User login
How long is the second stage of labor in women delivering twins?
, researchers say.
Although the analysis found statistically significant differences in second-stage labor lengths for twin and singleton deliveries, “ultimately I think the value in this is seeing that it is not much different,” said Nathan Fox, MD, a maternal-fetal medicine specialist who has studied twin pregnancies and delivery of twins.
Knowledge gap
While most twin births occur by cesarean delivery, vaginal delivery is a preferred method for diamniotic twins with the first twin in vertex presentation, wrote study author Gabriel Levin, MD, and colleagues. Prior studies, however, have not clearly established the duration of the second stage of labor in twin deliveries – that is, the time from 10-cm dilation until delivery of the first twin, they said.
Knowing “the parameters of the normal second stage of labor” for twin deliveries may help guide clinical practice and possibly avoid unnecessary operative deliveries, the researchers wrote.
To establish normal ranges for the second stage of labor in twin deliveries, Dr. Levin, of the department of obstetrics and gynecology at Hadassah-Hebrew University Medical Center, Jerusalem, and coauthors conducted a retrospective cohort study. They analyzed data from three large academic hospitals in Israel between 2011 and June 2020 and assessed the length of the second stage of labor by obstetric history and clinical characteristics.
The researchers included data from women who delivered the first of diamniotic twins spontaneously or delivered a singleton spontaneously. The researchers excluded twin pregnancies with fetal demise of one or both twins, structural anomaly or chromosomal abnormality, monochorionic complications, and first twin in a nonvertex presentation. They did not consider the delivery mode of the second twin.
The study included 2,009 twin deliveries and 135,217 singleton deliveries. Of the women with twin deliveries, 32.6% were nulliparous (that is, no previous vaginal deliveries), 61.5% were parous (one to four previous vaginal deliveries, and no cesarean deliveries), and 5.9% were grand multiparous (at least five previous deliveries).
Of the women with singleton deliveries, 29% were nulliparous.
For nulliparous women delivering twins, the median length of the second stage was 1 hour 27 minutes (interquartile range, 40-147 minutes), and the 95th percentile was 3 hours 51 minutes.
For parous women delivering twins, the median length of the second stage was 18 minutes (interquartile range, 8-36 minutes), and the 95th percentile was 1 hour 56 minutes.
For grand multiparous women, the median length of the second stage was 10 minutes.
In a multivariable analysis, epidural anesthesia and induction of labor were independently associated with increased length of the second stage of labor.
Second-stage labor longer than the 95th percentile based on parity and epidural status was associated with approximately twice the risk of admission to the neonatal intensive care unit (35.4% vs. 16.4%) and need for phototherapy, the researchers reported.
Compared with singleton deliveries, the second stage was longer in twin deliveries. Among nulliparous patients, the median length of the second stage of labor was 1 hour 18 minutes for singleton deliveries, versus 1 hour 30 minutes for twin deliveries. Among parous patients, the median length of the second stage was 19 minutes for twin deliveries, compared with 10 minutes for singleton deliveries.
The study was conducted in Israel, which may limit its generalizability, the authors noted. In addition, the researchers lacked data about maternal morbidity and had limited data about neonatal morbidity. “The exact time that the woman became 10-cm dilated cannot be known, a problem inherent to all such studies,” and cases where doctors artificially ended labor with operative delivery were not included, the researchers added. “More research is needed to determine at what point, if any, intervention is warranted to shorten the second stage in patients delivering twins,” Dr. Levin and colleagues wrote.
Providing a framework
“We always get more concerned if the labor process is happening in a way that is unusual,” and this study provides data that can provide a framework for that thought process, said Dr. Fox, who was not involved in the study.
The results demonstrate that the second stage of labor for twin deliveries may take a long time and “that is not necessarily a bad thing,” said Dr. Fox, clinical professor of obstetrics and gynecology and maternal and fetal medicine at the Icahn School of Medicine at Mount Sinai in New York.
For women having their first child, the second stage of labor tends to take much longer than it does for women who have had children. “That is well known for singletons, and everyone assumes it is the same for twins,” but this study quantifies the durations for twins, he said. “That is valuable, and it is also helpful for women to know what to expect.”
A study coauthor disclosed financial ties to PregnanTech and Anthem AI, and money paid to their institution from New Sight. Dr. Fox works at Maternal Fetal Medicine Associates and Carnegie Imaging for Women in New York and is the creator and host of the Healthful Woman Podcast. He had no relevant financial disclosures.
, researchers say.
Although the analysis found statistically significant differences in second-stage labor lengths for twin and singleton deliveries, “ultimately I think the value in this is seeing that it is not much different,” said Nathan Fox, MD, a maternal-fetal medicine specialist who has studied twin pregnancies and delivery of twins.
Knowledge gap
While most twin births occur by cesarean delivery, vaginal delivery is a preferred method for diamniotic twins with the first twin in vertex presentation, wrote study author Gabriel Levin, MD, and colleagues. Prior studies, however, have not clearly established the duration of the second stage of labor in twin deliveries – that is, the time from 10-cm dilation until delivery of the first twin, they said.
Knowing “the parameters of the normal second stage of labor” for twin deliveries may help guide clinical practice and possibly avoid unnecessary operative deliveries, the researchers wrote.
To establish normal ranges for the second stage of labor in twin deliveries, Dr. Levin, of the department of obstetrics and gynecology at Hadassah-Hebrew University Medical Center, Jerusalem, and coauthors conducted a retrospective cohort study. They analyzed data from three large academic hospitals in Israel between 2011 and June 2020 and assessed the length of the second stage of labor by obstetric history and clinical characteristics.
The researchers included data from women who delivered the first of diamniotic twins spontaneously or delivered a singleton spontaneously. The researchers excluded twin pregnancies with fetal demise of one or both twins, structural anomaly or chromosomal abnormality, monochorionic complications, and first twin in a nonvertex presentation. They did not consider the delivery mode of the second twin.
The study included 2,009 twin deliveries and 135,217 singleton deliveries. Of the women with twin deliveries, 32.6% were nulliparous (that is, no previous vaginal deliveries), 61.5% were parous (one to four previous vaginal deliveries, and no cesarean deliveries), and 5.9% were grand multiparous (at least five previous deliveries).
Of the women with singleton deliveries, 29% were nulliparous.
For nulliparous women delivering twins, the median length of the second stage was 1 hour 27 minutes (interquartile range, 40-147 minutes), and the 95th percentile was 3 hours 51 minutes.
For parous women delivering twins, the median length of the second stage was 18 minutes (interquartile range, 8-36 minutes), and the 95th percentile was 1 hour 56 minutes.
For grand multiparous women, the median length of the second stage was 10 minutes.
In a multivariable analysis, epidural anesthesia and induction of labor were independently associated with increased length of the second stage of labor.
Second-stage labor longer than the 95th percentile based on parity and epidural status was associated with approximately twice the risk of admission to the neonatal intensive care unit (35.4% vs. 16.4%) and need for phototherapy, the researchers reported.
Compared with singleton deliveries, the second stage was longer in twin deliveries. Among nulliparous patients, the median length of the second stage of labor was 1 hour 18 minutes for singleton deliveries, versus 1 hour 30 minutes for twin deliveries. Among parous patients, the median length of the second stage was 19 minutes for twin deliveries, compared with 10 minutes for singleton deliveries.
The study was conducted in Israel, which may limit its generalizability, the authors noted. In addition, the researchers lacked data about maternal morbidity and had limited data about neonatal morbidity. “The exact time that the woman became 10-cm dilated cannot be known, a problem inherent to all such studies,” and cases where doctors artificially ended labor with operative delivery were not included, the researchers added. “More research is needed to determine at what point, if any, intervention is warranted to shorten the second stage in patients delivering twins,” Dr. Levin and colleagues wrote.
Providing a framework
“We always get more concerned if the labor process is happening in a way that is unusual,” and this study provides data that can provide a framework for that thought process, said Dr. Fox, who was not involved in the study.
The results demonstrate that the second stage of labor for twin deliveries may take a long time and “that is not necessarily a bad thing,” said Dr. Fox, clinical professor of obstetrics and gynecology and maternal and fetal medicine at the Icahn School of Medicine at Mount Sinai in New York.
For women having their first child, the second stage of labor tends to take much longer than it does for women who have had children. “That is well known for singletons, and everyone assumes it is the same for twins,” but this study quantifies the durations for twins, he said. “That is valuable, and it is also helpful for women to know what to expect.”
A study coauthor disclosed financial ties to PregnanTech and Anthem AI, and money paid to their institution from New Sight. Dr. Fox works at Maternal Fetal Medicine Associates and Carnegie Imaging for Women in New York and is the creator and host of the Healthful Woman Podcast. He had no relevant financial disclosures.
, researchers say.
Although the analysis found statistically significant differences in second-stage labor lengths for twin and singleton deliveries, “ultimately I think the value in this is seeing that it is not much different,” said Nathan Fox, MD, a maternal-fetal medicine specialist who has studied twin pregnancies and delivery of twins.
Knowledge gap
While most twin births occur by cesarean delivery, vaginal delivery is a preferred method for diamniotic twins with the first twin in vertex presentation, wrote study author Gabriel Levin, MD, and colleagues. Prior studies, however, have not clearly established the duration of the second stage of labor in twin deliveries – that is, the time from 10-cm dilation until delivery of the first twin, they said.
Knowing “the parameters of the normal second stage of labor” for twin deliveries may help guide clinical practice and possibly avoid unnecessary operative deliveries, the researchers wrote.
To establish normal ranges for the second stage of labor in twin deliveries, Dr. Levin, of the department of obstetrics and gynecology at Hadassah-Hebrew University Medical Center, Jerusalem, and coauthors conducted a retrospective cohort study. They analyzed data from three large academic hospitals in Israel between 2011 and June 2020 and assessed the length of the second stage of labor by obstetric history and clinical characteristics.
The researchers included data from women who delivered the first of diamniotic twins spontaneously or delivered a singleton spontaneously. The researchers excluded twin pregnancies with fetal demise of one or both twins, structural anomaly or chromosomal abnormality, monochorionic complications, and first twin in a nonvertex presentation. They did not consider the delivery mode of the second twin.
The study included 2,009 twin deliveries and 135,217 singleton deliveries. Of the women with twin deliveries, 32.6% were nulliparous (that is, no previous vaginal deliveries), 61.5% were parous (one to four previous vaginal deliveries, and no cesarean deliveries), and 5.9% were grand multiparous (at least five previous deliveries).
Of the women with singleton deliveries, 29% were nulliparous.
For nulliparous women delivering twins, the median length of the second stage was 1 hour 27 minutes (interquartile range, 40-147 minutes), and the 95th percentile was 3 hours 51 minutes.
For parous women delivering twins, the median length of the second stage was 18 minutes (interquartile range, 8-36 minutes), and the 95th percentile was 1 hour 56 minutes.
For grand multiparous women, the median length of the second stage was 10 minutes.
In a multivariable analysis, epidural anesthesia and induction of labor were independently associated with increased length of the second stage of labor.
Second-stage labor longer than the 95th percentile based on parity and epidural status was associated with approximately twice the risk of admission to the neonatal intensive care unit (35.4% vs. 16.4%) and need for phototherapy, the researchers reported.
Compared with singleton deliveries, the second stage was longer in twin deliveries. Among nulliparous patients, the median length of the second stage of labor was 1 hour 18 minutes for singleton deliveries, versus 1 hour 30 minutes for twin deliveries. Among parous patients, the median length of the second stage was 19 minutes for twin deliveries, compared with 10 minutes for singleton deliveries.
The study was conducted in Israel, which may limit its generalizability, the authors noted. In addition, the researchers lacked data about maternal morbidity and had limited data about neonatal morbidity. “The exact time that the woman became 10-cm dilated cannot be known, a problem inherent to all such studies,” and cases where doctors artificially ended labor with operative delivery were not included, the researchers added. “More research is needed to determine at what point, if any, intervention is warranted to shorten the second stage in patients delivering twins,” Dr. Levin and colleagues wrote.
Providing a framework
“We always get more concerned if the labor process is happening in a way that is unusual,” and this study provides data that can provide a framework for that thought process, said Dr. Fox, who was not involved in the study.
The results demonstrate that the second stage of labor for twin deliveries may take a long time and “that is not necessarily a bad thing,” said Dr. Fox, clinical professor of obstetrics and gynecology and maternal and fetal medicine at the Icahn School of Medicine at Mount Sinai in New York.
For women having their first child, the second stage of labor tends to take much longer than it does for women who have had children. “That is well known for singletons, and everyone assumes it is the same for twins,” but this study quantifies the durations for twins, he said. “That is valuable, and it is also helpful for women to know what to expect.”
A study coauthor disclosed financial ties to PregnanTech and Anthem AI, and money paid to their institution from New Sight. Dr. Fox works at Maternal Fetal Medicine Associates and Carnegie Imaging for Women in New York and is the creator and host of the Healthful Woman Podcast. He had no relevant financial disclosures.
FROM OBSTETRICS AND GYNECOLOGY
Benefits of bremelanotide to women with HSDD questioned in analysis paper
Dr. Spielmans, professor of psychology at Metropolitan State University in Saint Paul, Minn., examined data from the FDA application for bremelanotide, clinicaltrials.gov entries for two phase 3 trials of the drug, and a 2019 article published in Obstetrics & Gynecology that described results from the 24-week trials.
In Dr. Speilman’s analysis, which was published online March 7 in the Journal of Sex Research, he notes that 42.1% of trial participants who received bremelanotide did not complete the trial, compared with 20.48% of participants who received placebo.
Of those who completed the study, 87.22% who received placebo wanted to continue treatment in an open-label extension, compared with 69.97% who received bremelanotide, he wrote.
Women “should be aware of the small degree of bremelanotide’s efficacy, that the protocol-specified outcomes of bremelanotide are mostly unknown, and that participants would rather take a placebo than bremelanotide,” Dr. Spielmans said.
Anita H. Clayton, MD, an author of the Obstetrics & Gynecology paper addressed in Dr. Spielmans’ analysis, says the Journal of Sex Research article does not provide new information and is a disservice to women because it questions accurate scientific data.
Measuring outcomes in HSDD is an evolving field, Dr. Clayton, a psychiatrist at the University of Virginia in Charlottesville, said in an interview. Initial FDA guidance relied on satisfying sexual events as an outcome measure, but this measure was derived from erectile dysfunction studies and is not necessarily adequate for assessing HSDD, she said. The FDA and drug developers agreed to use the desire subscale of the Female Sexual Function Index (FSFI-D) as a coprimary outcome measure instead, she noted.
Dr. Spielmans’ critique of Obstetrics & Gynecology paper
The article published in Obstetrics & Gynecology reporting bremelanotide trial results was noteworthy, although the various issues involved can be seen in reports about other drug trials, Dr. Spielmans said in an interview.
“It is well-established that journal articles reporting clinical trial data overstate benefits and understate harms,” he continued. In this case, “the very incomplete data reporting, reliance on many post-hoc measures of questionable validity, hiding the concerning number of dropouts due to adverse events, and putting a positive spin on efficacy and tolerability is both remarkable and highly problematic,” Dr. Spielmans said.
Dr. Clayton’s reaction
Data about dropout rates due to adverse events have been reported and presented at national meetings, she said in an interview. In addition, a questionnaire found that bremelanotide was superior to placebo in terms of patients feeling that the treatment had provided clinically meaningful benefit, Dr. Clayton said.
The available information enables patients to make informed treatment decisions, Dr. Clayton continued. “There is really this sexist attitude of women needing protection from their own decisions,” she said.
Diagnosing and treating HSDD
Eight of 11 efficacy outcomes in the clinicaltrials.gov study protocols for bremelanotide were not reported in the Obstetrics & Gynecology article in a way that was consistent with the protocols, Dr. Spielmans said. Changing a coprimary outcome to the key secondary outcome “occurred over a year after the trials had begun,” and the authors of the journal article “did not mention that this change occurred,” Dr. Spielmans wrote.
For the coprimary outcome measures of mean change on FSFI-D and Female Sexual Distress Scale–Desire/Arousal/Orgasm #13, “bremelanotide offers modest benefits over placebo,” Dr. Spielmans reported.
In addition to outlining his concerns about transparency in the reporting of trial data and raising questions about the outcome measures used in the Obstetrics & Gynecology article, Dr. Spielmans wrote that the diagnosis of HSDD is problematic.
“The lack of specifying symptom duration, questionable validity for the lack of sexual fantasies as a diagnostic criterion, difficulty in disentangling individual sexual problems from relational problems, and the failure to consider cultural influence (including the pressure on women to satisfy the sexual desires of their male partners) in the experience of sexuality all render HSDD as a problematic entity,” Dr. Spielmans wrote.
The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders replaced HSDD and female sexual arousal disorder with the combined condition female sexual interest/arousal disorder. HSDD is in the 11th edition of the International Classification of Diseases and can be applied to men or women, Dr. Spielmans said.
FDA acknowledged HSDD as an unmet medical need
Dr. Clayton pointed out that HSDD was described decades ago and the FDA acknowledged it as an unmet medical need, and she expressed dissatisfaction with the fact the hypoactive sexual desire disorder appears with quotation marks around it in the title of Dr. Spielmans’ article. This way of presenting HSDD indicates that “the author has no concept of sexual health or sexual dysfunction,” Dr. Clayton said. “Basically this is sort of a dramatic tool, I think, to act like this is not a real disorder,” she added.
Carl Spana, PhD, CEO and president of Palatin Technologies, the developer of bremelanotide, defined the article in the Journal of Sex Research as a “retrospective meta-analysis, and not a re-analysis of the data.
“As a meta-analysis, it is open to various interpretations and reflects the author’s interpretations, which appear to have clear biases,” Dr. Spana said in an interview. “We believe several of this author’s interpretations are contrary to the FDA’s positive assessment that led to Vyleesi’s approval as a safe and effective treatment for women suffering from hypoactive sexual desire disorder.”
The author is unaware of the validation that was conducted at the direction of the FDA to establish clinically meaningful cutoffs for patient-reported outcomes and to establish metrics that define clinical benefit, Dr. Spana said
“Vyleesi was approved by the FDA after a thorough analysis of data from two well-controlled phase 3 clinical studies and multiple clinical and preclinical safety studies,” he said. “The analyses in the New Drug Application were prespecified and conducted according to a statistical analysis plan that the sponsor and FDA agreed to prior to database lock.”
Dr. Spielmans disclosed holdings in Vanguard Healthcare, a mutual fund that invests in pharmaceutical firms. Dr. Clayton has received financial support from Palatin and AMAG Pharmaceuticals, the companies that developed bremelanotide, in previous years.
Dr. Spielmans, professor of psychology at Metropolitan State University in Saint Paul, Minn., examined data from the FDA application for bremelanotide, clinicaltrials.gov entries for two phase 3 trials of the drug, and a 2019 article published in Obstetrics & Gynecology that described results from the 24-week trials.
In Dr. Speilman’s analysis, which was published online March 7 in the Journal of Sex Research, he notes that 42.1% of trial participants who received bremelanotide did not complete the trial, compared with 20.48% of participants who received placebo.
Of those who completed the study, 87.22% who received placebo wanted to continue treatment in an open-label extension, compared with 69.97% who received bremelanotide, he wrote.
