of Neurology raise questions on how neurologists will strike a balance between the improved efficacy and safety of drugs in new therapeutic classes and their affordability for patients.

Natalia Rost, MD, vice chair of the AAN Science Committee, discussed phase III clinical trials (ARISE and STRIVE) in episodic migraine with erenumab, an investigational humanized monoclonal antibody against calcitonin gene-related peptide receptor; phase III clinical trials (ENDEAR and CHERISH) of the antisense oligonucleotide drug nusinersen (Spinraza) that was approved by the Food and Drug Administration for spinal muscular atrophy in late 2016; as well as phase III trials of a pharmaceutical-grade extract of the cannabis-derived compound cannabidiol in patients with Dravet syndrome and Lennox-Gastaut syndrome.

Erenumab and nusinersen are “disease-specific targeted biologics” that have been developed over decades to target a specific disease pathway, and hence translate into high prices, Dr. Rost said in a video interview at the meeting.

“How you value the cost of a drug against improvement in a physiological outcome is very difficult to measure,” she noted, for relatively small gains in reducing migraine days per month and improvements in functional outcome and disability against placebo.

But this calculation is different with the potentially lifesaving effects of nusinersen for spinal muscular atrophy patients, in which “we’re not talking about days of improvement, we’re talking about days of life,” said Dr. Rost, director of acute stroke services at Massachusetts General Hospital, Boston. “And so that becomes an ethical dilemma in terms of the cost of administration, who is paying for the drug, and how this is covered. Whom do you offer treatment to?”

The development of cannabidiol as a potential adjunctive treatment for Dravet and Lennox-Gastaut syndromes is a welcome addition to the armamentarium against these conditions, Dr. Rost added, because it offers an alternative to the unregulated use of herbal medications and supplements – particularly cannabis in its various forms – that patients ask about but are difficult to dose consistently and to ensure a pharmaceutical-grade level of purity.

jevans@frontlinemedcom.com

BOSTON – Some of the most influential clinical research reports coming out of the annual meeting of the American Academy of Neurology raise questions on how neurologists will strike a balance between the improved efficacy and safety of drugs in new therapeutic classes and their affordability for patients.

Natalia Rost, MD, vice chair of the AAN Science Committee, discussed phase III clinical trials (ARISE and STRIVE) in episodic migraine with erenumab, an investigational humanized monoclonal antibody against calcitonin gene-related peptide receptor; phase III clinical trials (ENDEAR and CHERISH) of the antisense oligonucleotide drug nusinersen (Spinraza) that was approved by the Food and Drug Administration for spinal muscular atrophy in late 2016; as well as phase III trials of a pharmaceutical-grade extract of the cannabis-derived compound cannabidiol in patients with Dravet syndrome and Lennox-Gastaut syndrome.

Erenumab and nusinersen are “disease-specific targeted biologics” that have been developed over decades to target a specific disease pathway, and hence translate into high prices, Dr. Rost said in a video interview at the meeting.

“How you value the cost of a drug against improvement in a physiological outcome is very difficult to measure,” she noted, for relatively small gains in reducing migraine days per month and improvements in functional outcome and disability against placebo.

But this calculation is different with the potentially lifesaving effects of nusinersen for spinal muscular atrophy patients, in which “we’re not talking about days of improvement, we’re talking about days of life,” said Dr. Rost, director of acute stroke services at Massachusetts General Hospital, Boston. “And so that becomes an ethical dilemma in terms of the cost of administration, who is paying for the drug, and how this is covered. Whom do you offer treatment to?”

The development of cannabidiol as a potential adjunctive treatment for Dravet and Lennox-Gastaut syndromes is a welcome addition to the armamentarium against these conditions, Dr. Rost added, because it offers an alternative to the unregulated use of herbal medications and supplements – particularly cannabis in its various forms – that patients ask about but are difficult to dose consistently and to ensure a pharmaceutical-grade level of purity.

jevans@frontlinemedcom.com

BOSTON – Some of the most influential clinical research reports coming out of the annual meeting of the American Academy of Neurology raise questions on how neurologists will strike a balance between the improved efficacy and safety of drugs in new therapeutic classes and their affordability for patients.

Natalia Rost, MD, vice chair of the AAN Science Committee, discussed phase III clinical trials (ARISE and STRIVE) in episodic migraine with erenumab, an investigational humanized monoclonal antibody against calcitonin gene-related peptide receptor; phase III clinical trials (ENDEAR and CHERISH) of the antisense oligonucleotide drug nusinersen (Spinraza) that was approved by the Food and Drug Administration for spinal muscular atrophy in late 2016; as well as phase III trials of a pharmaceutical-grade extract of the cannabis-derived compound cannabidiol in patients with Dravet syndrome and Lennox-Gastaut syndrome.

Erenumab and nusinersen are “disease-specific targeted biologics” that have been developed over decades to target a specific disease pathway, and hence translate into high prices, Dr. Rost said in a video interview at the meeting.

“How you value the cost of a drug against improvement in a physiological outcome is very difficult to measure,” she noted, for relatively small gains in reducing migraine days per month and improvements in functional outcome and disability against placebo.

