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Restroom, locker room restrictions foster abuse of transgender teens
Transgender youth with restricted restroom and locker room use at school were significantly more likely to experience sexual assault at school than those without such restrictions, based on surveys from more than 3,000 teens in the United States who identified as transgender or nonbinary.
“Little is known about risk factors for sexual assault in gender minority adolescents, but school policies and practices play an important role in other forms of victimization,” including restricting transgender students from using restrooms or locker rooms that match their gender identities, wrote Gabriel R. Murchison, MPH, of Harvard University, Boston, Mass., and colleagues in Pediatrics (2019 May 6. doi: https://doi.org/10.1542/peds.2018-2902).
To examine the relationship between school restroom/locker room policies and sexual assault on transgender teens, the researchers reviewed data from the Lesbian, Gay, Bisexual, Transgender, and Queer or Questioning (LGBTQ) Teen Study, an anonymous web-based survey of U.S. adolescents aged 13 to 17 years who could read and write in English. Participants were assigned to one of four gender groups: trans male, trans female, nonbinary who were assigned male at birth (AMAB), or nonbinary who were assigned female at birth (AFAB) based on the survey questions asking their sex assigned at birth and current gender identity. The final study population of 3,673 individuals included 1,359 boys and 1,947 nonbinary youth AFAB and 158 transgender girls and 209 nonbinary youth AMAB. The results were published in Pediatrics.
with risk ratios of 1.26 for transgender boys and 2.49 for transgender girls, and 1.42 for nonbinary AFAB youth. Restroom/locker room restrictions were not significantly associated with sexual abuse in nonbinary AMAB youth.
The 12-month prevalence of sexual assault was highest among nonbinary youth AFAB (27%), followed by 26.5% among transgender boys, 18.5% among transgender girls, and 17.6% among nonbinary youth AMAB.
Sexual assault was determined based on participants’ response to the question, “During the past 12 months, how many times did anyone force you to do sexual things that you did not want to do? (Count such things as kissing, touching, or being physically forced to have sexual intercourse.)” The researchers adjusted for multiple factors associated with adolescent sexual assault including alcohol use, family connectedness, and educational attainment of caregivers; as well as variables including exposure to antitransgender stigma and perception of teacher support at school.
The researchers also identified four mediating variables: sexual harassment, feeling safe in restrooms and locker rooms, feeling safe in other locations at school, and classmates’ knowledge of gender status.
“Significant indirect effects were present for all 4 mediating variables,” which included feel safe in restrooms and locker rooms, feel safe elsewhere in school, classmates know gender minority status, and sexual harassment. The fourth mediating variable mentioned fully explains “the association between restroom and locker room restrictions and sexual assault victimization,” the researchers wrote.
The findings were limited by several factors including the lack of racial diversity and the reliance on cross-sectional, nonprobability data, the researchers said.
However, the results are strengthened by the large sample size and suggest that avoiding restrictive policies at school can make a difference in reducing abuse of transgender teens, they wrote.
“From a prevention perspective, pediatricians are key advocates for transgender and nonbinary patients, and their role may include educating school officials and submitting letters confirming the patient’s need to express their gender identity,” that emphasize the importance of “safe, identity-congruent restrooms and locker rooms,” the researchers concluded.
The study was supported in part by the Office of Vice President for Research at the University of Connecticut, and the Human Rights Campaign Foundation provided in-kind support for the LGBTQ Teen Study. Mr. Murchison disclosed participation in survey development and data collection for the LGBTQ Teen Study as an employee of the Human Rights Campaign Foundation.
SOURCE: Murchison G et al. Pediatrics . 2019 May 6. doi: https://doi.org/10.1542/peds.2018-2902 .
The study findings “make a compelling case for what we as gender specialist providers witness every day in our work: failure to support transgender and gender-expansive youth in being able to fully live in their affirmed gender puts them at physical as well as psychological risk,” wrote Diane Ehrensaft, PhD, and Stephen M. Rosenthal, MD, in an accompanying editorial.
What can reduce the risk of these youth experiencing abuse and assault, according to the editorialists, is putting policies in place that support them. Dr. Ehrensaft and Dr. Rosenthal cited the state of California’s 2013 decision to allow all students in public schools, from kindergarten through 12th grade “the right to use the bathroom and locker room consistent with their affirmed gender identity” as an example of something pediatricians should be advocating for in other states.
Restrictions on bathroom use to their assigned birth identity may cause transgender youth to be at increased risk for verbal and physical harassment and abuse, they said. It may also lead some to avoid restroom use and increase their risk for urinary tract infections, impacted stool, and school avoidance, the editorialists noted. They added that “[such] policies are often fear based, with nontransgender students thought to be the ones at risk for sexual assault by transgender intruders, by anyone whose genitalia does not match the one associated with the sign on the door, or by predators posing as transgender students.” The editorialists noted that these attitudes can come from school personnel or parents and that pediatricians should be aware of “the high prevalence of sexual assault” on transgender and gender nonbinary youth” (Pediatrics. 2019 May 6. doi: 10.1542/peds.2019-0554).
Dr. Ehrensaft and Dr. Rosenthal are affiliated with the Benioff Children’s Hospital at the University of California, San Francisco. They had no financial conflicts to disclose.
The study findings “make a compelling case for what we as gender specialist providers witness every day in our work: failure to support transgender and gender-expansive youth in being able to fully live in their affirmed gender puts them at physical as well as psychological risk,” wrote Diane Ehrensaft, PhD, and Stephen M. Rosenthal, MD, in an accompanying editorial.
What can reduce the risk of these youth experiencing abuse and assault, according to the editorialists, is putting policies in place that support them. Dr. Ehrensaft and Dr. Rosenthal cited the state of California’s 2013 decision to allow all students in public schools, from kindergarten through 12th grade “the right to use the bathroom and locker room consistent with their affirmed gender identity” as an example of something pediatricians should be advocating for in other states.
Restrictions on bathroom use to their assigned birth identity may cause transgender youth to be at increased risk for verbal and physical harassment and abuse, they said. It may also lead some to avoid restroom use and increase their risk for urinary tract infections, impacted stool, and school avoidance, the editorialists noted. They added that “[such] policies are often fear based, with nontransgender students thought to be the ones at risk for sexual assault by transgender intruders, by anyone whose genitalia does not match the one associated with the sign on the door, or by predators posing as transgender students.” The editorialists noted that these attitudes can come from school personnel or parents and that pediatricians should be aware of “the high prevalence of sexual assault” on transgender and gender nonbinary youth” (Pediatrics. 2019 May 6. doi: 10.1542/peds.2019-0554).
Dr. Ehrensaft and Dr. Rosenthal are affiliated with the Benioff Children’s Hospital at the University of California, San Francisco. They had no financial conflicts to disclose.
The study findings “make a compelling case for what we as gender specialist providers witness every day in our work: failure to support transgender and gender-expansive youth in being able to fully live in their affirmed gender puts them at physical as well as psychological risk,” wrote Diane Ehrensaft, PhD, and Stephen M. Rosenthal, MD, in an accompanying editorial.
What can reduce the risk of these youth experiencing abuse and assault, according to the editorialists, is putting policies in place that support them. Dr. Ehrensaft and Dr. Rosenthal cited the state of California’s 2013 decision to allow all students in public schools, from kindergarten through 12th grade “the right to use the bathroom and locker room consistent with their affirmed gender identity” as an example of something pediatricians should be advocating for in other states.
Restrictions on bathroom use to their assigned birth identity may cause transgender youth to be at increased risk for verbal and physical harassment and abuse, they said. It may also lead some to avoid restroom use and increase their risk for urinary tract infections, impacted stool, and school avoidance, the editorialists noted. They added that “[such] policies are often fear based, with nontransgender students thought to be the ones at risk for sexual assault by transgender intruders, by anyone whose genitalia does not match the one associated with the sign on the door, or by predators posing as transgender students.” The editorialists noted that these attitudes can come from school personnel or parents and that pediatricians should be aware of “the high prevalence of sexual assault” on transgender and gender nonbinary youth” (Pediatrics. 2019 May 6. doi: 10.1542/peds.2019-0554).
Dr. Ehrensaft and Dr. Rosenthal are affiliated with the Benioff Children’s Hospital at the University of California, San Francisco. They had no financial conflicts to disclose.
Transgender youth with restricted restroom and locker room use at school were significantly more likely to experience sexual assault at school than those without such restrictions, based on surveys from more than 3,000 teens in the United States who identified as transgender or nonbinary.
“Little is known about risk factors for sexual assault in gender minority adolescents, but school policies and practices play an important role in other forms of victimization,” including restricting transgender students from using restrooms or locker rooms that match their gender identities, wrote Gabriel R. Murchison, MPH, of Harvard University, Boston, Mass., and colleagues in Pediatrics (2019 May 6. doi: https://doi.org/10.1542/peds.2018-2902).
To examine the relationship between school restroom/locker room policies and sexual assault on transgender teens, the researchers reviewed data from the Lesbian, Gay, Bisexual, Transgender, and Queer or Questioning (LGBTQ) Teen Study, an anonymous web-based survey of U.S. adolescents aged 13 to 17 years who could read and write in English. Participants were assigned to one of four gender groups: trans male, trans female, nonbinary who were assigned male at birth (AMAB), or nonbinary who were assigned female at birth (AFAB) based on the survey questions asking their sex assigned at birth and current gender identity. The final study population of 3,673 individuals included 1,359 boys and 1,947 nonbinary youth AFAB and 158 transgender girls and 209 nonbinary youth AMAB. The results were published in Pediatrics.
with risk ratios of 1.26 for transgender boys and 2.49 for transgender girls, and 1.42 for nonbinary AFAB youth. Restroom/locker room restrictions were not significantly associated with sexual abuse in nonbinary AMAB youth.
The 12-month prevalence of sexual assault was highest among nonbinary youth AFAB (27%), followed by 26.5% among transgender boys, 18.5% among transgender girls, and 17.6% among nonbinary youth AMAB.
Sexual assault was determined based on participants’ response to the question, “During the past 12 months, how many times did anyone force you to do sexual things that you did not want to do? (Count such things as kissing, touching, or being physically forced to have sexual intercourse.)” The researchers adjusted for multiple factors associated with adolescent sexual assault including alcohol use, family connectedness, and educational attainment of caregivers; as well as variables including exposure to antitransgender stigma and perception of teacher support at school.
The researchers also identified four mediating variables: sexual harassment, feeling safe in restrooms and locker rooms, feeling safe in other locations at school, and classmates’ knowledge of gender status.
“Significant indirect effects were present for all 4 mediating variables,” which included feel safe in restrooms and locker rooms, feel safe elsewhere in school, classmates know gender minority status, and sexual harassment. The fourth mediating variable mentioned fully explains “the association between restroom and locker room restrictions and sexual assault victimization,” the researchers wrote.
The findings were limited by several factors including the lack of racial diversity and the reliance on cross-sectional, nonprobability data, the researchers said.
However, the results are strengthened by the large sample size and suggest that avoiding restrictive policies at school can make a difference in reducing abuse of transgender teens, they wrote.
“From a prevention perspective, pediatricians are key advocates for transgender and nonbinary patients, and their role may include educating school officials and submitting letters confirming the patient’s need to express their gender identity,” that emphasize the importance of “safe, identity-congruent restrooms and locker rooms,” the researchers concluded.
The study was supported in part by the Office of Vice President for Research at the University of Connecticut, and the Human Rights Campaign Foundation provided in-kind support for the LGBTQ Teen Study. Mr. Murchison disclosed participation in survey development and data collection for the LGBTQ Teen Study as an employee of the Human Rights Campaign Foundation.
SOURCE: Murchison G et al. Pediatrics . 2019 May 6. doi: https://doi.org/10.1542/peds.2018-2902 .
Transgender youth with restricted restroom and locker room use at school were significantly more likely to experience sexual assault at school than those without such restrictions, based on surveys from more than 3,000 teens in the United States who identified as transgender or nonbinary.
“Little is known about risk factors for sexual assault in gender minority adolescents, but school policies and practices play an important role in other forms of victimization,” including restricting transgender students from using restrooms or locker rooms that match their gender identities, wrote Gabriel R. Murchison, MPH, of Harvard University, Boston, Mass., and colleagues in Pediatrics (2019 May 6. doi: https://doi.org/10.1542/peds.2018-2902).