Women “should be aware of the small degree of bremelanotide’s efficacy, that the protocol-specified outcomes of bremelanotide are mostly unknown, and that participants would rather take a placebo than bremelanotide,” Dr. Spielmans said.
Anita H. Clayton, MD, an author of the Obstetrics & Gynecology paper addressed in Dr. Spielmans’ analysis, says the Journal of Sex Research article does not provide new information and is a disservice to women because it questions accurate scientific data.
Measuring outcomes in HSDD is an evolving field, Dr. Clayton, a psychiatrist at the University of Virginia in Charlottesville, said in an interview. Initial FDA guidance relied on satisfying sexual events as an outcome measure, but this measure was derived from erectile dysfunction studies and is not necessarily adequate for assessing HSDD, she said. The FDA and drug developers agreed to use the desire subscale of the Female Sexual Function Index (FSFI-D) as a coprimary outcome measure instead, she noted.
Dr. Spielmans’ critique of Obstetrics & Gynecology paper
The article published in Obstetrics & Gynecology reporting bremelanotide trial results was noteworthy, although the various issues involved can be seen in reports about other drug trials, Dr. Spielmans said in an interview.
“It is well-established that journal articles reporting clinical trial data overstate benefits and understate harms,” he continued. In this case, “the very incomplete data reporting, reliance on many post-hoc measures of questionable validity, hiding the concerning number of dropouts due to adverse events, and putting a positive spin on efficacy and tolerability is both remarkable and highly problematic,” Dr. Spielmans said.
Dr. Clayton’s reaction
Data about dropout rates due to adverse events have been reported and presented at national meetings, she said in an interview. In addition, a questionnaire found that bremelanotide was superior to placebo in terms of patients feeling that the treatment had provided clinically meaningful benefit, Dr. Clayton said.
The available information enables patients to make informed treatment decisions, Dr. Clayton continued. “There is really this sexist attitude of women needing protection from their own decisions,” she said.
Diagnosing and treating HSDD
Eight of 11 efficacy outcomes in the clinicaltrials.gov study protocols for bremelanotide were not reported in the Obstetrics & Gynecology article in a way that was consistent with the protocols, Dr. Spielmans said. Changing a coprimary outcome to the key secondary outcome “occurred over a year after the trials had begun,” and the authors of the journal article “did not mention that this change occurred,” Dr. Spielmans wrote.
For the coprimary outcome measures of mean change on FSFI-D and Female Sexual Distress Scale–Desire/Arousal/Orgasm #13, “bremelanotide offers modest benefits over placebo,” Dr. Spielmans reported.
In addition to outlining his concerns about transparency in the reporting of trial data and raising questions about the outcome measures used in the Obstetrics & Gynecology article, Dr. Spielmans wrote that the diagnosis of HSDD is problematic.
“The lack of specifying symptom duration, questionable validity for the lack of sexual fantasies as a diagnostic criterion, difficulty in disentangling individual sexual problems from relational problems, and the failure to consider cultural influence (including the pressure on women to satisfy the sexual desires of their male partners) in the experience of sexuality all render HSDD as a problematic entity,” Dr. Spielmans wrote.
The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders replaced HSDD and female sexual arousal disorder with the combined condition female sexual interest/arousal disorder. HSDD is in the 11th edition of the International Classification of Diseases and can be applied to men or women, Dr. Spielmans said.
FDA acknowledged HSDD as an unmet medical need
Dr. Clayton pointed out that HSDD was described decades ago and the FDA acknowledged it as an unmet medical need, and she expressed dissatisfaction with the fact the hypoactive sexual desire disorder appears with quotation marks around it in the title of Dr. Spielmans’ article. This way of presenting HSDD indicates that “the author has no concept of sexual health or sexual dysfunction,” Dr. Clayton said. “Basically this is sort of a dramatic tool, I think, to act like this is not a real disorder,” she added.
Carl Spana, PhD, CEO and president of Palatin Technologies, the developer of bremelanotide, defined the article in the Journal of Sex Research as a “retrospective meta-analysis, and not a re-analysis of the data.
“As a meta-analysis, it is open to various interpretations and reflects the author’s interpretations, which appear to have clear biases,” Dr. Spana said in an interview. “We believe several of this author’s interpretations are contrary to the FDA’s positive assessment that led to Vyleesi’s approval as a safe and effective treatment for women suffering from hypoactive sexual desire disorder.”
The author is unaware of the validation that was conducted at the direction of the FDA to establish clinically meaningful cutoffs for patient-reported outcomes and to establish metrics that define clinical benefit, Dr. Spana said
“Vyleesi was approved by the FDA after a thorough analysis of data from two well-controlled phase 3 clinical studies and multiple clinical and preclinical safety studies,” he said. “The analyses in the New Drug Application were prespecified and conducted according to a statistical analysis plan that the sponsor and FDA agreed to prior to database lock.”
Dr. Spielmans disclosed holdings in Vanguard Healthcare, a mutual fund that invests in pharmaceutical firms. Dr. Clayton has received financial support from Palatin and AMAG Pharmaceuticals, the companies that developed bremelanotide, in previous years.
Dr. Spielmans, professor of psychology at Metropolitan State University in Saint Paul, Minn., examined data from the FDA application for bremelanotide, clinicaltrials.gov entries for two phase 3 trials of the drug, and a 2019 article published in Obstetrics & Gynecology that described results from the 24-week trials.
In Dr. Speilman’s analysis, which was published online March 7 in the Journal of Sex Research, he notes that 42.1% of trial participants who received bremelanotide did not complete the trial, compared with 20.48% of participants who received placebo.
Of those who completed the study, 87.22% who received placebo wanted to continue treatment in an open-label extension, compared with 69.97% who received bremelanotide, he wrote.
Women “should be aware of the small degree of bremelanotide’s efficacy, that the protocol-specified outcomes of bremelanotide are mostly unknown, and that participants would rather take a placebo than bremelanotide,” Dr. Spielmans said.
Anita H. Clayton, MD, an author of the Obstetrics & Gynecology paper addressed in Dr. Spielmans’ analysis, says the Journal of Sex Research article does not provide new information and is a disservice to women because it questions accurate scientific data.
Measuring outcomes in HSDD is an evolving field, Dr. Clayton, a psychiatrist at the University of Virginia in Charlottesville, said in an interview. Initial FDA guidance relied on satisfying sexual events as an outcome measure, but this measure was derived from erectile dysfunction studies and is not necessarily adequate for assessing HSDD, she said. The FDA and drug developers agreed to use the desire subscale of the Female Sexual Function Index (FSFI-D) as a coprimary outcome measure instead, she noted.
Dr. Spielmans’ critique of Obstetrics & Gynecology paper
The article published in Obstetrics & Gynecology reporting bremelanotide trial results was noteworthy, although the various issues involved can be seen in reports about other drug trials, Dr. Spielmans said in an interview.
“It is well-established that journal articles reporting clinical trial data overstate benefits and understate harms,” he continued. In this case, “the very incomplete data reporting, reliance on many post-hoc measures of questionable validity, hiding the concerning number of dropouts due to adverse events, and putting a positive spin on efficacy and tolerability is both remarkable and highly problematic,” Dr. Spielmans said.
Dr. Clayton’s reaction
Data about dropout rates due to adverse events have been reported and presented at national meetings, she said in an interview. In addition, a questionnaire found that bremelanotide was superior to placebo in terms of patients feeling that the treatment had provided clinically meaningful benefit, Dr. Clayton said.
The available information enables patients to make informed treatment decisions, Dr. Clayton continued. “There is really this sexist attitude of women needing protection from their own decisions,” she said.
Diagnosing and treating HSDD
Eight of 11 efficacy outcomes in the clinicaltrials.gov study protocols for bremelanotide were not reported in the Obstetrics & Gynecology article in a way that was consistent with the protocols, Dr. Spielmans said. Changing a coprimary outcome to the key secondary outcome “occurred over a year after the trials had begun,” and the authors of the journal article “did not mention that this change occurred,” Dr. Spielmans wrote.
For the coprimary outcome measures of mean change on FSFI-D and Female Sexual Distress Scale–Desire/Arousal/Orgasm #13, “bremelanotide offers modest benefits over placebo,” Dr. Spielmans reported.
In addition to outlining his concerns about transparency in the reporting of trial data and raising questions about the outcome measures used in the Obstetrics & Gynecology article, Dr. Spielmans wrote that the diagnosis of HSDD is problematic.
“The lack of specifying symptom duration, questionable validity for the lack of sexual fantasies as a diagnostic criterion, difficulty in disentangling individual sexual problems from relational problems, and the failure to consider cultural influence (including the pressure on women to satisfy the sexual desires of their male partners) in the experience of sexuality all render HSDD as a problematic entity,” Dr. Spielmans wrote.
The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders replaced HSDD and female sexual arousal disorder with the combined condition female sexual interest/arousal disorder. HSDD is in the 11th edition of the International Classification of Diseases and can be applied to men or women, Dr. Spielmans said.
FDA acknowledged HSDD as an unmet medical need
Dr. Clayton pointed out that HSDD was described decades ago and the FDA acknowledged it as an unmet medical need, and she expressed dissatisfaction with the fact the hypoactive sexual desire disorder appears with quotation marks around it in the title of Dr. Spielmans’ article. This way of presenting HSDD indicates that “the author has no concept of sexual health or sexual dysfunction,” Dr. Clayton said. “Basically this is sort of a dramatic tool, I think, to act like this is not a real disorder,” she added.
Carl Spana, PhD, CEO and president of Palatin Technologies, the developer of bremelanotide, defined the article in the Journal of Sex Research as a “retrospective meta-analysis, and not a re-analysis of the data.
“As a meta-analysis, it is open to various interpretations and reflects the author’s interpretations, which appear to have clear biases,” Dr. Spana said in an interview. “We believe several of this author’s interpretations are contrary to the FDA’s positive assessment that led to Vyleesi’s approval as a safe and effective treatment for women suffering from hypoactive sexual desire disorder.”
The author is unaware of the validation that was conducted at the direction of the FDA to establish clinically meaningful cutoffs for patient-reported outcomes and to establish metrics that define clinical benefit, Dr. Spana said
“Vyleesi was approved by the FDA after a thorough analysis of data from two well-controlled phase 3 clinical studies and multiple clinical and preclinical safety studies,” he said. “The analyses in the New Drug Application were prespecified and conducted according to a statistical analysis plan that the sponsor and FDA agreed to prior to database lock.”
Dr. Spielmans disclosed holdings in Vanguard Healthcare, a mutual fund that invests in pharmaceutical firms. Dr. Clayton has received financial support from Palatin and AMAG Pharmaceuticals, the companies that developed bremelanotide, in previous years.
FROM THE JOURNAL OF SEX RESEARCH
Missed visits during pandemic cause ‘detrimental ripple effects’
according to a new report from the Urban Institute.
Among the adults who postponed or missed care, 32.6% said the gap worsened one or more health conditions or limited their ability to work or perform daily activities. The findings highlight “the detrimental ripple effects of delaying or forgoing care on overall health, functioning, and well-being,” researchers write.
The survey, conducted among 4,007 U.S. adults aged 18-64 in September 2020, found that adults with one or more chronic conditions were more likely than adults without chronic conditions to have delayed or missed care (40.7% vs. 26.4%). Adults with a mental health condition were particularly likely to have delayed or gone without care, write Dulce Gonzalez, MPP, a research associate in the Health Policy Center at the Urban Institute, and colleagues.
Doctors are already seeing the consequences of the missed visits, says Jacqueline W. Fincher, MD, president of the American College of Physicians.
Two of her patients with chronic conditions missed appointments last year. By the time they resumed care in 2021, their previsit lab tests showed significant kidney deterioration.
“Lo and behold, their kidneys were in failure. … One was in the hospital for 3 days and the other one was in for 5 days,” said Dr. Fincher, who practices general internal medicine in Georgia.
Dr. Fincher’s office has been proactive about calling patients with chronic diseases who missed follow-up visits or laboratory testing or who may have run out of medication, she said.
In her experience, delays mainly have been because of patients postponing visits. “We have stayed open the whole time now,” Dr. Fincher said. Her office offers telemedicine visits and in-person visits with safety precautions.
Still, some patients have decided to postpone care during the pandemic instead of asking their primary care doctor what they should do.
“We do know that chronic problems left without appropriate follow-up can create worse problems for them in terms of stroke, heart attack, and end organ damage,” Dr. Fincher said.
Lost lives
Future studies may help researchers understand the effects of delayed and missed care during the pandemic, said Russell S. Phillips, MD, director of the Center for Primary Care at Harvard Medical School, Boston.
“Although it is still early, and more data on patient outcomes will need to be collected, I anticipate that the ... delays in diagnosis, in cancer screening, and in management of chronic illness will result in lost lives and will emphasize the important role that primary care plays in saving lives,” Dr. Phillips said.
During the first several months of the pandemic, there were fewer diagnoses of hypertension, diabetes, and depression, Dr. Phillips said.
“In addition, and most importantly, the mortality rate for non-COVID conditions increased, suggesting that patients were not seeking care for symptoms of stroke or heart attack, which can be fatal if untreated,” he said. “We have also seen substantial decreases in cancer screening tests such as colonoscopy, and modeling studies suggest this will cost more lives based on delayed diagnoses of cancer.”
Vaccinating patients against COVID-19 may help primary care practices and patients get back on track, Dr. Phillips suggested.
In the meantime, some patients remain reluctant to come in. “Volumes are still lower than prepandemic, so it is challenging to overcome what is likely to be pent-up demand,” he told this news organization in an email. “Additionally, the continued burden of evaluating, testing, and monitoring patients with COVID or COVID-like symptoms makes it difficult to focus on chronic illness.”
Care most often skipped
The Urban Institute survey asked respondents about delays in prescription drugs, general doctor and specialist visits, going to a hospital, preventive health screenings or medical tests, treatment or follow-up care, dental care, mental health care or counseling, treatment or counseling for alcohol or drug use, and other types of medical care.
Dental care was the most common type of care that adults delayed or did not receive because of the pandemic (25.3%), followed by general doctor or specialist visits (20.6%) and preventive health screenings or medical tests (15.5%).
Black adults were more likely than White or Hispanic/Latinx adults to have delayed or forgone care (39.7% vs. 34.3% and 35.5%), the researchers found. Compared with adults with higher incomes, adults with lower incomes were more likely to have missed multiple types of care (26.6% vs. 20.3%).
The report by the Urban Institute researchers was supported by the Robert Wood Johnson Foundation. Dr. Phillips is an adviser to two telemedicine companies, Bicycle Health and Grow Health. Dr. Fincher has disclosed no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
according to a new report from the Urban Institute.
Among the adults who postponed or missed care, 32.6% said the gap worsened one or more health conditions or limited their ability to work or perform daily activities. The findings highlight “the detrimental ripple effects of delaying or forgoing care on overall health, functioning, and well-being,” researchers write.
The survey, conducted among 4,007 U.S. adults aged 18-64 in September 2020, found that adults with one or more chronic conditions were more likely than adults without chronic conditions to have delayed or missed care (40.7% vs. 26.4%). Adults with a mental health condition were particularly likely to have delayed or gone without care, write Dulce Gonzalez, MPP, a research associate in the Health Policy Center at the Urban Institute, and colleagues.
Doctors are already seeing the consequences of the missed visits, says Jacqueline W. Fincher, MD, president of the American College of Physicians.
Two of her patients with chronic conditions missed appointments last year. By the time they resumed care in 2021, their previsit lab tests showed significant kidney deterioration.
“Lo and behold, their kidneys were in failure. … One was in the hospital for 3 days and the other one was in for 5 days,” said Dr. Fincher, who practices general internal medicine in Georgia.
Dr. Fincher’s office has been proactive about calling patients with chronic diseases who missed follow-up visits or laboratory testing or who may have run out of medication, she said.
In her experience, delays mainly have been because of patients postponing visits. “We have stayed open the whole time now,” Dr. Fincher said. Her office offers telemedicine visits and in-person visits with safety precautions.
Still, some patients have decided to postpone care during the pandemic instead of asking their primary care doctor what they should do.
“We do know that chronic problems left without appropriate follow-up can create worse problems for them in terms of stroke, heart attack, and end organ damage,” Dr. Fincher said.
Lost lives
Future studies may help researchers understand the effects of delayed and missed care during the pandemic, said Russell S. Phillips, MD, director of the Center for Primary Care at Harvard Medical School, Boston.
“Although it is still early, and more data on patient outcomes will need to be collected, I anticipate that the ... delays in diagnosis, in cancer screening, and in management of chronic illness will result in lost lives and will emphasize the important role that primary care plays in saving lives,” Dr. Phillips said.
During the first several months of the pandemic, there were fewer diagnoses of hypertension, diabetes, and depression, Dr. Phillips said.
“In addition, and most importantly, the mortality rate for non-COVID conditions increased, suggesting that patients were not seeking care for symptoms of stroke or heart attack, which can be fatal if untreated,” he said. “We have also seen substantial decreases in cancer screening tests such as colonoscopy, and modeling studies suggest this will cost more lives based on delayed diagnoses of cancer.”
Vaccinating patients against COVID-19 may help primary care practices and patients get back on track, Dr. Phillips suggested.
In the meantime, some patients remain reluctant to come in. “Volumes are still lower than prepandemic, so it is challenging to overcome what is likely to be pent-up demand,” he told this news organization in an email. “Additionally, the continued burden of evaluating, testing, and monitoring patients with COVID or COVID-like symptoms makes it difficult to focus on chronic illness.”
Care most often skipped
The Urban Institute survey asked respondents about delays in prescription drugs, general doctor and specialist visits, going to a hospital, preventive health screenings or medical tests, treatment or follow-up care, dental care, mental health care or counseling, treatment or counseling for alcohol or drug use, and other types of medical care.
Dental care was the most common type of care that adults delayed or did not receive because of the pandemic (25.3%), followed by general doctor or specialist visits (20.6%) and preventive health screenings or medical tests (15.5%).
Black adults were more likely than White or Hispanic/Latinx adults to have delayed or forgone care (39.7% vs. 34.3% and 35.5%), the researchers found. Compared with adults with higher incomes, adults with lower incomes were more likely to have missed multiple types of care (26.6% vs. 20.3%).
The report by the Urban Institute researchers was supported by the Robert Wood Johnson Foundation. Dr. Phillips is an adviser to two telemedicine companies, Bicycle Health and Grow Health. Dr. Fincher has disclosed no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
according to a new report from the Urban Institute.
Among the adults who postponed or missed care, 32.6% said the gap worsened one or more health conditions or limited their ability to work or perform daily activities. The findings highlight “the detrimental ripple effects of delaying or forgoing care on overall health, functioning, and well-being,” researchers write.
The survey, conducted among 4,007 U.S. adults aged 18-64 in September 2020, found that adults with one or more chronic conditions were more likely than adults without chronic conditions to have delayed or missed care (40.7% vs. 26.4%). Adults with a mental health condition were particularly likely to have delayed or gone without care, write Dulce Gonzalez, MPP, a research associate in the Health Policy Center at the Urban Institute, and colleagues.
Doctors are already seeing the consequences of the missed visits, says Jacqueline W. Fincher, MD, president of the American College of Physicians.
