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Delayed cord clamping didn’t drop maternal hemoglobin in term cesarean deliveries
LAS VEGAS – according to a recent study.
The change in maternal hemoglobin from preoperative level to postoperative day 1, the study’s primary outcome measure, was not significantly different whether the umbilical cord was clamped within 15 seconds of delivery or clamping was delayed for 1 minute.
For the 56 women who received immediate cord clamping, hemoglobin dropped a mean 1.78 g/dL; for the 57 women who received delayed cord clamping, the drop was 1.85 g/dL (P = .69). Mean estimated blood loss for the delayed clamping group was numerically higher at 884 mL, compared with 830 mL for the immediate clamping group, but this was not a statistically significant difference (P = .13)
However, the practice did result in significantly greater neonatal hemoglobin measured at 24-72 hours post delivery. Hemoglobin data were available for 90 infants, or about 80% of participants. For the 44 infants in the immediate clamping group, mean hemoglobin was 16.4 g/dL; for the delayed clamping group, the figure was 18.1 g/dL (P less than .01).
Although delayed cord clamping has clear benefits to the neonate, whether the practice adversely affects women undergoing cesarean was not clear, said Stephanie Purisch, MD, who discussed the findings of the two-site, randomized, clinical trial during a fellows research session at the meeting sponsored by the Society for Maternal-Fetal Medicine.
“Maternal outcomes have not been a focus of research” in the cord clamping literature, said Dr. Purisch, from Columbia University, New York. A 2013 Cochrane review found that delayed cord clamping did not change postpartum hemoglobin levels or increase blood loss or the need for transfusion. However, she said, the review included only healthy women who expected a vaginal delivery, so cesarean deliveries were undersampled in the data.
Of the 3,911 deliveries included in all prior randomized, controlled trials of delayed cord clamping, just 87, or 2.2%, were cesarean deliveries, she said. In cesarean deliveries, mean blood loss is double that of vaginal deliveries. Delayed clamping could further increase bleeding because the hysterotomy closure is delayed, said Dr. Purisch, so the question of safety in cesarean deliveries is clinically important.
Faced with this knowledge gap, Dr. Purisch and her colleagues constructed a prospective, randomized, controlled trial of delayed cord clamping in cesarean delivery at term, with the hypothesis that maternal blood loss would be increased by the practice.
Patients were eligible if they had singleton gestations with cesarean deliveries scheduled at 37 weeks’ gestation or more. Patients with known placentation problems, significant maternal or known fetal anemia, maternal bleeding disorders, and preeclampsia were excluded. The study also did not include pregnancies with known fetal anomalies or intrauterine growth retardation, or those in which cord blood banking was planned or the mother would refuse blood products.
In an intention-to-treat analysis, Dr. Purisch and her colleagues randomly assigned participants 1:1 to immediate cord clamping, defined as clamping the cord by 15 seconds after delivery, or delayed cord clamping, in which the umbilical cord was clamped 1 minute after delivery.
Oxytocin was routinely administered to each group on delivery, and there was no umbilical cord milking in either group. For the delayed-clamping group, the infant was kept at the level of the placenta and tended by the pediatric team during the minute before clamping. Dr. Purisch explained that cord clamping was performed before 60 seconds in the intervention group if needed for neonatal resuscitation.
Participants were similar in the two study arms, with a median gestational age of 39.1 weeks at delivery. Most women (60%-64%) had one prior cesarean delivery, with about a quarter having two or more prior cesarean deliveries. Preoperative maternal hemoglobin was 11.6-12.0 g/dL. About 41% of participants were Hispanic, and the median prepregnancy body mass index for participants was about 27 kg/m2.
Looking at secondary outcome measures, there was no difference in rates of postpartum hemorrhage or uterotonic administration between the two groups (P = .99 for both). Hemoglobin levels at postoperative day 1 were numerically higher for the delayed cord clamping group, but the difference wasn’t significant (10.2 vs. 9.8 g/dL; P = .18). Just two women, both in the immediate cord clamping group, required blood transfusions.
Additional neonatal secondary outcome measures included birth weight, Apgar scores at 1 and 5 minutes, the need for phototherapy for jaundice, and umbilical cord artery pH. There were no between-group differences except that umbilical cord artery pH was slightly lower in the delayed group (7.2 vs. 7.3; P = .04).
