User login
Preexposure prophylaxis among LGBT youth
Every prevention effort or treatment has its own risks. Gynecologists must consider the risk for blood clots from using estrogen-containing oral contraceptives versus the risk of blood clots from pregnancy. Endocrinologists must weigh the risk of decreased bone mineral density versus premature closure of growth plates when starting pubertal blockers for children suffering from precocious puberty. Psychologists and primary care providers must consider the risk for increased suicidal thoughts while on selective serotonin reuptake inhibitors versus the risk of completed suicide if the depression remains untreated.
In the United States alone, 22% of HIV infections occur in people aged 13-24 years. Among those with HIV infection, 81% are young men who have sex with men (MSM).1 Among those new infections, young MSM of color are nearly four times as likely to have HIV, compared with white young MSM.2 Moreover, the incidence of HIV infection among transgender individuals is three times higher than the national average.3
What further hampers public health prevention efforts is the stigma and discrimination LGBT youth face in trying to prevent HIV infections: 84% of those aged 15-24 years report recognizing stigma around HIV in the United States.4 In addition, black MSM were more likely than other MSMs to report this kind of stigma.5 And it isn’t enough that LGBT youth have to face stigma and discrimination. In fact, because of it, they often face serious financial challenges. It is estimated that 50% of homeless youth identify as LGBT, and 40% of them were forced out of their homes because of their sexual orientation or gender identity.6 Also, transgender youth have difficulty finding employment because of their gender identity.7 A combination of homelessness or chronic unemployment has driven many LGBT youth to survival sex or sex for money, which puts them at higher risk for HIV infection.7,8 The risk for HIV infection is so high that we should be using all available resources, including PrEP, to address these profound health disparities.
Studies, however, are forthcoming. One study by Hosek et al. that was published in September suggested that PrEP among adolescents can be safe and well tolerated, may not increase the rate of high-risk sexual behaviors, and may not increase the risk of other STDs such as gonorrhea and chlamydia. It must be noted, however, that incidence of HIV was fairly high – the HIV seroconversion rate was 6.4 per 100 person-years. Nevertheless, researchers found the rate of HIV seroconversion was higher among those with lower levels of Truvada in their bodies, compared with the seroconversion rate in those with higher levels of the medication. This suggests that adherence is key in using PrEP to prevent HIV infection.10 Although far from definitive, this small study provides some solid evidence that PrEP is safe and effective in preventing HIV among LGBT youth. More studies that will eventually support its effectiveness and safety are on the way.11
Dr. Montano is an assistant professor of pediatrics at the University of Pittsburgh and an adolescent medicine physician at Children’s Hospital of Pittsburgh of UPMC. Email him at pdnews@frontlinemedcom.com.
Resource
CDC website on PrEP: https://www.cdc.gov/hiv/risk/prep/index.html, with provider guidelines.
References
1. Centers for Disease Control and Prevention. HIV Among Youth fact sheet, April 2017.
2. Centers for Disease Control and Prevention. HIV Surveillance Report, 2015; vol. 27.
3. Centers for Disease Control and Prevention. HIV Among Transgender People.
4. Kaiser Family Foundation. National survey of teens and young adults on HIV/AIDS, Nov. 1, 2012. .
5. J Acquir Immune Defic Syndr. 2016;73(5):547-55.
6. Serving our youth: Findings from a national survey of services providers working with lesbian, gay, bisexual and transgender youth who are homeless or at risk of becoming homeless (The Williams Institute with True Colors and The Palette Fund, 2012).
7. Injustice at every turn: A report of the national transgender discrimination survey (National Center for Transgender Equality and National Gay and Lesbian Task Force, 2011).
8. J Acquir Immune Defic Syndr. 2010 Apr;53(5):661-4.
9. Centers for Disease Control and Prevention. Preexposure prophylaxis for the prevention of HIV infection in the United States: A clinical practice guideline, 2014.
10. JAMA Pediatr. 2017;171(11):1063-71.
11. J Int AIDS Soc. 2016;19. doi: 10.7448/IAS.19.7.21107.
Every prevention effort or treatment has its own risks. Gynecologists must consider the risk for blood clots from using estrogen-containing oral contraceptives versus the risk of blood clots from pregnancy. Endocrinologists must weigh the risk of decreased bone mineral density versus premature closure of growth plates when starting pubertal blockers for children suffering from precocious puberty. Psychologists and primary care providers must consider the risk for increased suicidal thoughts while on selective serotonin reuptake inhibitors versus the risk of completed suicide if the depression remains untreated.
In the United States alone, 22% of HIV infections occur in people aged 13-24 years. Among those with HIV infection, 81% are young men who have sex with men (MSM).1 Among those new infections, young MSM of color are nearly four times as likely to have HIV, compared with white young MSM.2 Moreover, the incidence of HIV infection among transgender individuals is three times higher than the national average.3
What further hampers public health prevention efforts is the stigma and discrimination LGBT youth face in trying to prevent HIV infections: 84% of those aged 15-24 years report recognizing stigma around HIV in the United States.4 In addition, black MSM were more likely than other MSMs to report this kind of stigma.5 And it isn’t enough that LGBT youth have to face stigma and discrimination. In fact, because of it, they often face serious financial challenges. It is estimated that 50% of homeless youth identify as LGBT, and 40% of them were forced out of their homes because of their sexual orientation or gender identity.6 Also, transgender youth have difficulty finding employment because of their gender identity.7 A combination of homelessness or chronic unemployment has driven many LGBT youth to survival sex or sex for money, which puts them at higher risk for HIV infection.7,8 The risk for HIV infection is so high that we should be using all available resources, including PrEP, to address these profound health disparities.
Studies, however, are forthcoming. One study by Hosek et al. that was published in September suggested that PrEP among adolescents can be safe and well tolerated, may not increase the rate of high-risk sexual behaviors, and may not increase the risk of other STDs such as gonorrhea and chlamydia. It must be noted, however, that incidence of HIV was fairly high – the HIV seroconversion rate was 6.4 per 100 person-years. Nevertheless, researchers found the rate of HIV seroconversion was higher among those with lower levels of Truvada in their bodies, compared with the seroconversion rate in those with higher levels of the medication. This suggests that adherence is key in using PrEP to prevent HIV infection.10 Although far from definitive, this small study provides some solid evidence that PrEP is safe and effective in preventing HIV among LGBT youth. More studies that will eventually support its effectiveness and safety are on the way.11
Dr. Montano is an assistant professor of pediatrics at the University of Pittsburgh and an adolescent medicine physician at Children’s Hospital of Pittsburgh of UPMC. Email him at pdnews@frontlinemedcom.com.
Resource
CDC website on PrEP: https://www.cdc.gov/hiv/risk/prep/index.html, with provider guidelines.
References
1. Centers for Disease Control and Prevention. HIV Among Youth fact sheet, April 2017.
2. Centers for Disease Control and Prevention. HIV Surveillance Report, 2015; vol. 27.
3. Centers for Disease Control and Prevention. HIV Among Transgender People.
4. Kaiser Family Foundation. National survey of teens and young adults on HIV/AIDS, Nov. 1, 2012. .
5. J Acquir Immune Defic Syndr. 2016;73(5):547-55.
6. Serving our youth: Findings from a national survey of services providers working with lesbian, gay, bisexual and transgender youth who are homeless or at risk of becoming homeless (The Williams Institute with True Colors and The Palette Fund, 2012).
7. Injustice at every turn: A report of the national transgender discrimination survey (National Center for Transgender Equality and National Gay and Lesbian Task Force, 2011).
8. J Acquir Immune Defic Syndr. 2010 Apr;53(5):661-4.
9. Centers for Disease Control and Prevention. Preexposure prophylaxis for the prevention of HIV infection in the United States: A clinical practice guideline, 2014.
10. JAMA Pediatr. 2017;171(11):1063-71.
11. J Int AIDS Soc. 2016;19. doi: 10.7448/IAS.19.7.21107.
Every prevention effort or treatment has its own risks. Gynecologists must consider the risk for blood clots from using estrogen-containing oral contraceptives versus the risk of blood clots from pregnancy. Endocrinologists must weigh the risk of decreased bone mineral density versus premature closure of growth plates when starting pubertal blockers for children suffering from precocious puberty. Psychologists and primary care providers must consider the risk for increased suicidal thoughts while on selective serotonin reuptake inhibitors versus the risk of completed suicide if the depression remains untreated.
In the United States alone, 22% of HIV infections occur in people aged 13-24 years. Among those with HIV infection, 81% are young men who have sex with men (MSM).1 Among those new infections, young MSM of color are nearly four times as likely to have HIV, compared with white young MSM.2 Moreover, the incidence of HIV infection among transgender individuals is three times higher than the national average.3
What further hampers public health prevention efforts is the stigma and discrimination LGBT youth face in trying to prevent HIV infections: 84% of those aged 15-24 years report recognizing stigma around HIV in the United States.4 In addition, black MSM were more likely than other MSMs to report this kind of stigma.5 And it isn’t enough that LGBT youth have to face stigma and discrimination. In fact, because of it, they often face serious financial challenges. It is estimated that 50% of homeless youth identify as LGBT, and 40% of them were forced out of their homes because of their sexual orientation or gender identity.6 Also, transgender youth have difficulty finding employment because of their gender identity.7 A combination of homelessness or chronic unemployment has driven many LGBT youth to survival sex or sex for money, which puts them at higher risk for HIV infection.7,8 The risk for HIV infection is so high that we should be using all available resources, including PrEP, to address these profound health disparities.
Studies, however, are forthcoming. One study by Hosek et al. that was published in September suggested that PrEP among adolescents can be safe and well tolerated, may not increase the rate of high-risk sexual behaviors, and may not increase the risk of other STDs such as gonorrhea and chlamydia. It must be noted, however, that incidence of HIV was fairly high – the HIV seroconversion rate was 6.4 per 100 person-years. Nevertheless, researchers found the rate of HIV seroconversion was higher among those with lower levels of Truvada in their bodies, compared with the seroconversion rate in those with higher levels of the medication. This suggests that adherence is key in using PrEP to prevent HIV infection.10 Although far from definitive, this small study provides some solid evidence that PrEP is safe and effective in preventing HIV among LGBT youth. More studies that will eventually support its effectiveness and safety are on the way.11
Dr. Montano is an assistant professor of pediatrics at the University of Pittsburgh and an adolescent medicine physician at Children’s Hospital of Pittsburgh of UPMC. Email him at pdnews@frontlinemedcom.com.
Resource
CDC website on PrEP: https://www.cdc.gov/hiv/risk/prep/index.html, with provider guidelines.
References
1. Centers for Disease Control and Prevention. HIV Among Youth fact sheet, April 2017.
2. Centers for Disease Control and Prevention. HIV Surveillance Report, 2015; vol. 27.
3. Centers for Disease Control and Prevention. HIV Among Transgender People.
4. Kaiser Family Foundation. National survey of teens and young adults on HIV/AIDS, Nov. 1, 2012. .
5. J Acquir Immune Defic Syndr. 2016;73(5):547-55.
6. Serving our youth: Findings from a national survey of services providers working with lesbian, gay, bisexual and transgender youth who are homeless or at risk of becoming homeless (The Williams Institute with True Colors and The Palette Fund, 2012).
7. Injustice at every turn: A report of the national transgender discrimination survey (National Center for Transgender Equality and National Gay and Lesbian Task Force, 2011).
8. J Acquir Immune Defic Syndr. 2010 Apr;53(5):661-4.
9. Centers for Disease Control and Prevention. Preexposure prophylaxis for the prevention of HIV infection in the United States: A clinical practice guideline, 2014.
10. JAMA Pediatr. 2017;171(11):1063-71.
11. J Int AIDS Soc. 2016;19. doi: 10.7448/IAS.19.7.21107.
Red Patches on a Newborn
The Diagnosis: Congenital Unilateral Nevoid Telangiectasia
Two weeks later the patches were noticeably lighter (Figures 1A and 1B). She continued to be in good health, but gynecomastia was notably present on examination (Figure 1C). At 3 months of age, all patches on the right arm, superior aspect of the chest, and superior aspect of the back had resolved, along with the gynecomastia (Figure 2).