Two of her patients with chronic conditions missed appointments last year. By the time they resumed care in 2021, their previsit lab tests showed significant kidney deterioration.
“Lo and behold, their kidneys were in failure. … One was in the hospital for 3 days and the other one was in for 5 days,” said Dr. Fincher, who practices general internal medicine in Georgia.
Dr. Fincher’s office has been proactive about calling patients with chronic diseases who missed follow-up visits or laboratory testing or who may have run out of medication, she said.
In her experience, delays mainly have been because of patients postponing visits. “We have stayed open the whole time now,” Dr. Fincher said. Her office offers telemedicine visits and in-person visits with safety precautions.
Still, some patients have decided to postpone care during the pandemic instead of asking their primary care doctor what they should do.
“We do know that chronic problems left without appropriate follow-up can create worse problems for them in terms of stroke, heart attack, and end organ damage,” Dr. Fincher said.
Lost lives
Future studies may help researchers understand the effects of delayed and missed care during the pandemic, said Russell S. Phillips, MD, director of the Center for Primary Care at Harvard Medical School, Boston.
“Although it is still early, and more data on patient outcomes will need to be collected, I anticipate that the ... delays in diagnosis, in cancer screening, and in management of chronic illness will result in lost lives and will emphasize the important role that primary care plays in saving lives,” Dr. Phillips said.
During the first several months of the pandemic, there were fewer diagnoses of hypertension, diabetes, and depression, Dr. Phillips said.
“In addition, and most importantly, the mortality rate for non-COVID conditions increased, suggesting that patients were not seeking care for symptoms of stroke or heart attack, which can be fatal if untreated,” he said. “We have also seen substantial decreases in cancer screening tests such as colonoscopy, and modeling studies suggest this will cost more lives based on delayed diagnoses of cancer.”
Vaccinating patients against COVID-19 may help primary care practices and patients get back on track, Dr. Phillips suggested.
In the meantime, some patients remain reluctant to come in. “Volumes are still lower than prepandemic, so it is challenging to overcome what is likely to be pent-up demand,” he told this news organization in an email. “Additionally, the continued burden of evaluating, testing, and monitoring patients with COVID or COVID-like symptoms makes it difficult to focus on chronic illness.”
Care most often skipped
The Urban Institute survey asked respondents about delays in prescription drugs, general doctor and specialist visits, going to a hospital, preventive health screenings or medical tests, treatment or follow-up care, dental care, mental health care or counseling, treatment or counseling for alcohol or drug use, and other types of medical care.
Dental care was the most common type of care that adults delayed or did not receive because of the pandemic (25.3%), followed by general doctor or specialist visits (20.6%) and preventive health screenings or medical tests (15.5%).
Black adults were more likely than White or Hispanic/Latinx adults to have delayed or forgone care (39.7% vs. 34.3% and 35.5%), the researchers found. Compared with adults with higher incomes, adults with lower incomes were more likely to have missed multiple types of care (26.6% vs. 20.3%).
The report by the Urban Institute researchers was supported by the Robert Wood Johnson Foundation. Dr. Phillips is an adviser to two telemedicine companies, Bicycle Health and Grow Health. Dr. Fincher has disclosed no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
Primary care clinicians neglect hearing loss, survey finds
But asking a single question – “Do you think you have hearing loss?” – may be an efficient way to identify patients who should receive further evaluation, researchers said.
Only 20% of adults aged 50-80 years report that their primary care physician has asked about their hearing in the past 2 years, according to the National Poll on Healthy Aging, published online March 2. Among adults who rated their hearing as fair or poor, only 26% said they had been asked about their hearing.
Michael McKee, MD, MPH, a family medicine physician and health services researcher at Michigan Medicine, the University of Michigan’s academic medical center, and colleagues surveyed 2,074 adults aged 50-80 years in June 2020. They asked participants about the screening and testing of hearing that they had undergone. The researchers weighted the sample to reflect population figures from the U.S. Census Bureau.
Men were more likely than women to have been asked about their hearing (24% vs. 17%), and adults aged 65-80 years were more likely than younger adults to have been asked about their hearing (25% vs. 16%).
The survey also found that 23% of adults had undergone a hearing test by a health care professional; 62% felt that it was at least somewhat important to have their hearing tested at least once every 2 years.
Overall, 16% of adults rated their hearing as fair or poor. Approximately a third rated their hearing as good, and about half rated their hearing as excellent or very good. Fair or poor hearing was more commonly reported by men than women (20% vs. 12%) and by older adults than younger adults (19% vs. 14%).
In all, 6% used a hearing aid or cochlear implant. Of the adults who used these devices, 13% rated their hearing as fair or poor.
Those with worse physical or mental health were more likely to rate their hearing as fair or poor and were less likely to have undergone testing.
Although “screening for hearing loss is expected as part of the Medicare Annual Wellness Visit,” the data suggest that most adults aged 65-80 years have not been screened recently, the researchers say.
“One efficient way to increase hearing evaluations among older adults in primary care is to use a single-question screener,” Dr. McKee and coauthors wrote.
“The response to the question ‘Do you think you have hearing loss?’ has been shown to be highly predictive of true hearing loss ... Age-related hearing loss remains a neglected primary care and public health concern. Consistent use of screening tools and improved access to assistive devices that treat hearing loss can enhance the health and well-being of older adults,” they wrote.
Philip Zazove, MD, chair of the department of family medicine at the University of Michigan, Ann Arbor, and one of the authors of the report, noted in a news release that health insurance coverage varies widely for hearing screening by primary care providers, testing by audiologists, and hearing aids and cochlear implants.
Implementing the single-question screener is “easy to do,” Dr. Zazove said in an interview. “The major barrier is remembering, considering all the things primary care needs to do.” Electronic prompts may be an effective reminder.
If a patient answers yes, then clinicians should discuss referral for testing. Still, some patients may not be ready for further testing or treatment, possibly owing to vanity, misunderstandings, or cultural barriers, Dr. Zazove said. “Unfortunately, most physicians are not comfortable dealing with hearing loss. We get relatively little education on that in medical school and even residency,” he said.
“Hearing screening isn’t difficult,” and primary care providers can accomplish it “with one quick screening question – as the authors note,” said Jan Blustein, MD, PhD, professor of health policy and medicine at New York University. “I believe that some providers may be reluctant to screen or make a referral because they know that many people can’t afford hearing aids ... However, I also believe that many providers just don’t appreciate how disabling hearing loss is. And many didn’t receive training in this area in medical school. Training in disability gets very short shrift at most schools, in my experience. This needs to change.”
The survey does not address whether screening practices for hearing loss has changed during the COVID-19 pandemic, though Dr. Zazove suspects that screening has decreased as a result. Even if patients are screened, some may not present for audiology testing “because of fear of COVID or the audiologist not being open,” he said.
Hearing loss is associated with increased risk for hospitalization and readmission, dementia, and depression. “We believe, though studies are needed to verify, that detection and intervention for these patients can ameliorate the adverse health, social, and economic outcomes,” Dr. Zazove said.
A version of this article first appeared on Medscape.com.
But asking a single question – “Do you think you have hearing loss?” – may be an efficient way to identify patients who should receive further evaluation, researchers said.
Only 20% of adults aged 50-80 years report that their primary care physician has asked about their hearing in the past 2 years, according to the National Poll on Healthy Aging, published online March 2. Among adults who rated their hearing as fair or poor, only 26% said they had been asked about their hearing.
Michael McKee, MD, MPH, a family medicine physician and health services researcher at Michigan Medicine, the University of Michigan’s academic medical center, and colleagues surveyed 2,074 adults aged 50-80 years in June 2020. They asked participants about the screening and testing of hearing that they had undergone. The researchers weighted the sample to reflect population figures from the U.S. Census Bureau.
Men were more likely than women to have been asked about their hearing (24% vs. 17%), and adults aged 65-80 years were more likely than younger adults to have been asked about their hearing (25% vs. 16%).
The survey also found that 23% of adults had undergone a hearing test by a health care professional; 62% felt that it was at least somewhat important to have their hearing tested at least once every 2 years.
Overall, 16% of adults rated their hearing as fair or poor. Approximately a third rated their hearing as good, and about half rated their hearing as excellent or very good. Fair or poor hearing was more commonly reported by men than women (20% vs. 12%) and by older adults than younger adults (19% vs. 14%).
In all, 6% used a hearing aid or cochlear implant. Of the adults who used these devices, 13% rated their hearing as fair or poor.
Those with worse physical or mental health were more likely to rate their hearing as fair or poor and were less likely to have undergone testing.
Although “screening for hearing loss is expected as part of the Medicare Annual Wellness Visit,” the data suggest that most adults aged 65-80 years have not been screened recently, the researchers say.
“One efficient way to increase hearing evaluations among older adults in primary care is to use a single-question screener,” Dr. McKee and coauthors wrote.
“The response to the question ‘Do you think you have hearing loss?’ has been shown to be highly predictive of true hearing loss ... Age-related hearing loss remains a neglected primary care and public health concern. Consistent use of screening tools and improved access to assistive devices that treat hearing loss can enhance the health and well-being of older adults,” they wrote.
Philip Zazove, MD, chair of the department of family medicine at the University of Michigan, Ann Arbor, and one of the authors of the report, noted in a news release that health insurance coverage varies widely for hearing screening by primary care providers, testing by audiologists, and hearing aids and cochlear implants.
Implementing the single-question screener is “easy to do,” Dr. Zazove said in an interview. “The major barrier is remembering, considering all the things primary care needs to do.” Electronic prompts may be an effective reminder.
If a patient answers yes, then clinicians should discuss referral for testing. Still, some patients may not be ready for further testing or treatment, possibly owing to vanity, misunderstandings, or cultural barriers, Dr. Zazove said. “Unfortunately, most physicians are not comfortable dealing with hearing loss. We get relatively little education on that in medical school and even residency,” he said.
“Hearing screening isn’t difficult,” and primary care providers can accomplish it “with one quick screening question – as the authors note,” said Jan Blustein, MD, PhD, professor of health policy and medicine at New York University. “I believe that some providers may be reluctant to screen or make a referral because they know that many people can’t afford hearing aids ... However, I also believe that many providers just don’t appreciate how disabling hearing loss is. And many didn’t receive training in this area in medical school. Training in disability gets very short shrift at most schools, in my experience. This needs to change.”
The survey does not address whether screening practices for hearing loss has changed during the COVID-19 pandemic, though Dr. Zazove suspects that screening has decreased as a result. Even if patients are screened, some may not present for audiology testing “because of fear of COVID or the audiologist not being open,” he said.
Hearing loss is associated with increased risk for hospitalization and readmission, dementia, and depression. “We believe, though studies are needed to verify, that detection and intervention for these patients can ameliorate the adverse health, social, and economic outcomes,” Dr. Zazove said.
A version of this article first appeared on Medscape.com.
But asking a single question – “Do you think you have hearing loss?” – may be an efficient way to identify patients who should receive further evaluation, researchers said.
Only 20% of adults aged 50-80 years report that their primary care physician has asked about their hearing in the past 2 years, according to the National Poll on Healthy Aging, published online March 2. Among adults who rated their hearing as fair or poor, only 26% said they had been asked about their hearing.
Michael McKee, MD, MPH, a family medicine physician and health services researcher at Michigan Medicine, the University of Michigan’s academic medical center, and colleagues surveyed 2,074 adults aged 50-80 years in June 2020. They asked participants about the screening and testing of hearing that they had undergone. The researchers weighted the sample to reflect population figures from the U.S. Census Bureau.
Men were more likely than women to have been asked about their hearing (24% vs. 17%), and adults aged 65-80 years were more likely than younger adults to have been asked about their hearing (25% vs. 16%).
The survey also found that 23% of adults had undergone a hearing test by a health care professional; 62% felt that it was at least somewhat important to have their hearing tested at least once every 2 years.
Overall, 16% of adults rated their hearing as fair or poor. Approximately a third rated their hearing as good, and about half rated their hearing as excellent or very good. Fair or poor hearing was more commonly reported by men than women (20% vs. 12%) and by older adults than younger adults (19% vs. 14%).
In all, 6% used a hearing aid or cochlear implant. Of the adults who used these devices, 13% rated their hearing as fair or poor.
Those with worse physical or mental health were more likely to rate their hearing as fair or poor and were less likely to have undergone testing.
Although “screening for hearing loss is expected as part of the Medicare Annual Wellness Visit,” the data suggest that most adults aged 65-80 years have not been screened recently, the researchers say.
“One efficient way to increase hearing evaluations among older adults in primary care is to use a single-question screener,” Dr. McKee and coauthors wrote.
“The response to the question ‘Do you think you have hearing loss?’ has been shown to be highly predictive of true hearing loss ... Age-related hearing loss remains a neglected primary care and public health concern. Consistent use of screening tools and improved access to assistive devices that treat hearing loss can enhance the health and well-being of older adults,” they wrote.
Philip Zazove, MD, chair of the department of family medicine at the University of Michigan, Ann Arbor, and one of the authors of the report, noted in a news release that health insurance coverage varies widely for hearing screening by primary care providers, testing by audiologists, and hearing aids and cochlear implants.
Implementing the single-question screener is “easy to do,” Dr. Zazove said in an interview. “The major barrier is remembering, considering all the things primary care needs to do.” Electronic prompts may be an effective reminder.
If a patient answers yes, then clinicians should discuss referral for testing. Still, some patients may not be ready for further testing or treatment, possibly owing to vanity, misunderstandings, or cultural barriers, Dr. Zazove said. “Unfortunately, most physicians are not comfortable dealing with hearing loss. We get relatively little education on that in medical school and even residency,” he said.
“Hearing screening isn’t difficult,” and primary care providers can accomplish it “with one quick screening question – as the authors note,” said Jan Blustein, MD, PhD, professor of health policy and medicine at New York University. “I believe that some providers may be reluctant to screen or make a referral because they know that many people can’t afford hearing aids ... However, I also believe that many providers just don’t appreciate how disabling hearing loss is. And many didn’t receive training in this area in medical school. Training in disability gets very short shrift at most schools, in my experience. This needs to change.”
The survey does not address whether screening practices for hearing loss has changed during the COVID-19 pandemic, though Dr. Zazove suspects that screening has decreased as a result. Even if patients are screened, some may not present for audiology testing “because of fear of COVID or the audiologist not being open,” he said.
Hearing loss is associated with increased risk for hospitalization and readmission, dementia, and depression. “We believe, though studies are needed to verify, that detection and intervention for these patients can ameliorate the adverse health, social, and economic outcomes,” Dr. Zazove said.
A version of this article first appeared on Medscape.com.
Metformin for pediatric obesity? Researchers review the evidence
Metformin has a modest favorable effect on body mass index z score and insulin resistance in children and adolescents with obesity, compared with placebo, according to a systematic review of trial data.
“The available evidence is of varying quality,” however, and the drug increases the likelihood of gastrointestinal adverse effects, reported Reem Masarwa, PharmD, PhD, and colleagues in Pediatrics. “Nonetheless, metformin may be considered for use as a pharmacologic therapy in this pediatric population because of its modest efficacy, availability, cost, and safety profile.”
The Food and Drug Administration has approved metformin for the treatment of type 2 diabetes in children and adolescents. Doctors have used the drug off label for weight loss in children with obesity, but this use “remains controversial,” the review authors said.
To assess the efficacy and safety of metformin plus lifestyle interventions compared with placebo plus lifestyle interventions in children and adolescents with obesity, Dr. Masarwa, with the Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, and the department of epidemiology, biostatistics, and occupational health, McGill University, Montreal, and colleagues systematically reviewed data from randomized controlled trials (RCTs). Their review was published online in Pediatrics.
The investigators focused on studies that examined outcomes such as body mass index, BMI z score, insulin resistance, and gastrointestinal adverse effects. They excluded studies of children with type 2 diabetes.
The researchers included 24 RCTs in their review. The studies included 1,623 children and adolescents who received metformin (861 participants) or placebo (762 participants). Indications included uncomplicated obesity in 10 studies, obesity with insulin resistance in 9 studies, prediabetes in 3 studies, and nonalcoholic fatty liver disease in 2 studies. One of the trials did not incorporate a lifestyle cointervention.
Participants ranged in age from 4 years to 19 years, and trial durations ranged from 2 months to 2 years. The total daily dose of metformin ranged from 500 mg to 2,000 mg.
In 14 RCTs that reported BMI, metformin generally decreased BMI (range of mean changes: –2.70 to 1.30), compared with placebo (range of mean changes: –1.12 to 1.90), although three trials suggested that metformin increased BMI. The average difference in the treatment effect between the metformin and placebo groups ranged from –2.72 to 0.70. “Importantly, the authors of many RCTs reported variable treatment effects, preventing definitive conclusions from being drawn from individual trials,” Dr. Masarwa and coauthors wrote.
In seven RCTs that reported BMI z score, metformin consistently decreased BMI z score (range of mean changes: –0.37 to –0.03), compared with placebo (range of mean changes: –0.22 to 0.15). The mean difference in the treatment effect between treatment groups ranged from –0.15 to –0.07. The largest decrease occurred in patients with nonalcoholic fatty liver disease.
The rate of gastrointestinal adverse events nearly doubled with metformin treatment, relative to placebo (rate range: 2%-74% for metformin vs. 0%-42% for placebo).
Metformin adherence rates ranged from 60% to 90%, and lifestyle cointerventions varied substantially across the trials, the researchers noted. The clinical significance and long-term effects of metformin treatment in this population “remain uncertain,” they said.
Off-label use may not be ideal
“Ideally, children with obesity should be entered into a clinical trial rather than placed on an off-label medication,” Vandana Raman, MD, and Carol M. Foster, MD, said in a related commentary. Still, treatment with metformin may be reasonable in certain cases, said Dr. Raman and Dr. Foster of the division of endocrinology in the department of pediatrics at the University of Utah in Salt Lake City. “Metformin is a low-cost option and may provide modest clinical benefit for weight loss with minimal side effects. If lifestyle modification has been pursued but has achieved minimal weight loss, it may be reasonable to try an agent such as metformin as adjunctive therapy,” they said.
Lifestyle modification therapy – including nutritional changes, physical activity, and behavior modification – has been the “mainstay of management” for patients with obesity, and this approach underpins successful weight loss, they said. But durable weight loss with lifestyle modification may be challenging, and pharmacologic treatments “are attractive options before proceeding to bariatric surgery,” they said.
For younger patients, FDA-approved medications for obesity include orlistat and liraglutide for patients aged 12 years and older, and phentermine for patients aged 16 years and older.
“Orlistat has been associated with modest BMI reduction but may cause intolerable gastrointestinal side effects and possible fat-soluble vitamin deficiency,” they said. “Phentermine is approved for short-term therapy only and may increase heart rate and blood pressure and cause irritability and insomnia.”
Liraglutide, which was approved for the treatment of pediatric obesity in December 2020, reduced BMI in a trial that included adolescents with obesity. About 43% of the participants who received liraglutide, compared with 18% who received placebo, had a 5% reduction in BMI. In addition, 26% and 8%, respectively, had a 10% reduction in BMI. The use of liraglutide “is limited by the need for daily subcutaneous injections and high frequency of gastrointestinal side effects and high cost,” however, the commentary authors noted.