To examine the relationship between school restroom/locker room policies and sexual assault on transgender teens, the researchers reviewed data from the Lesbian, Gay, Bisexual, Transgender, and Queer or Questioning (LGBTQ) Teen Study, an anonymous web-based survey of U.S. adolescents aged 13 to 17 years who could read and write in English. Participants were assigned to one of four gender groups: trans male, trans female, nonbinary who were assigned male at birth (AMAB), or nonbinary who were assigned female at birth (AFAB) based on the survey questions asking their sex assigned at birth and current gender identity. The final study population of 3,673 individuals included 1,359 boys and 1,947 nonbinary youth AFAB and 158 transgender girls and 209 nonbinary youth AMAB. The results were published in Pediatrics.
with risk ratios of 1.26 for transgender boys and 2.49 for transgender girls, and 1.42 for nonbinary AFAB youth. Restroom/locker room restrictions were not significantly associated with sexual abuse in nonbinary AMAB youth.
The 12-month prevalence of sexual assault was highest among nonbinary youth AFAB (27%), followed by 26.5% among transgender boys, 18.5% among transgender girls, and 17.6% among nonbinary youth AMAB.
Sexual assault was determined based on participants’ response to the question, “During the past 12 months, how many times did anyone force you to do sexual things that you did not want to do? (Count such things as kissing, touching, or being physically forced to have sexual intercourse.)” The researchers adjusted for multiple factors associated with adolescent sexual assault including alcohol use, family connectedness, and educational attainment of caregivers; as well as variables including exposure to antitransgender stigma and perception of teacher support at school.
The researchers also identified four mediating variables: sexual harassment, feeling safe in restrooms and locker rooms, feeling safe in other locations at school, and classmates’ knowledge of gender status.
“Significant indirect effects were present for all 4 mediating variables,” which included feel safe in restrooms and locker rooms, feel safe elsewhere in school, classmates know gender minority status, and sexual harassment. The fourth mediating variable mentioned fully explains “the association between restroom and locker room restrictions and sexual assault victimization,” the researchers wrote.
The findings were limited by several factors including the lack of racial diversity and the reliance on cross-sectional, nonprobability data, the researchers said.
However, the results are strengthened by the large sample size and suggest that avoiding restrictive policies at school can make a difference in reducing abuse of transgender teens, they wrote.
“From a prevention perspective, pediatricians are key advocates for transgender and nonbinary patients, and their role may include educating school officials and submitting letters confirming the patient’s need to express their gender identity,” that emphasize the importance of “safe, identity-congruent restrooms and locker rooms,” the researchers concluded.
The study was supported in part by the Office of Vice President for Research at the University of Connecticut, and the Human Rights Campaign Foundation provided in-kind support for the LGBTQ Teen Study. Mr. Murchison disclosed participation in survey development and data collection for the LGBTQ Teen Study as an employee of the Human Rights Campaign Foundation.
SOURCE: Murchison G et al. Pediatrics . 2019 May 6. doi: https://doi.org/10.1542/peds.2018-2902 .
FROM PEDIATRICS
Key clinical point: Restrictive restroom and locker room environments in schools promote abuse of transgender teens.
Major finding: Sexual assault was significantly more likely against transgender teens with restroom and locker room restrictions vs those without restrictions, with risk ratios of 1.26 for transgender boys and 2.49 for transgender girls.
Study details: The data came from web-based surveys of 3,673 teens aged 13 to 17 years who identified as transgender or nonbinary.
Disclosures: The study was supported in part by the Office of Vice President for Research at the University of Connecticut, and the Human Rights Campaign Foundation provided in-kind support for the LGBTQ Teen Study. Mr. Murchison disclosed participation in survey development and data collection for the LGBTQ Teen Study as an employee of the Human Rights Campaign Foundation.
Source: Murchison G et al. Pediatrics. 2019 May 6. doi: https://doi.org/10.1542/peds.2018-2902
Lifeline calls spike after Robin Williams’ suicide
Suicides and calls to the National Suicide Prevention Lifeline spiked after the suicide of actor Robin Williams, based on data from calls and website visits before and after his death.
Suicides in the United States tend to follow temporal patterns, with spikes in the spring and early summer, but “some events, including celebrity deaths, serve as ‘shocks’ that disrupt seasonal time trends and may prompt imitation,” wrote Rajeev Ramchand, PhD, of the National Institute of Mental Health, Bethesda, Md., and colleagues in a study published online in the journal Psychiatric Services in Advance (2019 Apr 30. doi: 10.1176/appi.ps.201900007).
The National Suicide Prevention Lifeline (NSPL) experienced a 300% increase in call volume the day after Mr. Williams’ death, however, only 57% of these calls were answered, the researchers said.
The researchers compared daily suicide data, NSPL call volume, and visits to two suicide prevention websites before and after Mr. Williams’ death on August 11, 2014.
Before August 11 in 2012, 2013, and 2014, the average number of daily suicides ranged from 113 to 117; after August 11, 2014, this average spiked to 142, an increase not seen in 2012 or 2013, according to data from the National Center for Health Statistics’ Compressed Mortality File. The NSPL received 12,972 calls on August 12, 2014, following Mr. Williams’ death, compared with a daily average of 4,116 to 6,302 calls during the week before his death. In addition, the Suicide Prevention Resource Center (SPRC), a website that provides technical assistance, training, and suicide prevention material; and Suicide Awareness Voices of Education (SAVE), a website with resources for individuals affected by suicide, as well educational information to raise public awareness, saw significant increases in visits on the day after Mr. Williams’ suicide.
The study findings were limited by several factors including the lack of information on whether calls to NSPL were information seekers or individuals in crisis, the researchers noted. However, the results suggest the need for surge capacity to prepare for increased demand in the wake of a celebrity suicide, they said.
The researchers had no financial conflicts to disclose.
SOURCE: Ramchand R et al. Psychiatric Services in Advance. 2019. doi: 10.1176/appi.ps.201900007 .
Suicides and calls to the National Suicide Prevention Lifeline spiked after the suicide of actor Robin Williams, based on data from calls and website visits before and after his death.
Suicides in the United States tend to follow temporal patterns, with spikes in the spring and early summer, but “some events, including celebrity deaths, serve as ‘shocks’ that disrupt seasonal time trends and may prompt imitation,” wrote Rajeev Ramchand, PhD, of the National Institute of Mental Health, Bethesda, Md., and colleagues in a study published online in the journal Psychiatric Services in Advance (2019 Apr 30. doi: 10.1176/appi.ps.201900007).
The National Suicide Prevention Lifeline (NSPL) experienced a 300% increase in call volume the day after Mr. Williams’ death, however, only 57% of these calls were answered, the researchers said.
The researchers compared daily suicide data, NSPL call volume, and visits to two suicide prevention websites before and after Mr. Williams’ death on August 11, 2014.
Before August 11 in 2012, 2013, and 2014, the average number of daily suicides ranged from 113 to 117; after August 11, 2014, this average spiked to 142, an increase not seen in 2012 or 2013, according to data from the National Center for Health Statistics’ Compressed Mortality File. The NSPL received 12,972 calls on August 12, 2014, following Mr. Williams’ death, compared with a daily average of 4,116 to 6,302 calls during the week before his death. In addition, the Suicide Prevention Resource Center (SPRC), a website that provides technical assistance, training, and suicide prevention material; and Suicide Awareness Voices of Education (SAVE), a website with resources for individuals affected by suicide, as well educational information to raise public awareness, saw significant increases in visits on the day after Mr. Williams’ suicide.
The study findings were limited by several factors including the lack of information on whether calls to NSPL were information seekers or individuals in crisis, the researchers noted. However, the results suggest the need for surge capacity to prepare for increased demand in the wake of a celebrity suicide, they said.
The researchers had no financial conflicts to disclose.
SOURCE: Ramchand R et al. Psychiatric Services in Advance. 2019. doi: 10.1176/appi.ps.201900007 .
Suicides and calls to the National Suicide Prevention Lifeline spiked after the suicide of actor Robin Williams, based on data from calls and website visits before and after his death.
Suicides in the United States tend to follow temporal patterns, with spikes in the spring and early summer, but “some events, including celebrity deaths, serve as ‘shocks’ that disrupt seasonal time trends and may prompt imitation,” wrote Rajeev Ramchand, PhD, of the National Institute of Mental Health, Bethesda, Md., and colleagues in a study published online in the journal Psychiatric Services in Advance (2019 Apr 30. doi: 10.1176/appi.ps.201900007).
The National Suicide Prevention Lifeline (NSPL) experienced a 300% increase in call volume the day after Mr. Williams’ death, however, only 57% of these calls were answered, the researchers said.
The researchers compared daily suicide data, NSPL call volume, and visits to two suicide prevention websites before and after Mr. Williams’ death on August 11, 2014.
Before August 11 in 2012, 2013, and 2014, the average number of daily suicides ranged from 113 to 117; after August 11, 2014, this average spiked to 142, an increase not seen in 2012 or 2013, according to data from the National Center for Health Statistics’ Compressed Mortality File. The NSPL received 12,972 calls on August 12, 2014, following Mr. Williams’ death, compared with a daily average of 4,116 to 6,302 calls during the week before his death. In addition, the Suicide Prevention Resource Center (SPRC), a website that provides technical assistance, training, and suicide prevention material; and Suicide Awareness Voices of Education (SAVE), a website with resources for individuals affected by suicide, as well educational information to raise public awareness, saw significant increases in visits on the day after Mr. Williams’ suicide.
The study findings were limited by several factors including the lack of information on whether calls to NSPL were information seekers or individuals in crisis, the researchers noted. However, the results suggest the need for surge capacity to prepare for increased demand in the wake of a celebrity suicide, they said.
The researchers had no financial conflicts to disclose.
SOURCE: Ramchand R et al. Psychiatric Services in Advance. 2019. doi: 10.1176/appi.ps.201900007 .
FROM PS IN ADVANCE
Alirocumab gains indication to reduce cardiovascular risks
Alirocumab has received an updated indication from the Food and Drug Administration for reducing the overall risk of major adverse cardiovascular events in patients with a recent acute coronary event.
Alirocumab is designed to inhibit the binding of PCSK9 (proprotein convertase subtilisin/kexin type 9) to LDL receptors, thereby lowering LDL cholesterol, according to manufacturer Regeneron, which is developing alirocumab in partnership with Sanofi.
The drug was previously approved in the United States as an adjunct treatment along with diet and maximally tolerated statin therapy to help lower LDL cholesterol in adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease.
The approval of the supplemental Biologics License Application was supported by data from the ODYSSEY Outcomes trial in which 18,924 patients who had an acute coronary syndrome were randomized to alirocumab or placebo plus background high-intensity statin therapy starting at a median of 2.6 months after the event. Over 3 years’ follow-up, a composite endpoint outcome including death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, or unstable angina occurred in 9.5% of alirocumab patients and 11.1% of placebo patients.
In the study, patients received subcutaneous dose of 75 mg of alirocumab every 2 weeks, which was adjusted to achieve an LDL cholesterol level of 25-50 mg/dL. The most significant benefits occurred among patients with a baseline LDL cholesterol of 100 mg/dL or higher who were taking high-intensity statins, which supports the role of LDL cholesterol reduction in improving outcomes for coronary syndrome patients, according to study investigators.
Alirocumab is given as a subcutaneous injection. The most common side effects include pain and tenderness at the injection site, and redness, itching, or swelling; some patients have reported symptoms of a common cold or flu.
More details of the ODYSSEY Outcomes trial were presented at the annual meeting of the American College of Cardiology.
Alirocumab has received an updated indication from the Food and Drug Administration for reducing the overall risk of major adverse cardiovascular events in patients with a recent acute coronary event.
Alirocumab is designed to inhibit the binding of PCSK9 (proprotein convertase subtilisin/kexin type 9) to LDL receptors, thereby lowering LDL cholesterol, according to manufacturer Regeneron, which is developing alirocumab in partnership with Sanofi.
The drug was previously approved in the United States as an adjunct treatment along with diet and maximally tolerated statin therapy to help lower LDL cholesterol in adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease.