This case describes the rare condition of congenital unilateral nevoid telangiectasia (UNT). Unilateral nevoid telangiectasia is a rare cutaneous vascular condition first described by Blaschko1 in 1899. It is characterized by the presence of unilateral superficial telangiectases occurring most often in the cervical and upper thoracic dermatomes in a linear pattern.2 Females are more often affected than males (2:1 ratio), and cases of UNT are either congenital or acquired.3 Although most UNT cases are acquired and often found in females, approximately 15% of cases are congenital and are comprised largely by males. Acquired cases have been hypothesized to occur in association with hyperestrogenemic states such as pregnancy, puberty, oral contraceptive use and hormonal therapy, alcoholism, and liver disease including hepatitis B and C infections.4,5 There is conflicting evidence as to whether there is an absolute increase in the presence of estrogen and progesterone receptors in the skin, as many case reports show no increase. Instead, others hypothesize that the condition is actually a result of somatic mosaicism and that the cutaneous lesions are genetically predisposed to becoming visibly evident under conditions of elevated estrogen.2
In our case, we hypothesize that the cause was elevated maternal estrogen levels present at higher than normal levels in the fetal circulation. The presence of gynecomastia seen in our patient supports the hypothesis that increased circulating estrogen may be present in infants with UNT.
- Blaschko A. Teleangiektasien. versammlungen. Berliner Dermatologische Gesellschaft. Monatschr prakt Dermat. 1899;28:451.
- Karakas¸ M, Durdu M, Sönmezoğlu S, et al. Unilateral nevoidtelangiectasia. J Dermatol. 2004;31:109-112.
- Wenson SF, Farhana J, Sepehr A. Unilateral nevoid telangiectasia syndrome: a case report and review of the literature. Dermatol Online J. 2011;17:2.
- Hynes LR, Shenefelt PD. Unilateral nevoid telangiectasia: occurrence in two patients with hepatitis C. J Am Acad Dermatol. 1997;36(5 pt 2):819-822.
- Guedes R, Leite L. Unilateral nevoid telangiectasia: a rare disease? Indian J Dermatol. 2012;57:138-140.
The Diagnosis: Congenital Unilateral Nevoid Telangiectasia
Two weeks later the patches were noticeably lighter (Figures 1A and 1B). She continued to be in good health, but gynecomastia was notably present on examination (Figure 1C). At 3 months of age, all patches on the right arm, superior aspect of the chest, and superior aspect of the back had resolved, along with the gynecomastia (Figure 2).
This case describes the rare condition of congenital unilateral nevoid telangiectasia (UNT). Unilateral nevoid telangiectasia is a rare cutaneous vascular condition first described by Blaschko1 in 1899. It is characterized by the presence of unilateral superficial telangiectases occurring most often in the cervical and upper thoracic dermatomes in a linear pattern.2 Females are more often affected than males (2:1 ratio), and cases of UNT are either congenital or acquired.3 Although most UNT cases are acquired and often found in females, approximately 15% of cases are congenital and are comprised largely by males. Acquired cases have been hypothesized to occur in association with hyperestrogenemic states such as pregnancy, puberty, oral contraceptive use and hormonal therapy, alcoholism, and liver disease including hepatitis B and C infections.4,5 There is conflicting evidence as to whether there is an absolute increase in the presence of estrogen and progesterone receptors in the skin, as many case reports show no increase. Instead, others hypothesize that the condition is actually a result of somatic mosaicism and that the cutaneous lesions are genetically predisposed to becoming visibly evident under conditions of elevated estrogen.2
In our case, we hypothesize that the cause was elevated maternal estrogen levels present at higher than normal levels in the fetal circulation. The presence of gynecomastia seen in our patient supports the hypothesis that increased circulating estrogen may be present in infants with UNT.
The Diagnosis: Congenital Unilateral Nevoid Telangiectasia
Two weeks later the patches were noticeably lighter (Figures 1A and 1B). She continued to be in good health, but gynecomastia was notably present on examination (Figure 1C). At 3 months of age, all patches on the right arm, superior aspect of the chest, and superior aspect of the back had resolved, along with the gynecomastia (Figure 2).
This case describes the rare condition of congenital unilateral nevoid telangiectasia (UNT). Unilateral nevoid telangiectasia is a rare cutaneous vascular condition first described by Blaschko1 in 1899. It is characterized by the presence of unilateral superficial telangiectases occurring most often in the cervical and upper thoracic dermatomes in a linear pattern.2 Females are more often affected than males (2:1 ratio), and cases of UNT are either congenital or acquired.3 Although most UNT cases are acquired and often found in females, approximately 15% of cases are congenital and are comprised largely by males. Acquired cases have been hypothesized to occur in association with hyperestrogenemic states such as pregnancy, puberty, oral contraceptive use and hormonal therapy, alcoholism, and liver disease including hepatitis B and C infections.4,5 There is conflicting evidence as to whether there is an absolute increase in the presence of estrogen and progesterone receptors in the skin, as many case reports show no increase. Instead, others hypothesize that the condition is actually a result of somatic mosaicism and that the cutaneous lesions are genetically predisposed to becoming visibly evident under conditions of elevated estrogen.2
In our case, we hypothesize that the cause was elevated maternal estrogen levels present at higher than normal levels in the fetal circulation. The presence of gynecomastia seen in our patient supports the hypothesis that increased circulating estrogen may be present in infants with UNT.
- Blaschko A. Teleangiektasien. versammlungen. Berliner Dermatologische Gesellschaft. Monatschr prakt Dermat. 1899;28:451.
- Karakas¸ M, Durdu M, Sönmezoğlu S, et al. Unilateral nevoidtelangiectasia. J Dermatol. 2004;31:109-112.
- Wenson SF, Farhana J, Sepehr A. Unilateral nevoid telangiectasia syndrome: a case report and review of the literature. Dermatol Online J. 2011;17:2.
- Hynes LR, Shenefelt PD. Unilateral nevoid telangiectasia: occurrence in two patients with hepatitis C. J Am Acad Dermatol. 1997;36(5 pt 2):819-822.
- Guedes R, Leite L. Unilateral nevoid telangiectasia: a rare disease? Indian J Dermatol. 2012;57:138-140.
- Blaschko A. Teleangiektasien. versammlungen. Berliner Dermatologische Gesellschaft. Monatschr prakt Dermat. 1899;28:451.
- Karakas¸ M, Durdu M, Sönmezoğlu S, et al. Unilateral nevoidtelangiectasia. J Dermatol. 2004;31:109-112.
- Wenson SF, Farhana J, Sepehr A. Unilateral nevoid telangiectasia syndrome: a case report and review of the literature. Dermatol Online J. 2011;17:2.
- Hynes LR, Shenefelt PD. Unilateral nevoid telangiectasia: occurrence in two patients with hepatitis C. J Am Acad Dermatol. 1997;36(5 pt 2):819-822.
- Guedes R, Leite L. Unilateral nevoid telangiectasia: a rare disease? Indian J Dermatol. 2012;57:138-140.
A 1-day-old female infant presented with red patches on the right arm that had been present since delivery. The patient was born to a healthy mother by spontaneous vaginal delivery without complications and with a good Apgar score. The newborn moved both arms and legs well and blood work was unremarkable. Her mother noted being healthy during pregnancy, and she had not taken any additional medications aside from prenatal vitamins. Examination of the infant revealed red blanchable reticulate patches in a dermatomal distribution extending from the posterior aspect of the right shoulder (top) down to the flexural aspect of the arm (bottom). There also were a few coalescing reticulate patches on the superior aspect of the right side of the chest and superior aspect of the right side of the back that resolved by 3 months of age.
Bright Futures 4th Edition gets a clinical refresher
CHICAGO – Bracing his audience for a whirlwind tour of the many updates to the fourth edition of Bright Futures, Joseph F. Hagan Jr., MD, said that it’s still completely possible to fit Bright Futures visits into a clinic day.
“I practice primary care pediatrics,” said Dr. Hagan, a pediatrician in private practice and clinical professor of pediatrics at the University of Vermont, both in Burlington. “I said to my Bright Futures colleagues, if I didn’t think I could do this in 18 minutes, I wouldn’t ask you to do it.”
The Bright Futures framework, described by Dr. Hagan as the health prevention and disease prevention component of the medical home for children and youth, emerges in the Fourth Edition with a significant evidence-based refresher. The changes and updates are built within the existing framework and encompass surveillance and screening recommendations as well as anticipatory guidance. All content, including family handouts, has been updated, said Dr. Hagan, a coeditor of the Fourth Edition of Bright Futures. He spoke at the annual meeting of the American Academy of Pediatrics.
New clinical content
“What’s new? Maternal depression screening is new,” said Dr. Hagan, noting that the recommendation has long been under discussion. Now, supported by a 2016 United States Preventative Task Force (USPSTF) recommendation that carries a grade B level of evidence, all mothers should be screened for depression at the 1-, 2-, 4-, and 6-month Bright Futures visits.
However, he said, know your local regulations. “State mandates to do more might overrule this.” And conversely, “Just because we’re doing it universally until 6 months doesn’t mean you couldn’t selectively screen later if you have concerns.”
Safe sleep is another area with new clinical focus, he said. The new recommendation for the child to sleep in the parent’s room for “at least 6 months” draws on data from European studies showing lower mortality for children who share a room with parents during this period.
Clinicians should continue to recommend that parents not sleep with their infants in couches, chairs, or beds. As before, parents should be told not to have loose blankets, stuffed toys, or crib bumpers in their babies’ cribs. Another key message, said Dr. Hagan, is that “There is no such thing as safe ‘breast-sleeping.’ ”
Parents should be reminded not to swaddle at nap – or bedtime. The risk is that even a 2-month-old infant may be capable of wriggling over from back to front, and a swaddled infant whose hands are trapped may not be able to move to protect her airway once prone. “Swaddle for comfort, swaddle for crying, swaddle for nursing, but don’t swaddle for sleep” is the message, said Dr. Hagan.
For breast-fed babies, iron supplementation should begin at the 4-month visit. The notion is to prevent progression from iron deficiency to frank anemia, said Dr. Hagan. “We know that we screen for iron deficiency anemia … but we also know that before you’re iron deficient anemic, you’re iron deficient,” he said, and iron’s also critical to brain development. For convenience, switching from vitamin D alone to a multivitamin drop with iron at 4 months is a practical choice.
New dental health recommendations bring prevention to the pediatrician’s office. “Fluoride varnish? Do it!” said Dr. Hagan. Although the USPSTF made a 2014 grade B recommendation that primary care clinicians apply fluoride varnish to primary teeth as soon as they erupt, “It’s new to the Bright Futures periodicity schedule,” he said; parents can be assured that fluoride varnish does not cause fluorosis.
The good news for clinicians, he noted. “Once it hits the periodicity schedule, now, it’s a billable service that must be paid” under Affordable Care Act regulations, said Dr. Hagan. “Don’t let your insurer say, ‘That’s part of what you’re already being paid for.’ ” He recommends avoiding the pressure to bundle this important service. Use the discrete CPT code 99188, “Application of a fluoride varnish by a physician or other qualified health care professional.”
Although Bright Futures has updated recommendations for dyslipidemia blood screening, the USPSTF found insufficient evidence to back lipid screening for those younger than 20 years of age, citing an inability to assess the balance of benefits and harms for universal, rather than risk-based, screening. However, said Dr. Hagan, the American Academy of Pediatrics (AAP), and the National Heart, Lung, and Blood Institute (NHLBI) were looking at this issue at about the same time, and they “did a really good job of showing their work,” to show that if family history alone guided screening in the pediatric population, it “just wasn’t getting done.” And AAP and NHLBI did demonstrate evidence sufficient to support this recommendation.
Accordingly, Bright Futures recommends one screening between ages 9 and 11 years and an additional screening between ages 17 and 21. These windows are designed to bracket puberty, said Dr. Hagan, because values can be skewed during that period. “It’s billable, it’s not bundle-able, and I’d recommend that you do it,” he said.
Developmental surveillance and screening
What’s new with developmental surveillance and screening? “Well, we could argue that the milestones are something to think about, because the milestones are the cornerstone of developmental surveillance,” said Dr. Hagan. “You’re in the room with the child. You’re trained, you’re experienced, you’re smart, your gestalt tells you if their development is good or bad.” 
As important as surveillance is, though, he said, it is “nowhere near as important as screening.” Surveillance happens at every well-child visit, but there’s no substitute for formal developmental screening. For the Fourth Edition guidance and toolkit, gross motor milestones have been adjusted to reflect what’s really being seen as more parents adopt the Back to Sleep recommendations as well.
A standardized developmental screening tool is used at the 9-, 18-, and 30-month visits, and when parents or caregivers express concern about development. Autism-specific screening happens at 18 and 24 months.
“Remember this, if you remember nothing else: If the screening is positive, and you believe there’s a problem, you’re going to refer,” not just to the appropriate specialist but also for early intervention services, so time isn’t lost as the child is waiting for further evaluation and a formal diagnosis, said Dr. Hagan. This coordinated effort appropriately places the responsibility for early identification of developmental delays and disorders at the doorstep of the child’s medical home.