In addition, the FDA has approved setmelanotide for children older than 6 years with obesity caused by three rare genetic conditions.
Some small studies have suggested that topiramate may lead to meaningful weight loss in children, but the medication has been associated with cognitive dysfunction, they said.
Considering surgery
“This is an important review of the efficacy of metformin as a tool for weight loss in children with obesity,” said Suzanne C. Boulter, MD, adjunct professor emeritus of pediatrics and community and family medicine at the Geisel School of Medicine at Dartmouth in Hanover, N.H. “Results showed modest decreases in BMI z scores compared to placebo but there were a significant percentage of GI side effects and dropouts from the trials.”
“Tools other than lifestyle changes are needed to address” pediatric obesity, Dr. Boulter said. “Another tool is gastric bypass which is now a recommended intervention in selected clinical sites for adolescents 14 years of age and older with BMIs greater than 35.”
Dr. Boulter highlighted a recent study in Pediatrics that examined data from more than 200 adolescents who underwent bariatric surgery. The researchers found that outcomes were similar for older and younger patients.
“It would be interesting to pediatricians in practice to see a comparison study between metformin and bariatric surgery long-term results,” Dr. Boulter added.
Dr. Masarwa and coauthors received support from the Quebec Foundation for Health Research and the Canadian Institutes of Health Research Drug Safety and Effectiveness Cross-Disciplinary Training Program. One coauthor also is supported by an award from McGill University.
The authors of the systematic review and the accompanying commentary had no relevant financial disclosures. Dr. Boulter is a member of the editorial advisory board for Pediatric News and had no relevant financial disclosures.
Metformin has a modest favorable effect on body mass index z score and insulin resistance in children and adolescents with obesity, compared with placebo, according to a systematic review of trial data.
“The available evidence is of varying quality,” however, and the drug increases the likelihood of gastrointestinal adverse effects, reported Reem Masarwa, PharmD, PhD, and colleagues in Pediatrics. “Nonetheless, metformin may be considered for use as a pharmacologic therapy in this pediatric population because of its modest efficacy, availability, cost, and safety profile.”
The Food and Drug Administration has approved metformin for the treatment of type 2 diabetes in children and adolescents. Doctors have used the drug off label for weight loss in children with obesity, but this use “remains controversial,” the review authors said.
To assess the efficacy and safety of metformin plus lifestyle interventions compared with placebo plus lifestyle interventions in children and adolescents with obesity, Dr. Masarwa, with the Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, and the department of epidemiology, biostatistics, and occupational health, McGill University, Montreal, and colleagues systematically reviewed data from randomized controlled trials (RCTs). Their review was published online in Pediatrics.
The investigators focused on studies that examined outcomes such as body mass index, BMI z score, insulin resistance, and gastrointestinal adverse effects. They excluded studies of children with type 2 diabetes.
The researchers included 24 RCTs in their review. The studies included 1,623 children and adolescents who received metformin (861 participants) or placebo (762 participants). Indications included uncomplicated obesity in 10 studies, obesity with insulin resistance in 9 studies, prediabetes in 3 studies, and nonalcoholic fatty liver disease in 2 studies. One of the trials did not incorporate a lifestyle cointervention.
Participants ranged in age from 4 years to 19 years, and trial durations ranged from 2 months to 2 years. The total daily dose of metformin ranged from 500 mg to 2,000 mg.
In 14 RCTs that reported BMI, metformin generally decreased BMI (range of mean changes: –2.70 to 1.30), compared with placebo (range of mean changes: –1.12 to 1.90), although three trials suggested that metformin increased BMI. The average difference in the treatment effect between the metformin and placebo groups ranged from –2.72 to 0.70. “Importantly, the authors of many RCTs reported variable treatment effects, preventing definitive conclusions from being drawn from individual trials,” Dr. Masarwa and coauthors wrote.
In seven RCTs that reported BMI z score, metformin consistently decreased BMI z score (range of mean changes: –0.37 to –0.03), compared with placebo (range of mean changes: –0.22 to 0.15). The mean difference in the treatment effect between treatment groups ranged from –0.15 to –0.07. The largest decrease occurred in patients with nonalcoholic fatty liver disease.
The rate of gastrointestinal adverse events nearly doubled with metformin treatment, relative to placebo (rate range: 2%-74% for metformin vs. 0%-42% for placebo).
Metformin adherence rates ranged from 60% to 90%, and lifestyle cointerventions varied substantially across the trials, the researchers noted. The clinical significance and long-term effects of metformin treatment in this population “remain uncertain,” they said.
Off-label use may not be ideal
“Ideally, children with obesity should be entered into a clinical trial rather than placed on an off-label medication,” Vandana Raman, MD, and Carol M. Foster, MD, said in a related commentary. Still, treatment with metformin may be reasonable in certain cases, said Dr. Raman and Dr. Foster of the division of endocrinology in the department of pediatrics at the University of Utah in Salt Lake City. “Metformin is a low-cost option and may provide modest clinical benefit for weight loss with minimal side effects. If lifestyle modification has been pursued but has achieved minimal weight loss, it may be reasonable to try an agent such as metformin as adjunctive therapy,” they said.
Lifestyle modification therapy – including nutritional changes, physical activity, and behavior modification – has been the “mainstay of management” for patients with obesity, and this approach underpins successful weight loss, they said. But durable weight loss with lifestyle modification may be challenging, and pharmacologic treatments “are attractive options before proceeding to bariatric surgery,” they said.
For younger patients, FDA-approved medications for obesity include orlistat and liraglutide for patients aged 12 years and older, and phentermine for patients aged 16 years and older.
“Orlistat has been associated with modest BMI reduction but may cause intolerable gastrointestinal side effects and possible fat-soluble vitamin deficiency,” they said. “Phentermine is approved for short-term therapy only and may increase heart rate and blood pressure and cause irritability and insomnia.”
Liraglutide, which was approved for the treatment of pediatric obesity in December 2020, reduced BMI in a trial that included adolescents with obesity. About 43% of the participants who received liraglutide, compared with 18% who received placebo, had a 5% reduction in BMI. In addition, 26% and 8%, respectively, had a 10% reduction in BMI. The use of liraglutide “is limited by the need for daily subcutaneous injections and high frequency of gastrointestinal side effects and high cost,” however, the commentary authors noted.
In addition, the FDA has approved setmelanotide for children older than 6 years with obesity caused by three rare genetic conditions.
Some small studies have suggested that topiramate may lead to meaningful weight loss in children, but the medication has been associated with cognitive dysfunction, they said.
Considering surgery
“This is an important review of the efficacy of metformin as a tool for weight loss in children with obesity,” said Suzanne C. Boulter, MD, adjunct professor emeritus of pediatrics and community and family medicine at the Geisel School of Medicine at Dartmouth in Hanover, N.H. “Results showed modest decreases in BMI z scores compared to placebo but there were a significant percentage of GI side effects and dropouts from the trials.”
“Tools other than lifestyle changes are needed to address” pediatric obesity, Dr. Boulter said. “Another tool is gastric bypass which is now a recommended intervention in selected clinical sites for adolescents 14 years of age and older with BMIs greater than 35.”
Dr. Boulter highlighted a recent study in Pediatrics that examined data from more than 200 adolescents who underwent bariatric surgery. The researchers found that outcomes were similar for older and younger patients.
“It would be interesting to pediatricians in practice to see a comparison study between metformin and bariatric surgery long-term results,” Dr. Boulter added.
Dr. Masarwa and coauthors received support from the Quebec Foundation for Health Research and the Canadian Institutes of Health Research Drug Safety and Effectiveness Cross-Disciplinary Training Program. One coauthor also is supported by an award from McGill University.
The authors of the systematic review and the accompanying commentary had no relevant financial disclosures. Dr. Boulter is a member of the editorial advisory board for Pediatric News and had no relevant financial disclosures.
Metformin has a modest favorable effect on body mass index z score and insulin resistance in children and adolescents with obesity, compared with placebo, according to a systematic review of trial data.
“The available evidence is of varying quality,” however, and the drug increases the likelihood of gastrointestinal adverse effects, reported Reem Masarwa, PharmD, PhD, and colleagues in Pediatrics. “Nonetheless, metformin may be considered for use as a pharmacologic therapy in this pediatric population because of its modest efficacy, availability, cost, and safety profile.”
The Food and Drug Administration has approved metformin for the treatment of type 2 diabetes in children and adolescents. Doctors have used the drug off label for weight loss in children with obesity, but this use “remains controversial,” the review authors said.
To assess the efficacy and safety of metformin plus lifestyle interventions compared with placebo plus lifestyle interventions in children and adolescents with obesity, Dr. Masarwa, with the Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, and the department of epidemiology, biostatistics, and occupational health, McGill University, Montreal, and colleagues systematically reviewed data from randomized controlled trials (RCTs). Their review was published online in Pediatrics.
The investigators focused on studies that examined outcomes such as body mass index, BMI z score, insulin resistance, and gastrointestinal adverse effects. They excluded studies of children with type 2 diabetes.
The researchers included 24 RCTs in their review. The studies included 1,623 children and adolescents who received metformin (861 participants) or placebo (762 participants). Indications included uncomplicated obesity in 10 studies, obesity with insulin resistance in 9 studies, prediabetes in 3 studies, and nonalcoholic fatty liver disease in 2 studies. One of the trials did not incorporate a lifestyle cointervention.
Participants ranged in age from 4 years to 19 years, and trial durations ranged from 2 months to 2 years. The total daily dose of metformin ranged from 500 mg to 2,000 mg.
In 14 RCTs that reported BMI, metformin generally decreased BMI (range of mean changes: –2.70 to 1.30), compared with placebo (range of mean changes: –1.12 to 1.90), although three trials suggested that metformin increased BMI. The average difference in the treatment effect between the metformin and placebo groups ranged from –2.72 to 0.70. “Importantly, the authors of many RCTs reported variable treatment effects, preventing definitive conclusions from being drawn from individual trials,” Dr. Masarwa and coauthors wrote.
In seven RCTs that reported BMI z score, metformin consistently decreased BMI z score (range of mean changes: –0.37 to –0.03), compared with placebo (range of mean changes: –0.22 to 0.15). The mean difference in the treatment effect between treatment groups ranged from –0.15 to –0.07. The largest decrease occurred in patients with nonalcoholic fatty liver disease.
The rate of gastrointestinal adverse events nearly doubled with metformin treatment, relative to placebo (rate range: 2%-74% for metformin vs. 0%-42% for placebo).
Metformin adherence rates ranged from 60% to 90%, and lifestyle cointerventions varied substantially across the trials, the researchers noted. The clinical significance and long-term effects of metformin treatment in this population “remain uncertain,” they said.
Off-label use may not be ideal
“Ideally, children with obesity should be entered into a clinical trial rather than placed on an off-label medication,” Vandana Raman, MD, and Carol M. Foster, MD, said in a related commentary. Still, treatment with metformin may be reasonable in certain cases, said Dr. Raman and Dr. Foster of the division of endocrinology in the department of pediatrics at the University of Utah in Salt Lake City. “Metformin is a low-cost option and may provide modest clinical benefit for weight loss with minimal side effects. If lifestyle modification has been pursued but has achieved minimal weight loss, it may be reasonable to try an agent such as metformin as adjunctive therapy,” they said.
Lifestyle modification therapy – including nutritional changes, physical activity, and behavior modification – has been the “mainstay of management” for patients with obesity, and this approach underpins successful weight loss, they said. But durable weight loss with lifestyle modification may be challenging, and pharmacologic treatments “are attractive options before proceeding to bariatric surgery,” they said.
For younger patients, FDA-approved medications for obesity include orlistat and liraglutide for patients aged 12 years and older, and phentermine for patients aged 16 years and older.
“Orlistat has been associated with modest BMI reduction but may cause intolerable gastrointestinal side effects and possible fat-soluble vitamin deficiency,” they said. “Phentermine is approved for short-term therapy only and may increase heart rate and blood pressure and cause irritability and insomnia.”
Liraglutide, which was approved for the treatment of pediatric obesity in December 2020, reduced BMI in a trial that included adolescents with obesity. About 43% of the participants who received liraglutide, compared with 18% who received placebo, had a 5% reduction in BMI. In addition, 26% and 8%, respectively, had a 10% reduction in BMI. The use of liraglutide “is limited by the need for daily subcutaneous injections and high frequency of gastrointestinal side effects and high cost,” however, the commentary authors noted.
In addition, the FDA has approved setmelanotide for children older than 6 years with obesity caused by three rare genetic conditions.
Some small studies have suggested that topiramate may lead to meaningful weight loss in children, but the medication has been associated with cognitive dysfunction, they said.
Considering surgery
“This is an important review of the efficacy of metformin as a tool for weight loss in children with obesity,” said Suzanne C. Boulter, MD, adjunct professor emeritus of pediatrics and community and family medicine at the Geisel School of Medicine at Dartmouth in Hanover, N.H. “Results showed modest decreases in BMI z scores compared to placebo but there were a significant percentage of GI side effects and dropouts from the trials.”
“Tools other than lifestyle changes are needed to address” pediatric obesity, Dr. Boulter said. “Another tool is gastric bypass which is now a recommended intervention in selected clinical sites for adolescents 14 years of age and older with BMIs greater than 35.”
Dr. Boulter highlighted a recent study in Pediatrics that examined data from more than 200 adolescents who underwent bariatric surgery. The researchers found that outcomes were similar for older and younger patients.
“It would be interesting to pediatricians in practice to see a comparison study between metformin and bariatric surgery long-term results,” Dr. Boulter added.
Dr. Masarwa and coauthors received support from the Quebec Foundation for Health Research and the Canadian Institutes of Health Research Drug Safety and Effectiveness Cross-Disciplinary Training Program. One coauthor also is supported by an award from McGill University.
The authors of the systematic review and the accompanying commentary had no relevant financial disclosures. Dr. Boulter is a member of the editorial advisory board for Pediatric News and had no relevant financial disclosures.
FROM PEDIATRICS
Study: Central sleep apnea is common in ticagrelor users post ACS
The prevalence of asymptomatic central sleep apnea after acute coronary syndrome is high and may be associated with the use of ticagrelor, a new study finds.
Prior studies have suggested that ticagrelor is associated with an increased likelihood of central sleep apnea. The drug’s label notes that two respiratory conditions – central sleep apnea and Cheyne-Stokes respiration – are adverse reactions that were identified after the drug’s approval in the United States in 2011. “Because these reactions are reported voluntarily from a population of an unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure,” the label says.
Among 80 patients receiving ticagrelor, 24 had central sleep apnea hypopnea syndrome (CSAHS), whereas of 41 patients not taking ticagrelor, 3 had this condition (30% vs. 7.3%, P = .004), in the new study published online Jan. 20, 2021, in Sleep Medicine. A multivariable analysis included in the paper found that age and ticagrelor administration were the only two factors associated with the occurrence of CSAHS.
Findings are ‘striking’
The different rates of central sleep apnea in the study are striking, but it is not clear that asymptomatic central sleep apnea in patients taking ticagrelor is a concern, Ofer Jacobowitz, MD, PhD, associate professor of otolaryngology at Hofstra University, Hempstead, N.Y, said in an interview.
“Whether this particular drug-induced central sleep apnea is consequential” is an open question, noted Dr. Jacobowitz. “There is no evidence that shows that this is definitely harmful.”
“The different types of central sleep apnea are caused by different mechanisms and this one, we don’t know,” Dr. Jacobwitz added.
Study author continues to prescribe ticagrelor
One of the study authors, Philippe Meurin, MD, said that he continues to prescribe ticagrelor every day and that the side effect is not necessarily important.
It is possible that central sleep apnea may resolve, although further studies would need to examine central sleep apnea over time to establish the duration of the condition, he added. Nevertheless, awareness of the association could have implications for clinical practice, Dr. Meurin said.
Central sleep apnea is rare, and if doctors detect it during a sleep study, they may perform extensive tests to assess for possible neurologic diseases, for example, when the cause may be attributed to the medication, he said. In addition, if a patient who is taking ticagrelor has dyspnea, the presence of central sleep apnea may suggest that dyspnea could be related to the drug, although this possibility needs further study, he noted.
Study included patients with ACS history, but no heart failure
Dr. Meurin, of Centre de Réadaptation Cardiaque de La Brie, Les Grands Prés, Villeneuve-Saint-Denis, France, and colleagues included in their study patients between 1 week and 1 year after acute coronary syndrome who did not have heart failure or a history of sleep apnea.
After an overnight sleep study, they classified patients as normal, as having CSAHS (i.e., an apnea-hypopnea index of 15 or greater, mostly with central sleep apneas), or as having obstructive sleep apnea hypopnea syndrome (OSAHS; i.e., an apnea-hypopnea index of 15 or greater, mostly with obstructive sleep apneas).
The prospective study included 121 consecutive patients between January 2018 and March 2020. Patients had a mean age of 56.8, and 88% were men.
Switching to another P2Y12 inhibitor ‘does not seem appropriate’
“CSAHS could be promoted by the use of ticagrelor, a relatively new drug that modifies the apneic threshold,” the study authors wrote. “Regarding underlying mechanisms, the most probable explanation seems to be increased chemosensitivity to hypercapnia by a direct P2Y12 inhibitory effect on the central nervous system.”
Doctors should not overestimate the severity of the adverse reaction or consider it the same way they do OSASH, they added.
Among patients with acute coronary syndrome in the PLATO study, ticagrelor, compared with clopidogrel, “significantly reduced the rate of death from vascular causes, myocardial infarction, or stroke,” Dr. Meurin and colleagues said. “Because in this study more than 9,000 patients received ticagrelor for 12 months, CSAHS (even if it seems frequent in our study) did not seem to impair the good efficacy/tolerance balance of the drug. Therefore, in asymptomatic CSAHS patients, switching from ticagrelor to another P2Y12 inhibitor does not seem appropriate.”
A recent analysis of data from randomized, controlled trials with ticagrelor did not find excess cases of sleep apnea with the drug. But an asymptomatic adverse event such as central sleep apnea “cannot emerge from a post hoc analysis,” Dr. Meurin and colleagues said.
The analysis of randomized trial data was conducted by Marc S. Sabatine, MD, MPH, chairman of the Thrombolysis in Myocardial Infarction (TIMI) Study Group at Brigham and Women’s Hospital, and coauthors. It was published in JACC: Cardiovascular Interventions in April 2020.
They “used the gold standard for medical evidence (randomized, placebo-controlled trials) and found 158 cases of sleep apnea reported, with absolutely no difference between ticagrelor and placebo,” Dr. Sabatine said in an interview. Their analysis examined clinically overt apnea, he noted.
“It is quite clear that when looking at large numbers in placebo-controlled trials, there is no excess,” Dr. Sabatine said. “Meurin et al. are examining a different outcome: the results of a lab test in what may be entirely asymptomatic patients.”
A randomized trial could confirm the association, he said.
“The association may be real, but also may be play of chance or confounded,” said Dr. Sabatine. “To convince the medical community, the next step would be for the investigators to do a randomized trial and test whether ticagrelor increases the risk of central sleep apnea.”