“Delayed cord clamping is not associated with increased maternal blood loss … but it does achieve higher neonatal hemoglobin levels at 24-72 hours of life,” said Dr. Purisch. “These results provide support for the application of current [American College of Obstetricians and Gynecologists] recommendations to women planned for cesarean delivery.”
The study was funded by the Columbia Maternal-Fetal Medicine Fellow Research Fund. Dr. Purisch reported no conflicts of interest.
SOURCE: Purisch, S. et al. Am J Obstet Gynecol. 2019 Jan;220(1):S37-38, Abstract 47.
LAS VEGAS – according to a recent study.
The change in maternal hemoglobin from preoperative level to postoperative day 1, the study’s primary outcome measure, was not significantly different whether the umbilical cord was clamped within 15 seconds of delivery or clamping was delayed for 1 minute.
For the 56 women who received immediate cord clamping, hemoglobin dropped a mean 1.78 g/dL; for the 57 women who received delayed cord clamping, the drop was 1.85 g/dL (P = .69). Mean estimated blood loss for the delayed clamping group was numerically higher at 884 mL, compared with 830 mL for the immediate clamping group, but this was not a statistically significant difference (P = .13)
However, the practice did result in significantly greater neonatal hemoglobin measured at 24-72 hours post delivery. Hemoglobin data were available for 90 infants, or about 80% of participants. For the 44 infants in the immediate clamping group, mean hemoglobin was 16.4 g/dL; for the delayed clamping group, the figure was 18.1 g/dL (P less than .01).
Although delayed cord clamping has clear benefits to the neonate, whether the practice adversely affects women undergoing cesarean was not clear, said Stephanie Purisch, MD, who discussed the findings of the two-site, randomized, clinical trial during a fellows research session at the meeting sponsored by the Society for Maternal-Fetal Medicine.
“Maternal outcomes have not been a focus of research” in the cord clamping literature, said Dr. Purisch, from Columbia University, New York. A 2013 Cochrane review found that delayed cord clamping did not change postpartum hemoglobin levels or increase blood loss or the need for transfusion. However, she said, the review included only healthy women who expected a vaginal delivery, so cesarean deliveries were undersampled in the data.
Of the 3,911 deliveries included in all prior randomized, controlled trials of delayed cord clamping, just 87, or 2.2%, were cesarean deliveries, she said. In cesarean deliveries, mean blood loss is double that of vaginal deliveries. Delayed clamping could further increase bleeding because the hysterotomy closure is delayed, said Dr. Purisch, so the question of safety in cesarean deliveries is clinically important.
Faced with this knowledge gap, Dr. Purisch and her colleagues constructed a prospective, randomized, controlled trial of delayed cord clamping in cesarean delivery at term, with the hypothesis that maternal blood loss would be increased by the practice.
Patients were eligible if they had singleton gestations with cesarean deliveries scheduled at 37 weeks’ gestation or more. Patients with known placentation problems, significant maternal or known fetal anemia, maternal bleeding disorders, and preeclampsia were excluded. The study also did not include pregnancies with known fetal anomalies or intrauterine growth retardation, or those in which cord blood banking was planned or the mother would refuse blood products.
In an intention-to-treat analysis, Dr. Purisch and her colleagues randomly assigned participants 1:1 to immediate cord clamping, defined as clamping the cord by 15 seconds after delivery, or delayed cord clamping, in which the umbilical cord was clamped 1 minute after delivery.
Oxytocin was routinely administered to each group on delivery, and there was no umbilical cord milking in either group. For the delayed-clamping group, the infant was kept at the level of the placenta and tended by the pediatric team during the minute before clamping. Dr. Purisch explained that cord clamping was performed before 60 seconds in the intervention group if needed for neonatal resuscitation.
Participants were similar in the two study arms, with a median gestational age of 39.1 weeks at delivery. Most women (60%-64%) had one prior cesarean delivery, with about a quarter having two or more prior cesarean deliveries. Preoperative maternal hemoglobin was 11.6-12.0 g/dL. About 41% of participants were Hispanic, and the median prepregnancy body mass index for participants was about 27 kg/m2.