But this calculation is different with the potentially lifesaving effects of nusinersen for spinal muscular atrophy patients, in which “we’re not talking about days of improvement, we’re talking about days of life,” said Dr. Rost, director of acute stroke services at Massachusetts General Hospital, Boston. “And so that becomes an ethical dilemma in terms of the cost of administration, who is paying for the drug, and how this is covered. Whom do you offer treatment to?”

The development of cannabidiol as a potential adjunctive treatment for Dravet and Lennox-Gastaut syndromes is a welcome addition to the armamentarium against these conditions, Dr. Rost added, because it offers an alternative to the unregulated use of herbal medications and supplements – particularly cannabis in its various forms – that patients ask about but are difficult to dose consistently and to ensure a pharmaceutical-grade level of purity.

jevans@frontlinemedcom.com

SAN FRANCISCO – Oral corticosteroids appear to be beneficial in treating flares of pediatric acute-onset neuropsychiatric syndrome, or PANS, according to Margo Thienemann, MD.

“Corticosteroids shorten the duration of flares, and if you treat patients early in their first episode, their overall course seems to be better,” said Dr. Thienemann, a child psychiatrist at Stanford (Calif.) Children’s Hospital.

She is part of a multidisciplinary Stanford PANS clinic, together with a pediatric immunologist, a pediatric rheumatologist, two nurse practitioners, a child psychologist, and a social worker, all devoted to the study and treatment of the debilitating condition.

Dr. Thienemann presented the findings of a retrospective, observational study of 98 patients at the PANS clinic who collectively had 403 disease flares. Eighty-five of the flares were treated with 102 courses of oral steroids, either in a 4- to 5-day burst or longer-duration regimens of up to 8 weeks. Dosing was weight based and averaged roughly 60 mg/day. Treatment response was assessed within 14 days after initiating short-burst therapy or at the end of a longer course.

bjancin@frontlinemedcom.com

SAN FRANCISCO – Oral corticosteroids appear to be beneficial in treating flares of pediatric acute-onset neuropsychiatric syndrome, or PANS, according to Margo Thienemann, MD.

“Corticosteroids shorten the duration of flares, and if you treat patients early in their first episode, their overall course seems to be better,” said Dr. Thienemann, a child psychiatrist at Stanford (Calif.) Children’s Hospital.

She is part of a multidisciplinary Stanford PANS clinic, together with a pediatric immunologist, a pediatric rheumatologist, two nurse practitioners, a child psychologist, and a social worker, all devoted to the study and treatment of the debilitating condition.

Dr. Thienemann presented the findings of a retrospective, observational study of 98 patients at the PANS clinic who collectively had 403 disease flares. Eighty-five of the flares were treated with 102 courses of oral steroids, either in a 4- to 5-day burst or longer-duration regimens of up to 8 weeks. Dosing was weight based and averaged roughly 60 mg/day. Treatment response was assessed within 14 days after initiating short-burst therapy or at the end of a longer course.

bjancin@frontlinemedcom.com

SAN FRANCISCO – Oral corticosteroids appear to be beneficial in treating flares of pediatric acute-onset neuropsychiatric syndrome, or PANS, according to Margo Thienemann, MD.

“Corticosteroids shorten the duration of flares, and if you treat patients early in their first episode, their overall course seems to be better,” said Dr. Thienemann, a child psychiatrist at Stanford (Calif.) Children’s Hospital.

She is part of a multidisciplinary Stanford PANS clinic, together with a pediatric immunologist, a pediatric rheumatologist, two nurse practitioners, a child psychologist, and a social worker, all devoted to the study and treatment of the debilitating condition.

Dr. Thienemann presented the findings of a retrospective, observational study of 98 patients at the PANS clinic who collectively had 403 disease flares. Eighty-five of the flares were treated with 102 courses of oral steroids, either in a 4- to 5-day burst or longer-duration regimens of up to 8 weeks. Dosing was weight based and averaged roughly 60 mg/day. Treatment response was assessed within 14 days after initiating short-burst therapy or at the end of a longer course.

bjancin@frontlinemedcom.com

Pes planus, or flat feet, is a common concern addressed during well-child visits. Many parents express concern more because of the appearance of the feet than actual symptomatology. But what is within the realm of normal and what is beyond?

Ninety percent of clinic visits for foot problems are for flat feet.¹ Historically, the treatment of flat feet was wearing orthopedic shoes that were unappealing, so parents fear that is the fate of their child. Although the exact incidence rate of flat feet has not been determined, it clearly is quite common. Other contributing factors are joint hypermobility, obesity, and age. All children under the age of 2 years have flat feet because of the fat pad that is present. By the age of 10 years, this fat pad regresses and the normal arch is formed.

Dr. Pearce is a pediatrician in Frankfort, Ill. She said she had no relevant financial disclosures. Email her at pdnews@frontlinemedcom.com.

References

1. Iran J Pediatr. 2013 Jun;23(3):247-60.

2. J Child Orthop. 2010;4(2):107-21.

Pes planus, or flat feet, is a common concern addressed during well-child visits. Many parents express concern more because of the appearance of the feet than actual symptomatology. But what is within the realm of normal and what is beyond?