The approval of the supplemental Biologics License Application was supported by data from the ODYSSEY Outcomes trial in which 18,924 patients who had an acute coronary syndrome were randomized to alirocumab or placebo plus background high-intensity statin therapy starting at a median of 2.6 months after the event. Over 3 years’ follow-up, a composite endpoint outcome including death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, or unstable angina occurred in 9.5% of alirocumab patients and 11.1% of placebo patients.
In the study, patients received subcutaneous dose of 75 mg of alirocumab every 2 weeks, which was adjusted to achieve an LDL cholesterol level of 25-50 mg/dL. The most significant benefits occurred among patients with a baseline LDL cholesterol of 100 mg/dL or higher who were taking high-intensity statins, which supports the role of LDL cholesterol reduction in improving outcomes for coronary syndrome patients, according to study investigators.
Alirocumab is given as a subcutaneous injection. The most common side effects include pain and tenderness at the injection site, and redness, itching, or swelling; some patients have reported symptoms of a common cold or flu.
More details of the ODYSSEY Outcomes trial were presented at the annual meeting of the American College of Cardiology.
Alirocumab has received an updated indication from the Food and Drug Administration for reducing the overall risk of major adverse cardiovascular events in patients with a recent acute coronary event.
Alirocumab is designed to inhibit the binding of PCSK9 (proprotein convertase subtilisin/kexin type 9) to LDL receptors, thereby lowering LDL cholesterol, according to manufacturer Regeneron, which is developing alirocumab in partnership with Sanofi.
The drug was previously approved in the United States as an adjunct treatment along with diet and maximally tolerated statin therapy to help lower LDL cholesterol in adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease.
The approval of the supplemental Biologics License Application was supported by data from the ODYSSEY Outcomes trial in which 18,924 patients who had an acute coronary syndrome were randomized to alirocumab or placebo plus background high-intensity statin therapy starting at a median of 2.6 months after the event. Over 3 years’ follow-up, a composite endpoint outcome including death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, or unstable angina occurred in 9.5% of alirocumab patients and 11.1% of placebo patients.
In the study, patients received subcutaneous dose of 75 mg of alirocumab every 2 weeks, which was adjusted to achieve an LDL cholesterol level of 25-50 mg/dL. The most significant benefits occurred among patients with a baseline LDL cholesterol of 100 mg/dL or higher who were taking high-intensity statins, which supports the role of LDL cholesterol reduction in improving outcomes for coronary syndrome patients, according to study investigators.
Alirocumab is given as a subcutaneous injection. The most common side effects include pain and tenderness at the injection site, and redness, itching, or swelling; some patients have reported symptoms of a common cold or flu.
More details of the ODYSSEY Outcomes trial were presented at the annual meeting of the American College of Cardiology.
FDA approves IL-23 inhibitor risankizumab for treating plaque psoriasis
Risankizumab, an interleukin-23 inhibitor, has been approved by the Food and Drug Administration for treating moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy, the manufacturer announced on April 23.
Risankizumab selectively inhibits interleukin-23 (IL-23), a key inflammatory protein, by binding to its p19 subunit. The drug is administered at a dose of 150 mg, in two subcutaneous injections, every 12 weeks, after starting doses at weeks 0 and 4. It will be available in early May, according to an AbbVie press release announcing the approval.
The approval was based in part on data from two phase 3, 2-year studies, In UltIMMA-1 and UltIMMA-2, at 16 weeks, 75% of risankizumab patients in both studies achieved a Psoriasis Area and Severity Index (PASI 90), compared with 5% and 2% of those on placebo, respectively. These results were published in 2018 (Lancet. 2018 Aug 25;392[10148]:650-61).
At 1 year, 82% and 81% of those treated with risankizumab in the two studies achieved a PASI 90, and 56% and 60% achieved a PASI 100, respectively, according to the company.
Approval was also based on additional phase 3 studies, IMMhance and IMMvent.
Upper respiratory infections were among the most common adverse events associated with risankizumab in trials, reported in 13%, according to the company. Other adverse events associated with treatment included headache (3.5 %), fatigue (2.5 %), injection site reactions (1.5%) and tinea infections (1.1%). The AbbVie release states that candidates for treatment should be evaluated for tuberculosis before starting therapy, and patients should be instructed to report signs and symptoms of infection.
Risankizumab, which will be marketed as Skyrizi, was recently approved in Canada for the same indication, and in Japan, for plaque psoriasis, generalized pustular psoriasis, erythrodermic psoriasis and psoriatic arthritis in adults. It currently is under review in Europe.
AbbVie and Boehringer Ingelheim are collaborating on the development of risankizumab, according to an AbbVie press release. Studies of risankizumab for treatment of psoriatic arthritis and Crohn’s disease are underway.
Risankizumab, an interleukin-23 inhibitor, has been approved by the Food and Drug Administration for treating moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy, the manufacturer announced on April 23.
Risankizumab selectively inhibits interleukin-23 (IL-23), a key inflammatory protein, by binding to its p19 subunit. The drug is administered at a dose of 150 mg, in two subcutaneous injections, every 12 weeks, after starting doses at weeks 0 and 4. It will be available in early May, according to an AbbVie press release announcing the approval.
The approval was based in part on data from two phase 3, 2-year studies, In UltIMMA-1 and UltIMMA-2, at 16 weeks, 75% of risankizumab patients in both studies achieved a Psoriasis Area and Severity Index (PASI 90), compared with 5% and 2% of those on placebo, respectively. These results were published in 2018 (Lancet. 2018 Aug 25;392[10148]:650-61).
At 1 year, 82% and 81% of those treated with risankizumab in the two studies achieved a PASI 90, and 56% and 60% achieved a PASI 100, respectively, according to the company.
Approval was also based on additional phase 3 studies, IMMhance and IMMvent.
Upper respiratory infections were among the most common adverse events associated with risankizumab in trials, reported in 13%, according to the company. Other adverse events associated with treatment included headache (3.5 %), fatigue (2.5 %), injection site reactions (1.5%) and tinea infections (1.1%). The AbbVie release states that candidates for treatment should be evaluated for tuberculosis before starting therapy, and patients should be instructed to report signs and symptoms of infection.
Risankizumab, which will be marketed as Skyrizi, was recently approved in Canada for the same indication, and in Japan, for plaque psoriasis, generalized pustular psoriasis, erythrodermic psoriasis and psoriatic arthritis in adults. It currently is under review in Europe.
AbbVie and Boehringer Ingelheim are collaborating on the development of risankizumab, according to an AbbVie press release. Studies of risankizumab for treatment of psoriatic arthritis and Crohn’s disease are underway.
Risankizumab, an interleukin-23 inhibitor, has been approved by the Food and Drug Administration for treating moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy, the manufacturer announced on April 23.
Risankizumab selectively inhibits interleukin-23 (IL-23), a key inflammatory protein, by binding to its p19 subunit. The drug is administered at a dose of 150 mg, in two subcutaneous injections, every 12 weeks, after starting doses at weeks 0 and 4. It will be available in early May, according to an AbbVie press release announcing the approval.
The approval was based in part on data from two phase 3, 2-year studies, In UltIMMA-1 and UltIMMA-2, at 16 weeks, 75% of risankizumab patients in both studies achieved a Psoriasis Area and Severity Index (PASI 90), compared with 5% and 2% of those on placebo, respectively. These results were published in 2018 (Lancet. 2018 Aug 25;392[10148]:650-61).
At 1 year, 82% and 81% of those treated with risankizumab in the two studies achieved a PASI 90, and 56% and 60% achieved a PASI 100, respectively, according to the company.
Approval was also based on additional phase 3 studies, IMMhance and IMMvent.
Upper respiratory infections were among the most common adverse events associated with risankizumab in trials, reported in 13%, according to the company. Other adverse events associated with treatment included headache (3.5 %), fatigue (2.5 %), injection site reactions (1.5%) and tinea infections (1.1%). The AbbVie release states that candidates for treatment should be evaluated for tuberculosis before starting therapy, and patients should be instructed to report signs and symptoms of infection.
Risankizumab, which will be marketed as Skyrizi, was recently approved in Canada for the same indication, and in Japan, for plaque psoriasis, generalized pustular psoriasis, erythrodermic psoriasis and psoriatic arthritis in adults. It currently is under review in Europe.
AbbVie and Boehringer Ingelheim are collaborating on the development of risankizumab, according to an AbbVie press release. Studies of risankizumab for treatment of psoriatic arthritis and Crohn’s disease are underway.
New sleep apnea guidelines offer evidence-based recommendations
New guidelines on treating obstructive sleep apnea with positive airway pressure include recommendations for using positive airway pressure (PAP) versus no therapy, using either continuous PAP (CPAP) or automatic PAP (APAP) for ongoing treatment, and providing educational interventions to patients starting PAP. The complete guidelines, issued by the American Academy of Sleep Medicine, were published in the Journal of Clinical Sleep Medicine.
The guidelines were driven by improvements in PAP adherence and device technology, wrote lead author Susheel P. Patil, MD, of Johns Hopkins University, Baltimore, and his colleagues.
The guidelines begin with a pair of Good Practice Statements to ensure effective and appropriate management of obstructive sleep apnea (OSA) in adults. First, “Treatment of OSA with PAP therapy should be based on a diagnosis of OSA established using objective sleep apnea testing.” Second, “Adequate follow-up, including troubleshooting and monitoring of objective efficacy and usage data to ensure adequate treatment and adherence, should occur following PAP therapy initiation and during treatment of OSA.”
The nine recommendations, approved by the AASM board of directors, include four strong recommendations that clinicians should follow under most circumstances, and five conditional recommendations that are suggested but lack strong clinical support for their appropriateness for all patients in all circumstances.
The first of the strong recommendations, for using PAP versus no therapy to treat adults with OSA and excessive sleepiness, was based on a high level of evidence from a meta-analysis of 38 randomized, controlled trials and the conclusion that the benefits of PAP outweighed the harms.
The second strong recommendation for using either CPAP or APAP for ongoing treatment was based on data from 26 trials that showed no clinically significant difference between the two. The third strong recommendation that PAP therapy be initiated using either APAP at home or in-laboratory PAP titration in adults with OSA and no significant comorbidities was supported by a meta-analysis of 10 trials that showed no clinically significant difference between at-home and laboratory initiation, and that each option has its benefits. The authors noted that “the majority of well-informed adult patients with OSA and without significant comorbidities would prefer initiation of PAP using the most rapid, convenient, and cost-effective strategy.” This comment supports the fourth strong recommendation for providing educational interventions to patients starting PAP.
The conditional recommendations include using PAP versus no therapy for adults with OSA and impaired quality of life related to poor sleep, such as insomnia, snoring, morning headaches, and daytime fatigue. Other conditional recommendations include using PAP versus no therapy for adults with OSA and comorbid hypertension, choosing CPAP or APAP over bilateral PAP for routine treatment of OSA in adults, providing behavioral interventions or troubleshooting during patients’ initial use of PAP, and using telemonitoring-guided interventions to monitor patients during their initial use of PAP.
“The ultimate judgment regarding any specific care must be made by the treating clinician and the patient, taking into consideration the individual circumstances of the patient, available treatment options, and resources,” the authors noted.
“When implementing the recommendations, providers should consider additional strategies that will maximize the individual patient’s comfort and adherence such as nasal/intranasal over oronasal mask interface and heated humidification,” they added.
The guidelines were developed by a task force commissioned by the AASM that included board-certified sleep specialists and experts in PAP use, and will be reviewed and updated as new information surfaces, the authors wrote.
Dr. Patil reported no financial conflicts; several coauthors reported conflicts that were managed by their not voting on guidelines related to those conflicts.
SOURCE: Patil SP et al. J Clin Sleep Med. 2018 Feb 15;15(2):335-43.
Octavian C. Ioachimescu, MD, FCCP, comments: The last guidelines and practice parameters for the use of positive airway pressure (PAP) as therapy for adult patients with obstructive sleep apnea, were published in 2006 and 2008, respectively. Since then, new technological advances, an ever-growing body of literature, and shifting practice patterns led to an acute need for a thorough reassessment, a comprehensive update of the previous recommendations, and the potential of issuing new ones for emerging areas. As such, the American Academy of Sleep Medicine commissioned a task force of content experts to review the existing evidence, to issue new guidelines and to publish an associated systematic review and a meta-analysis of the literature on this topic.