Looking at secondary outcome measures, there was no difference in rates of postpartum hemorrhage or uterotonic administration between the two groups (P = .99 for both). Hemoglobin levels at postoperative day 1 were numerically higher for the delayed cord clamping group, but the difference wasn’t significant (10.2 vs. 9.8 g/dL; P = .18). Just two women, both in the immediate cord clamping group, required blood transfusions.
Additional neonatal secondary outcome measures included birth weight, Apgar scores at 1 and 5 minutes, the need for phototherapy for jaundice, and umbilical cord artery pH. There were no between-group differences except that umbilical cord artery pH was slightly lower in the delayed group (7.2 vs. 7.3; P = .04).
“Delayed cord clamping is not associated with increased maternal blood loss … but it does achieve higher neonatal hemoglobin levels at 24-72 hours of life,” said Dr. Purisch. “These results provide support for the application of current [American College of Obstetricians and Gynecologists] recommendations to women planned for cesarean delivery.”
The study was funded by the Columbia Maternal-Fetal Medicine Fellow Research Fund. Dr. Purisch reported no conflicts of interest.
SOURCE: Purisch, S. et al. Am J Obstet Gynecol. 2019 Jan;220(1):S37-38, Abstract 47.
LAS VEGAS – according to a recent study.
The change in maternal hemoglobin from preoperative level to postoperative day 1, the study’s primary outcome measure, was not significantly different whether the umbilical cord was clamped within 15 seconds of delivery or clamping was delayed for 1 minute.
For the 56 women who received immediate cord clamping, hemoglobin dropped a mean 1.78 g/dL; for the 57 women who received delayed cord clamping, the drop was 1.85 g/dL (P = .69). Mean estimated blood loss for the delayed clamping group was numerically higher at 884 mL, compared with 830 mL for the immediate clamping group, but this was not a statistically significant difference (P = .13)
However, the practice did result in significantly greater neonatal hemoglobin measured at 24-72 hours post delivery. Hemoglobin data were available for 90 infants, or about 80% of participants. For the 44 infants in the immediate clamping group, mean hemoglobin was 16.4 g/dL; for the delayed clamping group, the figure was 18.1 g/dL (P less than .01).
Although delayed cord clamping has clear benefits to the neonate, whether the practice adversely affects women undergoing cesarean was not clear, said Stephanie Purisch, MD, who discussed the findings of the two-site, randomized, clinical trial during a fellows research session at the meeting sponsored by the Society for Maternal-Fetal Medicine.
“Maternal outcomes have not been a focus of research” in the cord clamping literature, said Dr. Purisch, from Columbia University, New York. A 2013 Cochrane review found that delayed cord clamping did not change postpartum hemoglobin levels or increase blood loss or the need for transfusion. However, she said, the review included only healthy women who expected a vaginal delivery, so cesarean deliveries were undersampled in the data.
Of the 3,911 deliveries included in all prior randomized, controlled trials of delayed cord clamping, just 87, or 2.2%, were cesarean deliveries, she said. In cesarean deliveries, mean blood loss is double that of vaginal deliveries. Delayed clamping could further increase bleeding because the hysterotomy closure is delayed, said Dr. Purisch, so the question of safety in cesarean deliveries is clinically important.
Faced with this knowledge gap, Dr. Purisch and her colleagues constructed a prospective, randomized, controlled trial of delayed cord clamping in cesarean delivery at term, with the hypothesis that maternal blood loss would be increased by the practice.
Patients were eligible if they had singleton gestations with cesarean deliveries scheduled at 37 weeks’ gestation or more. Patients with known placentation problems, significant maternal or known fetal anemia, maternal bleeding disorders, and preeclampsia were excluded. The study also did not include pregnancies with known fetal anomalies or intrauterine growth retardation, or those in which cord blood banking was planned or the mother would refuse blood products.
In an intention-to-treat analysis, Dr. Purisch and her colleagues randomly assigned participants 1:1 to immediate cord clamping, defined as clamping the cord by 15 seconds after delivery, or delayed cord clamping, in which the umbilical cord was clamped 1 minute after delivery.