The federally-coordinated Birth to 5: Watch Me Thrive! effort has aggregated research-based screening tools, users’ guides targeted at a variety of audiences, and resources to help caregivers, said Dr. Hagan.
Four commonly-used tools to consider using during the visit are the Parents’ Evaluation of Developmental Status, the Ages and Stages Questionnaire, the Child Health and Development Interactive System, and the Survey of Wellbeing of Young Children. Of these, said Dr. Hagan, the latter is the only tool that’s in the public domain. However, he said, they are “all really good.”
Consider having parents fill out screening questionnaires in the waiting room before the visit, said Dr. Hagan. “I always tell my colleagues, ‘Have them start the visit without you, if you want to get it done in 18 minutes.’ ”
Two questionnaires per visit are available in the Bright Futures toolkit. One questionnaire asks developmental surveillance and risk assessment questions for selective screening. The second questionnaire asks prescreening questions to help with the anticipatory guidance part of the visit, he said. Having families do these ahead of time, said Dr. Hagan, “allows you to become more focused.”
Paying attention to practicalities can make all this go more smoothly, and maximize reimbursement as well. In his own practice, Dr. Hagan said, screening tools and questionnaires are integrated into the EHR system, so that appropriate paperwork prints automatically ahead of the visit.
It’s also worth reviewing billing practices to make sure that CPT code 96110 is used when administering screening with a standardized instrument and completing scoring and documentation. According to the Bright Futures periodicity schedule, this may be done at the 9-, 18-, and 30-month visits for developmental screening, as well as at 18 and 24 months for autism-specific screening.
Promoting lifelong health
Since the initial Bright Futures guidelines were published in the late 1990s, said Dr. Hagan, the focus has always been on seeing the child as part of the family, who, in turn, are part of the community, forming a framework that addresses the social components of child health. “If you’re not looking at the whole picture, you’re not promoting health,” he said. “It’s no big surprise that we now have a specific, called-out focus on promoting lifelong health.”
In the Fourth Edition, the theme of promoting lifelong health for families and communities is woven throughout, with social determinants of health being a specific visit priority. For example, questions about food insecurity have been drawn from the published literature and are included. Also, said Dr. Hagan, there’s specific anticipatory guidance content that’s clearly marked as addressing social determinants of health.
The fundamental importance of socioeconomic status as a social determinant of health was brought home by the Robert Wood Johnson Foundation’s Commission to Build a Healthier America, which demonstrated that, “Your ZIP code is more important to your health than your genetic code,” said Dr. Hagan. “So your work in health supervision is important, and you have been leaders in this effort.”
Research guides Bright Futures updates
The fourth edition of Bright Futures builds on health promotion themes to support the mental and physical health of children and adolescents, and has a robust framework of evidence underpinning the guidelines, said Dr. Hagan.
The goal is for clinicians to “use evidence to decide upon content of their own health supervision visits,” he explained.
The chapter of the Bright Futures guidelines that addresses the evidence and rationale for the guidelines has been expanded to better answer two questions, said Dr. Hagan: “What evidence grounds our recommendations?” and “What rationale did we use when evidence was insufficient or lacking?”
When possible, the editors of the guidelines used evidence-based sources such as recommendations from the USPSTF, the Centers for Disease Control Community Guide, and the Cochrane Collaboration.
There were many more evidence-based recommendations available to those working on the 4th edition than there had been when writing the previous edition, when, said Dr. Hagan, the USPSTF had exactly two recommendations for those under the age of 21 years. The current expanded number of USPSTF pediatric recommendations was due in part to the attention the AAP was able to bring regarding the need for evidence-based recommendations in pediatrics, he said.
When guidelines were not available, the editors also turned to high quality studies from peer reviewed publications. When such high quality evidence was lacking in a particular area, the guidelines make clear what rationale was used to formulate a given recommendation, and that some recommendations should be interpreted with a degree of caution.
And, said Dr. Hagan, even science-based guidelines will change as more data accumulates. “Don’t forget about peanuts!” he said. “It was really logical 15 years ago when we said don’t give peanut products until 1 year of age. And about 2 years ago, we found out that it really didn’t work.”
Although there are specific updates to clinical content, there also were changes made in broader strokes throughout the 4th edition. One of these shifts embeds social determinants of health in many visits. This adjustment acknowledges the growing body of knowledge that “strengths and protective factors make a difference, and risk factors make a difference” in pediatric outcomes.
A greater focus on lifelong physical and mental health is included under the general rubric of promoting lifelong health for families and communities. More emphasis is placed on promoting health for children and youth who have special health care needs as well.
Nuts-and-bolts changes in the updated 4th edition include updates for milestones of development and accompanying developmental surveillance questions, new clinical content and guidance for implementation that have been added based on strong evidence, and a variety of updates for adolescent screenings in particular.
The full 4th edition Bright Futures toolkit will be available for use in 2018.
Dr. Hagan was a coeditor of the Fourth Edition of Bright Futures.
*This article was updated on December 21, 2017
CHICAGO – Bracing his audience for a whirlwind tour of the many updates to the fourth edition of Bright Futures, Joseph F. Hagan Jr., MD, said that it’s still completely possible to fit Bright Futures visits into a clinic day.
“I practice primary care pediatrics,” said Dr. Hagan, a pediatrician in private practice and clinical professor of pediatrics at the University of Vermont, both in Burlington. “I said to my Bright Futures colleagues, if I didn’t think I could do this in 18 minutes, I wouldn’t ask you to do it.”
The Bright Futures framework, described by Dr. Hagan as the health prevention and disease prevention component of the medical home for children and youth, emerges in the Fourth Edition with a significant evidence-based refresher. The changes and updates are built within the existing framework and encompass surveillance and screening recommendations as well as anticipatory guidance. All content, including family handouts, has been updated, said Dr. Hagan, a coeditor of the Fourth Edition of Bright Futures. He spoke at the annual meeting of the American Academy of Pediatrics.
New clinical content
“What’s new? Maternal depression screening is new,” said Dr. Hagan, noting that the recommendation has long been under discussion. Now, supported by a 2016 United States Preventative Task Force (USPSTF) recommendation that carries a grade B level of evidence, all mothers should be screened for depression at the 1-, 2-, 4-, and 6-month Bright Futures visits.
However, he said, know your local regulations. “State mandates to do more might overrule this.” And conversely, “Just because we’re doing it universally until 6 months doesn’t mean you couldn’t selectively screen later if you have concerns.”
Safe sleep is another area with new clinical focus, he said. The new recommendation for the child to sleep in the parent’s room for “at least 6 months” draws on data from European studies showing lower mortality for children who share a room with parents during this period.
Clinicians should continue to recommend that parents not sleep with their infants in couches, chairs, or beds. As before, parents should be told not to have loose blankets, stuffed toys, or crib bumpers in their babies’ cribs. Another key message, said Dr. Hagan, is that “There is no such thing as safe ‘breast-sleeping.’ ”
Parents should be reminded not to swaddle at nap – or bedtime. The risk is that even a 2-month-old infant may be capable of wriggling over from back to front, and a swaddled infant whose hands are trapped may not be able to move to protect her airway once prone. “Swaddle for comfort, swaddle for crying, swaddle for nursing, but don’t swaddle for sleep” is the message, said Dr. Hagan.
For breast-fed babies, iron supplementation should begin at the 4-month visit. The notion is to prevent progression from iron deficiency to frank anemia, said Dr. Hagan. “We know that we screen for iron deficiency anemia … but we also know that before you’re iron deficient anemic, you’re iron deficient,” he said, and iron’s also critical to brain development. For convenience, switching from vitamin D alone to a multivitamin drop with iron at 4 months is a practical choice.
New dental health recommendations bring prevention to the pediatrician’s office. “Fluoride varnish? Do it!” said Dr. Hagan. Although the USPSTF made a 2014 grade B recommendation that primary care clinicians apply fluoride varnish to primary teeth as soon as they erupt, “It’s new to the Bright Futures periodicity schedule,” he said; parents can be assured that fluoride varnish does not cause fluorosis.
The good news for clinicians, he noted. “Once it hits the periodicity schedule, now, it’s a billable service that must be paid” under Affordable Care Act regulations, said Dr. Hagan. “Don’t let your insurer say, ‘That’s part of what you’re already being paid for.’ ” He recommends avoiding the pressure to bundle this important service. Use the discrete CPT code 99188, “Application of a fluoride varnish by a physician or other qualified health care professional.”
Although Bright Futures has updated recommendations for dyslipidemia blood screening, the USPSTF found insufficient evidence to back lipid screening for those younger than 20 years of age, citing an inability to assess the balance of benefits and harms for universal, rather than risk-based, screening. However, said Dr. Hagan, the American Academy of Pediatrics (AAP), and the National Heart, Lung, and Blood Institute (NHLBI) were looking at this issue at about the same time, and they “did a really good job of showing their work,” to show that if family history alone guided screening in the pediatric population, it “just wasn’t getting done.” And AAP and NHLBI did demonstrate evidence sufficient to support this recommendation.
Accordingly, Bright Futures recommends one screening between ages 9 and 11 years and an additional screening between ages 17 and 21. These windows are designed to bracket puberty, said Dr. Hagan, because values can be skewed during that period. “It’s billable, it’s not bundle-able, and I’d recommend that you do it,” he said.
Developmental surveillance and screening
What’s new with developmental surveillance and screening? “Well, we could argue that the milestones are something to think about, because the milestones are the cornerstone of developmental surveillance,” said Dr. Hagan. “You’re in the room with the child. You’re trained, you’re experienced, you’re smart, your gestalt tells you if their development is good or bad.”
As important as surveillance is, though, he said, it is “nowhere near as important as screening.” Surveillance happens at every well-child visit, but there’s no substitute for formal developmental screening. For the Fourth Edition guidance and toolkit, gross motor milestones have been adjusted to reflect what’s really being seen as more parents adopt the Back to Sleep recommendations as well.
A standardized developmental screening tool is used at the 9-, 18-, and 30-month visits, and when parents or caregivers express concern about development. Autism-specific screening happens at 18 and 24 months.
“Remember this, if you remember nothing else: If the screening is positive, and you believe there’s a problem, you’re going to refer,” not just to the appropriate specialist but also for early intervention services, so time isn’t lost as the child is waiting for further evaluation and a formal diagnosis, said Dr. Hagan. This coordinated effort appropriately places the responsibility for early identification of developmental delays and disorders at the doorstep of the child’s medical home.
The federally-coordinated Birth to 5: Watch Me Thrive! effort has aggregated research-based screening tools, users’ guides targeted at a variety of audiences, and resources to help caregivers, said Dr. Hagan.
Four commonly-used tools to consider using during the visit are the Parents’ Evaluation of Developmental Status, the Ages and Stages Questionnaire, the Child Health and Development Interactive System, and the Survey of Wellbeing of Young Children. Of these, said Dr. Hagan, the latter is the only tool that’s in the public domain. However, he said, they are “all really good.”
Consider having parents fill out screening questionnaires in the waiting room before the visit, said Dr. Hagan. “I always tell my colleagues, ‘Have them start the visit without you, if you want to get it done in 18 minutes.’ ”
Two questionnaires per visit are available in the Bright Futures toolkit. One questionnaire asks developmental surveillance and risk assessment questions for selective screening. The second questionnaire asks prescreening questions to help with the anticipatory guidance part of the visit, he said. Having families do these ahead of time, said Dr. Hagan, “allows you to become more focused.”
Paying attention to practicalities can make all this go more smoothly, and maximize reimbursement as well. In his own practice, Dr. Hagan said, screening tools and questionnaires are integrated into the EHR system, so that appropriate paperwork prints automatically ahead of the visit.
It’s also worth reviewing billing practices to make sure that CPT code 96110 is used when administering screening with a standardized instrument and completing scoring and documentation. According to the Bright Futures periodicity schedule, this may be done at the 9-, 18-, and 30-month visits for developmental screening, as well as at 18 and 24 months for autism-specific screening.
Promoting lifelong health
Since the initial Bright Futures guidelines were published in the late 1990s, said Dr. Hagan, the focus has always been on seeing the child as part of the family, who, in turn, are part of the community, forming a framework that addresses the social components of child health. “If you’re not looking at the whole picture, you’re not promoting health,” he said. “It’s no big surprise that we now have a specific, called-out focus on promoting lifelong health.”
In the Fourth Edition, the theme of promoting lifelong health for families and communities is woven throughout, with social determinants of health being a specific visit priority. For example, questions about food insecurity have been drawn from the published literature and are included. Also, said Dr. Hagan, there’s specific anticipatory guidance content that’s clearly marked as addressing social determinants of health.