A welcome recommendation is the endorsement by the task force of the use of telemedicine capabilities in monitoring patients’ adherence to PAP therapy. Another interesting aspect is that, while our literature is represented by a mix of both randomized and nonrandomized controlled trials, occasionally there seems to be an interesting dichotomy in the results: Randomized trials tend to point in one direction, while nonrandomized studies pooled in the meta-analysis seem to point to the contrary or to give the impression of more definitive effects. While this is clearly not the place to make an extensive analysis of the strengths and the potential pitfalls of randomized versus nonrandomized studies, this clearly raises some issues. One is that our randomized studies are typically small, underpowered, and hence with nonconvincing risk or hazard reduction assessments. Second, the dichotomy in the results may be driven by publication bias, expense, and difficulty in performing adequately-powered, long-term trials that essentially may be studying small effects.
Guidelines are not intended to be used in an Occam’s razor approach, but in a fashion that would allow individualization of therapy while critically appraising the existing evidence for various interventions in specific conditions and maintaining a very stringent and critical view on generalizability, expected results, and adequate management of reasonable expectations. In addition, the areas that are unclear, with conflicting evidence or in which the guidelines allow “too much” latitude to the treating clinician, may be seen as either an invitation to remain “creative,” or one for abstaining from action in the name of equipoise. I would advise that both extremes are to be avoided.
Octavian C. Ioachimescu, MD, FCCP, comments: The last guidelines and practice parameters for the use of positive airway pressure (PAP) as therapy for adult patients with obstructive sleep apnea, were published in 2006 and 2008, respectively. Since then, new technological advances, an ever-growing body of literature, and shifting practice patterns led to an acute need for a thorough reassessment, a comprehensive update of the previous recommendations, and the potential of issuing new ones for emerging areas. As such, the American Academy of Sleep Medicine commissioned a task force of content experts to review the existing evidence, to issue new guidelines and to publish an associated systematic review and a meta-analysis of the literature on this topic.
A welcome recommendation is the endorsement by the task force of the use of telemedicine capabilities in monitoring patients’ adherence to PAP therapy. Another interesting aspect is that, while our literature is represented by a mix of both randomized and nonrandomized controlled trials, occasionally there seems to be an interesting dichotomy in the results: Randomized trials tend to point in one direction, while nonrandomized studies pooled in the meta-analysis seem to point to the contrary or to give the impression of more definitive effects. While this is clearly not the place to make an extensive analysis of the strengths and the potential pitfalls of randomized versus nonrandomized studies, this clearly raises some issues. One is that our randomized studies are typically small, underpowered, and hence with nonconvincing risk or hazard reduction assessments. Second, the dichotomy in the results may be driven by publication bias, expense, and difficulty in performing adequately-powered, long-term trials that essentially may be studying small effects.
Guidelines are not intended to be used in an Occam’s razor approach, but in a fashion that would allow individualization of therapy while critically appraising the existing evidence for various interventions in specific conditions and maintaining a very stringent and critical view on generalizability, expected results, and adequate management of reasonable expectations. In addition, the areas that are unclear, with conflicting evidence or in which the guidelines allow “too much” latitude to the treating clinician, may be seen as either an invitation to remain “creative,” or one for abstaining from action in the name of equipoise. I would advise that both extremes are to be avoided.
Octavian C. Ioachimescu, MD, FCCP, comments: The last guidelines and practice parameters for the use of positive airway pressure (PAP) as therapy for adult patients with obstructive sleep apnea, were published in 2006 and 2008, respectively. Since then, new technological advances, an ever-growing body of literature, and shifting practice patterns led to an acute need for a thorough reassessment, a comprehensive update of the previous recommendations, and the potential of issuing new ones for emerging areas. As such, the American Academy of Sleep Medicine commissioned a task force of content experts to review the existing evidence, to issue new guidelines and to publish an associated systematic review and a meta-analysis of the literature on this topic.
A welcome recommendation is the endorsement by the task force of the use of telemedicine capabilities in monitoring patients’ adherence to PAP therapy. Another interesting aspect is that, while our literature is represented by a mix of both randomized and nonrandomized controlled trials, occasionally there seems to be an interesting dichotomy in the results: Randomized trials tend to point in one direction, while nonrandomized studies pooled in the meta-analysis seem to point to the contrary or to give the impression of more definitive effects. While this is clearly not the place to make an extensive analysis of the strengths and the potential pitfalls of randomized versus nonrandomized studies, this clearly raises some issues. One is that our randomized studies are typically small, underpowered, and hence with nonconvincing risk or hazard reduction assessments. Second, the dichotomy in the results may be driven by publication bias, expense, and difficulty in performing adequately-powered, long-term trials that essentially may be studying small effects.
Guidelines are not intended to be used in an Occam’s razor approach, but in a fashion that would allow individualization of therapy while critically appraising the existing evidence for various interventions in specific conditions and maintaining a very stringent and critical view on generalizability, expected results, and adequate management of reasonable expectations. In addition, the areas that are unclear, with conflicting evidence or in which the guidelines allow “too much” latitude to the treating clinician, may be seen as either an invitation to remain “creative,” or one for abstaining from action in the name of equipoise. I would advise that both extremes are to be avoided.
New guidelines on treating obstructive sleep apnea with positive airway pressure include recommendations for using positive airway pressure (PAP) versus no therapy, using either continuous PAP (CPAP) or automatic PAP (APAP) for ongoing treatment, and providing educational interventions to patients starting PAP. The complete guidelines, issued by the American Academy of Sleep Medicine, were published in the Journal of Clinical Sleep Medicine.
The guidelines were driven by improvements in PAP adherence and device technology, wrote lead author Susheel P. Patil, MD, of Johns Hopkins University, Baltimore, and his colleagues.
The guidelines begin with a pair of Good Practice Statements to ensure effective and appropriate management of obstructive sleep apnea (OSA) in adults. First, “Treatment of OSA with PAP therapy should be based on a diagnosis of OSA established using objective sleep apnea testing.” Second, “Adequate follow-up, including troubleshooting and monitoring of objective efficacy and usage data to ensure adequate treatment and adherence, should occur following PAP therapy initiation and during treatment of OSA.”
The nine recommendations, approved by the AASM board of directors, include four strong recommendations that clinicians should follow under most circumstances, and five conditional recommendations that are suggested but lack strong clinical support for their appropriateness for all patients in all circumstances.
The first of the strong recommendations, for using PAP versus no therapy to treat adults with OSA and excessive sleepiness, was based on a high level of evidence from a meta-analysis of 38 randomized, controlled trials and the conclusion that the benefits of PAP outweighed the harms.
The second strong recommendation for using either CPAP or APAP for ongoing treatment was based on data from 26 trials that showed no clinically significant difference between the two. The third strong recommendation that PAP therapy be initiated using either APAP at home or in-laboratory PAP titration in adults with OSA and no significant comorbidities was supported by a meta-analysis of 10 trials that showed no clinically significant difference between at-home and laboratory initiation, and that each option has its benefits. The authors noted that “the majority of well-informed adult patients with OSA and without significant comorbidities would prefer initiation of PAP using the most rapid, convenient, and cost-effective strategy.” This comment supports the fourth strong recommendation for providing educational interventions to patients starting PAP.
The conditional recommendations include using PAP versus no therapy for adults with OSA and impaired quality of life related to poor sleep, such as insomnia, snoring, morning headaches, and daytime fatigue. Other conditional recommendations include using PAP versus no therapy for adults with OSA and comorbid hypertension, choosing CPAP or APAP over bilateral PAP for routine treatment of OSA in adults, providing behavioral interventions or troubleshooting during patients’ initial use of PAP, and using telemonitoring-guided interventions to monitor patients during their initial use of PAP.
“The ultimate judgment regarding any specific care must be made by the treating clinician and the patient, taking into consideration the individual circumstances of the patient, available treatment options, and resources,” the authors noted.
“When implementing the recommendations, providers should consider additional strategies that will maximize the individual patient’s comfort and adherence such as nasal/intranasal over oronasal mask interface and heated humidification,” they added.
The guidelines were developed by a task force commissioned by the AASM that included board-certified sleep specialists and experts in PAP use, and will be reviewed and updated as new information surfaces, the authors wrote.
Dr. Patil reported no financial conflicts; several coauthors reported conflicts that were managed by their not voting on guidelines related to those conflicts.
SOURCE: Patil SP et al. J Clin Sleep Med. 2018 Feb 15;15(2):335-43.
New guidelines on treating obstructive sleep apnea with positive airway pressure include recommendations for using positive airway pressure (PAP) versus no therapy, using either continuous PAP (CPAP) or automatic PAP (APAP) for ongoing treatment, and providing educational interventions to patients starting PAP. The complete guidelines, issued by the American Academy of Sleep Medicine, were published in the Journal of Clinical Sleep Medicine.
The guidelines were driven by improvements in PAP adherence and device technology, wrote lead author Susheel P. Patil, MD, of Johns Hopkins University, Baltimore, and his colleagues.
The guidelines begin with a pair of Good Practice Statements to ensure effective and appropriate management of obstructive sleep apnea (OSA) in adults. First, “Treatment of OSA with PAP therapy should be based on a diagnosis of OSA established using objective sleep apnea testing.” Second, “Adequate follow-up, including troubleshooting and monitoring of objective efficacy and usage data to ensure adequate treatment and adherence, should occur following PAP therapy initiation and during treatment of OSA.”
The nine recommendations, approved by the AASM board of directors, include four strong recommendations that clinicians should follow under most circumstances, and five conditional recommendations that are suggested but lack strong clinical support for their appropriateness for all patients in all circumstances.
The first of the strong recommendations, for using PAP versus no therapy to treat adults with OSA and excessive sleepiness, was based on a high level of evidence from a meta-analysis of 38 randomized, controlled trials and the conclusion that the benefits of PAP outweighed the harms.
The second strong recommendation for using either CPAP or APAP for ongoing treatment was based on data from 26 trials that showed no clinically significant difference between the two. The third strong recommendation that PAP therapy be initiated using either APAP at home or in-laboratory PAP titration in adults with OSA and no significant comorbidities was supported by a meta-analysis of 10 trials that showed no clinically significant difference between at-home and laboratory initiation, and that each option has its benefits. The authors noted that “the majority of well-informed adult patients with OSA and without significant comorbidities would prefer initiation of PAP using the most rapid, convenient, and cost-effective strategy.” This comment supports the fourth strong recommendation for providing educational interventions to patients starting PAP.
The conditional recommendations include using PAP versus no therapy for adults with OSA and impaired quality of life related to poor sleep, such as insomnia, snoring, morning headaches, and daytime fatigue. Other conditional recommendations include using PAP versus no therapy for adults with OSA and comorbid hypertension, choosing CPAP or APAP over bilateral PAP for routine treatment of OSA in adults, providing behavioral interventions or troubleshooting during patients’ initial use of PAP, and using telemonitoring-guided interventions to monitor patients during their initial use of PAP.
“The ultimate judgment regarding any specific care must be made by the treating clinician and the patient, taking into consideration the individual circumstances of the patient, available treatment options, and resources,” the authors noted.
“When implementing the recommendations, providers should consider additional strategies that will maximize the individual patient’s comfort and adherence such as nasal/intranasal over oronasal mask interface and heated humidification,” they added.
The guidelines were developed by a task force commissioned by the AASM that included board-certified sleep specialists and experts in PAP use, and will be reviewed and updated as new information surfaces, the authors wrote.
Dr. Patil reported no financial conflicts; several coauthors reported conflicts that were managed by their not voting on guidelines related to those conflicts.
SOURCE: Patil SP et al. J Clin Sleep Med. 2018 Feb 15;15(2):335-43.
FROM THE JOURNAL OF CLINICAL SLEEP MEDICINE
Data from routine lung cancer visits yield research insights
A continuously updating database of clinical and genomic details on patients with non–small cell lung cancer accurately represented correlations between genomics and outcomes, based on an analysis of more than 4,000 patients.