Ninety percent of clinic visits for foot problems are for flat feet.¹ Historically, the treatment of flat feet was wearing orthopedic shoes that were unappealing, so parents fear that is the fate of their child. Although the exact incidence rate of flat feet has not been determined, it clearly is quite common. Other contributing factors are joint hypermobility, obesity, and age. All children under the age of 2 years have flat feet because of the fat pad that is present. By the age of 10 years, this fat pad regresses and the normal arch is formed.

Dr. Pearce is a pediatrician in Frankfort, Ill. She said she had no relevant financial disclosures. Email her at pdnews@frontlinemedcom.com.

References

1. Iran J Pediatr. 2013 Jun;23(3):247-60.

2. J Child Orthop. 2010;4(2):107-21.

Pes planus, or flat feet, is a common concern addressed during well-child visits. Many parents express concern more because of the appearance of the feet than actual symptomatology. But what is within the realm of normal and what is beyond?

Ninety percent of clinic visits for foot problems are for flat feet.¹ Historically, the treatment of flat feet was wearing orthopedic shoes that were unappealing, so parents fear that is the fate of their child. Although the exact incidence rate of flat feet has not been determined, it clearly is quite common. Other contributing factors are joint hypermobility, obesity, and age. All children under the age of 2 years have flat feet because of the fat pad that is present. By the age of 10 years, this fat pad regresses and the normal arch is formed.

Dr. Pearce is a pediatrician in Frankfort, Ill. She said she had no relevant financial disclosures. Email her at pdnews@frontlinemedcom.com.

References

1. Iran J Pediatr. 2013 Jun;23(3):247-60.

2. J Child Orthop. 2010;4(2):107-21.

EXPERT ANALYSIS FROM ECCMID 2017

VIENNA – The first malaria vaccine to enter a national pilot project is not a silver bullet against the disease that kills half a million every year, but it still might be powerful enough to significantly reduce global disease burden, and even impact transmission, according to infectious disease specialist Nick Beeching, MD.

The vaccine, RTS,S (Mosquirix; GlaxoSmithKline), will be tested in three African countries beginning next year, the World Health Organization announced on April 25. The pilot programs will target 720,000 children aged 5-17 months in high-risk areas of the three countries.

Even though it’s the first malaria vaccine to pass its pivotal phase III trial, RTS,S isn’t terribly effective by any standards, said Dr. Beeching of the Royal Liverpool (England) University.

Michele Sullivan/Frontline Medical News

April 25, 2017, is World Malaria Day, and Anthony S. Fauci, MD, and B. Fenton Hall, MD, PhD, of the U.S. National Institute of Allergy and Infectious Diseases, said in a statement, “Safe and effective vaccines are critical tools for future efforts to control, eliminate, and, ultimately, eradicate malaria. NIAID is supporting the development of numerous malaria vaccine candidates, 10 of which are in clinical trials. In 2015, an estimated 212 million new malaria cases and 429,000 deaths occurred. Nearly 90% of these cases were among children under the age of 5 years in Africa, where malaria claims the life of a child every 2 minutes.”

GSK has been working on this vaccine since 1985, according to the company’s RTS,S literature. It is a recombinant protein that targets the circumsporozoite protein of the Plasmodium falciparum parasite at an early stage, before it enters the liver and begins to embed in erythrocytes. The aim, Dr. Beeching said, was to develop an antigen that would mobilize the immune system from the moment a mosquito injected the sporozoites through a bite, “well before they have a chance to hide in the liver.”

The 2- and 3-year follow-up results of the phase III trial, conducted in 15,500 children, were published in the Lancet in 2015. RTS,S was administered as a three-dose series, plus a booster dose, beginning at 5 months of age. The primary immunizations were given with a minimum 4-week interval between doses, with the booster administered 18 months after the last dose.

The primary series reduced clinical cases by 26%. With the booster dose, cases were reduced by 39% overall. The vaccine averted 1,774 episodes of clinical malaria per 1,000 vaccinated children, and 983 cases per 1,000 vaccinated infants. But vaccine efficacy waned over time, disappearing completely in children who got only the three-dose series. The booster dose improved response stability somewhat; during the 12 months after the fourth dose, vaccine efficacy was about 25%.

Based on these results, GSK received approval from the European Medicines Agency in 2015, and the WHO recommended a large-scale implementation of the vaccine be carried out last year. GSK will provide the vaccine at no cost, and each country’s government will decide which regions to include in the pilot study.

This real-world use will put RTS,S to the ultimate test, Dr. Beeching said: “There is always the practical problem of how do you get four doses of vaccine into people. It’s easy to do in a clinical trial, but the operations and the logistics of getting it right on the ground are what really matter. We don’t know how good less than four doses would be, and we still don’t know how long the protective effect of the full series plus booster will last. I think there’s concern that it might wane with time.”

Still, he said, even a 39% reduction in disease burden is worth aggressively pursuing, not only because of the thousands of children’s lives that could be saved, but because unvaccinated children and adults could potentially be protected as well: “We could see a knock-on effect. By reducing the burden of malaria in children, it may also reduce transmission to other people who haven’t been vaccinated.”