Oxytocin was routinely administered to each group on delivery, and there was no umbilical cord milking in either group. For the delayed-clamping group, the infant was kept at the level of the placenta and tended by the pediatric team during the minute before clamping. Dr. Purisch explained that cord clamping was performed before 60 seconds in the intervention group if needed for neonatal resuscitation.
Participants were similar in the two study arms, with a median gestational age of 39.1 weeks at delivery. Most women (60%-64%) had one prior cesarean delivery, with about a quarter having two or more prior cesarean deliveries. Preoperative maternal hemoglobin was 11.6-12.0 g/dL. About 41% of participants were Hispanic, and the median prepregnancy body mass index for participants was about 27 kg/m2.
Looking at secondary outcome measures, there was no difference in rates of postpartum hemorrhage or uterotonic administration between the two groups (P = .99 for both). Hemoglobin levels at postoperative day 1 were numerically higher for the delayed cord clamping group, but the difference wasn’t significant (10.2 vs. 9.8 g/dL; P = .18). Just two women, both in the immediate cord clamping group, required blood transfusions.
Additional neonatal secondary outcome measures included birth weight, Apgar scores at 1 and 5 minutes, the need for phototherapy for jaundice, and umbilical cord artery pH. There were no between-group differences except that umbilical cord artery pH was slightly lower in the delayed group (7.2 vs. 7.3; P = .04).
“Delayed cord clamping is not associated with increased maternal blood loss … but it does achieve higher neonatal hemoglobin levels at 24-72 hours of life,” said Dr. Purisch. “These results provide support for the application of current [American College of Obstetricians and Gynecologists] recommendations to women planned for cesarean delivery.”
The study was funded by the Columbia Maternal-Fetal Medicine Fellow Research Fund. Dr. Purisch reported no conflicts of interest.
SOURCE: Purisch, S. et al. Am J Obstet Gynecol. 2019 Jan;220(1):S37-38, Abstract 47.
REPORTING FROM THE PREGNANCY MEETING
Dental device borrowed from sports world no help in pushing
LAS VEGAS –
In a randomized, controlled trial of 346 nulliparous women, the device, adapted from a design used in athletics, made no difference in the duration of the second stage of labor overall or in passive descent or active pushing time. The findings were presented on behalf of first author Eric Bergh, MD, by Patricia Rekawek, MD, at a fellows abstract session at the meeting sponsored by the Society for Maternal-Fetal Medicine. Dr. Rekawek and Dr. Bergh are maternal-fetal medicine fellows at the Icahn School of Medicine at Mount Sinai, New York.
The dental support device (DSD) was actually used by 128 (74%) of the patients who were randomized to DSD usage. Of these patients, two thirds (n = 85) used the device for all second stage contractions. About one quarter (27%; n = 35) used it less than half the time, and a small minority (6%; n = 8) used it more than half the time but not for all pushing, noted Dr. Rekawek.
Most women (61%) who used the device agreed or strongly agreed that it was helpful. Most also found it comfortable (67%), and would use it again in a future delivery (61%). Having a custom-fit DSD, or spending more time practicing before labor, might help with efficacy in shortening the second stage of labor and merits study, the investigators said.
Reducing time spent in the second stage of labor could benefit both mother and neonate because “a prolonged second stage of labor is associated with multiple maternal and neonatal complications,” including increased risk for chorioamnionitis, neonatal sepsis, low umbilical artery pH, shoulder dystocia, and third- and fourth-degree lacerations, said Dr. Rekawek.
In athletics, a DSD “raises the vertical dimension of the deep bite and increases the size of the oropharynx” by introducing a 3-mm bite plate between the upper and lower rear molars. The DSD mouthpiece integrates the bite plates with a retainer-like band that wraps around the front incisors; speaking and drinking are possible with the DSD in place, said Dr. Rekawek.
She added that athletic evidence suggests that the DSD can lead to increased oxygenation, less head and neck tension, less muscle fatigue, and improved exercise capacity in some sports.
If these benefits translated to the maternal Valsalva maneuver during the second stage of labor, the increased isometric endurance could increase uterine pressure and optimize the expulsive effect of pushing, explained Dr. Rekawek. However, mixed results were seen in previous work that had women using a DSD during the second stage of labor.