“Most efforts to identify clinicogenomic associations currently rely on clinical trials, single-institution series, or national registries,” wrote Gaurav Singal, MD, of Foundation Medicine in Cambridge, Mass., and colleagues in JAMA.
To explore the feasibility of a clinicogenomic database, the researchers combined clinical data from electronic health records with comprehensive genetic profiling data from 28,889 patients; 4,064 adults with non–small cell lung cancer were included in the analysis of associations among tumor genomics, patient characteristics, and clinical outcomes. The data were collected between Jan. 1, 2011, and Jan. 1, 2018, from 275 U.S. oncology practices.
The researchers examined implications of clinical and genomic features for 3,522 patients with advanced disease. Among these, the median overall survival was 10.3 months and the 5-year survival rate was 3.8%. Factors influencing a longer overall survival included never smoking and having nonsquamous pathology; the presence of mutations in genes TP53 and RB1 were associated with shorter survival.
For each patient, researchers calculated the tumor mutational burden (TMB), defined as “a measure of the number of somatic mutations identified per megabase of DNA sequenced.” TMB was significantly higher among smokers, compared with nonsmokers, and “alterations in EGFR, ALK, ROS1, and RET were associated with significantly lower TMB than wild-type cases,” the researchers wrote.
Overall, the results “replicated previously described associations between clinical and genomic characteristics, driver mutations and response to targeted therapy, and TMB and response to immunotherapy,” the researchers wrote.
The findings were limited by several factors, notably the quality and completeness of mortality data, as well as potential biases from the inclusion of comprehensive genetic profiling results and analysis of therapeutic exposures in an unrandomized trial, as well as a study population limited to patients with advanced stage disease, the researchers noted.
However, the results support data from similar studies and further show that clinicogenomic databases can be used in research to augment drug development and improve the design of clinical trials, they wrote.
The study was supported by Flatiron Health and Foundation Medicine, which are both owned by the Roche Group. Dr. Singal and several coauthors are employees of Foundation Medicine.
SOURCE: Singal G et al. JAMA. 2019;321:1391-9.
A continuously updating database of clinical and genomic details on patients with non–small cell lung cancer accurately represented correlations between genomics and outcomes, based on an analysis of more than 4,000 patients.
“Most efforts to identify clinicogenomic associations currently rely on clinical trials, single-institution series, or national registries,” wrote Gaurav Singal, MD, of Foundation Medicine in Cambridge, Mass., and colleagues in JAMA.
To explore the feasibility of a clinicogenomic database, the researchers combined clinical data from electronic health records with comprehensive genetic profiling data from 28,889 patients; 4,064 adults with non–small cell lung cancer were included in the analysis of associations among tumor genomics, patient characteristics, and clinical outcomes. The data were collected between Jan. 1, 2011, and Jan. 1, 2018, from 275 U.S. oncology practices.
The researchers examined implications of clinical and genomic features for 3,522 patients with advanced disease. Among these, the median overall survival was 10.3 months and the 5-year survival rate was 3.8%. Factors influencing a longer overall survival included never smoking and having nonsquamous pathology; the presence of mutations in genes TP53 and RB1 were associated with shorter survival.
For each patient, researchers calculated the tumor mutational burden (TMB), defined as “a measure of the number of somatic mutations identified per megabase of DNA sequenced.” TMB was significantly higher among smokers, compared with nonsmokers, and “alterations in EGFR, ALK, ROS1, and RET were associated with significantly lower TMB than wild-type cases,” the researchers wrote.
Overall, the results “replicated previously described associations between clinical and genomic characteristics, driver mutations and response to targeted therapy, and TMB and response to immunotherapy,” the researchers wrote.
The findings were limited by several factors, notably the quality and completeness of mortality data, as well as potential biases from the inclusion of comprehensive genetic profiling results and analysis of therapeutic exposures in an unrandomized trial, as well as a study population limited to patients with advanced stage disease, the researchers noted.
However, the results support data from similar studies and further show that clinicogenomic databases can be used in research to augment drug development and improve the design of clinical trials, they wrote.
The study was supported by Flatiron Health and Foundation Medicine, which are both owned by the Roche Group. Dr. Singal and several coauthors are employees of Foundation Medicine.
SOURCE: Singal G et al. JAMA. 2019;321:1391-9.
A continuously updating database of clinical and genomic details on patients with non–small cell lung cancer accurately represented correlations between genomics and outcomes, based on an analysis of more than 4,000 patients.
“Most efforts to identify clinicogenomic associations currently rely on clinical trials, single-institution series, or national registries,” wrote Gaurav Singal, MD, of Foundation Medicine in Cambridge, Mass., and colleagues in JAMA.
To explore the feasibility of a clinicogenomic database, the researchers combined clinical data from electronic health records with comprehensive genetic profiling data from 28,889 patients; 4,064 adults with non–small cell lung cancer were included in the analysis of associations among tumor genomics, patient characteristics, and clinical outcomes. The data were collected between Jan. 1, 2011, and Jan. 1, 2018, from 275 U.S. oncology practices.
The researchers examined implications of clinical and genomic features for 3,522 patients with advanced disease. Among these, the median overall survival was 10.3 months and the 5-year survival rate was 3.8%. Factors influencing a longer overall survival included never smoking and having nonsquamous pathology; the presence of mutations in genes TP53 and RB1 were associated with shorter survival.
For each patient, researchers calculated the tumor mutational burden (TMB), defined as “a measure of the number of somatic mutations identified per megabase of DNA sequenced.” TMB was significantly higher among smokers, compared with nonsmokers, and “alterations in EGFR, ALK, ROS1, and RET were associated with significantly lower TMB than wild-type cases,” the researchers wrote.
Overall, the results “replicated previously described associations between clinical and genomic characteristics, driver mutations and response to targeted therapy, and TMB and response to immunotherapy,” the researchers wrote.
The findings were limited by several factors, notably the quality and completeness of mortality data, as well as potential biases from the inclusion of comprehensive genetic profiling results and analysis of therapeutic exposures in an unrandomized trial, as well as a study population limited to patients with advanced stage disease, the researchers noted.
However, the results support data from similar studies and further show that clinicogenomic databases can be used in research to augment drug development and improve the design of clinical trials, they wrote.
The study was supported by Flatiron Health and Foundation Medicine, which are both owned by the Roche Group. Dr. Singal and several coauthors are employees of Foundation Medicine.
SOURCE: Singal G et al. JAMA. 2019;321:1391-9.
FROM JAMA
USPSTF finds the evidence inconclusive for lead screening in young children, pregnant women
according to a recommendation from the U.S. Preventive Services Task Force.
Elevated blood lead levels are associated with potentially irreversible neurologic problems in children and with organ system impairment and adverse perinatal effects in pregnant women, according to the statement.
“Thus, the primary benefit of screening may be in preventing future exposures or exposure of others to environmental sources,” the task force members wrote in JAMA Pediatrics.
However, the task force issued I statements, meaning that “the current evidence is insufficient to assess the balance of benefits and harms of screening for elevated blood lead levels” in asymptomatic children aged 5 years and younger and in asymptomatic pregnant women.
The task force cited evidence that questionnaires and other clinical prediction tools are inaccurate at identifying elevated blood lead levels in asymptomatic children and pregnant women. In addition, the task force found adequate evidence that capillary blood testing identified elevated blood lead levels in children, but found inadequate evidence that treating elevated blood lead levels was effective in asymptomatic children aged 5 years and younger or in pregnant women.
In the evidence report accompanying the recommendation statement in JAMA Pediatrics, Amy G. Cantor, MD, MPH, of Oregon Health & Science University, Portland, and her colleagues reviewed data from a total of 24 studies including 11,433 individuals.
None of the studies evaluated the risks or benefits of blood lead screening in children. However, in three of four studies, capillary blood lead testing showed sensitivities ranging from 87% to 91% and specificities from 92% to 99%, based on a blood lead level cutoff of 10 mcg/dL or less.
“Evidence indicates that capillary sampling is slightly less sensitive than venous sampling, with comparable specificity,” Dr. Cantor and her colleagues wrote. “Both methods require confirmation.”
There is only limited evidence on whether intervening when children present with elevated blood lead levels results in better neurodevelopmental outcomes. One trial showed beneficial effects of dimercaptosuccinic acid chelation of lowering elevated blood lead levels (20-44 mcg/dL) at 1 year versus placebo, but no clear effect on longer term blood lead levels or neurodevelopmental outcomes, they reported.
For residential interventions, again evidence is limited and blood lead concentrations were not clearly affected. Evidence on calcium and iron interventions was poor quality and insufficient to tell if there was an effect on blood lead levels or clinical outcomes, Dr. Cantor and her colleagues wrote.
No studies of screening for elevated lead levels in pregnant women were identified, nor were studies of health outcomes after interventions to reduce blood lead levels in asymptomatic pregnant women, they noted.
Studies involving pregnant women were limited, and included data on the diagnostic accuracy of a clinical questionnaire and the effects of nutritional intervention during pregnancy, Dr. Cantor and her colleagues wrote.
“This update confirms there are no clear effects of interventions for lowering elevated blood levels in affected children or to improve neurodevelopmental outcomes,” they concluded. “Evidence to determine benefits and harms of screening or treating elevated lead levels during pregnancy remains extremely limited.”
The recommendation updates the last version issued in 2006. The USPSTF is supported by the Agency for Healthcare Research and Quality. The researchers for both articles reported no relevant financial disclosures.
SOURCE: Curry SJ et al. JAMA Pediatr. 2019 Apr 16. doi: 10.1001/jama.2019.3326; Cantor AG et al. JAMA Pediatr. 2019 Apr 16. doi: 10.1001/jama.2019.1004.
“The inconclusive findings of the new USPSTF [U.S. Preventive Services Task Force] recommendation does not mean that screening children for elevated lead levels is not necessary, nor does it shed light on whether screening should be targeted to children at high risk or whether it should be universally done,” Michael Weitzman, MD, wrote in an editorial in response to the USPSTF recommendations.
Dr. Weitzman noted that the recommendation is a consequence of the lack of quality studies on lead level screening, and wrote that, although the recommendations apply to asymptomatic children at both average risk and increased risk, the USPSTF does not recommend for or against screening or that screening be abandoned.
It is standard pediatric practice to counsel parents on lead exposure and screening for elevated blood lead levels in children aged 1-5 years, he wrote, adding that “the American Academy of Pediatrics, Bright Futures, the Centers for Disease Control and Prevention, and Medicaid all recommend universal blood lead screening or the screening of selected children believed to be at especially high risk of exposure at approximately age 1 and 2 years.”
More rigorous research is needed to make definitive recommendations, but in the meantime, clinicians should continue to work with local health departments, housing authorities, and schools to provide care for children with elevated lead levels while continuing with the screening practices recommended by the AAP and other organizations, and advocating for prevention of lead exposure, Dr. Weitzman wrote.
Dr. Weitzman is professor of pediatrics and professor of environmental medicine at New York University. This is a summary of the editorial Dr. Weitzman wrote to accompany the published USPSTF recommendation (JAMA Pediatr. 2019 Apr 16. doi:10.1001/jamapediatrics.2019.0855). He reported no relevant financial disclosures.
“The inconclusive findings of the new USPSTF [U.S. Preventive Services Task Force] recommendation does not mean that screening children for elevated lead levels is not necessary, nor does it shed light on whether screening should be targeted to children at high risk or whether it should be universally done,” Michael Weitzman, MD, wrote in an editorial in response to the USPSTF recommendations.
Dr. Weitzman noted that the recommendation is a consequence of the lack of quality studies on lead level screening, and wrote that, although the recommendations apply to asymptomatic children at both average risk and increased risk, the USPSTF does not recommend for or against screening or that screening be abandoned.
It is standard pediatric practice to counsel parents on lead exposure and screening for elevated blood lead levels in children aged 1-5 years, he wrote, adding that “the American Academy of Pediatrics, Bright Futures, the Centers for Disease Control and Prevention, and Medicaid all recommend universal blood lead screening or the screening of selected children believed to be at especially high risk of exposure at approximately age 1 and 2 years.”
More rigorous research is needed to make definitive recommendations, but in the meantime, clinicians should continue to work with local health departments, housing authorities, and schools to provide care for children with elevated lead levels while continuing with the screening practices recommended by the AAP and other organizations, and advocating for prevention of lead exposure, Dr. Weitzman wrote.