Dr. Meurin and the study coauthors had no disclosures. The analysis of randomized, controlled trial data by Dr. Sabatine and colleagues was funded by AstraZeneca, which distributes ticagrelor under the trade name Brilinta. Dr. Sabatine has been a consultant for AstraZeneca and received research grants through Brigham and Women’s Hospital from AstraZeneca. He has consulted for and received grants through the hospital from other companies as well. Dr. Jacobowitz had no relevant disclosures.
[email protected]
The prevalence of asymptomatic central sleep apnea after acute coronary syndrome is high and may be associated with the use of ticagrelor, a new study finds.
Prior studies have suggested that ticagrelor is associated with an increased likelihood of central sleep apnea. The drug’s label notes that two respiratory conditions – central sleep apnea and Cheyne-Stokes respiration – are adverse reactions that were identified after the drug’s approval in the United States in 2011. “Because these reactions are reported voluntarily from a population of an unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure,” the label says.
Among 80 patients receiving ticagrelor, 24 had central sleep apnea hypopnea syndrome (CSAHS), whereas of 41 patients not taking ticagrelor, 3 had this condition (30% vs. 7.3%, P = .004), in the new study published online Jan. 20, 2021, in Sleep Medicine. A multivariable analysis included in the paper found that age and ticagrelor administration were the only two factors associated with the occurrence of CSAHS.
Findings are ‘striking’
The different rates of central sleep apnea in the study are striking, but it is not clear that asymptomatic central sleep apnea in patients taking ticagrelor is a concern, Ofer Jacobowitz, MD, PhD, associate professor of otolaryngology at Hofstra University, Hempstead, N.Y, said in an interview.
“Whether this particular drug-induced central sleep apnea is consequential” is an open question, noted Dr. Jacobowitz. “There is no evidence that shows that this is definitely harmful.”
“The different types of central sleep apnea are caused by different mechanisms and this one, we don’t know,” Dr. Jacobwitz added.
Study author continues to prescribe ticagrelor
One of the study authors, Philippe Meurin, MD, said that he continues to prescribe ticagrelor every day and that the side effect is not necessarily important.
It is possible that central sleep apnea may resolve, although further studies would need to examine central sleep apnea over time to establish the duration of the condition, he added. Nevertheless, awareness of the association could have implications for clinical practice, Dr. Meurin said.
Central sleep apnea is rare, and if doctors detect it during a sleep study, they may perform extensive tests to assess for possible neurologic diseases, for example, when the cause may be attributed to the medication, he said. In addition, if a patient who is taking ticagrelor has dyspnea, the presence of central sleep apnea may suggest that dyspnea could be related to the drug, although this possibility needs further study, he noted.
Study included patients with ACS history, but no heart failure
Dr. Meurin, of Centre de Réadaptation Cardiaque de La Brie, Les Grands Prés, Villeneuve-Saint-Denis, France, and colleagues included in their study patients between 1 week and 1 year after acute coronary syndrome who did not have heart failure or a history of sleep apnea.
After an overnight sleep study, they classified patients as normal, as having CSAHS (i.e., an apnea-hypopnea index of 15 or greater, mostly with central sleep apneas), or as having obstructive sleep apnea hypopnea syndrome (OSAHS; i.e., an apnea-hypopnea index of 15 or greater, mostly with obstructive sleep apneas).
The prospective study included 121 consecutive patients between January 2018 and March 2020. Patients had a mean age of 56.8, and 88% were men.
Switching to another P2Y12 inhibitor ‘does not seem appropriate’
“CSAHS could be promoted by the use of ticagrelor, a relatively new drug that modifies the apneic threshold,” the study authors wrote. “Regarding underlying mechanisms, the most probable explanation seems to be increased chemosensitivity to hypercapnia by a direct P2Y12 inhibitory effect on the central nervous system.”
Doctors should not overestimate the severity of the adverse reaction or consider it the same way they do OSASH, they added.
Among patients with acute coronary syndrome in the PLATO study, ticagrelor, compared with clopidogrel, “significantly reduced the rate of death from vascular causes, myocardial infarction, or stroke,” Dr. Meurin and colleagues said. “Because in this study more than 9,000 patients received ticagrelor for 12 months, CSAHS (even if it seems frequent in our study) did not seem to impair the good efficacy/tolerance balance of the drug. Therefore, in asymptomatic CSAHS patients, switching from ticagrelor to another P2Y12 inhibitor does not seem appropriate.”
A recent analysis of data from randomized, controlled trials with ticagrelor did not find excess cases of sleep apnea with the drug. But an asymptomatic adverse event such as central sleep apnea “cannot emerge from a post hoc analysis,” Dr. Meurin and colleagues said.
The analysis of randomized trial data was conducted by Marc S. Sabatine, MD, MPH, chairman of the Thrombolysis in Myocardial Infarction (TIMI) Study Group at Brigham and Women’s Hospital, and coauthors. It was published in JACC: Cardiovascular Interventions in April 2020.
They “used the gold standard for medical evidence (randomized, placebo-controlled trials) and found 158 cases of sleep apnea reported, with absolutely no difference between ticagrelor and placebo,” Dr. Sabatine said in an interview. Their analysis examined clinically overt apnea, he noted.
“It is quite clear that when looking at large numbers in placebo-controlled trials, there is no excess,” Dr. Sabatine said. “Meurin et al. are examining a different outcome: the results of a lab test in what may be entirely asymptomatic patients.”
A randomized trial could confirm the association, he said.
“The association may be real, but also may be play of chance or confounded,” said Dr. Sabatine. “To convince the medical community, the next step would be for the investigators to do a randomized trial and test whether ticagrelor increases the risk of central sleep apnea.”
Dr. Meurin and the study coauthors had no disclosures. The analysis of randomized, controlled trial data by Dr. Sabatine and colleagues was funded by AstraZeneca, which distributes ticagrelor under the trade name Brilinta. Dr. Sabatine has been a consultant for AstraZeneca and received research grants through Brigham and Women’s Hospital from AstraZeneca. He has consulted for and received grants through the hospital from other companies as well. Dr. Jacobowitz had no relevant disclosures.
[email protected]
The prevalence of asymptomatic central sleep apnea after acute coronary syndrome is high and may be associated with the use of ticagrelor, a new study finds.
Prior studies have suggested that ticagrelor is associated with an increased likelihood of central sleep apnea. The drug’s label notes that two respiratory conditions – central sleep apnea and Cheyne-Stokes respiration – are adverse reactions that were identified after the drug’s approval in the United States in 2011. “Because these reactions are reported voluntarily from a population of an unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure,” the label says.
Among 80 patients receiving ticagrelor, 24 had central sleep apnea hypopnea syndrome (CSAHS), whereas of 41 patients not taking ticagrelor, 3 had this condition (30% vs. 7.3%, P = .004), in the new study published online Jan. 20, 2021, in Sleep Medicine. A multivariable analysis included in the paper found that age and ticagrelor administration were the only two factors associated with the occurrence of CSAHS.
Findings are ‘striking’
The different rates of central sleep apnea in the study are striking, but it is not clear that asymptomatic central sleep apnea in patients taking ticagrelor is a concern, Ofer Jacobowitz, MD, PhD, associate professor of otolaryngology at Hofstra University, Hempstead, N.Y, said in an interview.
“Whether this particular drug-induced central sleep apnea is consequential” is an open question, noted Dr. Jacobowitz. “There is no evidence that shows that this is definitely harmful.”
“The different types of central sleep apnea are caused by different mechanisms and this one, we don’t know,” Dr. Jacobwitz added.
Study author continues to prescribe ticagrelor
One of the study authors, Philippe Meurin, MD, said that he continues to prescribe ticagrelor every day and that the side effect is not necessarily important.
It is possible that central sleep apnea may resolve, although further studies would need to examine central sleep apnea over time to establish the duration of the condition, he added. Nevertheless, awareness of the association could have implications for clinical practice, Dr. Meurin said.
Central sleep apnea is rare, and if doctors detect it during a sleep study, they may perform extensive tests to assess for possible neurologic diseases, for example, when the cause may be attributed to the medication, he said. In addition, if a patient who is taking ticagrelor has dyspnea, the presence of central sleep apnea may suggest that dyspnea could be related to the drug, although this possibility needs further study, he noted.
Study included patients with ACS history, but no heart failure
Dr. Meurin, of Centre de Réadaptation Cardiaque de La Brie, Les Grands Prés, Villeneuve-Saint-Denis, France, and colleagues included in their study patients between 1 week and 1 year after acute coronary syndrome who did not have heart failure or a history of sleep apnea.
After an overnight sleep study, they classified patients as normal, as having CSAHS (i.e., an apnea-hypopnea index of 15 or greater, mostly with central sleep apneas), or as having obstructive sleep apnea hypopnea syndrome (OSAHS; i.e., an apnea-hypopnea index of 15 or greater, mostly with obstructive sleep apneas).
The prospective study included 121 consecutive patients between January 2018 and March 2020. Patients had a mean age of 56.8, and 88% were men.
Switching to another P2Y12 inhibitor ‘does not seem appropriate’
“CSAHS could be promoted by the use of ticagrelor, a relatively new drug that modifies the apneic threshold,” the study authors wrote. “Regarding underlying mechanisms, the most probable explanation seems to be increased chemosensitivity to hypercapnia by a direct P2Y12 inhibitory effect on the central nervous system.”
Doctors should not overestimate the severity of the adverse reaction or consider it the same way they do OSASH, they added.
Among patients with acute coronary syndrome in the PLATO study, ticagrelor, compared with clopidogrel, “significantly reduced the rate of death from vascular causes, myocardial infarction, or stroke,” Dr. Meurin and colleagues said. “Because in this study more than 9,000 patients received ticagrelor for 12 months, CSAHS (even if it seems frequent in our study) did not seem to impair the good efficacy/tolerance balance of the drug. Therefore, in asymptomatic CSAHS patients, switching from ticagrelor to another P2Y12 inhibitor does not seem appropriate.”
A recent analysis of data from randomized, controlled trials with ticagrelor did not find excess cases of sleep apnea with the drug. But an asymptomatic adverse event such as central sleep apnea “cannot emerge from a post hoc analysis,” Dr. Meurin and colleagues said.
The analysis of randomized trial data was conducted by Marc S. Sabatine, MD, MPH, chairman of the Thrombolysis in Myocardial Infarction (TIMI) Study Group at Brigham and Women’s Hospital, and coauthors. It was published in JACC: Cardiovascular Interventions in April 2020.
They “used the gold standard for medical evidence (randomized, placebo-controlled trials) and found 158 cases of sleep apnea reported, with absolutely no difference between ticagrelor and placebo,” Dr. Sabatine said in an interview. Their analysis examined clinically overt apnea, he noted.
“It is quite clear that when looking at large numbers in placebo-controlled trials, there is no excess,” Dr. Sabatine said. “Meurin et al. are examining a different outcome: the results of a lab test in what may be entirely asymptomatic patients.”
A randomized trial could confirm the association, he said.
“The association may be real, but also may be play of chance or confounded,” said Dr. Sabatine. “To convince the medical community, the next step would be for the investigators to do a randomized trial and test whether ticagrelor increases the risk of central sleep apnea.”
Dr. Meurin and the study coauthors had no disclosures. The analysis of randomized, controlled trial data by Dr. Sabatine and colleagues was funded by AstraZeneca, which distributes ticagrelor under the trade name Brilinta. Dr. Sabatine has been a consultant for AstraZeneca and received research grants through Brigham and Women’s Hospital from AstraZeneca. He has consulted for and received grants through the hospital from other companies as well. Dr. Jacobowitz had no relevant disclosures.
[email protected]
FROM SLEEP MEDICINE
Antibiotic exposure in pregnancy linked to childhood asthma risk in study
in a Danish birth cohort study.
The reason behind the correlation is unclear. Maternal infections, rather than antibiotics, “could explain the observed association,” said study author Cecilie Skaarup Uldbjerg, a researcher in the department of public health at Aarhus University in Denmark.
Still, the “results are in keeping with the hypothesis that effects of antibiotics impact the maternally derived microbiome in vaginally born children and that this may increase the odds of childhood asthma,” Ms. Uldbjerg and coauthors wrote in their study, which was published online Feb. 9 in Archives of Disease in Childhood . “However, this observational study did not address underlying mechanisms, and this interpretation, while plausible, remains speculative.”
Antibiotic use in pregnancy likely to continue
Patrick Duff, MD, who was not involved in the research, does not expect the findings will alter clinical practice.
The association was relatively weak, and the study does not account for factors such as antibiotic exposure during early childhood or tobacco smoke in the house, said Dr. Duff, professor of maternal-fetal medicine at University of Florida, Gainesville.
“Although I agree that we should not use antibiotics indiscriminately during pregnancy, we definitely need to treat certain infections,” Dr. Duff said. “Thus we cannot avoid some degree of antibiotic exposure.”
Although prior research has indicated that antibiotic use in pregnancy may increase the risk of asthma in children, results have been inconsistent.
To study whether antibiotic exposure during pregnancy is associated with childhood asthma and whether the timing of antibiotic exposure or mode of delivery influence the relationship, the investigators analyzed data from more than 32,000 children in the Danish National Birth Cohort, which was established in 1996.
Children of mothers who took and did not take antibiotics compared
In all, 17% of the children were born to mothers who used antibiotics during pregnancy. Compared with mothers who did not take antibiotics, those who did reported more maternal asthma, smoking during pregnancy, and having overweight or obesity. In addition, they were less likely to have been in their first pregnancy.
During follow-up at age 11 years, 4,238 children (13%) had asthma, including 12.7% of those whose mothers had not been exposed to antibiotics, and 14.6% of those whose mothers had used antibiotics during pregnancy.
In adjusted analyses, children born to mothers who received antibiotics were more likely to have asthma (OR, 1.14).
Antibiotic exposure in the second to third trimester, but not in the first trimester, was associated with asthma. The association was observed in vaginally born children, but not in children born by cesarean section.
The study is limited by its reliance on maternal reporting for data about antibiotics and asthma diagnoses, the authors noted. Mothers completed telephone interviews twice during pregnancy and once at 6 months postpartum. They completed online questionnaires to provide follow-up information at 11 years.
Mode of delivery may matter
The researchers said their analysis indicates that mode of delivery may modify the association between antibiotic exposure during pregnancy and childhood asthma.
Fourteen percent of the children in the study were delivered by cesarean section. Further research may clarify the relationship between antibiotics in pregnancy, mode of delivery, and asthma risk, another doctor who was not involved the study added.
“I do not think that the evidence indicates that mode of delivery clearly has an impact,” said Santina J. G. Wheat, MD, MPH, associate professor of family and community medicine at Northwestern University in Chicago, “as the number of cesarean deliveries was not large enough to fully support such a statement.
“It will be interesting to see if an association holds in future studies with increased cesarean deliveries,” Dr. Wheat said.
How and why antibiotics were used may be other important factors to investigate, Dr. Duff suggested.
“The authors did not provide any specific information about which antibiotics were used by the mothers, duration of use, and indication for use. Those are very important confounders,” Dr. Duff said. “Perhaps the key exposure is to a particular maternal infection rather than to the antibiotic per se.”
The Danish National Birth Cohort was established with a grant from the Danish National Research Foundation and support from regional committees and other organizations. Its biobank has been supported by the Novo Nordisk Foundation and the Lundbeck Foundation, and follow-up of mothers and children has been supported by the Danish Medical Research Council, the Lundbeck Foundation, Innovation Fund Denmark, the Nordea Foundation, Aarhus Ideas, a University of Copenhagen strategic grant, and the Danish Council for Independent Research. The study was partially funded by the Health Research Fund of Central Denmark Region, which supported one of the authors. Other authors were supported by the DHB Foundation and the Australian National Health and Medical Research Council. One author is affiliated with Murdoch Children’s Research Institute in Australia, where the Victorian Government’s Operational Infrastructure Support Program supports research.
The authors had no competing interests. Dr. Wheat serves on the editorial advisory board of Family Practice News. Dr. Duff had no relevant financial disclosures.
in a Danish birth cohort study.
The reason behind the correlation is unclear. Maternal infections, rather than antibiotics, “could explain the observed association,” said study author Cecilie Skaarup Uldbjerg, a researcher in the department of public health at Aarhus University in Denmark.
Still, the “results are in keeping with the hypothesis that effects of antibiotics impact the maternally derived microbiome in vaginally born children and that this may increase the odds of childhood asthma,” Ms. Uldbjerg and coauthors wrote in their study, which was published online Feb. 9 in Archives of Disease in Childhood . “However, this observational study did not address underlying mechanisms, and this interpretation, while plausible, remains speculative.”
Antibiotic use in pregnancy likely to continue
Patrick Duff, MD, who was not involved in the research, does not expect the findings will alter clinical practice.
The association was relatively weak, and the study does not account for factors such as antibiotic exposure during early childhood or tobacco smoke in the house, said Dr. Duff, professor of maternal-fetal medicine at University of Florida, Gainesville.
“Although I agree that we should not use antibiotics indiscriminately during pregnancy, we definitely need to treat certain infections,” Dr. Duff said. “Thus we cannot avoid some degree of antibiotic exposure.”
Although prior research has indicated that antibiotic use in pregnancy may increase the risk of asthma in children, results have been inconsistent.
To study whether antibiotic exposure during pregnancy is associated with childhood asthma and whether the timing of antibiotic exposure or mode of delivery influence the relationship, the investigators analyzed data from more than 32,000 children in the Danish National Birth Cohort, which was established in 1996.
Children of mothers who took and did not take antibiotics compared
In all, 17% of the children were born to mothers who used antibiotics during pregnancy. Compared with mothers who did not take antibiotics, those who did reported more maternal asthma, smoking during pregnancy, and having overweight or obesity. In addition, they were less likely to have been in their first pregnancy.
During follow-up at age 11 years, 4,238 children (13%) had asthma, including 12.7% of those whose mothers had not been exposed to antibiotics, and 14.6% of those whose mothers had used antibiotics during pregnancy.
In adjusted analyses, children born to mothers who received antibiotics were more likely to have asthma (OR, 1.14).
Antibiotic exposure in the second to third trimester, but not in the first trimester, was associated with asthma. The association was observed in vaginally born children, but not in children born by cesarean section.
The study is limited by its reliance on maternal reporting for data about antibiotics and asthma diagnoses, the authors noted. Mothers completed telephone interviews twice during pregnancy and once at 6 months postpartum. They completed online questionnaires to provide follow-up information at 11 years.
Mode of delivery may matter
The researchers said their analysis indicates that mode of delivery may modify the association between antibiotic exposure during pregnancy and childhood asthma.
Fourteen percent of the children in the study were delivered by cesarean section. Further research may clarify the relationship between antibiotics in pregnancy, mode of delivery, and asthma risk, another doctor who was not involved the study added.
“I do not think that the evidence indicates that mode of delivery clearly has an impact,” said Santina J. G. Wheat, MD, MPH, associate professor of family and community medicine at Northwestern University in Chicago, “as the number of cesarean deliveries was not large enough to fully support such a statement.
“It will be interesting to see if an association holds in future studies with increased cesarean deliveries,” Dr. Wheat said.
How and why antibiotics were used may be other important factors to investigate, Dr. Duff suggested.