The vaccine certainly won’t eradicate malaria, Dr. Beeching said. It needs to be viewed as an addition to WHO’s core vector control strategy, which includes insecticide-impregnated bed nets and mosquito eradication programs.

Cost is an unresolved issue. According to the Malaria Vaccine Initiative, which is partnering with GSK to launch RTS,S, the company won’t charge for the vaccine in the pilot project, and is committed to making sure the children who need it get it.

“In many African countries, childhood vaccines are provided at no cost to children or their families, thanks to existing international and national financing mechanisms,” the company said in a press release. “The RTS,S partnership anticipates that similar mechanisms would be implemented for a malaria vaccine. A shared goal is to have the cost of a malaria vaccine not be a barrier to access.

“GSK has previously stated that the price of RTS,S will cover the cost of manufacturing the vaccine together with a small return of around 5%, which will be reinvested in research and development for next-generation malaria vaccines or vaccines against other neglected tropical diseases.”

Finally, Dr. Beeching said, there’s no way to know to know how long any malaria vaccine would retain its effectiveness.

“Making a malaria vaccine has been a dream for years, and a tough one. The antigens change according to the stage of the parasite, and there is always continuous genetic variation. So there is a possibility of escape from vaccine coverage. These are very clever parasites,” he said.

Dr. Beeching has no financial interest in the vaccine.

msullivan@frontlinemedcom.com

On Twitter @Alz_gal

EXPERT ANALYSIS FROM ECCMID 2017

VIENNA – The first malaria vaccine to enter a national pilot project is not a silver bullet against the disease that kills half a million every year, but it still might be powerful enough to significantly reduce global disease burden, and even impact transmission, according to infectious disease specialist Nick Beeching, MD.

The vaccine, RTS,S (Mosquirix; GlaxoSmithKline), will be tested in three African countries beginning next year, the World Health Organization announced on April 25. The pilot programs will target 720,000 children aged 5-17 months in high-risk areas of the three countries.

Even though it’s the first malaria vaccine to pass its pivotal phase III trial, RTS,S isn’t terribly effective by any standards, said Dr. Beeching of the Royal Liverpool (England) University.

Michele Sullivan/Frontline Medical News

April 25, 2017, is World Malaria Day, and Anthony S. Fauci, MD, and B. Fenton Hall, MD, PhD, of the U.S. National Institute of Allergy and Infectious Diseases, said in a statement, “Safe and effective vaccines are critical tools for future efforts to control, eliminate, and, ultimately, eradicate malaria. NIAID is supporting the development of numerous malaria vaccine candidates, 10 of which are in clinical trials. In 2015, an estimated 212 million new malaria cases and 429,000 deaths occurred. Nearly 90% of these cases were among children under the age of 5 years in Africa, where malaria claims the life of a child every 2 minutes.”

GSK has been working on this vaccine since 1985, according to the company’s RTS,S literature. It is a recombinant protein that targets the circumsporozoite protein of the Plasmodium falciparum parasite at an early stage, before it enters the liver and begins to embed in erythrocytes. The aim, Dr. Beeching said, was to develop an antigen that would mobilize the immune system from the moment a mosquito injected the sporozoites through a bite, “well before they have a chance to hide in the liver.”

The 2- and 3-year follow-up results of the phase III trial, conducted in 15,500 children, were published in the Lancet in 2015. RTS,S was administered as a three-dose series, plus a booster dose, beginning at 5 months of age. The primary immunizations were given with a minimum 4-week interval between doses, with the booster administered 18 months after the last dose.

The primary series reduced clinical cases by 26%. With the booster dose, cases were reduced by 39% overall. The vaccine averted 1,774 episodes of clinical malaria per 1,000 vaccinated children, and 983 cases per 1,000 vaccinated infants. But vaccine efficacy waned over time, disappearing completely in children who got only the three-dose series. The booster dose improved response stability somewhat; during the 12 months after the fourth dose, vaccine efficacy was about 25%.

Based on these results, GSK received approval from the European Medicines Agency in 2015, and the WHO recommended a large-scale implementation of the vaccine be carried out last year. GSK will provide the vaccine at no cost, and each country’s government will decide which regions to include in the pilot study.

This real-world use will put RTS,S to the ultimate test, Dr. Beeching said: “There is always the practical problem of how do you get four doses of vaccine into people. It’s easy to do in a clinical trial, but the operations and the logistics of getting it right on the ground are what really matter. We don’t know how good less than four doses would be, and we still don’t know how long the protective effect of the full series plus booster will last. I think there’s concern that it might wane with time.”

Still, he said, even a 39% reduction in disease burden is worth aggressively pursuing, not only because of the thousands of children’s lives that could be saved, but because unvaccinated children and adults could potentially be protected as well: “We could see a knock-on effect. By reducing the burden of malaria in children, it may also reduce transmission to other people who haven’t been vaccinated.”

The vaccine certainly won’t eradicate malaria, Dr. Beeching said. It needs to be viewed as an addition to WHO’s core vector control strategy, which includes insecticide-impregnated bed nets and mosquito eradication programs.