Dr. Weitzman is professor of pediatrics and professor of environmental medicine at New York University. This is a summary of the editorial Dr. Weitzman wrote to accompany the published USPSTF recommendation (JAMA Pediatr. 2019 Apr 16. doi:10.1001/jamapediatrics.2019.0855). He reported no relevant financial disclosures.
“The inconclusive findings of the new USPSTF [U.S. Preventive Services Task Force] recommendation does not mean that screening children for elevated lead levels is not necessary, nor does it shed light on whether screening should be targeted to children at high risk or whether it should be universally done,” Michael Weitzman, MD, wrote in an editorial in response to the USPSTF recommendations.
Dr. Weitzman noted that the recommendation is a consequence of the lack of quality studies on lead level screening, and wrote that, although the recommendations apply to asymptomatic children at both average risk and increased risk, the USPSTF does not recommend for or against screening or that screening be abandoned.
It is standard pediatric practice to counsel parents on lead exposure and screening for elevated blood lead levels in children aged 1-5 years, he wrote, adding that “the American Academy of Pediatrics, Bright Futures, the Centers for Disease Control and Prevention, and Medicaid all recommend universal blood lead screening or the screening of selected children believed to be at especially high risk of exposure at approximately age 1 and 2 years.”
More rigorous research is needed to make definitive recommendations, but in the meantime, clinicians should continue to work with local health departments, housing authorities, and schools to provide care for children with elevated lead levels while continuing with the screening practices recommended by the AAP and other organizations, and advocating for prevention of lead exposure, Dr. Weitzman wrote.
Dr. Weitzman is professor of pediatrics and professor of environmental medicine at New York University. This is a summary of the editorial Dr. Weitzman wrote to accompany the published USPSTF recommendation (JAMA Pediatr. 2019 Apr 16. doi:10.1001/jamapediatrics.2019.0855). He reported no relevant financial disclosures.
according to a recommendation from the U.S. Preventive Services Task Force.
Elevated blood lead levels are associated with potentially irreversible neurologic problems in children and with organ system impairment and adverse perinatal effects in pregnant women, according to the statement.
“Thus, the primary benefit of screening may be in preventing future exposures or exposure of others to environmental sources,” the task force members wrote in JAMA Pediatrics.
However, the task force issued I statements, meaning that “the current evidence is insufficient to assess the balance of benefits and harms of screening for elevated blood lead levels” in asymptomatic children aged 5 years and younger and in asymptomatic pregnant women.
The task force cited evidence that questionnaires and other clinical prediction tools are inaccurate at identifying elevated blood lead levels in asymptomatic children and pregnant women. In addition, the task force found adequate evidence that capillary blood testing identified elevated blood lead levels in children, but found inadequate evidence that treating elevated blood lead levels was effective in asymptomatic children aged 5 years and younger or in pregnant women.
In the evidence report accompanying the recommendation statement in JAMA Pediatrics, Amy G. Cantor, MD, MPH, of Oregon Health & Science University, Portland, and her colleagues reviewed data from a total of 24 studies including 11,433 individuals.
None of the studies evaluated the risks or benefits of blood lead screening in children. However, in three of four studies, capillary blood lead testing showed sensitivities ranging from 87% to 91% and specificities from 92% to 99%, based on a blood lead level cutoff of 10 mcg/dL or less.
“Evidence indicates that capillary sampling is slightly less sensitive than venous sampling, with comparable specificity,” Dr. Cantor and her colleagues wrote. “Both methods require confirmation.”
There is only limited evidence on whether intervening when children present with elevated blood lead levels results in better neurodevelopmental outcomes. One trial showed beneficial effects of dimercaptosuccinic acid chelation of lowering elevated blood lead levels (20-44 mcg/dL) at 1 year versus placebo, but no clear effect on longer term blood lead levels or neurodevelopmental outcomes, they reported.
For residential interventions, again evidence is limited and blood lead concentrations were not clearly affected. Evidence on calcium and iron interventions was poor quality and insufficient to tell if there was an effect on blood lead levels or clinical outcomes, Dr. Cantor and her colleagues wrote.
No studies of screening for elevated lead levels in pregnant women were identified, nor were studies of health outcomes after interventions to reduce blood lead levels in asymptomatic pregnant women, they noted.
Studies involving pregnant women were limited, and included data on the diagnostic accuracy of a clinical questionnaire and the effects of nutritional intervention during pregnancy, Dr. Cantor and her colleagues wrote.
“This update confirms there are no clear effects of interventions for lowering elevated blood levels in affected children or to improve neurodevelopmental outcomes,” they concluded. “Evidence to determine benefits and harms of screening or treating elevated lead levels during pregnancy remains extremely limited.”
The recommendation updates the last version issued in 2006. The USPSTF is supported by the Agency for Healthcare Research and Quality. The researchers for both articles reported no relevant financial disclosures.
SOURCE: Curry SJ et al. JAMA Pediatr. 2019 Apr 16. doi: 10.1001/jama.2019.3326; Cantor AG et al. JAMA Pediatr. 2019 Apr 16. doi: 10.1001/jama.2019.1004.
according to a recommendation from the U.S. Preventive Services Task Force.
Elevated blood lead levels are associated with potentially irreversible neurologic problems in children and with organ system impairment and adverse perinatal effects in pregnant women, according to the statement.
“Thus, the primary benefit of screening may be in preventing future exposures or exposure of others to environmental sources,” the task force members wrote in JAMA Pediatrics.
However, the task force issued I statements, meaning that “the current evidence is insufficient to assess the balance of benefits and harms of screening for elevated blood lead levels” in asymptomatic children aged 5 years and younger and in asymptomatic pregnant women.
The task force cited evidence that questionnaires and other clinical prediction tools are inaccurate at identifying elevated blood lead levels in asymptomatic children and pregnant women. In addition, the task force found adequate evidence that capillary blood testing identified elevated blood lead levels in children, but found inadequate evidence that treating elevated blood lead levels was effective in asymptomatic children aged 5 years and younger or in pregnant women.
In the evidence report accompanying the recommendation statement in JAMA Pediatrics, Amy G. Cantor, MD, MPH, of Oregon Health & Science University, Portland, and her colleagues reviewed data from a total of 24 studies including 11,433 individuals.
None of the studies evaluated the risks or benefits of blood lead screening in children. However, in three of four studies, capillary blood lead testing showed sensitivities ranging from 87% to 91% and specificities from 92% to 99%, based on a blood lead level cutoff of 10 mcg/dL or less.
“Evidence indicates that capillary sampling is slightly less sensitive than venous sampling, with comparable specificity,” Dr. Cantor and her colleagues wrote. “Both methods require confirmation.”
There is only limited evidence on whether intervening when children present with elevated blood lead levels results in better neurodevelopmental outcomes. One trial showed beneficial effects of dimercaptosuccinic acid chelation of lowering elevated blood lead levels (20-44 mcg/dL) at 1 year versus placebo, but no clear effect on longer term blood lead levels or neurodevelopmental outcomes, they reported.
For residential interventions, again evidence is limited and blood lead concentrations were not clearly affected. Evidence on calcium and iron interventions was poor quality and insufficient to tell if there was an effect on blood lead levels or clinical outcomes, Dr. Cantor and her colleagues wrote.
No studies of screening for elevated lead levels in pregnant women were identified, nor were studies of health outcomes after interventions to reduce blood lead levels in asymptomatic pregnant women, they noted.
Studies involving pregnant women were limited, and included data on the diagnostic accuracy of a clinical questionnaire and the effects of nutritional intervention during pregnancy, Dr. Cantor and her colleagues wrote.
“This update confirms there are no clear effects of interventions for lowering elevated blood levels in affected children or to improve neurodevelopmental outcomes,” they concluded. “Evidence to determine benefits and harms of screening or treating elevated lead levels during pregnancy remains extremely limited.”
The recommendation updates the last version issued in 2006. The USPSTF is supported by the Agency for Healthcare Research and Quality. The researchers for both articles reported no relevant financial disclosures.
SOURCE: Curry SJ et al. JAMA Pediatr. 2019 Apr 16. doi: 10.1001/jama.2019.3326; Cantor AG et al. JAMA Pediatr. 2019 Apr 16. doi: 10.1001/jama.2019.1004.
FROM JAMA PEDIATRICS
Bendamustine/rituximab combo proves viable for comorbid CLL
A combination of bendamustine and rituximab generated an 88% overall response rate and 96% overall survival rate at 2 years among patients with chronic lymphocytic leukemia (CLL) in a study of 83 patients aged 53-83 years.
Although combined fludarabine, cyclophosphamide, and rituximab has demonstrated success in younger patients with CLL, this therapy is often considered too aggressive for the majority of CLL patients, who tend to be older and have multiple comorbidities, wrote Martin Špacek, MD, of Charles University and General University Hospital in Prague and his colleagues.
The alternative treatment combination of bendamustine and rituximab (BR) has not been well studied in patients with comorbidities, they said.
In a study published in Leukemia Research, the researchers enrolled 83 previously untreated adults with progressive CLL. The average age of the participants was 71 years, and 61% were men. The median creatinine clearance for the study population was 65 mL/min, and all patients had comorbidities, defined as scores greater than 6 on the Cumulative Illness Rating Scale (CIRS).
All patients were prescribed 90 mg/m2 bendamustine on days 1 and 2 combined with 375 mg/m2 rituximab on day 0 of the first course, and 500 mg/m2 rituximab on day 1 during subsequent courses every 28 days for a maximum of six cycles.
The overall response rate to BR was 88.0%, with a complete response rate of 20.5%. At 2 years, progression-free survival and overall survival rates were 69.9% and 96.2%, respectively.
A total of 51 patients (61.4%) experienced at least one grade 3 or 4 adverse event. The most common hematologic effects were neutropenia (40 patients), thrombocytopenia (14 patients), and anemia (8 patients). The most common nonhematologic effects were grade 3– or grade 4–level infections in 12 patients. Six patients developed severe skin rash.
Additionally, one patient developed sepsis during treatment and died after the first course of therapy.
“Age and CIRS failed to predict any severe toxicities or BR dose reduction,” the researchers noted.
The findings support data from previous studies and represent the largest study of CLL patients with significant comorbidities to be treated with BR, the researchers said.
More prospective research is needed, but the results demonstrate that “chemoimmunotherapy with BR is an effective therapeutic option with manageable toxicity for the initial treatment of CLL patients with significant comorbidities,” the investigators wrote.
The study was supported by the Ministry of Health, Czech Republic, the Charles University Progres program, and the Czech CLL Study Group. Researchers reported honoraria and travel grants from Mundipharma and Roche.
SOURCE: Spacek M et al. Leuk Res. 2019;79:17-21.
A combination of bendamustine and rituximab generated an 88% overall response rate and 96% overall survival rate at 2 years among patients with chronic lymphocytic leukemia (CLL) in a study of 83 patients aged 53-83 years.
Although combined fludarabine, cyclophosphamide, and rituximab has demonstrated success in younger patients with CLL, this therapy is often considered too aggressive for the majority of CLL patients, who tend to be older and have multiple comorbidities, wrote Martin Špacek, MD, of Charles University and General University Hospital in Prague and his colleagues.
The alternative treatment combination of bendamustine and rituximab (BR) has not been well studied in patients with comorbidities, they said.
In a study published in Leukemia Research, the researchers enrolled 83 previously untreated adults with progressive CLL. The average age of the participants was 71 years, and 61% were men. The median creatinine clearance for the study population was 65 mL/min, and all patients had comorbidities, defined as scores greater than 6 on the Cumulative Illness Rating Scale (CIRS).
All patients were prescribed 90 mg/m2 bendamustine on days 1 and 2 combined with 375 mg/m2 rituximab on day 0 of the first course, and 500 mg/m2 rituximab on day 1 during subsequent courses every 28 days for a maximum of six cycles.
The overall response rate to BR was 88.0%, with a complete response rate of 20.5%. At 2 years, progression-free survival and overall survival rates were 69.9% and 96.2%, respectively.