The current study was powered to detect a difference of 20% in the duration of the second stage of labor for nulliparous women who were randomized either to use or not use a DSD while pushing. Women and their caregivers learned their random allocation by opening a sealed envelope at the beginning of the second stage of labor.
The study included nulliparous women who were carrying a singleton pregnancy of at least 37 weeks’ gestation and without known fetal anomalies. Enrollment occurred before the second stage of labor, and 173 women participated in each arm of the study.
For those who were assigned to use the DSD, the second stage of labor lasted a median 84 minutes, whereas the median for the control group was 92 minutes (P = .11) in an intention-to-treat analysis. Passive descent and active pushing lasted a median 14 and 50 minutes, respectively, for the DSD group, compared with 13 and 55 minutes for the control group (P = .22 and P = .29, respectively).
Another analysis of the primary outcome measure used Kaplan-Meier curves to compare the curves of the women who remained pregnant in each group across the period of the second stage of labor. There was no significant difference between the groups when the data were examined in this manner (log rank P = .18).
Secondary maternal outcomes included the mode of delivery. Most women (83%-85%) in each group had a normal spontaneous vaginal delivery, with no differences in any mode of delivery (P = .93). Neonatal outcomes also were similar between groups, with no significant differences in sex, birth weight, arterial pH, and neonatal intensive care unit admissions.
The investigators tracked whether patients were admitted in spontaneous labor, for labor induction with active membranes, or with premature rupture of membranes. Also, they looked at the degree of cervical dilation at admission, whether oxytocin or epidural anesthesia were used in labor, and anesthetic administered during the second stage of labor. There were no differences between groups in these variables.
Dr. Rekawek noted that the study benefited from a large sample size and a prospective, randomized design. Blinding lasted only until pushing began. Also, although all patients were taught how to use the device, they didn’t have an opportunity to practice.
Dr. Rekawek presented on behalf of Dr. Bergh because he became a new father the day before the presentation. His wife, said Dr. Rekawek, didn’t use a dental support device.
The authors reported that they have no relevant financial disclosures.
SOURCE: Bergh E et al. Am J Obstet Gynecol. 2019 Jan;220(1):S39, Abstract 49.
LAS VEGAS –
In a randomized, controlled trial of 346 nulliparous women, the device, adapted from a design used in athletics, made no difference in the duration of the second stage of labor overall or in passive descent or active pushing time. The findings were presented on behalf of first author Eric Bergh, MD, by Patricia Rekawek, MD, at a fellows abstract session at the meeting sponsored by the Society for Maternal-Fetal Medicine. Dr. Rekawek and Dr. Bergh are maternal-fetal medicine fellows at the Icahn School of Medicine at Mount Sinai, New York.
The dental support device (DSD) was actually used by 128 (74%) of the patients who were randomized to DSD usage. Of these patients, two thirds (n = 85) used the device for all second stage contractions. About one quarter (27%; n = 35) used it less than half the time, and a small minority (6%; n = 8) used it more than half the time but not for all pushing, noted Dr. Rekawek.
Most women (61%) who used the device agreed or strongly agreed that it was helpful. Most also found it comfortable (67%), and would use it again in a future delivery (61%). Having a custom-fit DSD, or spending more time practicing before labor, might help with efficacy in shortening the second stage of labor and merits study, the investigators said.
Reducing time spent in the second stage of labor could benefit both mother and neonate because “a prolonged second stage of labor is associated with multiple maternal and neonatal complications,” including increased risk for chorioamnionitis, neonatal sepsis, low umbilical artery pH, shoulder dystocia, and third- and fourth-degree lacerations, said Dr. Rekawek.
In athletics, a DSD “raises the vertical dimension of the deep bite and increases the size of the oropharynx” by introducing a 3-mm bite plate between the upper and lower rear molars. The DSD mouthpiece integrates the bite plates with a retainer-like band that wraps around the front incisors; speaking and drinking are possible with the DSD in place, said Dr. Rekawek.
She added that athletic evidence suggests that the DSD can lead to increased oxygenation, less head and neck tension, less muscle fatigue, and improved exercise capacity in some sports.
If these benefits translated to the maternal Valsalva maneuver during the second stage of labor, the increased isometric endurance could increase uterine pressure and optimize the expulsive effect of pushing, explained Dr. Rekawek. However, mixed results were seen in previous work that had women using a DSD during the second stage of labor.