Cost is an unresolved issue. According to the Malaria Vaccine Initiative, which is partnering with GSK to launch RTS,S, the company won’t charge for the vaccine in the pilot project, and is committed to making sure the children who need it get it.

“In many African countries, childhood vaccines are provided at no cost to children or their families, thanks to existing international and national financing mechanisms,” the company said in a press release. “The RTS,S partnership anticipates that similar mechanisms would be implemented for a malaria vaccine. A shared goal is to have the cost of a malaria vaccine not be a barrier to access.

“GSK has previously stated that the price of RTS,S will cover the cost of manufacturing the vaccine together with a small return of around 5%, which will be reinvested in research and development for next-generation malaria vaccines or vaccines against other neglected tropical diseases.”

Finally, Dr. Beeching said, there’s no way to know to know how long any malaria vaccine would retain its effectiveness.

“Making a malaria vaccine has been a dream for years, and a tough one. The antigens change according to the stage of the parasite, and there is always continuous genetic variation. So there is a possibility of escape from vaccine coverage. These are very clever parasites,” he said.

Dr. Beeching has no financial interest in the vaccine.

msullivan@frontlinemedcom.com

On Twitter @Alz_gal

EXPERT ANALYSIS FROM ECCMID 2017

VIENNA – The first malaria vaccine to enter a national pilot project is not a silver bullet against the disease that kills half a million every year, but it still might be powerful enough to significantly reduce global disease burden, and even impact transmission, according to infectious disease specialist Nick Beeching, MD.

The vaccine, RTS,S (Mosquirix; GlaxoSmithKline), will be tested in three African countries beginning next year, the World Health Organization announced on April 25. The pilot programs will target 720,000 children aged 5-17 months in high-risk areas of the three countries.

Even though it’s the first malaria vaccine to pass its pivotal phase III trial, RTS,S isn’t terribly effective by any standards, said Dr. Beeching of the Royal Liverpool (England) University.

Michele Sullivan/Frontline Medical News

April 25, 2017, is World Malaria Day, and Anthony S. Fauci, MD, and B. Fenton Hall, MD, PhD, of the U.S. National Institute of Allergy and Infectious Diseases, said in a statement, “Safe and effective vaccines are critical tools for future efforts to control, eliminate, and, ultimately, eradicate malaria. NIAID is supporting the development of numerous malaria vaccine candidates, 10 of which are in clinical trials. In 2015, an estimated 212 million new malaria cases and 429,000 deaths occurred. Nearly 90% of these cases were among children under the age of 5 years in Africa, where malaria claims the life of a child every 2 minutes.”

GSK has been working on this vaccine since 1985, according to the company’s RTS,S literature. It is a recombinant protein that targets the circumsporozoite protein of the Plasmodium falciparum parasite at an early stage, before it enters the liver and begins to embed in erythrocytes. The aim, Dr. Beeching said, was to develop an antigen that would mobilize the immune system from the moment a mosquito injected the sporozoites through a bite, “well before they have a chance to hide in the liver.”

The 2- and 3-year follow-up results of the phase III trial, conducted in 15,500 children, were published in the Lancet in 2015. RTS,S was administered as a three-dose series, plus a booster dose, beginning at 5 months of age. The primary immunizations were given with a minimum 4-week interval between doses, with the booster administered 18 months after the last dose.

The primary series reduced clinical cases by 26%. With the booster dose, cases were reduced by 39% overall. The vaccine averted 1,774 episodes of clinical malaria per 1,000 vaccinated children, and 983 cases per 1,000 vaccinated infants. But vaccine efficacy waned over time, disappearing completely in children who got only the three-dose series. The booster dose improved response stability somewhat; during the 12 months after the fourth dose, vaccine efficacy was about 25%.

Based on these results, GSK received approval from the European Medicines Agency in 2015, and the WHO recommended a large-scale implementation of the vaccine be carried out last year. GSK will provide the vaccine at no cost, and each country’s government will decide which regions to include in the pilot study.

This real-world use will put RTS,S to the ultimate test, Dr. Beeching said: “There is always the practical problem of how do you get four doses of vaccine into people. It’s easy to do in a clinical trial, but the operations and the logistics of getting it right on the ground are what really matter. We don’t know how good less than four doses would be, and we still don’t know how long the protective effect of the full series plus booster will last. I think there’s concern that it might wane with time.”

Still, he said, even a 39% reduction in disease burden is worth aggressively pursuing, not only because of the thousands of children’s lives that could be saved, but because unvaccinated children and adults could potentially be protected as well: “We could see a knock-on effect. By reducing the burden of malaria in children, it may also reduce transmission to other people who haven’t been vaccinated.”

The vaccine certainly won’t eradicate malaria, Dr. Beeching said. It needs to be viewed as an addition to WHO’s core vector control strategy, which includes insecticide-impregnated bed nets and mosquito eradication programs.

Cost is an unresolved issue. According to the Malaria Vaccine Initiative, which is partnering with GSK to launch RTS,S, the company won’t charge for the vaccine in the pilot project, and is committed to making sure the children who need it get it.

“In many African countries, childhood vaccines are provided at no cost to children or their families, thanks to existing international and national financing mechanisms,” the company said in a press release. “The RTS,S partnership anticipates that similar mechanisms would be implemented for a malaria vaccine. A shared goal is to have the cost of a malaria vaccine not be a barrier to access.