A total of 51 patients (61.4%) experienced at least one grade 3 or 4 adverse event. The most common hematologic effects were neutropenia (40 patients), thrombocytopenia (14 patients), and anemia (8 patients). The most common nonhematologic effects were grade 3– or grade 4–level infections in 12 patients. Six patients developed severe skin rash.
Additionally, one patient developed sepsis during treatment and died after the first course of therapy.
“Age and CIRS failed to predict any severe toxicities or BR dose reduction,” the researchers noted.
The findings support data from previous studies and represent the largest study of CLL patients with significant comorbidities to be treated with BR, the researchers said.
More prospective research is needed, but the results demonstrate that “chemoimmunotherapy with BR is an effective therapeutic option with manageable toxicity for the initial treatment of CLL patients with significant comorbidities,” the investigators wrote.
The study was supported by the Ministry of Health, Czech Republic, the Charles University Progres program, and the Czech CLL Study Group. Researchers reported honoraria and travel grants from Mundipharma and Roche.
SOURCE: Spacek M et al. Leuk Res. 2019;79:17-21.
A combination of bendamustine and rituximab generated an 88% overall response rate and 96% overall survival rate at 2 years among patients with chronic lymphocytic leukemia (CLL) in a study of 83 patients aged 53-83 years.
Although combined fludarabine, cyclophosphamide, and rituximab has demonstrated success in younger patients with CLL, this therapy is often considered too aggressive for the majority of CLL patients, who tend to be older and have multiple comorbidities, wrote Martin Špacek, MD, of Charles University and General University Hospital in Prague and his colleagues.
The alternative treatment combination of bendamustine and rituximab (BR) has not been well studied in patients with comorbidities, they said.
In a study published in Leukemia Research, the researchers enrolled 83 previously untreated adults with progressive CLL. The average age of the participants was 71 years, and 61% were men. The median creatinine clearance for the study population was 65 mL/min, and all patients had comorbidities, defined as scores greater than 6 on the Cumulative Illness Rating Scale (CIRS).
All patients were prescribed 90 mg/m2 bendamustine on days 1 and 2 combined with 375 mg/m2 rituximab on day 0 of the first course, and 500 mg/m2 rituximab on day 1 during subsequent courses every 28 days for a maximum of six cycles.
The overall response rate to BR was 88.0%, with a complete response rate of 20.5%. At 2 years, progression-free survival and overall survival rates were 69.9% and 96.2%, respectively.
A total of 51 patients (61.4%) experienced at least one grade 3 or 4 adverse event. The most common hematologic effects were neutropenia (40 patients), thrombocytopenia (14 patients), and anemia (8 patients). The most common nonhematologic effects were grade 3– or grade 4–level infections in 12 patients. Six patients developed severe skin rash.
Additionally, one patient developed sepsis during treatment and died after the first course of therapy.
“Age and CIRS failed to predict any severe toxicities or BR dose reduction,” the researchers noted.
The findings support data from previous studies and represent the largest study of CLL patients with significant comorbidities to be treated with BR, the researchers said.
More prospective research is needed, but the results demonstrate that “chemoimmunotherapy with BR is an effective therapeutic option with manageable toxicity for the initial treatment of CLL patients with significant comorbidities,” the investigators wrote.
The study was supported by the Ministry of Health, Czech Republic, the Charles University Progres program, and the Czech CLL Study Group. Researchers reported honoraria and travel grants from Mundipharma and Roche.
SOURCE: Spacek M et al. Leuk Res. 2019;79:17-21.
FROM LEUKEMIA RESEARCH
Key clinical point:
Major finding: The overall response rate for the combination therapy was 88.0%; complete response was 20.5%.
Study details: A prospective, observational study of 83 patients with chronic lymphocytic leukemia.
Disclosures: The study was supported by the Ministry of Health, Czech Republic, the Charles University Progres program, and the Czech CLL Study Group. Researchers reported honoraria and travel grants from Mundipharma and Roche.
Source: Spacek M et al. Leuk Res. 2019;79:17-21.
Oscillatory ventilation reduced reintubation risk for preterm infants
Nasal high-frequency oscillatory ventilation, in a randomized trial of 206 preterm infants with respiratory failure.
Previous studies have supported the use of NHFOV as more effective for reducing CO2 and for lowering the risk of reintubation compared with NCPAP. But no randomized, controlled trials had compared the outcomes for preterm infants in particular, wrote Long Chen, MD, PhD, of Children’s Hospital of Chongqing Medical University, Chongqing, China, and colleagues.
Their study, published in Chest, was conducted at a single tertiary NICU in China between May 2017 and May 2018, and randomized infants with a gestational age less than 37 weeks to NHFOV (103 infants) or NCPAP (103 infants). Infants with major congenital abnormalities were excluded. The infants included 127 (61.7%) diagnosed with respiratory distress syndrome (RDS), 53 (25.7%) diagnosed with acute RDS (ARDS), and 26 (12.6%) diagnosed with both RDS and ARDS.
Overall, the reintubation rate within 6 hours was significantly lower among infants treated with NHFOV compared with those treated with NCPAP (15.5% vs. 34%, P = .002), and in the subset of infants with ARDS (23.5% vs. 52.6%, P = .032). Among infants with a gestational age of 32 weeks or less, reintuibation rates were also significantly lower among those treated with NHFOV (26.1% vs. 55.6%, P = .004).
In addition, PCO2 levels, 6 hours after extubation, were significantly lower among infants on NHFOV, compared with those on NCPAP (49.6 vs. 56.9 P = .00). The hospital stay, a secondary outcome, was significantly shorter among the infants treated with NHFOV, than those treated with NCPAP (22 days, vs. 27.6 days, P =.011).
Although the researchers observed some nasal trauma in NHFOV-treated patients, and intestinal dilation in both groups similar to side effects seen in previous studies, no feeding intolerance or skin lesions were associated with NHFOV. The study findings were consistent with those from previous studies, and suggested that the causes of respiratory failure might account for the differences between the treatment groups, they noted.
“RDS is primarily restrictive in the acute phase, and the high frequency oscillation over CPAP does not therefore bring any benefit. However, ARDS is both restrictive and obstructive in the acute phase due to the nature of ARDS,” and NHFOV is “able to improve oxygenation,” they added.
The study findings were limited by several factors including the use of data from a single center and the small number of infants younger than 28 weeks’ gestation, the researchers noted. However, they added, two international, multicenter, randomized controlled trials are in the works.
The study was supported by Social Livelihood Program of 38 Chongqing Science and Technology Commission, China. The researchers had no financial conflicts to disclose.
SOURCE: Long C et al. Chest. 2019; 155(4): 740-8.
Nasal high-frequency oscillatory ventilation, in a randomized trial of 206 preterm infants with respiratory failure.
Previous studies have supported the use of NHFOV as more effective for reducing CO2 and for lowering the risk of reintubation compared with NCPAP. But no randomized, controlled trials had compared the outcomes for preterm infants in particular, wrote Long Chen, MD, PhD, of Children’s Hospital of Chongqing Medical University, Chongqing, China, and colleagues.
Their study, published in Chest, was conducted at a single tertiary NICU in China between May 2017 and May 2018, and randomized infants with a gestational age less than 37 weeks to NHFOV (103 infants) or NCPAP (103 infants). Infants with major congenital abnormalities were excluded. The infants included 127 (61.7%) diagnosed with respiratory distress syndrome (RDS), 53 (25.7%) diagnosed with acute RDS (ARDS), and 26 (12.6%) diagnosed with both RDS and ARDS.
Overall, the reintubation rate within 6 hours was significantly lower among infants treated with NHFOV compared with those treated with NCPAP (15.5% vs. 34%, P = .002), and in the subset of infants with ARDS (23.5% vs. 52.6%, P = .032). Among infants with a gestational age of 32 weeks or less, reintuibation rates were also significantly lower among those treated with NHFOV (26.1% vs. 55.6%, P = .004).
In addition, PCO2 levels, 6 hours after extubation, were significantly lower among infants on NHFOV, compared with those on NCPAP (49.6 vs. 56.9 P = .00). The hospital stay, a secondary outcome, was significantly shorter among the infants treated with NHFOV, than those treated with NCPAP (22 days, vs. 27.6 days, P =.011).
Although the researchers observed some nasal trauma in NHFOV-treated patients, and intestinal dilation in both groups similar to side effects seen in previous studies, no feeding intolerance or skin lesions were associated with NHFOV. The study findings were consistent with those from previous studies, and suggested that the causes of respiratory failure might account for the differences between the treatment groups, they noted.
“RDS is primarily restrictive in the acute phase, and the high frequency oscillation over CPAP does not therefore bring any benefit. However, ARDS is both restrictive and obstructive in the acute phase due to the nature of ARDS,” and NHFOV is “able to improve oxygenation,” they added.
The study findings were limited by several factors including the use of data from a single center and the small number of infants younger than 28 weeks’ gestation, the researchers noted. However, they added, two international, multicenter, randomized controlled trials are in the works.
The study was supported by Social Livelihood Program of 38 Chongqing Science and Technology Commission, China. The researchers had no financial conflicts to disclose.
SOURCE: Long C et al. Chest. 2019; 155(4): 740-8.
Nasal high-frequency oscillatory ventilation, in a randomized trial of 206 preterm infants with respiratory failure.
Previous studies have supported the use of NHFOV as more effective for reducing CO2 and for lowering the risk of reintubation compared with NCPAP. But no randomized, controlled trials had compared the outcomes for preterm infants in particular, wrote Long Chen, MD, PhD, of Children’s Hospital of Chongqing Medical University, Chongqing, China, and colleagues.
Their study, published in Chest, was conducted at a single tertiary NICU in China between May 2017 and May 2018, and randomized infants with a gestational age less than 37 weeks to NHFOV (103 infants) or NCPAP (103 infants). Infants with major congenital abnormalities were excluded. The infants included 127 (61.7%) diagnosed with respiratory distress syndrome (RDS), 53 (25.7%) diagnosed with acute RDS (ARDS), and 26 (12.6%) diagnosed with both RDS and ARDS.
Overall, the reintubation rate within 6 hours was significantly lower among infants treated with NHFOV compared with those treated with NCPAP (15.5% vs. 34%, P = .002), and in the subset of infants with ARDS (23.5% vs. 52.6%, P = .032). Among infants with a gestational age of 32 weeks or less, reintuibation rates were also significantly lower among those treated with NHFOV (26.1% vs. 55.6%, P = .004).
In addition, PCO2 levels, 6 hours after extubation, were significantly lower among infants on NHFOV, compared with those on NCPAP (49.6 vs. 56.9 P = .00). The hospital stay, a secondary outcome, was significantly shorter among the infants treated with NHFOV, than those treated with NCPAP (22 days, vs. 27.6 days, P =.011).
Although the researchers observed some nasal trauma in NHFOV-treated patients, and intestinal dilation in both groups similar to side effects seen in previous studies, no feeding intolerance or skin lesions were associated with NHFOV. The study findings were consistent with those from previous studies, and suggested that the causes of respiratory failure might account for the differences between the treatment groups, they noted.
“RDS is primarily restrictive in the acute phase, and the high frequency oscillation over CPAP does not therefore bring any benefit. However, ARDS is both restrictive and obstructive in the acute phase due to the nature of ARDS,” and NHFOV is “able to improve oxygenation,” they added.
The study findings were limited by several factors including the use of data from a single center and the small number of infants younger than 28 weeks’ gestation, the researchers noted. However, they added, two international, multicenter, randomized controlled trials are in the works.
The study was supported by Social Livelihood Program of 38 Chongqing Science and Technology Commission, China. The researchers had no financial conflicts to disclose.
SOURCE: Long C et al. Chest. 2019; 155(4): 740-8.
FROM CHEST
Poor oral health predicts children’s school problems
Poor oral health was significantly associated with poor academic performance in children aged 6-17 years, based on data from more than 45,000 children in the United States.
The study, published in the Journal of Pediatrics, updates an assessment from 2007 of a similarly representative sample of U.S. children.
“Providing an updated analysis is especially important to understand the dynamics between children’s oral health status and academic performance, given reported improvements in dental care use among children and dental treatment quality and the implementation or expansion of some state-level preventive strategies,” wrote Carol Cristina Guarnizo-Herreño, DDS, PhD, of Universidad Nacional de Colombia, Bogotá, and her colleagues.