The current study was powered to detect a difference of 20% in the duration of the second stage of labor for nulliparous women who were randomized either to use or not use a DSD while pushing. Women and their caregivers learned their random allocation by opening a sealed envelope at the beginning of the second stage of labor.
The study included nulliparous women who were carrying a singleton pregnancy of at least 37 weeks’ gestation and without known fetal anomalies. Enrollment occurred before the second stage of labor, and 173 women participated in each arm of the study.
For those who were assigned to use the DSD, the second stage of labor lasted a median 84 minutes, whereas the median for the control group was 92 minutes (P = .11) in an intention-to-treat analysis. Passive descent and active pushing lasted a median 14 and 50 minutes, respectively, for the DSD group, compared with 13 and 55 minutes for the control group (P = .22 and P = .29, respectively).
Another analysis of the primary outcome measure used Kaplan-Meier curves to compare the curves of the women who remained pregnant in each group across the period of the second stage of labor. There was no significant difference between the groups when the data were examined in this manner (log rank P = .18).
Secondary maternal outcomes included the mode of delivery. Most women (83%-85%) in each group had a normal spontaneous vaginal delivery, with no differences in any mode of delivery (P = .93). Neonatal outcomes also were similar between groups, with no significant differences in sex, birth weight, arterial pH, and neonatal intensive care unit admissions.
The investigators tracked whether patients were admitted in spontaneous labor, for labor induction with active membranes, or with premature rupture of membranes. Also, they looked at the degree of cervical dilation at admission, whether oxytocin or epidural anesthesia were used in labor, and anesthetic administered during the second stage of labor. There were no differences between groups in these variables.
Dr. Rekawek noted that the study benefited from a large sample size and a prospective, randomized design. Blinding lasted only until pushing began. Also, although all patients were taught how to use the device, they didn’t have an opportunity to practice.
Dr. Rekawek presented on behalf of Dr. Bergh because he became a new father the day before the presentation. His wife, said Dr. Rekawek, didn’t use a dental support device.
The authors reported that they have no relevant financial disclosures.
SOURCE: Bergh E et al. Am J Obstet Gynecol. 2019 Jan;220(1):S39, Abstract 49.
LAS VEGAS –
In a randomized, controlled trial of 346 nulliparous women, the device, adapted from a design used in athletics, made no difference in the duration of the second stage of labor overall or in passive descent or active pushing time. The findings were presented on behalf of first author Eric Bergh, MD, by Patricia Rekawek, MD, at a fellows abstract session at the meeting sponsored by the Society for Maternal-Fetal Medicine. Dr. Rekawek and Dr. Bergh are maternal-fetal medicine fellows at the Icahn School of Medicine at Mount Sinai, New York.
The dental support device (DSD) was actually used by 128 (74%) of the patients who were randomized to DSD usage. Of these patients, two thirds (n = 85) used the device for all second stage contractions. About one quarter (27%; n = 35) used it less than half the time, and a small minority (6%; n = 8) used it more than half the time but not for all pushing, noted Dr. Rekawek.
Most women (61%) who used the device agreed or strongly agreed that it was helpful. Most also found it comfortable (67%), and would use it again in a future delivery (61%). Having a custom-fit DSD, or spending more time practicing before labor, might help with efficacy in shortening the second stage of labor and merits study, the investigators said.
Reducing time spent in the second stage of labor could benefit both mother and neonate because “a prolonged second stage of labor is associated with multiple maternal and neonatal complications,” including increased risk for chorioamnionitis, neonatal sepsis, low umbilical artery pH, shoulder dystocia, and third- and fourth-degree lacerations, said Dr. Rekawek.
In athletics, a DSD “raises the vertical dimension of the deep bite and increases the size of the oropharynx” by introducing a 3-mm bite plate between the upper and lower rear molars. The DSD mouthpiece integrates the bite plates with a retainer-like band that wraps around the front incisors; speaking and drinking are possible with the DSD in place, said Dr. Rekawek.
She added that athletic evidence suggests that the DSD can lead to increased oxygenation, less head and neck tension, less muscle fatigue, and improved exercise capacity in some sports.