“GSK has previously stated that the price of RTS,S will cover the cost of manufacturing the vaccine together with a small return of around 5%, which will be reinvested in research and development for next-generation malaria vaccines or vaccines against other neglected tropical diseases.”

Finally, Dr. Beeching said, there’s no way to know to know how long any malaria vaccine would retain its effectiveness.

“Making a malaria vaccine has been a dream for years, and a tough one. The antigens change according to the stage of the parasite, and there is always continuous genetic variation. So there is a possibility of escape from vaccine coverage. These are very clever parasites,” he said.

Dr. Beeching has no financial interest in the vaccine.

msullivan@frontlinemedcom.com

On Twitter @Alz_gal

Recently North Carolina proposed a bill (House Bill 780) that will ban same-sex marriage in the state, even though the U.S. Supreme Court ruled in 2015 that no states can ban same-sex marriage because doing so violates the 14th Amendment. Although many mainly will argue that H.B. 780 is unconstitutional, this bill also can be detrimental to the health of lesbian, gay, and bisexual (LGB) youth.

In March 2017, JAMA Pediatrics published a study on the association between same-sex marriage laws and the rates of suicide attempts.¹ Using data from the Youth Risk Behavior Surveillance System, they analyzed the relationship between state policies that permitted same-sex marriage and self-report of suicide attempts within the last 12 months. Thirty percent of LGB youth (13% of the survey population) reported a suicide attempt in the past year prior to any state policies that permitted same-sex marriage, compared with about 9% of the general population. After states implemented pro–same-sex marriage policies, LGB youth suicide attempts dropped to about 26% – a 14% relative decline. This was not limited to LGB youth. The general youth suicide rates declined from 8.6% to 8% – a 7% relative decline. Although the change in suicide attempts was small, the authors determined that the likelihood it occurred by chance was very slim, and concluded that policies enabling same-sex marriage may be associated with an improvement in population health, especially for LGB youth.

This was not the first study examining the relationship between policies and the health of LGB youth. Mark Hatzenbuehler, PhD, of Columbia University, New York, and his associates have published multiple studies on this topic. Four years earlier, Hatzenbuehler et al. published a study on the relationship between antibullying policies and suicide among LGB youth. Using data from the Oregon Healthy Teen survey (2006-2008), he found that LGB youth who live in counties where there are fewer districts with antibullying policies are more than twice as likely to attempt suicide, compared with LGB youth who live in counties where more districts had antibullying policies. Furthermore, the type of antibullying policy mattered. If a district’s antibullying policy did not prohibit bullying based on sexual orientation, then it had no impact on the suicide attempt rates of LGB youth in that area.² Similar results were found when the relationship between anti–homophobic bullying policies and LGB suicide attempts was examined in the larger Youth Risk Behavior Surveillance System.³

State and local policies also influence other health outcomes among LGB youth. Hatzenbuehler et al. did another study that examined community-level determinants of tobacco use among LGB youth. Again using the data from the Oregon Healthy Teen Survey, they found that LGB youth living in communities that were more supportive of LGB youth (i.e., communities with a high proportion of same-sex couples living in the area, a high proportion of gay-straight alliances at schools, and LGB-specific antibullying policies) were less likely to smoke cigarettes, compared with LGB youth living in communities that were less supportive.⁴ A similar study in Canada by Konishi et al. found that schools with gay-straight alliances and anti–homophobic bullying policies were less likely to have LGB youth engaging in risky alcohol or illicit drug use.⁵

Why do these policies matter? A common theme among these policies is that they can either cause or alleviate stress for LGB youth. States that restrict same-sex marriages or schools that do not have any gay-straight alliances may signal to LGB youth that they are not valued or welcomed, or at the very worse, are despised. This creates a hostile and stressful environment for LGB youth, which raises the risk for mental health problems, such as depression and anxiety, which in turn, raises the risk for substance use and suicide.⁶ Conversely, the presence of a gay-straight alliance at school or a state that allows same-sex marriage may indicate to LGB youth that they are welcomed, if not just tolerated, and may alleviate this risk. Furthermore, antibullying policies seem to reduce the stress associated with bullying among LGB youth because it may serve as a deterrent to bullying based on sexual orientation. Although passing pro-LGB policies will not solve all the health problems among LGB youth, these policies certainly have an impact.

There might be trepidation among some pediatricians about being vocal on a politically charged policy proposal such as H.B. 780. However, suicide and substance use are major concerns for all physicians – especially pediatricians. Policy makers considering passing laws that can affect their LGB constituents should read these studies to see what kind of influence these proposals can have on the health and well-being of LGB youth. Moreover, health care providers should use their expertise, influence, and standing in their community to support policies that encourage protection for LGB youth and oppose policies that can harm LGB youth. These leaders are responsible for ensuring the health of the people they serve.
 

Dr. Montano is clinical instructor of pediatrics at the University of Pittsburgh and an adolescent medicine physician at Children’s Hospital of Pittsburgh of UPMC.