The fundamental importance of socioeconomic status as a social determinant of health was brought home by the Robert Wood Johnson Foundation’s Commission to Build a Healthier America, which demonstrated that, “Your ZIP code is more important to your health than your genetic code,” said Dr. Hagan. “So your work in health supervision is important, and you have been leaders in this effort.”
Research guides Bright Futures updates
The fourth edition of Bright Futures builds on health promotion themes to support the mental and physical health of children and adolescents, and has a robust framework of evidence underpinning the guidelines, said Dr. Hagan.
The goal is for clinicians to “use evidence to decide upon content of their own health supervision visits,” he explained.
The chapter of the Bright Futures guidelines that addresses the evidence and rationale for the guidelines has been expanded to better answer two questions, said Dr. Hagan: “What evidence grounds our recommendations?” and “What rationale did we use when evidence was insufficient or lacking?”
When possible, the editors of the guidelines used evidence-based sources such as recommendations from the USPSTF, the Centers for Disease Control Community Guide, and the Cochrane Collaboration.
There were many more evidence-based recommendations available to those working on the 4th edition than there had been when writing the previous edition, when, said Dr. Hagan, the USPSTF had exactly two recommendations for those under the age of 21 years. The current expanded number of USPSTF pediatric recommendations was due in part to the attention the AAP was able to bring regarding the need for evidence-based recommendations in pediatrics, he said.
When guidelines were not available, the editors also turned to high quality studies from peer reviewed publications. When such high quality evidence was lacking in a particular area, the guidelines make clear what rationale was used to formulate a given recommendation, and that some recommendations should be interpreted with a degree of caution.
And, said Dr. Hagan, even science-based guidelines will change as more data accumulates. “Don’t forget about peanuts!” he said. “It was really logical 15 years ago when we said don’t give peanut products until 1 year of age. And about 2 years ago, we found out that it really didn’t work.”
Although there are specific updates to clinical content, there also were changes made in broader strokes throughout the 4th edition. One of these shifts embeds social determinants of health in many visits. This adjustment acknowledges the growing body of knowledge that “strengths and protective factors make a difference, and risk factors make a difference” in pediatric outcomes.
A greater focus on lifelong physical and mental health is included under the general rubric of promoting lifelong health for families and communities. More emphasis is placed on promoting health for children and youth who have special health care needs as well.
Nuts-and-bolts changes in the updated 4th edition include updates for milestones of development and accompanying developmental surveillance questions, new clinical content and guidance for implementation that have been added based on strong evidence, and a variety of updates for adolescent screenings in particular.
The full 4th edition Bright Futures toolkit will be available for use in 2018.
Dr. Hagan was a coeditor of the Fourth Edition of Bright Futures.
*This article was updated on December 21, 2017
CHICAGO – Bracing his audience for a whirlwind tour of the many updates to the fourth edition of Bright Futures, Joseph F. Hagan Jr., MD, said that it’s still completely possible to fit Bright Futures visits into a clinic day.
“I practice primary care pediatrics,” said Dr. Hagan, a pediatrician in private practice and clinical professor of pediatrics at the University of Vermont, both in Burlington. “I said to my Bright Futures colleagues, if I didn’t think I could do this in 18 minutes, I wouldn’t ask you to do it.”
The Bright Futures framework, described by Dr. Hagan as the health prevention and disease prevention component of the medical home for children and youth, emerges in the Fourth Edition with a significant evidence-based refresher. The changes and updates are built within the existing framework and encompass surveillance and screening recommendations as well as anticipatory guidance. All content, including family handouts, has been updated, said Dr. Hagan, a coeditor of the Fourth Edition of Bright Futures. He spoke at the annual meeting of the American Academy of Pediatrics.
New clinical content
“What’s new? Maternal depression screening is new,” said Dr. Hagan, noting that the recommendation has long been under discussion. Now, supported by a 2016 United States Preventative Task Force (USPSTF) recommendation that carries a grade B level of evidence, all mothers should be screened for depression at the 1-, 2-, 4-, and 6-month Bright Futures visits.
However, he said, know your local regulations. “State mandates to do more might overrule this.” And conversely, “Just because we’re doing it universally until 6 months doesn’t mean you couldn’t selectively screen later if you have concerns.”
Safe sleep is another area with new clinical focus, he said. The new recommendation for the child to sleep in the parent’s room for “at least 6 months” draws on data from European studies showing lower mortality for children who share a room with parents during this period.
Clinicians should continue to recommend that parents not sleep with their infants in couches, chairs, or beds. As before, parents should be told not to have loose blankets, stuffed toys, or crib bumpers in their babies’ cribs. Another key message, said Dr. Hagan, is that “There is no such thing as safe ‘breast-sleeping.’ ”
Parents should be reminded not to swaddle at nap – or bedtime. The risk is that even a 2-month-old infant may be capable of wriggling over from back to front, and a swaddled infant whose hands are trapped may not be able to move to protect her airway once prone. “Swaddle for comfort, swaddle for crying, swaddle for nursing, but don’t swaddle for sleep” is the message, said Dr. Hagan.
For breast-fed babies, iron supplementation should begin at the 4-month visit. The notion is to prevent progression from iron deficiency to frank anemia, said Dr. Hagan. “We know that we screen for iron deficiency anemia … but we also know that before you’re iron deficient anemic, you’re iron deficient,” he said, and iron’s also critical to brain development. For convenience, switching from vitamin D alone to a multivitamin drop with iron at 4 months is a practical choice.
New dental health recommendations bring prevention to the pediatrician’s office. “Fluoride varnish? Do it!” said Dr. Hagan. Although the USPSTF made a 2014 grade B recommendation that primary care clinicians apply fluoride varnish to primary teeth as soon as they erupt, “It’s new to the Bright Futures periodicity schedule,” he said; parents can be assured that fluoride varnish does not cause fluorosis.
The good news for clinicians, he noted. “Once it hits the periodicity schedule, now, it’s a billable service that must be paid” under Affordable Care Act regulations, said Dr. Hagan. “Don’t let your insurer say, ‘That’s part of what you’re already being paid for.’ ” He recommends avoiding the pressure to bundle this important service. Use the discrete CPT code 99188, “Application of a fluoride varnish by a physician or other qualified health care professional.”
Although Bright Futures has updated recommendations for dyslipidemia blood screening, the USPSTF found insufficient evidence to back lipid screening for those younger than 20 years of age, citing an inability to assess the balance of benefits and harms for universal, rather than risk-based, screening. However, said Dr. Hagan, the American Academy of Pediatrics (AAP), and the National Heart, Lung, and Blood Institute (NHLBI) were looking at this issue at about the same time, and they “did a really good job of showing their work,” to show that if family history alone guided screening in the pediatric population, it “just wasn’t getting done.” And AAP and NHLBI did demonstrate evidence sufficient to support this recommendation.
Accordingly, Bright Futures recommends one screening between ages 9 and 11 years and an additional screening between ages 17 and 21. These windows are designed to bracket puberty, said Dr. Hagan, because values can be skewed during that period. “It’s billable, it’s not bundle-able, and I’d recommend that you do it,” he said.
Developmental surveillance and screening
What’s new with developmental surveillance and screening? “Well, we could argue that the milestones are something to think about, because the milestones are the cornerstone of developmental surveillance,” said Dr. Hagan. “You’re in the room with the child. You’re trained, you’re experienced, you’re smart, your gestalt tells you if their development is good or bad.”
As important as surveillance is, though, he said, it is “nowhere near as important as screening.” Surveillance happens at every well-child visit, but there’s no substitute for formal developmental screening. For the Fourth Edition guidance and toolkit, gross motor milestones have been adjusted to reflect what’s really being seen as more parents adopt the Back to Sleep recommendations as well.
A standardized developmental screening tool is used at the 9-, 18-, and 30-month visits, and when parents or caregivers express concern about development. Autism-specific screening happens at 18 and 24 months.
“Remember this, if you remember nothing else: If the screening is positive, and you believe there’s a problem, you’re going to refer,” not just to the appropriate specialist but also for early intervention services, so time isn’t lost as the child is waiting for further evaluation and a formal diagnosis, said Dr. Hagan. This coordinated effort appropriately places the responsibility for early identification of developmental delays and disorders at the doorstep of the child’s medical home.
The federally-coordinated Birth to 5: Watch Me Thrive! effort has aggregated research-based screening tools, users’ guides targeted at a variety of audiences, and resources to help caregivers, said Dr. Hagan.
Four commonly-used tools to consider using during the visit are the Parents’ Evaluation of Developmental Status, the Ages and Stages Questionnaire, the Child Health and Development Interactive System, and the Survey of Wellbeing of Young Children. Of these, said Dr. Hagan, the latter is the only tool that’s in the public domain. However, he said, they are “all really good.”
Consider having parents fill out screening questionnaires in the waiting room before the visit, said Dr. Hagan. “I always tell my colleagues, ‘Have them start the visit without you, if you want to get it done in 18 minutes.’ ”
Two questionnaires per visit are available in the Bright Futures toolkit. One questionnaire asks developmental surveillance and risk assessment questions for selective screening. The second questionnaire asks prescreening questions to help with the anticipatory guidance part of the visit, he said. Having families do these ahead of time, said Dr. Hagan, “allows you to become more focused.”
Paying attention to practicalities can make all this go more smoothly, and maximize reimbursement as well. In his own practice, Dr. Hagan said, screening tools and questionnaires are integrated into the EHR system, so that appropriate paperwork prints automatically ahead of the visit.
It’s also worth reviewing billing practices to make sure that CPT code 96110 is used when administering screening with a standardized instrument and completing scoring and documentation. According to the Bright Futures periodicity schedule, this may be done at the 9-, 18-, and 30-month visits for developmental screening, as well as at 18 and 24 months for autism-specific screening.
Promoting lifelong health
Since the initial Bright Futures guidelines were published in the late 1990s, said Dr. Hagan, the focus has always been on seeing the child as part of the family, who, in turn, are part of the community, forming a framework that addresses the social components of child health. “If you’re not looking at the whole picture, you’re not promoting health,” he said. “It’s no big surprise that we now have a specific, called-out focus on promoting lifelong health.”
In the Fourth Edition, the theme of promoting lifelong health for families and communities is woven throughout, with social determinants of health being a specific visit priority. For example, questions about food insecurity have been drawn from the published literature and are included. Also, said Dr. Hagan, there’s specific anticipatory guidance content that’s clearly marked as addressing social determinants of health.
The fundamental importance of socioeconomic status as a social determinant of health was brought home by the Robert Wood Johnson Foundation’s Commission to Build a Healthier America, which demonstrated that, “Your ZIP code is more important to your health than your genetic code,” said Dr. Hagan. “So your work in health supervision is important, and you have been leaders in this effort.”
Research guides Bright Futures updates
The fourth edition of Bright Futures builds on health promotion themes to support the mental and physical health of children and adolescents, and has a robust framework of evidence underpinning the guidelines, said Dr. Hagan.
The goal is for clinicians to “use evidence to decide upon content of their own health supervision visits,” he explained.
The chapter of the Bright Futures guidelines that addresses the evidence and rationale for the guidelines has been expanded to better answer two questions, said Dr. Hagan: “What evidence grounds our recommendations?” and “What rationale did we use when evidence was insufficient or lacking?”
When possible, the editors of the guidelines used evidence-based sources such as recommendations from the USPSTF, the Centers for Disease Control Community Guide, and the Cochrane Collaboration.
There were many more evidence-based recommendations available to those working on the 4th edition than there had been when writing the previous edition, when, said Dr. Hagan, the USPSTF had exactly two recommendations for those under the age of 21 years. The current expanded number of USPSTF pediatric recommendations was due in part to the attention the AAP was able to bring regarding the need for evidence-based recommendations in pediatrics, he said.
When guidelines were not available, the editors also turned to high quality studies from peer reviewed publications. When such high quality evidence was lacking in a particular area, the guidelines make clear what rationale was used to formulate a given recommendation, and that some recommendations should be interpreted with a degree of caution.
And, said Dr. Hagan, even science-based guidelines will change as more data accumulates. “Don’t forget about peanuts!” he said. “It was really logical 15 years ago when we said don’t give peanut products until 1 year of age. And about 2 years ago, we found out that it really didn’t work.”
Although there are specific updates to clinical content, there also were changes made in broader strokes throughout the 4th edition. One of these shifts embeds social determinants of health in many visits. This adjustment acknowledges the growing body of knowledge that “strengths and protective factors make a difference, and risk factors make a difference” in pediatric outcomes.