If these benefits translated to the maternal Valsalva maneuver during the second stage of labor, the increased isometric endurance could increase uterine pressure and optimize the expulsive effect of pushing, explained Dr. Rekawek. However, mixed results were seen in previous work that had women using a DSD during the second stage of labor.
The current study was powered to detect a difference of 20% in the duration of the second stage of labor for nulliparous women who were randomized either to use or not use a DSD while pushing. Women and their caregivers learned their random allocation by opening a sealed envelope at the beginning of the second stage of labor.
The study included nulliparous women who were carrying a singleton pregnancy of at least 37 weeks’ gestation and without known fetal anomalies. Enrollment occurred before the second stage of labor, and 173 women participated in each arm of the study.
For those who were assigned to use the DSD, the second stage of labor lasted a median 84 minutes, whereas the median for the control group was 92 minutes (P = .11) in an intention-to-treat analysis. Passive descent and active pushing lasted a median 14 and 50 minutes, respectively, for the DSD group, compared with 13 and 55 minutes for the control group (P = .22 and P = .29, respectively).
Another analysis of the primary outcome measure used Kaplan-Meier curves to compare the curves of the women who remained pregnant in each group across the period of the second stage of labor. There was no significant difference between the groups when the data were examined in this manner (log rank P = .18).
Secondary maternal outcomes included the mode of delivery. Most women (83%-85%) in each group had a normal spontaneous vaginal delivery, with no differences in any mode of delivery (P = .93). Neonatal outcomes also were similar between groups, with no significant differences in sex, birth weight, arterial pH, and neonatal intensive care unit admissions.
The investigators tracked whether patients were admitted in spontaneous labor, for labor induction with active membranes, or with premature rupture of membranes. Also, they looked at the degree of cervical dilation at admission, whether oxytocin or epidural anesthesia were used in labor, and anesthetic administered during the second stage of labor. There were no differences between groups in these variables.
Dr. Rekawek noted that the study benefited from a large sample size and a prospective, randomized design. Blinding lasted only until pushing began. Also, although all patients were taught how to use the device, they didn’t have an opportunity to practice.
Dr. Rekawek presented on behalf of Dr. Bergh because he became a new father the day before the presentation. His wife, said Dr. Rekawek, didn’t use a dental support device.
The authors reported that they have no relevant financial disclosures.
SOURCE: Bergh E et al. Am J Obstet Gynecol. 2019 Jan;220(1):S39, Abstract 49.
REPORTING FROM THE PREGNANCY MEETING
One postdelivery antibiotic dose nearly halves infection in operative delivery
LAS VEGAS – A randomized controlled trial comparing a single postdelivery intravenous dose of antibiotic after operative delivery found that antibiotics nearly halved the risk for maternal infection.
For women who received a single dose of amoxicillin-clavulanic acid, the risk ratio was 0.58 for suspected or confirmed infection, compared with those who received an intravenous dose of saline solution (95% confidence interval, 0.49-0.69, P less than .001). Culture-confirmed systemic infections were similarly reduced by a risk ratio (RR) of 0.44 (95% CI, 0.22-0.89; P =.018).
Superficial and deep incisional infections were also significantly less likely in the women who had received antibiotics (RRs 0.53 and 0.46, respectively; P less than .001 for both). Although sepsis occurred in numerically fewer women who received antibiotics, the numbers were, overall, small and not statistically significant.
By 6 weeks after delivery, patients receiving antibiotics were less likely to have outpatient or home visits for perineal problems or concerns as well (P less than .001).
“This trial shows clear benefit of a single dose of prophylactic antibiotic after operative vaginal birth, and this should be introduced into routine practice,” said Marian Knight, MBChB, DPhil.
Dr. Knight presented findings of the randomized trial, dubbed ANODE, at a late-breaking abstract session of the meeting, which was sponsored by the Society for Maternal-Fetal Medicine. Dr. Knight, professor of maternal and child population health at the University of Oxford (England), explained that ANODE aimed to determine whether a single dose of prophylactic amoxicillin-clavulanic acid was clinically effective in preventing confirmed or suspected maternal infection after operative vaginal birth.
The study tips the scales in favor of the anti-infective properties of the single antibiotic dose after operative delivery, and comes at a time when unacceptable levels of maternal morbidity and mortality coexist with pressing worries about antibiotic resistance, Dr. Knight said.