“The authors did not provide any specific information about which antibiotics were used by the mothers, duration of use, and indication for use. Those are very important confounders,” Dr. Duff said. “Perhaps the key exposure is to a particular maternal infection rather than to the antibiotic per se.”
The Danish National Birth Cohort was established with a grant from the Danish National Research Foundation and support from regional committees and other organizations. Its biobank has been supported by the Novo Nordisk Foundation and the Lundbeck Foundation, and follow-up of mothers and children has been supported by the Danish Medical Research Council, the Lundbeck Foundation, Innovation Fund Denmark, the Nordea Foundation, Aarhus Ideas, a University of Copenhagen strategic grant, and the Danish Council for Independent Research. The study was partially funded by the Health Research Fund of Central Denmark Region, which supported one of the authors. Other authors were supported by the DHB Foundation and the Australian National Health and Medical Research Council. One author is affiliated with Murdoch Children’s Research Institute in Australia, where the Victorian Government’s Operational Infrastructure Support Program supports research.
The authors had no competing interests. Dr. Wheat serves on the editorial advisory board of Family Practice News. Dr. Duff had no relevant financial disclosures.
in a Danish birth cohort study.
The reason behind the correlation is unclear. Maternal infections, rather than antibiotics, “could explain the observed association,” said study author Cecilie Skaarup Uldbjerg, a researcher in the department of public health at Aarhus University in Denmark.
Still, the “results are in keeping with the hypothesis that effects of antibiotics impact the maternally derived microbiome in vaginally born children and that this may increase the odds of childhood asthma,” Ms. Uldbjerg and coauthors wrote in their study, which was published online Feb. 9 in Archives of Disease in Childhood . “However, this observational study did not address underlying mechanisms, and this interpretation, while plausible, remains speculative.”
Antibiotic use in pregnancy likely to continue
Patrick Duff, MD, who was not involved in the research, does not expect the findings will alter clinical practice.
The association was relatively weak, and the study does not account for factors such as antibiotic exposure during early childhood or tobacco smoke in the house, said Dr. Duff, professor of maternal-fetal medicine at University of Florida, Gainesville.
“Although I agree that we should not use antibiotics indiscriminately during pregnancy, we definitely need to treat certain infections,” Dr. Duff said. “Thus we cannot avoid some degree of antibiotic exposure.”
Although prior research has indicated that antibiotic use in pregnancy may increase the risk of asthma in children, results have been inconsistent.
To study whether antibiotic exposure during pregnancy is associated with childhood asthma and whether the timing of antibiotic exposure or mode of delivery influence the relationship, the investigators analyzed data from more than 32,000 children in the Danish National Birth Cohort, which was established in 1996.
Children of mothers who took and did not take antibiotics compared
In all, 17% of the children were born to mothers who used antibiotics during pregnancy. Compared with mothers who did not take antibiotics, those who did reported more maternal asthma, smoking during pregnancy, and having overweight or obesity. In addition, they were less likely to have been in their first pregnancy.
During follow-up at age 11 years, 4,238 children (13%) had asthma, including 12.7% of those whose mothers had not been exposed to antibiotics, and 14.6% of those whose mothers had used antibiotics during pregnancy.
In adjusted analyses, children born to mothers who received antibiotics were more likely to have asthma (OR, 1.14).
Antibiotic exposure in the second to third trimester, but not in the first trimester, was associated with asthma. The association was observed in vaginally born children, but not in children born by cesarean section.
The study is limited by its reliance on maternal reporting for data about antibiotics and asthma diagnoses, the authors noted. Mothers completed telephone interviews twice during pregnancy and once at 6 months postpartum. They completed online questionnaires to provide follow-up information at 11 years.
Mode of delivery may matter
The researchers said their analysis indicates that mode of delivery may modify the association between antibiotic exposure during pregnancy and childhood asthma.
Fourteen percent of the children in the study were delivered by cesarean section. Further research may clarify the relationship between antibiotics in pregnancy, mode of delivery, and asthma risk, another doctor who was not involved the study added.
“I do not think that the evidence indicates that mode of delivery clearly has an impact,” said Santina J. G. Wheat, MD, MPH, associate professor of family and community medicine at Northwestern University in Chicago, “as the number of cesarean deliveries was not large enough to fully support such a statement.
“It will be interesting to see if an association holds in future studies with increased cesarean deliveries,” Dr. Wheat said.
How and why antibiotics were used may be other important factors to investigate, Dr. Duff suggested.
“The authors did not provide any specific information about which antibiotics were used by the mothers, duration of use, and indication for use. Those are very important confounders,” Dr. Duff said. “Perhaps the key exposure is to a particular maternal infection rather than to the antibiotic per se.”
The Danish National Birth Cohort was established with a grant from the Danish National Research Foundation and support from regional committees and other organizations. Its biobank has been supported by the Novo Nordisk Foundation and the Lundbeck Foundation, and follow-up of mothers and children has been supported by the Danish Medical Research Council, the Lundbeck Foundation, Innovation Fund Denmark, the Nordea Foundation, Aarhus Ideas, a University of Copenhagen strategic grant, and the Danish Council for Independent Research. The study was partially funded by the Health Research Fund of Central Denmark Region, which supported one of the authors. Other authors were supported by the DHB Foundation and the Australian National Health and Medical Research Council. One author is affiliated with Murdoch Children’s Research Institute in Australia, where the Victorian Government’s Operational Infrastructure Support Program supports research.
The authors had no competing interests. Dr. Wheat serves on the editorial advisory board of Family Practice News. Dr. Duff had no relevant financial disclosures.
FROM ARCHIVES OF DISEASE IN CHILDHOOD
Study tests ways to increase autism screening and referrals
To improve autism screening rates, researchers in Utah tried a range of interventions.
They added automatic reminders to the electronic health record (EHR). They started using a shorter, more sensitive screening instrument. And they trained clinicians to perform autism-specific evaluations in a primary care clinic.
The researchers found that these interventions were associated with increased rates of autism screening and referrals.
At the same time, they looked at screening and referral rates at other community clinics in their health care system. These clinics incorporated EHR reminders but not all of the other changes.
“The community clinics had an increase in screening frequency with only automatic reminders,” the researchers reported. At the two intervention clinics, however, screening rates increased more than they did at the community clinics. Referrals did not significantly increase at the community clinics.
Kathleen Campbell, MD, MHSc, a pediatric resident at the University of Utah in Salt Lake City, and colleagues described their research in a study published in Pediatrics.
Three phases
They examined more than 12,000 well-child visits for children aged 16-30 months between July 2017 and June 2019.
In all, 4,155 visits occurred at the 2 intervention clinics, and 8,078 visits occurred at the 27 community clinics in the University of Utah health care system.
From baseline through the interventions, the proportion of visits with screening increased by 51% in the intervention clinics (from 58.6% to 88.8%), and by 21% in the community clinics (from 43.4% to 52.4%). The proportion of referrals increased 1.5-fold in intervention clinics, from 1.3% to 3.3%, the authors said.
The American Academy of Pediatrics (AAP) supports screening for autism in all children starting at age 18 months, but “only 44% of children with autism have had a comprehensive autism evaluation before age 36 months,” Dr. Campbell and colleagues wrote.
In their system, about half of the children were being screened for autism, and 0.5% had autism diagnosed.
In an effort to increase the proportion of visits with screening for autism and the proportion of visits with referrals for autism evaluation, Dr. Campbell and colleagues designed a quality improvement study.
Following a baseline period, they implemented interventions in three phases.
Initially, all clinics used the Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R) for autism screening. For the first phase starting in July 2018, the researchers changed the screening instrument at the two intervention clinics to the Parent’s Observation of Social Interaction (POSI). This instrument “is embedded in a broadband developmental screen, is shorter than the M-CHAT-R, and includes questions about the consistency of the child’s behavior,” the authors said. “The POSI has greater sensitivity than the M-CHAT-R ... and similar, although somewhat lower, specificity.”
In intervention phase 2 starting in November 2018, the researchers “added an automatic reminder for autism screening to the EHR health maintenance screen.” Both the intervention clinics and the community clinics received the automatic reminders.
In intervention phase 3 starting in February 2019, they “added a referral option that clinicians could use for rapid access to autism-specific evaluation ... for children who had a POSI result suggestive of autism and for whom the clinician had sufficient concerns about autism that would indicate the need for referral for autism evaluation,” the researchers said.
“Using an online tutorial, we trained three clinicians in the intervention clinics to administer an observational assessment known as the Screening Tool for Autism in Toddlers (STAT),” which requires a 30-minute visit, they said. “Children who had a STAT result suggestive of autism were referred for expedited autism diagnostic evaluation, which was performed by a multidisciplinary team in our university-based developmental assessment clinic. Children who had a STAT result that did not suggest autism did not receive further autism evaluations unless the clinician felt they still needed further evaluation at the developmental clinic.”
After the switch to POSI, the percentage of visits with a positive screen result increased from 4.7% to 13.5% in the intervention clinics.
Furthermore, referrals were 3.4 times more frequent for visits during phase 3 in the intervention clinics, relative to the baseline period.
Potential to overwhelm
“The change to a more sensitive screening instrument increased the frequency of screening results suggestive of autism and informed our improvement team of the need to implement autism evaluation in primary care to avoid overwhelming our referral system,” Dr. Campbell and coauthors reported.
Future studies may assess whether increased screening and referrals speed the time to diagnosis and treatment and improve long-term functional abilities of children with autism. Some children in the study have received an autism diagnosis, while others have not yet been evaluated.
The use of STAT in primary care may be limited by “the barriers of training providers and purchasing materials,” the authors noted. “However, the time-based billing for lengthier appointments and billing for developmental testing help to cover cost.”
The intervention clinics and community clinics were staffed by pediatric providers, including residents and attendings, said Dr. Campbell.
“The staffing is similar at the community and intervention clinics, with mostly pediatricians and some nurse practitioners,” Dr. Campbell said. “One difference is that there are a few family medicine physicians in the community clinics, but we did not study whether that made a difference in screening. At the beginning of the study the approach to screening was the same.”
From the start, the community clinics were screening for autism and referring for further autism evaluation less often than the intervention clinics. “I don’t know why they were screening less, but they did improve with the automatic reminders,” said Dr. Campbell. “We didn’t examine type of provider or type of practice in this study, but the literature suggests that family physicians do not screen for autism as often as pediatricians.”
Payment and referral challenges
In theory, the approach in the study is a great idea, but it may not be feasible to implement for many private practices, said Herschel Lessin, MD. Dr. Lessin is a senior partner of the Children’s Medical Group in New York.
“We desperately need autism screening in a primary care setting,” Dr. Lessin said. “These authors found that wasn’t being done as recommended by the AAP Bright Futures, which is a problem.”
However, the researchers incorporated the interventions in a health care system with “far more resources than most people in practice would ever have” and substituted a less familiar screening tool.
In addition, the ability to use confirmatory STAT for primary care evaluations may be limited. “Unless you can find pediatricians willing to commit 30 to 45 minutes on one of these evaluations ... few are going to do that,” he said.
“The whole problem is that there are no referrals available or very few referrals available, and that insurance payments so underpay for developmental screening and evaluation that it does not justify the time doing it, so a lot of doctors are unable to do it,” said Dr. Lessin. When a referral is warranted, developmental pediatricians may have 6- to 12-month waiting lists, he said.
“For people in clinical practice, this is not news,” Dr. Lessin said. “We know we should screen for autism. The problem is it’s time consuming. Nobody pays for it. We have no place to send them even when we are suspicious.”
From screening to diagnosis to treatment
“Autism screen approaches vary but with educational efforts on the part of the AAP, CDC, and family organizations the rates for autism screening have dramatically improved,” said Susan L. Hyman, MD, professor of pediatrics at the University of Rochester in New York. “I do not know if screening rates have been impacted by COVID.”
Dr. Hyman and coauthors wrote an AAP clinical report on the identification, evaluation, and management of children with autism spectrum disorder. The report was published in the January 2020 issue of Pediatrics.
After screening and diagnostic testing, patients most importantly need to be able to access “timely and equitable evidence-based intervention,” which should be available, said Dr. Hyman.
Although researchers have proposed training primary care providers in autism diagnostics, “older, more complex patients with co-occurring behavioral health or other developmental disorders may need more specialized diagnostic assessment than could be accomplished in a primary care setting,” Dr. Hyman added.
“However, it is very important to identify children with therapeutic needs as early as possible and move them through the continuum from screening to diagnosis to treatment in a timely fashion. It would be wonderful if symptoms could be addressed without the need for diagnosis in the very youngest children,” Dr. Hyman said. “Early symptoms, even if not autism, are likely to be appropriate for intervention – whether it is speech therapy, attention to food selectivity, sleep problems – things that impact quality of life and potential future symptoms.”
The research was supported by the Utah Stimulating Access to Research in Residency Transition Scholar award, which is funded by the National Institutes of Health.
Dr. Campbell is an inventor on a patent related to screening for autism. The study authors otherwise had no disclosures. Dr. Lessin is on the editorial advisory board for Pediatric News and is on an advisory board for Cognoa, which is developing a medical device to diagnose autism and he is also the co-editor of the AAP's current ADHD Toolkit. Dr. Hyman had no relevant financial disclosures.
*This story was updated on Feb. 11, 2021.
To improve autism screening rates, researchers in Utah tried a range of interventions.
They added automatic reminders to the electronic health record (EHR). They started using a shorter, more sensitive screening instrument. And they trained clinicians to perform autism-specific evaluations in a primary care clinic.
The researchers found that these interventions were associated with increased rates of autism screening and referrals.
At the same time, they looked at screening and referral rates at other community clinics in their health care system. These clinics incorporated EHR reminders but not all of the other changes.
“The community clinics had an increase in screening frequency with only automatic reminders,” the researchers reported. At the two intervention clinics, however, screening rates increased more than they did at the community clinics. Referrals did not significantly increase at the community clinics.
Kathleen Campbell, MD, MHSc, a pediatric resident at the University of Utah in Salt Lake City, and colleagues described their research in a study published in Pediatrics.
Three phases
They examined more than 12,000 well-child visits for children aged 16-30 months between July 2017 and June 2019.
In all, 4,155 visits occurred at the 2 intervention clinics, and 8,078 visits occurred at the 27 community clinics in the University of Utah health care system.
From baseline through the interventions, the proportion of visits with screening increased by 51% in the intervention clinics (from 58.6% to 88.8%), and by 21% in the community clinics (from 43.4% to 52.4%). The proportion of referrals increased 1.5-fold in intervention clinics, from 1.3% to 3.3%, the authors said.
The American Academy of Pediatrics (AAP) supports screening for autism in all children starting at age 18 months, but “only 44% of children with autism have had a comprehensive autism evaluation before age 36 months,” Dr. Campbell and colleagues wrote.
In their system, about half of the children were being screened for autism, and 0.5% had autism diagnosed.
In an effort to increase the proportion of visits with screening for autism and the proportion of visits with referrals for autism evaluation, Dr. Campbell and colleagues designed a quality improvement study.
Following a baseline period, they implemented interventions in three phases.
Initially, all clinics used the Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R) for autism screening. For the first phase starting in July 2018, the researchers changed the screening instrument at the two intervention clinics to the Parent’s Observation of Social Interaction (POSI). This instrument “is embedded in a broadband developmental screen, is shorter than the M-CHAT-R, and includes questions about the consistency of the child’s behavior,” the authors said. “The POSI has greater sensitivity than the M-CHAT-R ... and similar, although somewhat lower, specificity.”
In intervention phase 2 starting in November 2018, the researchers “added an automatic reminder for autism screening to the EHR health maintenance screen.” Both the intervention clinics and the community clinics received the automatic reminders.
In intervention phase 3 starting in February 2019, they “added a referral option that clinicians could use for rapid access to autism-specific evaluation ... for children who had a POSI result suggestive of autism and for whom the clinician had sufficient concerns about autism that would indicate the need for referral for autism evaluation,” the researchers said.
“Using an online tutorial, we trained three clinicians in the intervention clinics to administer an observational assessment known as the Screening Tool for Autism in Toddlers (STAT),” which requires a 30-minute visit, they said. “Children who had a STAT result suggestive of autism were referred for expedited autism diagnostic evaluation, which was performed by a multidisciplinary team in our university-based developmental assessment clinic. Children who had a STAT result that did not suggest autism did not receive further autism evaluations unless the clinician felt they still needed further evaluation at the developmental clinic.”
After the switch to POSI, the percentage of visits with a positive screen result increased from 4.7% to 13.5% in the intervention clinics.
Furthermore, referrals were 3.4 times more frequent for visits during phase 3 in the intervention clinics, relative to the baseline period.
Potential to overwhelm
“The change to a more sensitive screening instrument increased the frequency of screening results suggestive of autism and informed our improvement team of the need to implement autism evaluation in primary care to avoid overwhelming our referral system,” Dr. Campbell and coauthors reported.
Future studies may assess whether increased screening and referrals speed the time to diagnosis and treatment and improve long-term functional abilities of children with autism. Some children in the study have received an autism diagnosis, while others have not yet been evaluated.
The use of STAT in primary care may be limited by “the barriers of training providers and purchasing materials,” the authors noted. “However, the time-based billing for lengthier appointments and billing for developmental testing help to cover cost.”
The intervention clinics and community clinics were staffed by pediatric providers, including residents and attendings, said Dr. Campbell.
“The staffing is similar at the community and intervention clinics, with mostly pediatricians and some nurse practitioners,” Dr. Campbell said. “One difference is that there are a few family medicine physicians in the community clinics, but we did not study whether that made a difference in screening. At the beginning of the study the approach to screening was the same.”
From the start, the community clinics were screening for autism and referring for further autism evaluation less often than the intervention clinics. “I don’t know why they were screening less, but they did improve with the automatic reminders,” said Dr. Campbell. “We didn’t examine type of provider or type of practice in this study, but the literature suggests that family physicians do not screen for autism as often as pediatricians.”
Payment and referral challenges
In theory, the approach in the study is a great idea, but it may not be feasible to implement for many private practices, said Herschel Lessin, MD. Dr. Lessin is a senior partner of the Children’s Medical Group in New York.
“We desperately need autism screening in a primary care setting,” Dr. Lessin said. “These authors found that wasn’t being done as recommended by the AAP Bright Futures, which is a problem.”
However, the researchers incorporated the interventions in a health care system with “far more resources than most people in practice would ever have” and substituted a less familiar screening tool.
In addition, the ability to use confirmatory STAT for primary care evaluations may be limited. “Unless you can find pediatricians willing to commit 30 to 45 minutes on one of these evaluations ... few are going to do that,” he said.
“The whole problem is that there are no referrals available or very few referrals available, and that insurance payments so underpay for developmental screening and evaluation that it does not justify the time doing it, so a lot of doctors are unable to do it,” said Dr. Lessin. When a referral is warranted, developmental pediatricians may have 6- to 12-month waiting lists, he said.
“For people in clinical practice, this is not news,” Dr. Lessin said. “We know we should screen for autism. The problem is it’s time consuming. Nobody pays for it. We have no place to send them even when we are suspicious.”
From screening to diagnosis to treatment
“Autism screen approaches vary but with educational efforts on the part of the AAP, CDC, and family organizations the rates for autism screening have dramatically improved,” said Susan L. Hyman, MD, professor of pediatrics at the University of Rochester in New York. “I do not know if screening rates have been impacted by COVID.”