A greater focus on lifelong physical and mental health is included under the general rubric of promoting lifelong health for families and communities. More emphasis is placed on promoting health for children and youth who have special health care needs as well.
Nuts-and-bolts changes in the updated 4th edition include updates for milestones of development and accompanying developmental surveillance questions, new clinical content and guidance for implementation that have been added based on strong evidence, and a variety of updates for adolescent screenings in particular.
The full 4th edition Bright Futures toolkit will be available for use in 2018.
Dr. Hagan was a coeditor of the Fourth Edition of Bright Futures.
*This article was updated on December 21, 2017
EXPERT ANALYSIS FROM AAP 2017
Efficacy of neurostimulation for epilepsy underestimated with patient reports
WASHINGTON – The benefit of implanting a responsive brain stimulator for the control of refractory epilepsy may be grossly underestimated without relying on an objective measure of baseline seizure activity rather than patient reports, according to a study presented at the annual meeting of the American Epilepsy Society.
In a retrospective evaluation at one center, the efficacy of the Responsive Neurostimulation System (RNS) came nowhere near that observed in the pivotal clinical trial until objective measures of seizure activity were analyzed, reported Michael Young, DO, a neurophysiology fellow in the department of neurology at the University of California, Irvine (UCI).
In this study, investigators evaluated seizure frequency in the first 2 months after RNS implantation with the ECoG component of the RNS device. They assessed change in seizure frequency relative to this baseline at 3, 6, and 12 months, and also compared the reduction in seizures against the patient self-report of baseline seizure activity.
The differences were large. On patient report, the reduction in seizure activity at month 3 was just 10%, compared with 85% when measured on ECoG.
“Our results with the RNS compare favorably to the pivotal trial only when using the ECoG seizure frequency baseline. The reason for this discrepancy is due to underreporting of seizures by patients and consequently a falsely low seizure frequency,” Dr. Young explained at the meeting.
The RNS system has been implanted for refractory focal or partial seizures in adult patients at UCI since 2015. The device is indicated for adjunctive use in patients not adequately controlled on at least two antiepileptic medications. Twelve patients have been treated, but two were excluded from this analysis because they had surgical resection at the time of the RNS implantation and one because of an infection related to the implantation.
In general, patients treated at UCI had characteristics similar to those in the pivotal trial, which was published more than 3 years ago (Epilepsia. 2014;55[3]:432-41). In that 191-patient trial, the reduction in seizure frequency at the end of 5 months of blinded analysis with RNS was 37.9% versus 17.3% for a sham procedure. Progressive further reductions in seizure activity were observed during an extended open-label follow-up.
In the UCI analysis, the mean reduction in seizure frequency at 12 months was 56% relative to the patient-reported baseline but 78% on the basis of the ECoG analysis. Although only four of the nine patients have 12 or more months of follow-up, three were considered to be responders to RNS whether evaluated in relation to the patient-reported baseline seizure activity or in relation to ECoG. The responder rate at 3 months on the basis of patient-reported baseline activity, however, was only 56%, compared with 100% based on ECoG.
“The big issue is underreporting of seizures by patients,” Dr. Young explained. He cited numerous other studies demonstrating the same phenomenon. He noted that noncompliance is only one reason patients underreport. In many cases, patients are simply unaware of seizure activity.
Based on these data, “we think ECoG may be a more objective way to track patient response to RNS,” Dr. Young said. He acknowledged that the number of patients limits this study and suggested that larger studies are needed to confirm the findings.
Dr. Young reported having no potential conflicts of interest related to this topic.
SOURCE: Young M et al. AES abstract 3.109.
WASHINGTON – The benefit of implanting a responsive brain stimulator for the control of refractory epilepsy may be grossly underestimated without relying on an objective measure of baseline seizure activity rather than patient reports, according to a study presented at the annual meeting of the American Epilepsy Society.
In a retrospective evaluation at one center, the efficacy of the Responsive Neurostimulation System (RNS) came nowhere near that observed in the pivotal clinical trial until objective measures of seizure activity were analyzed, reported Michael Young, DO, a neurophysiology fellow in the department of neurology at the University of California, Irvine (UCI).
In this study, investigators evaluated seizure frequency in the first 2 months after RNS implantation with the ECoG component of the RNS device. They assessed change in seizure frequency relative to this baseline at 3, 6, and 12 months, and also compared the reduction in seizures against the patient self-report of baseline seizure activity.
The differences were large. On patient report, the reduction in seizure activity at month 3 was just 10%, compared with 85% when measured on ECoG.
“Our results with the RNS compare favorably to the pivotal trial only when using the ECoG seizure frequency baseline. The reason for this discrepancy is due to underreporting of seizures by patients and consequently a falsely low seizure frequency,” Dr. Young explained at the meeting.
The RNS system has been implanted for refractory focal or partial seizures in adult patients at UCI since 2015. The device is indicated for adjunctive use in patients not adequately controlled on at least two antiepileptic medications. Twelve patients have been treated, but two were excluded from this analysis because they had surgical resection at the time of the RNS implantation and one because of an infection related to the implantation.
In general, patients treated at UCI had characteristics similar to those in the pivotal trial, which was published more than 3 years ago (Epilepsia. 2014;55[3]:432-41). In that 191-patient trial, the reduction in seizure frequency at the end of 5 months of blinded analysis with RNS was 37.9% versus 17.3% for a sham procedure. Progressive further reductions in seizure activity were observed during an extended open-label follow-up.
In the UCI analysis, the mean reduction in seizure frequency at 12 months was 56% relative to the patient-reported baseline but 78% on the basis of the ECoG analysis. Although only four of the nine patients have 12 or more months of follow-up, three were considered to be responders to RNS whether evaluated in relation to the patient-reported baseline seizure activity or in relation to ECoG. The responder rate at 3 months on the basis of patient-reported baseline activity, however, was only 56%, compared with 100% based on ECoG.
“The big issue is underreporting of seizures by patients,” Dr. Young explained. He cited numerous other studies demonstrating the same phenomenon. He noted that noncompliance is only one reason patients underreport. In many cases, patients are simply unaware of seizure activity.
Based on these data, “we think ECoG may be a more objective way to track patient response to RNS,” Dr. Young said. He acknowledged that the number of patients limits this study and suggested that larger studies are needed to confirm the findings.
Dr. Young reported having no potential conflicts of interest related to this topic.
SOURCE: Young M et al. AES abstract 3.109.
WASHINGTON – The benefit of implanting a responsive brain stimulator for the control of refractory epilepsy may be grossly underestimated without relying on an objective measure of baseline seizure activity rather than patient reports, according to a study presented at the annual meeting of the American Epilepsy Society.
In a retrospective evaluation at one center, the efficacy of the Responsive Neurostimulation System (RNS) came nowhere near that observed in the pivotal clinical trial until objective measures of seizure activity were analyzed, reported Michael Young, DO, a neurophysiology fellow in the department of neurology at the University of California, Irvine (UCI).
In this study, investigators evaluated seizure frequency in the first 2 months after RNS implantation with the ECoG component of the RNS device. They assessed change in seizure frequency relative to this baseline at 3, 6, and 12 months, and also compared the reduction in seizures against the patient self-report of baseline seizure activity.
The differences were large. On patient report, the reduction in seizure activity at month 3 was just 10%, compared with 85% when measured on ECoG.
“Our results with the RNS compare favorably to the pivotal trial only when using the ECoG seizure frequency baseline. The reason for this discrepancy is due to underreporting of seizures by patients and consequently a falsely low seizure frequency,” Dr. Young explained at the meeting.
The RNS system has been implanted for refractory focal or partial seizures in adult patients at UCI since 2015. The device is indicated for adjunctive use in patients not adequately controlled on at least two antiepileptic medications. Twelve patients have been treated, but two were excluded from this analysis because they had surgical resection at the time of the RNS implantation and one because of an infection related to the implantation.
In general, patients treated at UCI had characteristics similar to those in the pivotal trial, which was published more than 3 years ago (Epilepsia. 2014;55[3]:432-41). In that 191-patient trial, the reduction in seizure frequency at the end of 5 months of blinded analysis with RNS was 37.9% versus 17.3% for a sham procedure. Progressive further reductions in seizure activity were observed during an extended open-label follow-up.
In the UCI analysis, the mean reduction in seizure frequency at 12 months was 56% relative to the patient-reported baseline but 78% on the basis of the ECoG analysis. Although only four of the nine patients have 12 or more months of follow-up, three were considered to be responders to RNS whether evaluated in relation to the patient-reported baseline seizure activity or in relation to ECoG. The responder rate at 3 months on the basis of patient-reported baseline activity, however, was only 56%, compared with 100% based on ECoG.
“The big issue is underreporting of seizures by patients,” Dr. Young explained. He cited numerous other studies demonstrating the same phenomenon. He noted that noncompliance is only one reason patients underreport. In many cases, patients are simply unaware of seizure activity.
Based on these data, “we think ECoG may be a more objective way to track patient response to RNS,” Dr. Young said. He acknowledged that the number of patients limits this study and suggested that larger studies are needed to confirm the findings.
Dr. Young reported having no potential conflicts of interest related to this topic.
SOURCE: Young M et al. AES abstract 3.109.
REPORTING FROM AES 2017
Key clinical point:
Major finding: At 3 months after implantation, seizure activity was reduced 10% by patient report but 85% by objective measurement.
Data source: Retrospective study of nine patients implanted with the Responsive Neurostimulation System.
Disclosures: Dr. Young reported having no potential conflicts of interest related to this topic.
Source: Young M et al. AES abstract 3.109.
Toy stethoscopes
Many of my articles are inspired when I observe discordant things juxtaposed. As we move deep into winter, once again I am confronted with the issue of infection control in the office and on the ward. Hospitals have gowns, gloves, masks, and toy stethoscopes. My outpatient offices rarely used more than the sink. In urgent care clinic, each evening I would swab three or four throats for strep, with one or two turning positive. I thought nothing of it, other than being glad when gagging a patient that I wear glasses. In the hospital, I must gown, glove, and mask for a patient with strep throat. The variations in practice between hospitals (I’ve been credentialed in 30) do not make me confident in the evidence base for infection control practices. I mentioned the Red Book to a second-year resident last week. He said he had seen it on a shelf but never actually used it.
In medical school, I was taught that the most important part of a stethoscope is between the ears. I believe that statement is true, but in a similar way to how I choose wines. My palate can’t tell the difference between a $15 and a $50 bottle of wine, so buying more expensive wine is a waste. However, a $3 bottle of wine is clearly inferior, if not undrinkable. There are oenophiles (one a distant cousin in Norway) who have trained their palates to tell the difference in wines, just as there are audiophiles who support the sales of $1,000 stereo speakers. Some fraction of those snobs may have justification. So, if cardiologists have strong opinions on stethoscopes, I won’t begrudge them their choice of a more expensive model. Their tastes do not mean that the average person should spend that much on wine, speakers, or stethoscopes. I will assert that there was a time when I could tell a day or two in advance that my otoscope bulb was going to burn out. The color balance was wrong. I carried a pocket otoscope for a few years when rounding in the hospital, but never found it as accurate as my original one. Every craftsman gets accustomed to their best tools.
A professional should be aware of the minimum quality of tool needed to get the job done.
Toy isolation stethoscopes ($3 each retail in bulk) add nothing to my discernment of an infant with bronchiolitis who is distressed, so I consider that equipment a waste of money and polluting to the environment. I typically use my stethoscope and foam it on leaving the room. There is evidence that either foam or alcohol pads are effective1 in killing germs, but no proof that this hygiene makes a difference clinically.2 The myriad researchers who have published about stethoscope contamination have stopped at padding their academic portfolios with something easy to publish, which basically is a high school science project using agar plates. They then make insinuations about policy, without any cost-benefit analysis. They really haven’t been bothered enough to advance the science of clinical medicine and actually measure a clinical impact of these policies. It is a corruption of science created by the publish-or-perish environment.
One survey found that 45% of physicians disinfect their stethoscope annually or less. Laundering of white coats follows a similar pattern, which is why the British National Health Service banned lab coats for physicians 10 years ago. No ties or long sleeve shirts either. I am smug knowing that my sartorial sense was ahead of my time in this regard.
The quality-improvement work of Ignaz Semmelweis should be required reading for all physicians. The control chart3 he published on puerperal fever in Vienna in the 1840s is spectacular. Infection control is important. Modern medical science cannot produce a similar control chart to justify the amount of dollars spent annually on gowns, gloves, masks, and toy stethoscopes. Sad.
Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at pdnews@frontlinemedcom.com.