The researchers analyzed data from the 2016 and 2017 versions of National Survey of Children’s Health that included 45,711 children aged 6-17 years. Survey data were collected from parents or other primary caregivers. In the study population, 16% of the children had a least one dental problem, defined as toothache, tooth decay or cavities, or bleeding gums, and 25% of the children had school problems: 67% missed any school, 23% missed more than 3 days of school, and 10% missed more than 6 days of school.
Overall, children with at least 1 dental problem were significantly more likely than those without dental problems to have problems at school (odds ratio, 1.56) or miss at least 1 school day (OR, 1.54) – more than 50% more likely. In addition, children with at least one dental problem were approximately 40% more likely to miss more than 3 days or more than 6 days of school (OR, 1.39 for both).
The association increased when the investigators used children’s oral health ratings; those with oral health rated as poor/fair were approximately 80% more likely to have school problems (OR, 1.77), almost 60% more likely to miss more than 3 days of school (OR, 1.56), and 90% more likely to miss more than 6 days of school, compared with children with oral health rankings of good, very good, or excellent.
Despite some variations in subgroups when the population was stratified by age, sex, race, household income, and health insurance, the associations between oral health problems and academic problems showed “remarkable stability,” across demographic and socioeconomic categories, the researchers said.
The study results were limited by several factors including the inability to identify the mechanisms behind the oral health and academic outcomes relationship, as well as the potential errors in parent or caregiver reports of children’s oral health and school performance, Dr. Guarnizo-Herreño and her associates said. However, the findings support those from an earlier study using 2007 data, and suggest that the link between poor oral health and poor academic performance has lasted for the past decade.
“The relationship between oral health and academic achievement is complex and likely involves multiple and intertwined pathways,” such as the impact of oral pain or discomfort on eating and sleeping that may affect academic performance, they said.
“These findings highlight the need for broad population-wide policies and integrated approaches to promote children’s development and reduce academic deficits that include among other components initiatives to improve oral health through prevention and treatment access strategies,” Dr. Guarnizo-Herreño and her associates concluded.
The study was supported by the National Institute of Dental and Craniofacial Research. The researchers had no financial conflicts to disclose.
SOURCE: Guarnizo-Herreño C et al. J Pediatr. 2019. doi: 10.1016/j.jpeds.2019.01.045.
“Dental caries remains the most common chronic disease of childhood in the United States and is known to affect multiple domains of health and well-being. Academic success is an important predictor of future employment and economic performance, as well as life and health outcomes. Therefore, it is important that we understand the impact oral disease has on academic performance,” Melinda Clark, MD, said in an interview. “This study demonstrated that middle schoolers are at greatest risk of dental disease impacting school performance, with poor dental health doubling the risk of having problems at school and missing school days in children 12-14 years of age.
“Pediatricians care a great deal about the overall health and academic success of children, and the science informs us that poor oral health adversely impacts both of those domains. Pediatric primary care providers can adopt the Department of Health and Human Services Oral Health Framework to combat dental caries by integrating oral health services into practice and advocating for community water fluoridation. Application of fluoride varnish in the primary care office for all children from tooth eruption to age 6 years is recommended by the U.S. Preventive Services Task Force, the American Academy of Pediatrics, and is on the Bright Futures Periodicity schedule.
“Now is the time for action. The majority of dental disease in children is preventable with timely risk assessment, healthy diet choices, oral hygiene, and relatively simple office interventions. Future research should examine the effects of oral health changes on children’s academic outcomes to capture the full impact on children’s well-being.”
Dr. Clark is an associate professor of pediatrics at the Albany Medical Center, New York, and a member of the Pediatric News editorial advisory board. She was asked to comment on the article by Dr. Guarnizo-Herreño and associates. She has no relevant financial disclosures.
“Dental caries remains the most common chronic disease of childhood in the United States and is known to affect multiple domains of health and well-being. Academic success is an important predictor of future employment and economic performance, as well as life and health outcomes. Therefore, it is important that we understand the impact oral disease has on academic performance,” Melinda Clark, MD, said in an interview. “This study demonstrated that middle schoolers are at greatest risk of dental disease impacting school performance, with poor dental health doubling the risk of having problems at school and missing school days in children 12-14 years of age.
“Pediatricians care a great deal about the overall health and academic success of children, and the science informs us that poor oral health adversely impacts both of those domains. Pediatric primary care providers can adopt the Department of Health and Human Services Oral Health Framework to combat dental caries by integrating oral health services into practice and advocating for community water fluoridation. Application of fluoride varnish in the primary care office for all children from tooth eruption to age 6 years is recommended by the U.S. Preventive Services Task Force, the American Academy of Pediatrics, and is on the Bright Futures Periodicity schedule.
“Now is the time for action. The majority of dental disease in children is preventable with timely risk assessment, healthy diet choices, oral hygiene, and relatively simple office interventions. Future research should examine the effects of oral health changes on children’s academic outcomes to capture the full impact on children’s well-being.”
Dr. Clark is an associate professor of pediatrics at the Albany Medical Center, New York, and a member of the Pediatric News editorial advisory board. She was asked to comment on the article by Dr. Guarnizo-Herreño and associates. She has no relevant financial disclosures.
“Dental caries remains the most common chronic disease of childhood in the United States and is known to affect multiple domains of health and well-being. Academic success is an important predictor of future employment and economic performance, as well as life and health outcomes. Therefore, it is important that we understand the impact oral disease has on academic performance,” Melinda Clark, MD, said in an interview. “This study demonstrated that middle schoolers are at greatest risk of dental disease impacting school performance, with poor dental health doubling the risk of having problems at school and missing school days in children 12-14 years of age.
“Pediatricians care a great deal about the overall health and academic success of children, and the science informs us that poor oral health adversely impacts both of those domains. Pediatric primary care providers can adopt the Department of Health and Human Services Oral Health Framework to combat dental caries by integrating oral health services into practice and advocating for community water fluoridation. Application of fluoride varnish in the primary care office for all children from tooth eruption to age 6 years is recommended by the U.S. Preventive Services Task Force, the American Academy of Pediatrics, and is on the Bright Futures Periodicity schedule.
“Now is the time for action. The majority of dental disease in children is preventable with timely risk assessment, healthy diet choices, oral hygiene, and relatively simple office interventions. Future research should examine the effects of oral health changes on children’s academic outcomes to capture the full impact on children’s well-being.”
Dr. Clark is an associate professor of pediatrics at the Albany Medical Center, New York, and a member of the Pediatric News editorial advisory board. She was asked to comment on the article by Dr. Guarnizo-Herreño and associates. She has no relevant financial disclosures.
Poor oral health was significantly associated with poor academic performance in children aged 6-17 years, based on data from more than 45,000 children in the United States.
The study, published in the Journal of Pediatrics, updates an assessment from 2007 of a similarly representative sample of U.S. children.
“Providing an updated analysis is especially important to understand the dynamics between children’s oral health status and academic performance, given reported improvements in dental care use among children and dental treatment quality and the implementation or expansion of some state-level preventive strategies,” wrote Carol Cristina Guarnizo-Herreño, DDS, PhD, of Universidad Nacional de Colombia, Bogotá, and her colleagues.
The researchers analyzed data from the 2016 and 2017 versions of National Survey of Children’s Health that included 45,711 children aged 6-17 years. Survey data were collected from parents or other primary caregivers. In the study population, 16% of the children had a least one dental problem, defined as toothache, tooth decay or cavities, or bleeding gums, and 25% of the children had school problems: 67% missed any school, 23% missed more than 3 days of school, and 10% missed more than 6 days of school.
Overall, children with at least 1 dental problem were significantly more likely than those without dental problems to have problems at school (odds ratio, 1.56) or miss at least 1 school day (OR, 1.54) – more than 50% more likely. In addition, children with at least one dental problem were approximately 40% more likely to miss more than 3 days or more than 6 days of school (OR, 1.39 for both).
The association increased when the investigators used children’s oral health ratings; those with oral health rated as poor/fair were approximately 80% more likely to have school problems (OR, 1.77), almost 60% more likely to miss more than 3 days of school (OR, 1.56), and 90% more likely to miss more than 6 days of school, compared with children with oral health rankings of good, very good, or excellent.
Despite some variations in subgroups when the population was stratified by age, sex, race, household income, and health insurance, the associations between oral health problems and academic problems showed “remarkable stability,” across demographic and socioeconomic categories, the researchers said.
The study results were limited by several factors including the inability to identify the mechanisms behind the oral health and academic outcomes relationship, as well as the potential errors in parent or caregiver reports of children’s oral health and school performance, Dr. Guarnizo-Herreño and her associates said. However, the findings support those from an earlier study using 2007 data, and suggest that the link between poor oral health and poor academic performance has lasted for the past decade.
“The relationship between oral health and academic achievement is complex and likely involves multiple and intertwined pathways,” such as the impact of oral pain or discomfort on eating and sleeping that may affect academic performance, they said.
“These findings highlight the need for broad population-wide policies and integrated approaches to promote children’s development and reduce academic deficits that include among other components initiatives to improve oral health through prevention and treatment access strategies,” Dr. Guarnizo-Herreño and her associates concluded.
The study was supported by the National Institute of Dental and Craniofacial Research. The researchers had no financial conflicts to disclose.
SOURCE: Guarnizo-Herreño C et al. J Pediatr. 2019. doi: 10.1016/j.jpeds.2019.01.045.
Poor oral health was significantly associated with poor academic performance in children aged 6-17 years, based on data from more than 45,000 children in the United States.
The study, published in the Journal of Pediatrics, updates an assessment from 2007 of a similarly representative sample of U.S. children.
“Providing an updated analysis is especially important to understand the dynamics between children’s oral health status and academic performance, given reported improvements in dental care use among children and dental treatment quality and the implementation or expansion of some state-level preventive strategies,” wrote Carol Cristina Guarnizo-Herreño, DDS, PhD, of Universidad Nacional de Colombia, Bogotá, and her colleagues.
The researchers analyzed data from the 2016 and 2017 versions of National Survey of Children’s Health that included 45,711 children aged 6-17 years. Survey data were collected from parents or other primary caregivers. In the study population, 16% of the children had a least one dental problem, defined as toothache, tooth decay or cavities, or bleeding gums, and 25% of the children had school problems: 67% missed any school, 23% missed more than 3 days of school, and 10% missed more than 6 days of school.
Overall, children with at least 1 dental problem were significantly more likely than those without dental problems to have problems at school (odds ratio, 1.56) or miss at least 1 school day (OR, 1.54) – more than 50% more likely. In addition, children with at least one dental problem were approximately 40% more likely to miss more than 3 days or more than 6 days of school (OR, 1.39 for both).
The association increased when the investigators used children’s oral health ratings; those with oral health rated as poor/fair were approximately 80% more likely to have school problems (OR, 1.77), almost 60% more likely to miss more than 3 days of school (OR, 1.56), and 90% more likely to miss more than 6 days of school, compared with children with oral health rankings of good, very good, or excellent.
Despite some variations in subgroups when the population was stratified by age, sex, race, household income, and health insurance, the associations between oral health problems and academic problems showed “remarkable stability,” across demographic and socioeconomic categories, the researchers said.
The study results were limited by several factors including the inability to identify the mechanisms behind the oral health and academic outcomes relationship, as well as the potential errors in parent or caregiver reports of children’s oral health and school performance, Dr. Guarnizo-Herreño and her associates said. However, the findings support those from an earlier study using 2007 data, and suggest that the link between poor oral health and poor academic performance has lasted for the past decade.
“The relationship between oral health and academic achievement is complex and likely involves multiple and intertwined pathways,” such as the impact of oral pain or discomfort on eating and sleeping that may affect academic performance, they said.
“These findings highlight the need for broad population-wide policies and integrated approaches to promote children’s development and reduce academic deficits that include among other components initiatives to improve oral health through prevention and treatment access strategies,” Dr. Guarnizo-Herreño and her associates concluded.
The study was supported by the National Institute of Dental and Craniofacial Research. The researchers had no financial conflicts to disclose.
SOURCE: Guarnizo-Herreño C et al. J Pediatr. 2019. doi: 10.1016/j.jpeds.2019.01.045.
FROM THE JOURNAL OF PEDIATRICS