Dr. Hyman and coauthors wrote an AAP clinical report on the identification, evaluation, and management of children with autism spectrum disorder. The report was published in the January 2020 issue of Pediatrics.
After screening and diagnostic testing, patients most importantly need to be able to access “timely and equitable evidence-based intervention,” which should be available, said Dr. Hyman.
Although researchers have proposed training primary care providers in autism diagnostics, “older, more complex patients with co-occurring behavioral health or other developmental disorders may need more specialized diagnostic assessment than could be accomplished in a primary care setting,” Dr. Hyman added.
“However, it is very important to identify children with therapeutic needs as early as possible and move them through the continuum from screening to diagnosis to treatment in a timely fashion. It would be wonderful if symptoms could be addressed without the need for diagnosis in the very youngest children,” Dr. Hyman said. “Early symptoms, even if not autism, are likely to be appropriate for intervention – whether it is speech therapy, attention to food selectivity, sleep problems – things that impact quality of life and potential future symptoms.”
The research was supported by the Utah Stimulating Access to Research in Residency Transition Scholar award, which is funded by the National Institutes of Health.
Dr. Campbell is an inventor on a patent related to screening for autism. The study authors otherwise had no disclosures. Dr. Lessin is on the editorial advisory board for Pediatric News and is on an advisory board for Cognoa, which is developing a medical device to diagnose autism and he is also the co-editor of the AAP's current ADHD Toolkit. Dr. Hyman had no relevant financial disclosures.
*This story was updated on Feb. 11, 2021.
To improve autism screening rates, researchers in Utah tried a range of interventions.
They added automatic reminders to the electronic health record (EHR). They started using a shorter, more sensitive screening instrument. And they trained clinicians to perform autism-specific evaluations in a primary care clinic.
The researchers found that these interventions were associated with increased rates of autism screening and referrals.
At the same time, they looked at screening and referral rates at other community clinics in their health care system. These clinics incorporated EHR reminders but not all of the other changes.
“The community clinics had an increase in screening frequency with only automatic reminders,” the researchers reported. At the two intervention clinics, however, screening rates increased more than they did at the community clinics. Referrals did not significantly increase at the community clinics.
Kathleen Campbell, MD, MHSc, a pediatric resident at the University of Utah in Salt Lake City, and colleagues described their research in a study published in Pediatrics.
Three phases
They examined more than 12,000 well-child visits for children aged 16-30 months between July 2017 and June 2019.
In all, 4,155 visits occurred at the 2 intervention clinics, and 8,078 visits occurred at the 27 community clinics in the University of Utah health care system.
From baseline through the interventions, the proportion of visits with screening increased by 51% in the intervention clinics (from 58.6% to 88.8%), and by 21% in the community clinics (from 43.4% to 52.4%). The proportion of referrals increased 1.5-fold in intervention clinics, from 1.3% to 3.3%, the authors said.
The American Academy of Pediatrics (AAP) supports screening for autism in all children starting at age 18 months, but “only 44% of children with autism have had a comprehensive autism evaluation before age 36 months,” Dr. Campbell and colleagues wrote.
In their system, about half of the children were being screened for autism, and 0.5% had autism diagnosed.
In an effort to increase the proportion of visits with screening for autism and the proportion of visits with referrals for autism evaluation, Dr. Campbell and colleagues designed a quality improvement study.
Following a baseline period, they implemented interventions in three phases.
Initially, all clinics used the Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R) for autism screening. For the first phase starting in July 2018, the researchers changed the screening instrument at the two intervention clinics to the Parent’s Observation of Social Interaction (POSI). This instrument “is embedded in a broadband developmental screen, is shorter than the M-CHAT-R, and includes questions about the consistency of the child’s behavior,” the authors said. “The POSI has greater sensitivity than the M-CHAT-R ... and similar, although somewhat lower, specificity.”
In intervention phase 2 starting in November 2018, the researchers “added an automatic reminder for autism screening to the EHR health maintenance screen.” Both the intervention clinics and the community clinics received the automatic reminders.
In intervention phase 3 starting in February 2019, they “added a referral option that clinicians could use for rapid access to autism-specific evaluation ... for children who had a POSI result suggestive of autism and for whom the clinician had sufficient concerns about autism that would indicate the need for referral for autism evaluation,” the researchers said.
“Using an online tutorial, we trained three clinicians in the intervention clinics to administer an observational assessment known as the Screening Tool for Autism in Toddlers (STAT),” which requires a 30-minute visit, they said. “Children who had a STAT result suggestive of autism were referred for expedited autism diagnostic evaluation, which was performed by a multidisciplinary team in our university-based developmental assessment clinic. Children who had a STAT result that did not suggest autism did not receive further autism evaluations unless the clinician felt they still needed further evaluation at the developmental clinic.”
After the switch to POSI, the percentage of visits with a positive screen result increased from 4.7% to 13.5% in the intervention clinics.
Furthermore, referrals were 3.4 times more frequent for visits during phase 3 in the intervention clinics, relative to the baseline period.
Potential to overwhelm
“The change to a more sensitive screening instrument increased the frequency of screening results suggestive of autism and informed our improvement team of the need to implement autism evaluation in primary care to avoid overwhelming our referral system,” Dr. Campbell and coauthors reported.
Future studies may assess whether increased screening and referrals speed the time to diagnosis and treatment and improve long-term functional abilities of children with autism. Some children in the study have received an autism diagnosis, while others have not yet been evaluated.
The use of STAT in primary care may be limited by “the barriers of training providers and purchasing materials,” the authors noted. “However, the time-based billing for lengthier appointments and billing for developmental testing help to cover cost.”
The intervention clinics and community clinics were staffed by pediatric providers, including residents and attendings, said Dr. Campbell.
“The staffing is similar at the community and intervention clinics, with mostly pediatricians and some nurse practitioners,” Dr. Campbell said. “One difference is that there are a few family medicine physicians in the community clinics, but we did not study whether that made a difference in screening. At the beginning of the study the approach to screening was the same.”
From the start, the community clinics were screening for autism and referring for further autism evaluation less often than the intervention clinics. “I don’t know why they were screening less, but they did improve with the automatic reminders,” said Dr. Campbell. “We didn’t examine type of provider or type of practice in this study, but the literature suggests that family physicians do not screen for autism as often as pediatricians.”
Payment and referral challenges
In theory, the approach in the study is a great idea, but it may not be feasible to implement for many private practices, said Herschel Lessin, MD. Dr. Lessin is a senior partner of the Children’s Medical Group in New York.
“We desperately need autism screening in a primary care setting,” Dr. Lessin said. “These authors found that wasn’t being done as recommended by the AAP Bright Futures, which is a problem.”
However, the researchers incorporated the interventions in a health care system with “far more resources than most people in practice would ever have” and substituted a less familiar screening tool.
In addition, the ability to use confirmatory STAT for primary care evaluations may be limited. “Unless you can find pediatricians willing to commit 30 to 45 minutes on one of these evaluations ... few are going to do that,” he said.
“The whole problem is that there are no referrals available or very few referrals available, and that insurance payments so underpay for developmental screening and evaluation that it does not justify the time doing it, so a lot of doctors are unable to do it,” said Dr. Lessin. When a referral is warranted, developmental pediatricians may have 6- to 12-month waiting lists, he said.
“For people in clinical practice, this is not news,” Dr. Lessin said. “We know we should screen for autism. The problem is it’s time consuming. Nobody pays for it. We have no place to send them even when we are suspicious.”
From screening to diagnosis to treatment
“Autism screen approaches vary but with educational efforts on the part of the AAP, CDC, and family organizations the rates for autism screening have dramatically improved,” said Susan L. Hyman, MD, professor of pediatrics at the University of Rochester in New York. “I do not know if screening rates have been impacted by COVID.”
Dr. Hyman and coauthors wrote an AAP clinical report on the identification, evaluation, and management of children with autism spectrum disorder. The report was published in the January 2020 issue of Pediatrics.
After screening and diagnostic testing, patients most importantly need to be able to access “timely and equitable evidence-based intervention,” which should be available, said Dr. Hyman.
Although researchers have proposed training primary care providers in autism diagnostics, “older, more complex patients with co-occurring behavioral health or other developmental disorders may need more specialized diagnostic assessment than could be accomplished in a primary care setting,” Dr. Hyman added.
“However, it is very important to identify children with therapeutic needs as early as possible and move them through the continuum from screening to diagnosis to treatment in a timely fashion. It would be wonderful if symptoms could be addressed without the need for diagnosis in the very youngest children,” Dr. Hyman said. “Early symptoms, even if not autism, are likely to be appropriate for intervention – whether it is speech therapy, attention to food selectivity, sleep problems – things that impact quality of life and potential future symptoms.”
The research was supported by the Utah Stimulating Access to Research in Residency Transition Scholar award, which is funded by the National Institutes of Health.
Dr. Campbell is an inventor on a patent related to screening for autism. The study authors otherwise had no disclosures. Dr. Lessin is on the editorial advisory board for Pediatric News and is on an advisory board for Cognoa, which is developing a medical device to diagnose autism and he is also the co-editor of the AAP's current ADHD Toolkit. Dr. Hyman had no relevant financial disclosures.
*This story was updated on Feb. 11, 2021.
FROM PEDIATRICS
Levonorgestrel IUD effective as emergency contraception
A levonorgestrel 52-mg intrauterine device is noninferior to a copper IUD for emergency contraception, according to randomized trial results published online in the New England Journal of Medicine.
Although the trial didn’t directly compare emergency oral contraception to the hormonal IUD, the authors speculated, on the basis of prior findings, that the levonorgestrel IUD is more effective than oral emergency contraceptive pills. In addition, there is no delay in providing ongoing contraception as there is when ulipristal acetate is used for emergency contraception.
Prior research has found that copper IUDs are a highly effective method of emergency contraception, but studies of the use of other IUDs as emergency contraception have been lacking.
To examine whether the levonorgestrel IUD is noninferior to the copper IUD as emergency contraception after unprotected sexual intercourse during the previous 5 days, David K. Turok, MD, MPH, associate professor of obstetrics and gynecology at the University of Utah Health, Salt Lake City, and colleagues conducted a trial at six Planned Parenthood health centers in Utah.
Researchers enrolled patients between August 2016 and December 2019. Trial sites purchased levonorgestrel 52-mg IUDs (Liletta) and copper T380A IUDs (ParaGard) for the study. The companies that distribute the IUDs were not involved in the trial.
Pregnancy rates were 1 of 317 participants (0.3%) among those who received the levonorgestrel IUD, and 0 of 321 (0%) among those who received the copper IUD. The difference between the two arms was well within the prespecified noninferiority margin of 2.5%.
Adverse event rates were generally similar between the two groups, with 5.2% of participants in the levonorgestrel IUD group seeking medical care in the month after IUD placement, compared with 4.9% in the copper IUD group.
A welcome option
The study “benefits women by allowing us to introduce a new option into the method mix of emergency contraception,” commented Wing Kay Fok, MD, a clinical assistant professor of obstetrics and gynecology at Weill Cornell Medicine, New York.
Specialists in family planning had followed preliminary data from this study and were anticipating the final results. Clinicians who are comfortable placing a copper IUD for emergency contraception are likely to be comfortable placing a levonorgestrel 52-mg IUD, given these data, Dr. Fok said.
“This is definitely – from what we can tell – a more effective method than the pill,” she said.
Gabriela Aguilar, MD, MPH, fellow and clinical instructor in the department of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn., said she is reassured by the data and is prepared to offer the 52-mg levonorgestrel IUD as emergency contraception.
The trial is “an important clinical study that has the ability to significantly change clinical practice,” Dr. Aguilar said. She credited the University of Utah and Planned Parenthood for their roles in it.
“Anytime that there are more options, ideally, that means that access is also increased,” Dr. Aguilar said.
Many patients will still prefer oral emergency contraceptive pills, she said. “But for those who are interested in an IUD ... for the immediate and ongoing birth control after that, now they have the two options instead of just the one IUD option.”
One pregnancy
The trial included women aged 18-35 years who requested emergency contraception after unprotected sexual intercourse within the previous 5 days. Other inclusion criteria were that participants had a desire to initiate use of an IUD; a desire to prevent pregnancy for at least 1 year; a negative result on urine pregnancy testing; a history of regular menstrual cycles; and a known date of the last menstrual period. The investigators did not exclude individuals who had unprotected sexual intercourse more than 5 days before IUD placement.
Participants were unaware of their assigned intervention. The nurse practitioners and certified nurse midwives who performed the IUD insertions were aware of the IUD type.
The primary outcome was pregnancy, as determined by a positive result on urine pregnancy testing 1 month after IUD insertion or by a review of survey and health record data.
One pregnancy “occurred in a participant who reported a single episode of unprotected sexual intercourse 48 hours before IUD placement,” the study authors wrote. “Pregnancy dating by an ultrasound examination at 10 weeks was consistent with conception occurring as a result of an emergency contraception failure. The pregnancy ended in a spontaneous abortion at 10 weeks with the IUD still in place.”
“We hope that providers can begin to deliver this method to everyone who wants and needs it and that people considering both emergency contraception and an ongoing method of birth control know that they now have the option of a hormonal IUD in addition to the nonhormonal, copper IUD,” Dr. Turok said in a news release from Planned Parenthood.
The study used a hormonal IUD manufactured by Liletta; Mirena also manufactures a levonorgestrel 52-mg IUD. The results of the study would apply to Mirena’s product too, according to Planned Parenthood.
“There are various IUDs on the market that are at lower doses, and so those IUDs may not demonstrate similar results,” Dr. Aguilar said.
The research was supported by the National Institutes of Health and the University of Utah. Dr. Turok is the director of surgical services for Planned Parenthood Association of Utah; the trial was conducted at PPAU centers, but Dr. Turok does not work at the sites where the study was conducted. Dr. Turok has consulted for Sebela Pharmaceuticals as the principal investigator for two phase 3 studies that assessed novel IUDs. Dr. Turok and one coauthor received grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Fok and Dr. Aguilar disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A levonorgestrel 52-mg intrauterine device is noninferior to a copper IUD for emergency contraception, according to randomized trial results published online in the New England Journal of Medicine.
Although the trial didn’t directly compare emergency oral contraception to the hormonal IUD, the authors speculated, on the basis of prior findings, that the levonorgestrel IUD is more effective than oral emergency contraceptive pills. In addition, there is no delay in providing ongoing contraception as there is when ulipristal acetate is used for emergency contraception.
Prior research has found that copper IUDs are a highly effective method of emergency contraception, but studies of the use of other IUDs as emergency contraception have been lacking.
To examine whether the levonorgestrel IUD is noninferior to the copper IUD as emergency contraception after unprotected sexual intercourse during the previous 5 days, David K. Turok, MD, MPH, associate professor of obstetrics and gynecology at the University of Utah Health, Salt Lake City, and colleagues conducted a trial at six Planned Parenthood health centers in Utah.
Researchers enrolled patients between August 2016 and December 2019. Trial sites purchased levonorgestrel 52-mg IUDs (Liletta) and copper T380A IUDs (ParaGard) for the study. The companies that distribute the IUDs were not involved in the trial.
Pregnancy rates were 1 of 317 participants (0.3%) among those who received the levonorgestrel IUD, and 0 of 321 (0%) among those who received the copper IUD. The difference between the two arms was well within the prespecified noninferiority margin of 2.5%.
Adverse event rates were generally similar between the two groups, with 5.2% of participants in the levonorgestrel IUD group seeking medical care in the month after IUD placement, compared with 4.9% in the copper IUD group.
A welcome option
The study “benefits women by allowing us to introduce a new option into the method mix of emergency contraception,” commented Wing Kay Fok, MD, a clinical assistant professor of obstetrics and gynecology at Weill Cornell Medicine, New York.
Specialists in family planning had followed preliminary data from this study and were anticipating the final results. Clinicians who are comfortable placing a copper IUD for emergency contraception are likely to be comfortable placing a levonorgestrel 52-mg IUD, given these data, Dr. Fok said.
“This is definitely – from what we can tell – a more effective method than the pill,” she said.
Gabriela Aguilar, MD, MPH, fellow and clinical instructor in the department of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn., said she is reassured by the data and is prepared to offer the 52-mg levonorgestrel IUD as emergency contraception.
The trial is “an important clinical study that has the ability to significantly change clinical practice,” Dr. Aguilar said. She credited the University of Utah and Planned Parenthood for their roles in it.
“Anytime that there are more options, ideally, that means that access is also increased,” Dr. Aguilar said.
Many patients will still prefer oral emergency contraceptive pills, she said. “But for those who are interested in an IUD ... for the immediate and ongoing birth control after that, now they have the two options instead of just the one IUD option.”
One pregnancy
The trial included women aged 18-35 years who requested emergency contraception after unprotected sexual intercourse within the previous 5 days. Other inclusion criteria were that participants had a desire to initiate use of an IUD; a desire to prevent pregnancy for at least 1 year; a negative result on urine pregnancy testing; a history of regular menstrual cycles; and a known date of the last menstrual period. The investigators did not exclude individuals who had unprotected sexual intercourse more than 5 days before IUD placement.
Participants were unaware of their assigned intervention. The nurse practitioners and certified nurse midwives who performed the IUD insertions were aware of the IUD type.
The primary outcome was pregnancy, as determined by a positive result on urine pregnancy testing 1 month after IUD insertion or by a review of survey and health record data.
One pregnancy “occurred in a participant who reported a single episode of unprotected sexual intercourse 48 hours before IUD placement,” the study authors wrote. “Pregnancy dating by an ultrasound examination at 10 weeks was consistent with conception occurring as a result of an emergency contraception failure. The pregnancy ended in a spontaneous abortion at 10 weeks with the IUD still in place.”
“We hope that providers can begin to deliver this method to everyone who wants and needs it and that people considering both emergency contraception and an ongoing method of birth control know that they now have the option of a hormonal IUD in addition to the nonhormonal, copper IUD,” Dr. Turok said in a news release from Planned Parenthood.
The study used a hormonal IUD manufactured by Liletta; Mirena also manufactures a levonorgestrel 52-mg IUD. The results of the study would apply to Mirena’s product too, according to Planned Parenthood.
“There are various IUDs on the market that are at lower doses, and so those IUDs may not demonstrate similar results,” Dr. Aguilar said.
The research was supported by the National Institutes of Health and the University of Utah. Dr. Turok is the director of surgical services for Planned Parenthood Association of Utah; the trial was conducted at PPAU centers, but Dr. Turok does not work at the sites where the study was conducted. Dr. Turok has consulted for Sebela Pharmaceuticals as the principal investigator for two phase 3 studies that assessed novel IUDs. Dr. Turok and one coauthor received grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Fok and Dr. Aguilar disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A levonorgestrel 52-mg intrauterine device is noninferior to a copper IUD for emergency contraception, according to randomized trial results published online in the New England Journal of Medicine.
Although the trial didn’t directly compare emergency oral contraception to the hormonal IUD, the authors speculated, on the basis of prior findings, that the levonorgestrel IUD is more effective than oral emergency contraceptive pills. In addition, there is no delay in providing ongoing contraception as there is when ulipristal acetate is used for emergency contraception.