References

1. JAMA Pediatr. 2017. doi: 10.1001/jamapediatrics.2016.4529.

2. J Adolesc Health. 2013:S21-6. doi: 10.1016/j.jadohealth.2012.08.010.

3. Am J Public Health. 2014. doi: 10.2105/AJPH.2013.301508.

4. Arch Pediatr Adolesc Med. 2011. doi: 10.1001/archpediatrics.2011.64.

5. Prev Med. 2013. doi: 10.1016/j.ypmed.2013.06.031.

6. Psychol Bull. 2003. doi: 10.1037/0033-2909.129.5.674.

Recently North Carolina proposed a bill (House Bill 780) that will ban same-sex marriage in the state, even though the U.S. Supreme Court ruled in 2015 that no states can ban same-sex marriage because doing so violates the 14th Amendment. Although many mainly will argue that H.B. 780 is unconstitutional, this bill also can be detrimental to the health of lesbian, gay, and bisexual (LGB) youth.

In March 2017, JAMA Pediatrics published a study on the association between same-sex marriage laws and the rates of suicide attempts.¹ Using data from the Youth Risk Behavior Surveillance System, they analyzed the relationship between state policies that permitted same-sex marriage and self-report of suicide attempts within the last 12 months. Thirty percent of LGB youth (13% of the survey population) reported a suicide attempt in the past year prior to any state policies that permitted same-sex marriage, compared with about 9% of the general population. After states implemented pro–same-sex marriage policies, LGB youth suicide attempts dropped to about 26% – a 14% relative decline. This was not limited to LGB youth. The general youth suicide rates declined from 8.6% to 8% – a 7% relative decline. Although the change in suicide attempts was small, the authors determined that the likelihood it occurred by chance was very slim, and concluded that policies enabling same-sex marriage may be associated with an improvement in population health, especially for LGB youth.

This was not the first study examining the relationship between policies and the health of LGB youth. Mark Hatzenbuehler, PhD, of Columbia University, New York, and his associates have published multiple studies on this topic. Four years earlier, Hatzenbuehler et al. published a study on the relationship between antibullying policies and suicide among LGB youth. Using data from the Oregon Healthy Teen survey (2006-2008), he found that LGB youth who live in counties where there are fewer districts with antibullying policies are more than twice as likely to attempt suicide, compared with LGB youth who live in counties where more districts had antibullying policies. Furthermore, the type of antibullying policy mattered. If a district’s antibullying policy did not prohibit bullying based on sexual orientation, then it had no impact on the suicide attempt rates of LGB youth in that area.² Similar results were found when the relationship between anti–homophobic bullying policies and LGB suicide attempts was examined in the larger Youth Risk Behavior Surveillance System.³

State and local policies also influence other health outcomes among LGB youth. Hatzenbuehler et al. did another study that examined community-level determinants of tobacco use among LGB youth. Again using the data from the Oregon Healthy Teen Survey, they found that LGB youth living in communities that were more supportive of LGB youth (i.e., communities with a high proportion of same-sex couples living in the area, a high proportion of gay-straight alliances at schools, and LGB-specific antibullying policies) were less likely to smoke cigarettes, compared with LGB youth living in communities that were less supportive.⁴ A similar study in Canada by Konishi et al. found that schools with gay-straight alliances and anti–homophobic bullying policies were less likely to have LGB youth engaging in risky alcohol or illicit drug use.⁵

Why do these policies matter? A common theme among these policies is that they can either cause or alleviate stress for LGB youth. States that restrict same-sex marriages or schools that do not have any gay-straight alliances may signal to LGB youth that they are not valued or welcomed, or at the very worse, are despised. This creates a hostile and stressful environment for LGB youth, which raises the risk for mental health problems, such as depression and anxiety, which in turn, raises the risk for substance use and suicide.⁶ Conversely, the presence of a gay-straight alliance at school or a state that allows same-sex marriage may indicate to LGB youth that they are welcomed, if not just tolerated, and may alleviate this risk. Furthermore, antibullying policies seem to reduce the stress associated with bullying among LGB youth because it may serve as a deterrent to bullying based on sexual orientation. Although passing pro-LGB policies will not solve all the health problems among LGB youth, these policies certainly have an impact.

There might be trepidation among some pediatricians about being vocal on a politically charged policy proposal such as H.B. 780. However, suicide and substance use are major concerns for all physicians – especially pediatricians. Policy makers considering passing laws that can affect their LGB constituents should read these studies to see what kind of influence these proposals can have on the health and well-being of LGB youth. Moreover, health care providers should use their expertise, influence, and standing in their community to support policies that encourage protection for LGB youth and oppose policies that can harm LGB youth. These leaders are responsible for ensuring the health of the people they serve.
 

Dr. Montano is clinical instructor of pediatrics at the University of Pittsburgh and an adolescent medicine physician at Children’s Hospital of Pittsburgh of UPMC.