References
1. Am J Infect Control. 2009 Apr;37(3):241-3.
2. J Hosp Infect. 2015 Sep;91(1):1-7.
3. https://en.wikipedia.org/wiki/Historical_mortality_rates_of_puerperal_fever
Many of my articles are inspired when I observe discordant things juxtaposed. As we move deep into winter, once again I am confronted with the issue of infection control in the office and on the ward. Hospitals have gowns, gloves, masks, and toy stethoscopes. My outpatient offices rarely used more than the sink. In urgent care clinic, each evening I would swab three or four throats for strep, with one or two turning positive. I thought nothing of it, other than being glad when gagging a patient that I wear glasses. In the hospital, I must gown, glove, and mask for a patient with strep throat. The variations in practice between hospitals (I’ve been credentialed in 30) do not make me confident in the evidence base for infection control practices. I mentioned the Red Book to a second-year resident last week. He said he had seen it on a shelf but never actually used it.
In medical school, I was taught that the most important part of a stethoscope is between the ears. I believe that statement is true, but in a similar way to how I choose wines. My palate can’t tell the difference between a $15 and a $50 bottle of wine, so buying more expensive wine is a waste. However, a $3 bottle of wine is clearly inferior, if not undrinkable. There are oenophiles (one a distant cousin in Norway) who have trained their palates to tell the difference in wines, just as there are audiophiles who support the sales of $1,000 stereo speakers. Some fraction of those snobs may have justification. So, if cardiologists have strong opinions on stethoscopes, I won’t begrudge them their choice of a more expensive model. Their tastes do not mean that the average person should spend that much on wine, speakers, or stethoscopes. I will assert that there was a time when I could tell a day or two in advance that my otoscope bulb was going to burn out. The color balance was wrong. I carried a pocket otoscope for a few years when rounding in the hospital, but never found it as accurate as my original one. Every craftsman gets accustomed to their best tools.
A professional should be aware of the minimum quality of tool needed to get the job done.
Toy isolation stethoscopes ($3 each retail in bulk) add nothing to my discernment of an infant with bronchiolitis who is distressed, so I consider that equipment a waste of money and polluting to the environment. I typically use my stethoscope and foam it on leaving the room. There is evidence that either foam or alcohol pads are effective1 in killing germs, but no proof that this hygiene makes a difference clinically.2 The myriad researchers who have published about stethoscope contamination have stopped at padding their academic portfolios with something easy to publish, which basically is a high school science project using agar plates. They then make insinuations about policy, without any cost-benefit analysis. They really haven’t been bothered enough to advance the science of clinical medicine and actually measure a clinical impact of these policies. It is a corruption of science created by the publish-or-perish environment.
One survey found that 45% of physicians disinfect their stethoscope annually or less. Laundering of white coats follows a similar pattern, which is why the British National Health Service banned lab coats for physicians 10 years ago. No ties or long sleeve shirts either. I am smug knowing that my sartorial sense was ahead of my time in this regard.
The quality-improvement work of Ignaz Semmelweis should be required reading for all physicians. The control chart3 he published on puerperal fever in Vienna in the 1840s is spectacular. Infection control is important. Modern medical science cannot produce a similar control chart to justify the amount of dollars spent annually on gowns, gloves, masks, and toy stethoscopes. Sad.
Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at pdnews@frontlinemedcom.com.
References
1. Am J Infect Control. 2009 Apr;37(3):241-3.
2. J Hosp Infect. 2015 Sep;91(1):1-7.
3. https://en.wikipedia.org/wiki/Historical_mortality_rates_of_puerperal_fever
Many of my articles are inspired when I observe discordant things juxtaposed. As we move deep into winter, once again I am confronted with the issue of infection control in the office and on the ward. Hospitals have gowns, gloves, masks, and toy stethoscopes. My outpatient offices rarely used more than the sink. In urgent care clinic, each evening I would swab three or four throats for strep, with one or two turning positive. I thought nothing of it, other than being glad when gagging a patient that I wear glasses. In the hospital, I must gown, glove, and mask for a patient with strep throat. The variations in practice between hospitals (I’ve been credentialed in 30) do not make me confident in the evidence base for infection control practices. I mentioned the Red Book to a second-year resident last week. He said he had seen it on a shelf but never actually used it.
In medical school, I was taught that the most important part of a stethoscope is between the ears. I believe that statement is true, but in a similar way to how I choose wines. My palate can’t tell the difference between a $15 and a $50 bottle of wine, so buying more expensive wine is a waste. However, a $3 bottle of wine is clearly inferior, if not undrinkable. There are oenophiles (one a distant cousin in Norway) who have trained their palates to tell the difference in wines, just as there are audiophiles who support the sales of $1,000 stereo speakers. Some fraction of those snobs may have justification. So, if cardiologists have strong opinions on stethoscopes, I won’t begrudge them their choice of a more expensive model. Their tastes do not mean that the average person should spend that much on wine, speakers, or stethoscopes. I will assert that there was a time when I could tell a day or two in advance that my otoscope bulb was going to burn out. The color balance was wrong. I carried a pocket otoscope for a few years when rounding in the hospital, but never found it as accurate as my original one. Every craftsman gets accustomed to their best tools.
A professional should be aware of the minimum quality of tool needed to get the job done.
Toy isolation stethoscopes ($3 each retail in bulk) add nothing to my discernment of an infant with bronchiolitis who is distressed, so I consider that equipment a waste of money and polluting to the environment. I typically use my stethoscope and foam it on leaving the room. There is evidence that either foam or alcohol pads are effective1 in killing germs, but no proof that this hygiene makes a difference clinically.2 The myriad researchers who have published about stethoscope contamination have stopped at padding their academic portfolios with something easy to publish, which basically is a high school science project using agar plates. They then make insinuations about policy, without any cost-benefit analysis. They really haven’t been bothered enough to advance the science of clinical medicine and actually measure a clinical impact of these policies. It is a corruption of science created by the publish-or-perish environment.
One survey found that 45% of physicians disinfect their stethoscope annually or less. Laundering of white coats follows a similar pattern, which is why the British National Health Service banned lab coats for physicians 10 years ago. No ties or long sleeve shirts either. I am smug knowing that my sartorial sense was ahead of my time in this regard.
The quality-improvement work of Ignaz Semmelweis should be required reading for all physicians. The control chart3 he published on puerperal fever in Vienna in the 1840s is spectacular. Infection control is important. Modern medical science cannot produce a similar control chart to justify the amount of dollars spent annually on gowns, gloves, masks, and toy stethoscopes. Sad.
Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at pdnews@frontlinemedcom.com.
References
1. Am J Infect Control. 2009 Apr;37(3):241-3.
2. J Hosp Infect. 2015 Sep;91(1):1-7.
3. https://en.wikipedia.org/wiki/Historical_mortality_rates_of_puerperal_fever
Many Vets Lack Easy Access to Healthy Food Outlets
The nearly 21 million military veterans living in the U.S. are heavier than the civilian population, with 64% of the women and 76% of the men being overweight or obese. Why? It may have a lot to do with where they live, according to a study by researchers from University of Illinois at Chicago and Edward Hines, Jr. VA Hospital, among others. According to the study, 89% of veterans live in areas with few nearby food outlets that offer healthy, affordable food and fewer facilities for recreational activities.
The researchers used American Community Survey data to determine the percentage of veterans among the adult population in all continental U.S. census tracts in 2013. They then used proprietary data to construct measures of availability of food and recreational venues per census tract.
Related: Food Insecurity Among Veterans
In census tracts with high concentrations of veterans, residents had, on average, 0.5 supermarkets within a 1-mile radius, compared with census tracts with low concentrations of veterans, which had 3.2 supermarkets. Patterns were similar for grocery and convenience stores, fast food restaurants, parks, and commercial fitness facilities. Put another way, the residents in a high-concentration census tract were 72% less likely to live within 1 mile of a supermarket.
The researchers note that veterans’ residential patterns differ from those of the general population. Some states have a “disproportionate” number of veterans, partly because they tend to cluster near military installations and in rural areas. They also state that veterans may be more vulnerable to weight gain because of factors including service-connected disability, depression, and anxiety.
Related: Smoking and Food Insecurity: How to Solve a Dual Challenge?
Given recent recognition of the importance of availability of healthy foods and recreational venues to diet and physical activity, the researchers say, the environmental variations they found “raise questions about their potential effect on veterans’ health.”
The nearly 21 million military veterans living in the U.S. are heavier than the civilian population, with 64% of the women and 76% of the men being overweight or obese. Why? It may have a lot to do with where they live, according to a study by researchers from University of Illinois at Chicago and Edward Hines, Jr. VA Hospital, among others. According to the study, 89% of veterans live in areas with few nearby food outlets that offer healthy, affordable food and fewer facilities for recreational activities.
The researchers used American Community Survey data to determine the percentage of veterans among the adult population in all continental U.S. census tracts in 2013. They then used proprietary data to construct measures of availability of food and recreational venues per census tract.
Related: Food Insecurity Among Veterans
In census tracts with high concentrations of veterans, residents had, on average, 0.5 supermarkets within a 1-mile radius, compared with census tracts with low concentrations of veterans, which had 3.2 supermarkets. Patterns were similar for grocery and convenience stores, fast food restaurants, parks, and commercial fitness facilities. Put another way, the residents in a high-concentration census tract were 72% less likely to live within 1 mile of a supermarket.
The researchers note that veterans’ residential patterns differ from those of the general population. Some states have a “disproportionate” number of veterans, partly because they tend to cluster near military installations and in rural areas. They also state that veterans may be more vulnerable to weight gain because of factors including service-connected disability, depression, and anxiety.
Related: Smoking and Food Insecurity: How to Solve a Dual Challenge?
Given recent recognition of the importance of availability of healthy foods and recreational venues to diet and physical activity, the researchers say, the environmental variations they found “raise questions about their potential effect on veterans’ health.”
The nearly 21 million military veterans living in the U.S. are heavier than the civilian population, with 64% of the women and 76% of the men being overweight or obese. Why? It may have a lot to do with where they live, according to a study by researchers from University of Illinois at Chicago and Edward Hines, Jr. VA Hospital, among others. According to the study, 89% of veterans live in areas with few nearby food outlets that offer healthy, affordable food and fewer facilities for recreational activities.
The researchers used American Community Survey data to determine the percentage of veterans among the adult population in all continental U.S. census tracts in 2013. They then used proprietary data to construct measures of availability of food and recreational venues per census tract.
Related: Food Insecurity Among Veterans
In census tracts with high concentrations of veterans, residents had, on average, 0.5 supermarkets within a 1-mile radius, compared with census tracts with low concentrations of veterans, which had 3.2 supermarkets. Patterns were similar for grocery and convenience stores, fast food restaurants, parks, and commercial fitness facilities. Put another way, the residents in a high-concentration census tract were 72% less likely to live within 1 mile of a supermarket.
The researchers note that veterans’ residential patterns differ from those of the general population. Some states have a “disproportionate” number of veterans, partly because they tend to cluster near military installations and in rural areas. They also state that veterans may be more vulnerable to weight gain because of factors including service-connected disability, depression, and anxiety.
Related: Smoking and Food Insecurity: How to Solve a Dual Challenge?
Given recent recognition of the importance of availability of healthy foods and recreational venues to diet and physical activity, the researchers say, the environmental variations they found “raise questions about their potential effect on veterans’ health.”
Edoxaban noninferior to dalteparin for VTE in cancer
ATLANTA—Edoxaban is noninferior to dalteparin for the treatment of cancer-associated venous thromboembolism (VTE), a phase 3 study suggests.
In the Hokusai-VTE CANCER study, patients who received edoxaban had a lower rate of VTE recurrence but a higher rate of major bleeding than patients who received dalteparin.
Rates of VTE recurrence and major bleeding combined were similar between the treatment groups, as were rates of survival free from VTE or major bleeding.
Gary E. Raskob, PhD, of the University of Oklahoma Health Sciences Center in Oklahoma City, presented these results at the 2017 ASH Annual Meeting (LBA-6).
Results were simultaneously published in NEJM. The study was funded by Daiichi Sankyo.
Patients and treatment
Hokusai-VTE CANCER enrolled 1050 adult cancer patients with acute VTE confirmed by imaging. Patients had either active cancer or had been diagnosed with cancer within 2 years from study enrollment. Patients with basal-cell or squamous-cell skin cancer were excluded.
Patients were randomized to receive edoxaban or dalteparin for at least 6 months and up to 12 months.
Edoxaban was given at 60 mg once daily (reduced to 30 mg for patients with creatinine clearance 30-50 mL/min, body weight ≤ 60 kg, or concomitant use of P-glycoprotein inhibitors), following treatment with low-molecular-weight heparin for at least 5 days.