Prior research has found that copper IUDs are a highly effective method of emergency contraception, but studies of the use of other IUDs as emergency contraception have been lacking.
To examine whether the levonorgestrel IUD is noninferior to the copper IUD as emergency contraception after unprotected sexual intercourse during the previous 5 days, David K. Turok, MD, MPH, associate professor of obstetrics and gynecology at the University of Utah Health, Salt Lake City, and colleagues conducted a trial at six Planned Parenthood health centers in Utah.
Researchers enrolled patients between August 2016 and December 2019. Trial sites purchased levonorgestrel 52-mg IUDs (Liletta) and copper T380A IUDs (ParaGard) for the study. The companies that distribute the IUDs were not involved in the trial.
Pregnancy rates were 1 of 317 participants (0.3%) among those who received the levonorgestrel IUD, and 0 of 321 (0%) among those who received the copper IUD. The difference between the two arms was well within the prespecified noninferiority margin of 2.5%.
Adverse event rates were generally similar between the two groups, with 5.2% of participants in the levonorgestrel IUD group seeking medical care in the month after IUD placement, compared with 4.9% in the copper IUD group.
A welcome option
The study “benefits women by allowing us to introduce a new option into the method mix of emergency contraception,” commented Wing Kay Fok, MD, a clinical assistant professor of obstetrics and gynecology at Weill Cornell Medicine, New York.
Specialists in family planning had followed preliminary data from this study and were anticipating the final results. Clinicians who are comfortable placing a copper IUD for emergency contraception are likely to be comfortable placing a levonorgestrel 52-mg IUD, given these data, Dr. Fok said.
“This is definitely – from what we can tell – a more effective method than the pill,” she said.
Gabriela Aguilar, MD, MPH, fellow and clinical instructor in the department of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn., said she is reassured by the data and is prepared to offer the 52-mg levonorgestrel IUD as emergency contraception.
The trial is “an important clinical study that has the ability to significantly change clinical practice,” Dr. Aguilar said. She credited the University of Utah and Planned Parenthood for their roles in it.
“Anytime that there are more options, ideally, that means that access is also increased,” Dr. Aguilar said.
Many patients will still prefer oral emergency contraceptive pills, she said. “But for those who are interested in an IUD ... for the immediate and ongoing birth control after that, now they have the two options instead of just the one IUD option.”
One pregnancy
The trial included women aged 18-35 years who requested emergency contraception after unprotected sexual intercourse within the previous 5 days. Other inclusion criteria were that participants had a desire to initiate use of an IUD; a desire to prevent pregnancy for at least 1 year; a negative result on urine pregnancy testing; a history of regular menstrual cycles; and a known date of the last menstrual period. The investigators did not exclude individuals who had unprotected sexual intercourse more than 5 days before IUD placement.
Participants were unaware of their assigned intervention. The nurse practitioners and certified nurse midwives who performed the IUD insertions were aware of the IUD type.
The primary outcome was pregnancy, as determined by a positive result on urine pregnancy testing 1 month after IUD insertion or by a review of survey and health record data.
One pregnancy “occurred in a participant who reported a single episode of unprotected sexual intercourse 48 hours before IUD placement,” the study authors wrote. “Pregnancy dating by an ultrasound examination at 10 weeks was consistent with conception occurring as a result of an emergency contraception failure. The pregnancy ended in a spontaneous abortion at 10 weeks with the IUD still in place.”
“We hope that providers can begin to deliver this method to everyone who wants and needs it and that people considering both emergency contraception and an ongoing method of birth control know that they now have the option of a hormonal IUD in addition to the nonhormonal, copper IUD,” Dr. Turok said in a news release from Planned Parenthood.
The study used a hormonal IUD manufactured by Liletta; Mirena also manufactures a levonorgestrel 52-mg IUD. The results of the study would apply to Mirena’s product too, according to Planned Parenthood.
“There are various IUDs on the market that are at lower doses, and so those IUDs may not demonstrate similar results,” Dr. Aguilar said.
The research was supported by the National Institutes of Health and the University of Utah. Dr. Turok is the director of surgical services for Planned Parenthood Association of Utah; the trial was conducted at PPAU centers, but Dr. Turok does not work at the sites where the study was conducted. Dr. Turok has consulted for Sebela Pharmaceuticals as the principal investigator for two phase 3 studies that assessed novel IUDs. Dr. Turok and one coauthor received grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Fok and Dr. Aguilar disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Oral contraceptives may reduce ovarian and endometrial cancer risk 35 years after discontinuation
At the same time, oral contraceptive use is associated with a short-term increased risk of breast cancer after discontinuation, although the lifetime risk of breast cancer is not significantly different, the researchers found.
The absolute risk of breast cancer after discontinuation is “extremely small” and should be a limited factor when deciding whether to start oral contraceptive pills (OCPs), a doctor said.
The study was conducted by Torgny Karlsson, PhD, a researcher in the department of immunology, genetics, and pathology at Uppsala (Sweden) University, and colleagues and published online in Cancer Research.
Reinforcing and extending knowledge
“These findings are generally consistent with what is known, but extend that knowledge, most notably by the longer-term follow-up for the cohort,” commented Nancy L. Keating, MD, MPH, professor of health care policy and medicine at Harvard Medical School and a physician at Brigham and Women’s Hospital, both in Boston. “Other studies have also shown that OCPs lower risk of ovarian and endometrial cancer. This study suggests that this protective benefit extends up to 30-35 years after discontinuing OCPs.”
The results “reinforce the message to patients of the protective effect of OCPs on risk of ovarian and endometrial cancer,” Dr. Keating said. “Women concerned about these cancers can be reassured that this protective effect appears to persist for decades after discontinuing use.”
Prior studies have indicated that oral contraceptives may be associated with an increased risk of breast cancer.
In terms of breast cancer risk, the study “again extends follow-up and shows that risk of breast cancer was higher for current and ever users through age 50,” although the lifetime risk was not elevated, Dr. Keating said.
“The counseling regarding the effect on breast cancer is more complex,” she said. “I tell women about the very small increased risk of breast cancer during and immediately after use. Because cancer is very rare among women at the ages when OCPs are typically prescribed, the absolute risk increase is extremely small. This paper adds reassurance that this small increase in risk does not persist.”
For certain patients, the association may be more relevant.
“For most women, this risk is so small that it should be a limited factor in their decision to start OCPs,” Dr. Keating said. “However, for women with a substantially higher risk of breast cancer, or a family history of breast cancer at a young age, the small increased risk of breast cancer during and immediately after OCP use is more relevant, and counseling should include carefully weighing the benefits and harms of OCPs with other forms of contraception (and no contraception).”
Although the protective effects of oral contraceptives on ovarian and endometrial cancer were well known, the study describes long-term outcomes that can further inform patient counseling, said Samuel S. Badalian, MD, PhD, chief of the department of obstetrics and gynecology at Bassett Medical Center in Cooperstown, N.Y., and clinical professor of obstetrics and gynecology at the State University of New York, Syracuse.
“Women with individual or family risk factors of ovarian or endometrial cancers will need to know about the protective effects of oral contraceptives and long-term benefits related with their use (30-35 years after discontinuation),” Dr. Badalian said. “Women with family history of breast cancer need to know that lifetime risk of breast cancer might not differ between ever and never users, even if there is an increased short-term risk.”
Data from the U.K. Biobank
To examine the time-dependent effects between long-term oral contraceptive use and cancer risk, the researchers examined data from 256,661 women from the U.K. Biobank who were born between 1939 and 1970. The researchers identified cancer diagnoses using information from national registers and self-reported data until March 2019.
Of the women included in the study, 82% had used or still were using oral contraceptives, whereas 18% had never used oral contraceptives. Overall, ever users were younger, more frequently smokers, and had a lower body mass index, compared with never users. Most women started using oral contraceptives between 1969 and 1978. Last use of oral contraceptives occurred on average 10.7 years after starting.
The researchers adjusted for covariates and used logistic regression analyses to measure the cumulative risk of cancer. They used Cox regression analysis to examine instantaneous risk, measured using hazard ratios.
In all, there were 17,739 cases of breast cancer (6.9%), 1,966 cases of ovarian cancer (0.76%), and 2,462 cases of endometrial cancer (0.96%).
Among ever users, the likelihood of ovarian cancer (OR, 0.72) and endometrial cancer (OR, 0.68) was lower, compared with never users. “However, we did not see a significant association between oral contraceptive use and breast cancer” for the study period as a whole, the researchers reported. When the researchers limited follow-up to age 50 years, however, the odds ratio for breast cancer was increased (OR, 1.09).
“Surprisingly, we only found a small increased risk of breast cancer among oral contraceptive users, and the increased risk disappeared within a few years after discontinuation,” Åsa Johansson, PhD, a researcher in the department of immunology, genetics, and pathology at Uppsala University and one of the study authors, said in a news release. “Our results suggest that the lifetime risk of breast cancer might not differ between ever and never users, even if there is an increased short-term risk.”
Oral contraceptives today typically use lower doses of estrogen and other types of progesterone, compared with formulas commonly used when participants in the study started taking them, so the results may not directly apply to patients currently taking oral contraceptives, the researchers noted.
The study was supported by the Swedish Research Council, the Swedish Cancer Society, and the Kjell and Märta Beijers, the Marcus Borgström, the Åke Wiberg, and the A and M Rudbergs foundations. The authors, Dr. Keating, and Dr. Badalian had no conflicts of interest.
At the same time, oral contraceptive use is associated with a short-term increased risk of breast cancer after discontinuation, although the lifetime risk of breast cancer is not significantly different, the researchers found.
The absolute risk of breast cancer after discontinuation is “extremely small” and should be a limited factor when deciding whether to start oral contraceptive pills (OCPs), a doctor said.
The study was conducted by Torgny Karlsson, PhD, a researcher in the department of immunology, genetics, and pathology at Uppsala (Sweden) University, and colleagues and published online in Cancer Research.
Reinforcing and extending knowledge
“These findings are generally consistent with what is known, but extend that knowledge, most notably by the longer-term follow-up for the cohort,” commented Nancy L. Keating, MD, MPH, professor of health care policy and medicine at Harvard Medical School and a physician at Brigham and Women’s Hospital, both in Boston. “Other studies have also shown that OCPs lower risk of ovarian and endometrial cancer. This study suggests that this protective benefit extends up to 30-35 years after discontinuing OCPs.”
The results “reinforce the message to patients of the protective effect of OCPs on risk of ovarian and endometrial cancer,” Dr. Keating said. “Women concerned about these cancers can be reassured that this protective effect appears to persist for decades after discontinuing use.”
Prior studies have indicated that oral contraceptives may be associated with an increased risk of breast cancer.
In terms of breast cancer risk, the study “again extends follow-up and shows that risk of breast cancer was higher for current and ever users through age 50,” although the lifetime risk was not elevated, Dr. Keating said.
“The counseling regarding the effect on breast cancer is more complex,” she said. “I tell women about the very small increased risk of breast cancer during and immediately after use. Because cancer is very rare among women at the ages when OCPs are typically prescribed, the absolute risk increase is extremely small. This paper adds reassurance that this small increase in risk does not persist.”
For certain patients, the association may be more relevant.
“For most women, this risk is so small that it should be a limited factor in their decision to start OCPs,” Dr. Keating said. “However, for women with a substantially higher risk of breast cancer, or a family history of breast cancer at a young age, the small increased risk of breast cancer during and immediately after OCP use is more relevant, and counseling should include carefully weighing the benefits and harms of OCPs with other forms of contraception (and no contraception).”
Although the protective effects of oral contraceptives on ovarian and endometrial cancer were well known, the study describes long-term outcomes that can further inform patient counseling, said Samuel S. Badalian, MD, PhD, chief of the department of obstetrics and gynecology at Bassett Medical Center in Cooperstown, N.Y., and clinical professor of obstetrics and gynecology at the State University of New York, Syracuse.
“Women with individual or family risk factors of ovarian or endometrial cancers will need to know about the protective effects of oral contraceptives and long-term benefits related with their use (30-35 years after discontinuation),” Dr. Badalian said. “Women with family history of breast cancer need to know that lifetime risk of breast cancer might not differ between ever and never users, even if there is an increased short-term risk.”
Data from the U.K. Biobank
To examine the time-dependent effects between long-term oral contraceptive use and cancer risk, the researchers examined data from 256,661 women from the U.K. Biobank who were born between 1939 and 1970. The researchers identified cancer diagnoses using information from national registers and self-reported data until March 2019.
Of the women included in the study, 82% had used or still were using oral contraceptives, whereas 18% had never used oral contraceptives. Overall, ever users were younger, more frequently smokers, and had a lower body mass index, compared with never users. Most women started using oral contraceptives between 1969 and 1978. Last use of oral contraceptives occurred on average 10.7 years after starting.
The researchers adjusted for covariates and used logistic regression analyses to measure the cumulative risk of cancer. They used Cox regression analysis to examine instantaneous risk, measured using hazard ratios.
In all, there were 17,739 cases of breast cancer (6.9%), 1,966 cases of ovarian cancer (0.76%), and 2,462 cases of endometrial cancer (0.96%).
Among ever users, the likelihood of ovarian cancer (OR, 0.72) and endometrial cancer (OR, 0.68) was lower, compared with never users. “However, we did not see a significant association between oral contraceptive use and breast cancer” for the study period as a whole, the researchers reported. When the researchers limited follow-up to age 50 years, however, the odds ratio for breast cancer was increased (OR, 1.09).
“Surprisingly, we only found a small increased risk of breast cancer among oral contraceptive users, and the increased risk disappeared within a few years after discontinuation,” Åsa Johansson, PhD, a researcher in the department of immunology, genetics, and pathology at Uppsala University and one of the study authors, said in a news release. “Our results suggest that the lifetime risk of breast cancer might not differ between ever and never users, even if there is an increased short-term risk.”
Oral contraceptives today typically use lower doses of estrogen and other types of progesterone, compared with formulas commonly used when participants in the study started taking them, so the results may not directly apply to patients currently taking oral contraceptives, the researchers noted.
The study was supported by the Swedish Research Council, the Swedish Cancer Society, and the Kjell and Märta Beijers, the Marcus Borgström, the Åke Wiberg, and the A and M Rudbergs foundations. The authors, Dr. Keating, and Dr. Badalian had no conflicts of interest.
At the same time, oral contraceptive use is associated with a short-term increased risk of breast cancer after discontinuation, although the lifetime risk of breast cancer is not significantly different, the researchers found.
The absolute risk of breast cancer after discontinuation is “extremely small” and should be a limited factor when deciding whether to start oral contraceptive pills (OCPs), a doctor said.
The study was conducted by Torgny Karlsson, PhD, a researcher in the department of immunology, genetics, and pathology at Uppsala (Sweden) University, and colleagues and published online in Cancer Research.
Reinforcing and extending knowledge
“These findings are generally consistent with what is known, but extend that knowledge, most notably by the longer-term follow-up for the cohort,” commented Nancy L. Keating, MD, MPH, professor of health care policy and medicine at Harvard Medical School and a physician at Brigham and Women’s Hospital, both in Boston. “Other studies have also shown that OCPs lower risk of ovarian and endometrial cancer. This study suggests that this protective benefit extends up to 30-35 years after discontinuing OCPs.”
The results “reinforce the message to patients of the protective effect of OCPs on risk of ovarian and endometrial cancer,” Dr. Keating said. “Women concerned about these cancers can be reassured that this protective effect appears to persist for decades after discontinuing use.”
Prior studies have indicated that oral contraceptives may be associated with an increased risk of breast cancer.
In terms of breast cancer risk, the study “again extends follow-up and shows that risk of breast cancer was higher for current and ever users through age 50,” although the lifetime risk was not elevated, Dr. Keating said.
“The counseling regarding the effect on breast cancer is more complex,” she said. “I tell women about the very small increased risk of breast cancer during and immediately after use. Because cancer is very rare among women at the ages when OCPs are typically prescribed, the absolute risk increase is extremely small. This paper adds reassurance that this small increase in risk does not persist.”
For certain patients, the association may be more relevant.
“For most women, this risk is so small that it should be a limited factor in their decision to start OCPs,” Dr. Keating said. “However, for women with a substantially higher risk of breast cancer, or a family history of breast cancer at a young age, the small increased risk of breast cancer during and immediately after OCP use is more relevant, and counseling should include carefully weighing the benefits and harms of OCPs with other forms of contraception (and no contraception).”
Although the protective effects of oral contraceptives on ovarian and endometrial cancer were well known, the study describes long-term outcomes that can further inform patient counseling, said Samuel S. Badalian, MD, PhD, chief of the department of obstetrics and gynecology at Bassett Medical Center in Cooperstown, N.Y., and clinical professor of obstetrics and gynecology at the State University of New York, Syracuse.
“Women with individual or family risk factors of ovarian or endometrial cancers will need to know about the protective effects of oral contraceptives and long-term benefits related with their use (30-35 years after discontinuation),” Dr. Badalian said. “Women with family history of breast cancer need to know that lifetime risk of breast cancer might not differ between ever and never users, even if there is an increased short-term risk.”
Data from the U.K. Biobank
To examine the time-dependent effects between long-term oral contraceptive use and cancer risk, the researchers examined data from 256,661 women from the U.K. Biobank who were born between 1939 and 1970. The researchers identified cancer diagnoses using information from national registers and self-reported data until March 2019.
Of the women included in the study, 82% had used or still were using oral contraceptives, whereas 18% had never used oral contraceptives. Overall, ever users were younger, more frequently smokers, and had a lower body mass index, compared with never users. Most women started using oral contraceptives between 1969 and 1978. Last use of oral contraceptives occurred on average 10.7 years after starting.
The researchers adjusted for covariates and used logistic regression analyses to measure the cumulative risk of cancer. They used Cox regression analysis to examine instantaneous risk, measured using hazard ratios.
In all, there were 17,739 cases of breast cancer (6.9%), 1,966 cases of ovarian cancer (0.76%), and 2,462 cases of endometrial cancer (0.96%).
Among ever users, the likelihood of ovarian cancer (OR, 0.72) and endometrial cancer (OR, 0.68) was lower, compared with never users. “However, we did not see a significant association between oral contraceptive use and breast cancer” for the study period as a whole, the researchers reported. When the researchers limited follow-up to age 50 years, however, the odds ratio for breast cancer was increased (OR, 1.09).
“Surprisingly, we only found a small increased risk of breast cancer among oral contraceptive users, and the increased risk disappeared within a few years after discontinuation,” Åsa Johansson, PhD, a researcher in the department of immunology, genetics, and pathology at Uppsala University and one of the study authors, said in a news release. “Our results suggest that the lifetime risk of breast cancer might not differ between ever and never users, even if there is an increased short-term risk.”
Oral contraceptives today typically use lower doses of estrogen and other types of progesterone, compared with formulas commonly used when participants in the study started taking them, so the results may not directly apply to patients currently taking oral contraceptives, the researchers noted.
The study was supported by the Swedish Research Council, the Swedish Cancer Society, and the Kjell and Märta Beijers, the Marcus Borgström, the Åke Wiberg, and the A and M Rudbergs foundations. The authors, Dr. Keating, and Dr. Badalian had no conflicts of interest.
FROM CANCER RESEARCH