References

1. JAMA Pediatr. 2017. doi: 10.1001/jamapediatrics.2016.4529.

2. J Adolesc Health. 2013:S21-6. doi: 10.1016/j.jadohealth.2012.08.010.

3. Am J Public Health. 2014. doi: 10.2105/AJPH.2013.301508.

4. Arch Pediatr Adolesc Med. 2011. doi: 10.1001/archpediatrics.2011.64.

5. Prev Med. 2013. doi: 10.1016/j.ypmed.2013.06.031.

6. Psychol Bull. 2003. doi: 10.1037/0033-2909.129.5.674.

Recently North Carolina proposed a bill (House Bill 780) that will ban same-sex marriage in the state, even though the U.S. Supreme Court ruled in 2015 that no states can ban same-sex marriage because doing so violates the 14th Amendment. Although many mainly will argue that H.B. 780 is unconstitutional, this bill also can be detrimental to the health of lesbian, gay, and bisexual (LGB) youth.

In March 2017, JAMA Pediatrics published a study on the association between same-sex marriage laws and the rates of suicide attempts.¹ Using data from the Youth Risk Behavior Surveillance System, they analyzed the relationship between state policies that permitted same-sex marriage and self-report of suicide attempts within the last 12 months. Thirty percent of LGB youth (13% of the survey population) reported a suicide attempt in the past year prior to any state policies that permitted same-sex marriage, compared with about 9% of the general population. After states implemented pro–same-sex marriage policies, LGB youth suicide attempts dropped to about 26% – a 14% relative decline. This was not limited to LGB youth. The general youth suicide rates declined from 8.6% to 8% – a 7% relative decline. Although the change in suicide attempts was small, the authors determined that the likelihood it occurred by chance was very slim, and concluded that policies enabling same-sex marriage may be associated with an improvement in population health, especially for LGB youth.

This was not the first study examining the relationship between policies and the health of LGB youth. Mark Hatzenbuehler, PhD, of Columbia University, New York, and his associates have published multiple studies on this topic. Four years earlier, Hatzenbuehler et al. published a study on the relationship between antibullying policies and suicide among LGB youth. Using data from the Oregon Healthy Teen survey (2006-2008), he found that LGB youth who live in counties where there are fewer districts with antibullying policies are more than twice as likely to attempt suicide, compared with LGB youth who live in counties where more districts had antibullying policies. Furthermore, the type of antibullying policy mattered. If a district’s antibullying policy did not prohibit bullying based on sexual orientation, then it had no impact on the suicide attempt rates of LGB youth in that area.² Similar results were found when the relationship between anti–homophobic bullying policies and LGB suicide attempts was examined in the larger Youth Risk Behavior Surveillance System.³

State and local policies also influence other health outcomes among LGB youth. Hatzenbuehler et al. did another study that examined community-level determinants of tobacco use among LGB youth. Again using the data from the Oregon Healthy Teen Survey, they found that LGB youth living in communities that were more supportive of LGB youth (i.e., communities with a high proportion of same-sex couples living in the area, a high proportion of gay-straight alliances at schools, and LGB-specific antibullying policies) were less likely to smoke cigarettes, compared with LGB youth living in communities that were less supportive.⁴ A similar study in Canada by Konishi et al. found that schools with gay-straight alliances and anti–homophobic bullying policies were less likely to have LGB youth engaging in risky alcohol or illicit drug use.⁵

Why do these policies matter? A common theme among these policies is that they can either cause or alleviate stress for LGB youth. States that restrict same-sex marriages or schools that do not have any gay-straight alliances may signal to LGB youth that they are not valued or welcomed, or at the very worse, are despised. This creates a hostile and stressful environment for LGB youth, which raises the risk for mental health problems, such as depression and anxiety, which in turn, raises the risk for substance use and suicide.⁶ Conversely, the presence of a gay-straight alliance at school or a state that allows same-sex marriage may indicate to LGB youth that they are welcomed, if not just tolerated, and may alleviate this risk. Furthermore, antibullying policies seem to reduce the stress associated with bullying among LGB youth because it may serve as a deterrent to bullying based on sexual orientation. Although passing pro-LGB policies will not solve all the health problems among LGB youth, these policies certainly have an impact.

There might be trepidation among some pediatricians about being vocal on a politically charged policy proposal such as H.B. 780. However, suicide and substance use are major concerns for all physicians – especially pediatricians. Policy makers considering passing laws that can affect their LGB constituents should read these studies to see what kind of influence these proposals can have on the health and well-being of LGB youth. Moreover, health care providers should use their expertise, influence, and standing in their community to support policies that encourage protection for LGB youth and oppose policies that can harm LGB youth. These leaders are responsible for ensuring the health of the people they serve.
 

Dr. Montano is clinical instructor of pediatrics at the University of Pittsburgh and an adolescent medicine physician at Children’s Hospital of Pittsburgh of UPMC.

References

1. JAMA Pediatr. 2017. doi: 10.1001/jamapediatrics.2016.4529.

2. J Adolesc Health. 2013:S21-6. doi: 10.1016/j.jadohealth.2012.08.010.

3. Am J Public Health. 2014. doi: 10.2105/AJPH.2013.301508.

4. Arch Pediatr Adolesc Med. 2011. doi: 10.1001/archpediatrics.2011.64.

5. Prev Med. 2013. doi: 10.1016/j.ypmed.2013.06.031.

6. Psychol Bull. 2003. doi: 10.1037/0033-2909.129.5.674.