Dalteparin was given at 200 IU/kg once daily for 30 days, then at 150 IU/kg once daily for the remainder of the study.
The median treatment duration was 211 days (interquartile range, 76 to 357) in the edoxaban arm and 184 days (interquartile range, 85 to 341) in the dalteparin arm.
Baseline characteristics were similar between the treatment arms. The median age was 64 in both arms, and about half of patients in each arm were male.
Roughly 98% of patients in each arm had active cancer, 53% had metastatic disease, 29% (dalteparin) and 31% (edoxaban) had recurrent cancer, and 72% (edoxaban) and 73% (dalteparin) had received cancer treatment in the previous 4 weeks.
About 63% of patients in each arm had pulmonary embolism (PE) with or without deep-vein thrombosis (DVT), and 37% had DVT only.
About 18% of patients had 0 risk factors for bleeding, 28% (edoxaban) and 29% (dalteparin) had 1 risk factor, 30% (dalteparin) and 33% (edoxaban) had 2 risk factors, and 21% (edoxaban) and 23% (dalteparin) had 3 or more risk factors for bleeding.
Results
The study’s primary outcome was a composite of first recurrent VTE and major bleeding event during the 12 months after randomization, regardless of treatment duration.
This outcome occurred in 12.8% (67/522) of patients in the edoxaban arm and 13.5% (71/524) of patients in the dalteparin arm. The hazard ratio (HR) with edoxaban was 0.97 (P=0.006 for non-inferiority, P=0.87 for superiority).
“Oral edoxaban is noninferior to subcutaneous dalteparin for the primary outcome of recurrent VTE or major bleeding,” Dr Raskob noted. “The lower rate of recurrent VTE observed with edoxaban was offset by a similar increase in the risk of major bleeding.”
The rate of recurrent VTE during the 12-month study period was 7.9% (n=41) in the edoxaban arm and 11.3% (n=59) in the dalteparin arm (HR=0.71, P=0.09). The rates of recurrent DVT were 3.6% and 6.7%, respectively (HR=0.56), and the rates of recurrent PE were 5.2% and 5.3%, respectively (HR=1.00).
The rate of major bleeding during the 12-month period was 6.9% (n=36) in the edoxaban arm and 4.0% (n=21) in the dalteparin arm (HR=1.77, P=0.04). The rates of clinically relevant nonmajor bleeding were 14.6% and 11.1%, respectively (HR=1.38), and the rates of major or clinically relevant nonmajor bleeding were 18.6% and 13.9%, respectively (HR=1.40).
“There was more upper GI [gastrointestinal] bleeding with edoxaban,” Dr Raskob noted. “It occurred predominantly in patients with GI cancer at the time of entry in the study.”
Death from any cause occurred in 39.5% of patients in the edoxaban arm and 36.6% of patients in the dalteparin arm (HR=1.12).
The rate of event-free survival (absence of recurrent VTE, major bleeding, and death) was 55.0% in the edoxaban arm and 56.5% in the dalteparin arm (HR=0.93).
“The bottom line for patients and oncologists is, ‘Does the patient survive free of these complications?’” Dr Raskob said. “Survival free of recurrent VTE or major bleeding was similar with these regimens.” 
ATLANTA—Edoxaban is noninferior to dalteparin for the treatment of cancer-associated venous thromboembolism (VTE), a phase 3 study suggests.
In the Hokusai-VTE CANCER study, patients who received edoxaban had a lower rate of VTE recurrence but a higher rate of major bleeding than patients who received dalteparin.
Rates of VTE recurrence and major bleeding combined were similar between the treatment groups, as were rates of survival free from VTE or major bleeding.
Gary E. Raskob, PhD, of the University of Oklahoma Health Sciences Center in Oklahoma City, presented these results at the 2017 ASH Annual Meeting (LBA-6).
Results were simultaneously published in NEJM. The study was funded by Daiichi Sankyo.
Patients and treatment
Hokusai-VTE CANCER enrolled 1050 adult cancer patients with acute VTE confirmed by imaging. Patients had either active cancer or had been diagnosed with cancer within 2 years from study enrollment. Patients with basal-cell or squamous-cell skin cancer were excluded.
Patients were randomized to receive edoxaban or dalteparin for at least 6 months and up to 12 months.
Edoxaban was given at 60 mg once daily (reduced to 30 mg for patients with creatinine clearance 30-50 mL/min, body weight ≤ 60 kg, or concomitant use of P-glycoprotein inhibitors), following treatment with low-molecular-weight heparin for at least 5 days.
Dalteparin was given at 200 IU/kg once daily for 30 days, then at 150 IU/kg once daily for the remainder of the study.
The median treatment duration was 211 days (interquartile range, 76 to 357) in the edoxaban arm and 184 days (interquartile range, 85 to 341) in the dalteparin arm.
Baseline characteristics were similar between the treatment arms. The median age was 64 in both arms, and about half of patients in each arm were male.
Roughly 98% of patients in each arm had active cancer, 53% had metastatic disease, 29% (dalteparin) and 31% (edoxaban) had recurrent cancer, and 72% (edoxaban) and 73% (dalteparin) had received cancer treatment in the previous 4 weeks.
About 63% of patients in each arm had pulmonary embolism (PE) with or without deep-vein thrombosis (DVT), and 37% had DVT only.
About 18% of patients had 0 risk factors for bleeding, 28% (edoxaban) and 29% (dalteparin) had 1 risk factor, 30% (dalteparin) and 33% (edoxaban) had 2 risk factors, and 21% (edoxaban) and 23% (dalteparin) had 3 or more risk factors for bleeding.
Results
The study’s primary outcome was a composite of first recurrent VTE and major bleeding event during the 12 months after randomization, regardless of treatment duration.
This outcome occurred in 12.8% (67/522) of patients in the edoxaban arm and 13.5% (71/524) of patients in the dalteparin arm. The hazard ratio (HR) with edoxaban was 0.97 (P=0.006 for non-inferiority, P=0.87 for superiority).
“Oral edoxaban is noninferior to subcutaneous dalteparin for the primary outcome of recurrent VTE or major bleeding,” Dr Raskob noted. “The lower rate of recurrent VTE observed with edoxaban was offset by a similar increase in the risk of major bleeding.”
The rate of recurrent VTE during the 12-month study period was 7.9% (n=41) in the edoxaban arm and 11.3% (n=59) in the dalteparin arm (HR=0.71, P=0.09). The rates of recurrent DVT were 3.6% and 6.7%, respectively (HR=0.56), and the rates of recurrent PE were 5.2% and 5.3%, respectively (HR=1.00).
The rate of major bleeding during the 12-month period was 6.9% (n=36) in the edoxaban arm and 4.0% (n=21) in the dalteparin arm (HR=1.77, P=0.04). The rates of clinically relevant nonmajor bleeding were 14.6% and 11.1%, respectively (HR=1.38), and the rates of major or clinically relevant nonmajor bleeding were 18.6% and 13.9%, respectively (HR=1.40).
“There was more upper GI [gastrointestinal] bleeding with edoxaban,” Dr Raskob noted. “It occurred predominantly in patients with GI cancer at the time of entry in the study.”
Death from any cause occurred in 39.5% of patients in the edoxaban arm and 36.6% of patients in the dalteparin arm (HR=1.12).
The rate of event-free survival (absence of recurrent VTE, major bleeding, and death) was 55.0% in the edoxaban arm and 56.5% in the dalteparin arm (HR=0.93).
“The bottom line for patients and oncologists is, ‘Does the patient survive free of these complications?’” Dr Raskob said. “Survival free of recurrent VTE or major bleeding was similar with these regimens.”
ATLANTA—Edoxaban is noninferior to dalteparin for the treatment of cancer-associated venous thromboembolism (VTE), a phase 3 study suggests.
In the Hokusai-VTE CANCER study, patients who received edoxaban had a lower rate of VTE recurrence but a higher rate of major bleeding than patients who received dalteparin.
Rates of VTE recurrence and major bleeding combined were similar between the treatment groups, as were rates of survival free from VTE or major bleeding.
Gary E. Raskob, PhD, of the University of Oklahoma Health Sciences Center in Oklahoma City, presented these results at the 2017 ASH Annual Meeting (LBA-6).
Results were simultaneously published in NEJM. The study was funded by Daiichi Sankyo.
Patients and treatment
Hokusai-VTE CANCER enrolled 1050 adult cancer patients with acute VTE confirmed by imaging. Patients had either active cancer or had been diagnosed with cancer within 2 years from study enrollment. Patients with basal-cell or squamous-cell skin cancer were excluded.
Patients were randomized to receive edoxaban or dalteparin for at least 6 months and up to 12 months.
Edoxaban was given at 60 mg once daily (reduced to 30 mg for patients with creatinine clearance 30-50 mL/min, body weight ≤ 60 kg, or concomitant use of P-glycoprotein inhibitors), following treatment with low-molecular-weight heparin for at least 5 days.
Dalteparin was given at 200 IU/kg once daily for 30 days, then at 150 IU/kg once daily for the remainder of the study.
The median treatment duration was 211 days (interquartile range, 76 to 357) in the edoxaban arm and 184 days (interquartile range, 85 to 341) in the dalteparin arm.
Baseline characteristics were similar between the treatment arms. The median age was 64 in both arms, and about half of patients in each arm were male.
Roughly 98% of patients in each arm had active cancer, 53% had metastatic disease, 29% (dalteparin) and 31% (edoxaban) had recurrent cancer, and 72% (edoxaban) and 73% (dalteparin) had received cancer treatment in the previous 4 weeks.
About 63% of patients in each arm had pulmonary embolism (PE) with or without deep-vein thrombosis (DVT), and 37% had DVT only.
About 18% of patients had 0 risk factors for bleeding, 28% (edoxaban) and 29% (dalteparin) had 1 risk factor, 30% (dalteparin) and 33% (edoxaban) had 2 risk factors, and 21% (edoxaban) and 23% (dalteparin) had 3 or more risk factors for bleeding.
Results
The study’s primary outcome was a composite of first recurrent VTE and major bleeding event during the 12 months after randomization, regardless of treatment duration.
This outcome occurred in 12.8% (67/522) of patients in the edoxaban arm and 13.5% (71/524) of patients in the dalteparin arm. The hazard ratio (HR) with edoxaban was 0.97 (P=0.006 for non-inferiority, P=0.87 for superiority).
“Oral edoxaban is noninferior to subcutaneous dalteparin for the primary outcome of recurrent VTE or major bleeding,” Dr Raskob noted. “The lower rate of recurrent VTE observed with edoxaban was offset by a similar increase in the risk of major bleeding.”
The rate of recurrent VTE during the 12-month study period was 7.9% (n=41) in the edoxaban arm and 11.3% (n=59) in the dalteparin arm (HR=0.71, P=0.09). The rates of recurrent DVT were 3.6% and 6.7%, respectively (HR=0.56), and the rates of recurrent PE were 5.2% and 5.3%, respectively (HR=1.00).
The rate of major bleeding during the 12-month period was 6.9% (n=36) in the edoxaban arm and 4.0% (n=21) in the dalteparin arm (HR=1.77, P=0.04). The rates of clinically relevant nonmajor bleeding were 14.6% and 11.1%, respectively (HR=1.38), and the rates of major or clinically relevant nonmajor bleeding were 18.6% and 13.9%, respectively (HR=1.40).
“There was more upper GI [gastrointestinal] bleeding with edoxaban,” Dr Raskob noted. “It occurred predominantly in patients with GI cancer at the time of entry in the study.”
Death from any cause occurred in 39.5% of patients in the edoxaban arm and 36.6% of patients in the dalteparin arm (HR=1.12).
The rate of event-free survival (absence of recurrent VTE, major bleeding, and death) was 55.0% in the edoxaban arm and 56.5% in the dalteparin arm (HR=0.93).
“The bottom line for patients and oncologists is, ‘Does the patient survive free of these complications?’” Dr Raskob said. “Survival free of recurrent VTE or major bleeding was similar with these regimens.”
FDA lifts clinical hold on fitusiran trials
The US Food and Drug Administration (FDA) has lifted the hold on clinical trials of fitusiran, an RNAi therapeutic being developed to treat patients with hemophilia A and B, with and without inhibitors.
The hold encompassed a phase 2 open-label extension study and the ATLAS phase 3 program, which includes 3 separate trials.
Dosing was suspended in these trials after a fatal thrombotic event was reported in a patient enrolled on the phase 2 trial.
The patient had hemophilia A without inhibitors. He developed exercise-induced right hip pain that was treated with 3 doses of factor VIII concentrate (31-46 IU/kg) on 3 separate days.
The patient then developed a cerebral venous sinus thrombosis that was considered possibly related to treatment. He ultimately died of cerebral edema.
As a result of this death, Alnylam Pharmaceuticals, Inc., (the company developing fitusiran with Sanofi Genzyme) announced the hold on fitusiran trials in September.
Since then, Alnylam has reached an agreement with the FDA on new clinical risk mitigation measures for fitusiran trials. This includes protocol-specified guidelines and additional investigator and patient education concerning reduced doses of replacement factor or bypassing agent to treat any breakthrough bleeds in fitusiran studies.
With these protocol amendments in place and clinical materials updated, the FDA has lifted the hold on fitusiran trials.
“We are pleased with the FDA’s decision to lift the clinical hold, as fitusiran holds the potential to help improve the lives of people living with hemophilia,” said Akin Akinc, PhD, vice-president and general manager of fitusiran at Alnylam.
“With the additional risk mitigation measures in place, we look forward to the continued late-stage development of fitusiran and expect to resume dosing around year-end.”
About fitusiran
Fitusiran is an investigational, once-monthly, subcutaneously administered RNAi therapeutic targeting antithrombin. It is in development for the treatment of hemophilia A and B, with and without inhibitors.
Fitusiran is designed to lower levels of antithrombin with the goal of promoting sufficient thrombin generation to restore hemostasis and prevent bleeding.
Fitusiran is under investigation in a phase 2 open-label extension study of patients with moderate or severe hemophilia A or B who have participated in a previous clinical study of fitusiran.
The therapy is also being tested in the phase 3 ATLAS program, which includes 3 trials.
The ATLAS-INH trial is a 9-month, randomized, active controlled study designed to enroll approximately 50 patients with hemophilia A or B with inhibitors who received prior on-demand therapy.
The ATLAS-A/B trial is a 9-month, randomized, active controlled study designed to enroll approximately 100 patients with hemophilia A or B without inhibitors who received prior on-demand therapy.
The ATLAS-PPX trial is a one-way crossover study designed to enroll approximately 100 patients with hemophilia A or B, with or without inhibitors, receiving prophylaxis therapy as prior standard of care.
In ATLAS-PPX, patients receive standard of care prophylaxis for 6 months and then transition to fitusiran treatment for 7 months. The study’s primary endpoint is the annualized bleeding rate in the fitusiran period and in the factor/bypassing agent prophylaxis period.
The US Food and Drug Administration (FDA) has lifted the hold on clinical trials of fitusiran, an RNAi therapeutic being developed to treat patients with hemophilia A and B, with and without inhibitors.
The hold encompassed a phase 2 open-label extension study and the ATLAS phase 3 program, which includes 3 separate trials.
Dosing was suspended in these trials after a fatal thrombotic event was reported in a patient enrolled on the phase 2 trial.
The patient had hemophilia A without inhibitors. He developed exercise-induced right hip pain that was treated with 3 doses of factor VIII concentrate (31-46 IU/kg) on 3 separate days.
The patient then developed a cerebral venous sinus thrombosis that was considered possibly related to treatment. He ultimately died of cerebral edema.
As a result of this death, Alnylam Pharmaceuticals, Inc., (the company developing fitusiran with Sanofi Genzyme) announced the hold on fitusiran trials in September.
Since then, Alnylam has reached an agreement with the FDA on new clinical risk mitigation measures for fitusiran trials. This includes protocol-specified guidelines and additional investigator and patient education concerning reduced doses of replacement factor or bypassing agent to treat any breakthrough bleeds in fitusiran studies.
With these protocol amendments in place and clinical materials updated, the FDA has lifted the hold on fitusiran trials.
“We are pleased with the FDA’s decision to lift the clinical hold, as fitusiran holds the potential to help improve the lives of people living with hemophilia,” said Akin Akinc, PhD, vice-president and general manager of fitusiran at Alnylam.
“With the additional risk mitigation measures in place, we look forward to the continued late-stage development of fitusiran and expect to resume dosing around year-end.”
About fitusiran
Fitusiran is an investigational, once-monthly, subcutaneously administered RNAi therapeutic targeting antithrombin. It is in development for the treatment of hemophilia A and B, with and without inhibitors.
Fitusiran is designed to lower levels of antithrombin with the goal of promoting sufficient thrombin generation to restore hemostasis and prevent bleeding.
Fitusiran is under investigation in a phase 2 open-label extension study of patients with moderate or severe hemophilia A or B who have participated in a previous clinical study of fitusiran.
The therapy is also being tested in the phase 3 ATLAS program, which includes 3 trials.
The ATLAS-INH trial is a 9-month, randomized, active controlled study designed to enroll approximately 50 patients with hemophilia A or B with inhibitors who received prior on-demand therapy.
The ATLAS-A/B trial is a 9-month, randomized, active controlled study designed to enroll approximately 100 patients with hemophilia A or B without inhibitors who received prior on-demand therapy.
The ATLAS-PPX trial is a one-way crossover study designed to enroll approximately 100 patients with hemophilia A or B, with or without inhibitors, receiving prophylaxis therapy as prior standard of care.
In ATLAS-PPX, patients receive standard of care prophylaxis for 6 months and then transition to fitusiran treatment for 7 months. The study’s primary endpoint is the annualized bleeding rate in the fitusiran period and in the factor/bypassing agent prophylaxis period.
The US Food and Drug Administration (FDA) has lifted the hold on clinical trials of fitusiran, an RNAi therapeutic being developed to treat patients with hemophilia A and B, with and without inhibitors.
The hold encompassed a phase 2 open-label extension study and the ATLAS phase 3 program, which includes 3 separate trials.
Dosing was suspended in these trials after a fatal thrombotic event was reported in a patient enrolled on the phase 2 trial.
The patient had hemophilia A without inhibitors. He developed exercise-induced right hip pain that was treated with 3 doses of factor VIII concentrate (31-46 IU/kg) on 3 separate days.
The patient then developed a cerebral venous sinus thrombosis that was considered possibly related to treatment. He ultimately died of cerebral edema.
As a result of this death, Alnylam Pharmaceuticals, Inc., (the company developing fitusiran with Sanofi Genzyme) announced the hold on fitusiran trials in September.
Since then, Alnylam has reached an agreement with the FDA on new clinical risk mitigation measures for fitusiran trials. This includes protocol-specified guidelines and additional investigator and patient education concerning reduced doses of replacement factor or bypassing agent to treat any breakthrough bleeds in fitusiran studies.
With these protocol amendments in place and clinical materials updated, the FDA has lifted the hold on fitusiran trials.
“We are pleased with the FDA’s decision to lift the clinical hold, as fitusiran holds the potential to help improve the lives of people living with hemophilia,” said Akin Akinc, PhD, vice-president and general manager of fitusiran at Alnylam.
“With the additional risk mitigation measures in place, we look forward to the continued late-stage development of fitusiran and expect to resume dosing around year-end.”
About fitusiran
Fitusiran is an investigational, once-monthly, subcutaneously administered RNAi therapeutic targeting antithrombin. It is in development for the treatment of hemophilia A and B, with and without inhibitors.
Fitusiran is designed to lower levels of antithrombin with the goal of promoting sufficient thrombin generation to restore hemostasis and prevent bleeding.
Fitusiran is under investigation in a phase 2 open-label extension study of patients with moderate or severe hemophilia A or B who have participated in a previous clinical study of fitusiran.
The therapy is also being tested in the phase 3 ATLAS program, which includes 3 trials.
The ATLAS-INH trial is a 9-month, randomized, active controlled study designed to enroll approximately 50 patients with hemophilia A or B with inhibitors who received prior on-demand therapy.
The ATLAS-A/B trial is a 9-month, randomized, active controlled study designed to enroll approximately 100 patients with hemophilia A or B without inhibitors who received prior on-demand therapy.
The ATLAS-PPX trial is a one-way crossover study designed to enroll approximately 100 patients with hemophilia A or B, with or without inhibitors, receiving prophylaxis therapy as prior standard of care.
In ATLAS-PPX, patients receive standard of care prophylaxis for 6 months and then transition to fitusiran treatment for 7 months. The study’s primary endpoint is the annualized bleeding rate in the fitusiran period and in the factor/bypassing agent prophylaxis period.
NK cell product receives orphan designation
The European Commission has granted orphan designation to a natural killer (NK) cell product for the treatment of multiple myeloma.
The product, called CellProtect, is manufactured from a patient’s own blood.
It consists of NK cells that have been activated and expanded so they can recognize and attack cancer cells.
CellProtect has been studied in a phase 1/2 trial of patients with multiple myeloma.
In this trial, the NK cell product was used as a supplement to autologous stem cell transplant.
CellProtect exhibited a good safety profile and signals of effect in the trial, according to CellProtect Nordic Pharmaceuticals AB, the company developing CellProtect.
Results from the trial are expected to be published in 2018.
“The decision from the commission is based on a recommendation from the European Medicines Agency’s Committee for Orphan Medicinal Products and confirms that a future product is considered to be of significant benefit to those suffering from multiple myeloma,” said Karin Mellström, chief executive officer of CellProtect Nordic Pharmaceuticals AB.
“We can now proceed and plan for additional clinical trials in order to receive approval to market CellProtect.”
Orphan designation from the European Commission provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if a therapy receives regulatory approval.
The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.
The European Medicines Agency’s Committee for Orphan Medicinal Products adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision.
The European Commission has granted orphan designation to a natural killer (NK) cell product for the treatment of multiple myeloma.
The product, called CellProtect, is manufactured from a patient’s own blood.
It consists of NK cells that have been activated and expanded so they can recognize and attack cancer cells.
CellProtect has been studied in a phase 1/2 trial of patients with multiple myeloma.
In this trial, the NK cell product was used as a supplement to autologous stem cell transplant.
CellProtect exhibited a good safety profile and signals of effect in the trial, according to CellProtect Nordic Pharmaceuticals AB, the company developing CellProtect.
Results from the trial are expected to be published in 2018.
“The decision from the commission is based on a recommendation from the European Medicines Agency’s Committee for Orphan Medicinal Products and confirms that a future product is considered to be of significant benefit to those suffering from multiple myeloma,” said Karin Mellström, chief executive officer of CellProtect Nordic Pharmaceuticals AB.
“We can now proceed and plan for additional clinical trials in order to receive approval to market CellProtect.”
Orphan designation from the European Commission provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if a therapy receives regulatory approval.
The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.
The European Medicines Agency’s Committee for Orphan Medicinal Products adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision.
The European Commission has granted orphan designation to a natural killer (NK) cell product for the treatment of multiple myeloma.
The product, called CellProtect, is manufactured from a patient’s own blood.
It consists of NK cells that have been activated and expanded so they can recognize and attack cancer cells.
CellProtect has been studied in a phase 1/2 trial of patients with multiple myeloma.
In this trial, the NK cell product was used as a supplement to autologous stem cell transplant.
CellProtect exhibited a good safety profile and signals of effect in the trial, according to CellProtect Nordic Pharmaceuticals AB, the company developing CellProtect.
Results from the trial are expected to be published in 2018.
“The decision from the commission is based on a recommendation from the European Medicines Agency’s Committee for Orphan Medicinal Products and confirms that a future product is considered to be of significant benefit to those suffering from multiple myeloma,” said Karin Mellström, chief executive officer of CellProtect Nordic Pharmaceuticals AB.
“We can now proceed and plan for additional clinical trials in order to receive approval to market CellProtect.”
Orphan designation from the European Commission provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if a therapy receives regulatory approval.
The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.
The European Medicines Agency’s Committee for Orphan Medicinal Products adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision.
FDA approves topical antibiotic for impetigo infections
The Food and Drug Administration has approved in patients aged 2 months or older.
This is the first topical treatment for impetigo to be approved in more than 10 years, according to the press release from the manufacturer, Medimetriks Pharmaceuticals.
Ozenoxacin is a quinolone antimicrobial. The prescribing information is available on the FDA website.
The Food and Drug Administration has approved in patients aged 2 months or older.
This is the first topical treatment for impetigo to be approved in more than 10 years, according to the press release from the manufacturer, Medimetriks Pharmaceuticals.
Ozenoxacin is a quinolone antimicrobial. The prescribing information is available on the FDA website.
The Food and Drug Administration has approved in patients aged 2 months or older.
This is the first topical treatment for impetigo to be approved in more than 10 years, according to the press release from the manufacturer, Medimetriks Pharmaceuticals.
Ozenoxacin is a quinolone antimicrobial. The prescribing information is available on the FDA website.