The multicenter randomized, blinded, placebo-controlled trial was conducted at 27 sites in the United Kingdom between March 2016 and June 2018.
Women at the study sites who underwent operative delivery, whether by forceps or vacuum extraction, received either a single dose of intravenous amoxicillin-clavulanic acid (1 gm/200 mg), or a placebo dose of saline solution. Antibiotics were given in the window of 0 to 6 hours post-delivery.
The primary outcome measure was confirmed or suspected maternal infection within 6 weeks of delivery. Women were positive for infection if they were prescribed antibiotics for perineal wound infections, if they experienced endometrial or uterine infections, if they had urinary tract infections with “systemic features, or if they had other systemic infections. Other criteria for infection were culture-confirmed systemic infection, or endometritis by criteria established by the Centers for Disease Control and Prevention.
Dr. Knight and her colleagues used an intention-to-treat analysis that looked at the primary outcome as a risk ratio, with a 95% CI. Secondary outcomes, also presented as risk ratios, were considered with a 99% CI.
A total of 3,427 women were randomized. In all, 1,715 women in the active arm and 1,705 in the placebo arm were included in the outcomes analyses. Women were interviewed by telephone, they completed questionnaires, and they received a questionnaire by mail or completed one online. Slightly more than 1,500 women in each arm completed the phone interview, and nearly 1,300 in each arm completed the initial questionnaire.
The mean age was 30 years, and most of the participants (84%-87%) were white. Most were of normal weight, with a median body mass index at the initial prenatal visit of 25 kg/m2.
Though women with multiple pregnancies were included in the study, just 11 in the active arm and 9 in the placebo arm delivered twins. There were no triplets. Most women (76%-78%) were primiparous, and just 7%-8% of women had prior cesarean delivery.
The mode of operative delivery for most of the participants (63%-67%) was forceps, with all but 10 of the remaining women receiving vacuum extraction (the remaining 10 had spontaneous vaginal deliveries).
The reasons for instrumental delivery were approximately evenly divided between failure of labor to progress and fetal compromise.
Nearly 90% of the women – more than 1,500 in each study arm – received episiotomies, a figure that Dr. Knight said she found surprising. She noted that mediolateral incisions are the standard of care in the United Kingdom. Still, 29%-33% of the women experienced a tear, with most being second-degree tears. Third- and fourth-degree tears occurred in two women overall. Almost all of the women (99%) had their wounds sutured.
Three serious adverse events were reported. One woman in the placebo arm required intensive care unit admission for severe sepsis, and another placebo participant required a transfusion after postpartum hemorrhage. One patient who received antibiotic had immediate diffuse itching and a swollen throat. However, antibiotic side effects were reported in only 2 of the 1,715 active arm participants, Dr. Knight said.
The competing concerns of maternal safety and antibiotic stewardship are weighed against a global backdrop of high maternal infection rates, Dr. Knight said. Sepsis causes 11% of global maternal deaths, a rate that drops to about 5% in higher-income nations. However, she pointed out, that figure rises to about 13% in the United States.
“For every woman that dies from pregnancy-related infection, a further 70 have severe infection and survive,” she said.
Known risk factors for infection include operative vaginal delivery and cesarean deliveries. For cesareans performed after the onset of labor, the adjusted odds ratio reaches 6.7 for severe infection, Dr. Knight said (PLoS Med. 2014;11:e1001672). A systematic review estimated that the rate for any infection following cesarean delivery approaches one in four women, she said (Cochrane Database Syst Rev. 2014 Oct 28;[10]:CD007482).
The same systematic review found that prophylactic antibiotics reduced incidence of wound infection, endometritis, and serious maternal wound infection after cesarean delivery (RR 0.40, 0.38, and 0.31, respectively).
For operative vaginal deliveries, however, a Cochrane review found one study of 393 women. Although no women given antibiotics developed endometritis compared with seven cases of endometritis in the no-antibiotics group for a RR of .07, the 95% confidence interval in the Cochrane analysis included zero, so the findings weren’t statistically significant. Hospital length of stay didn’t differ between the two groups (Cochrane Database Syst Rev. 2014 Oct 13;[10]:CD004455).
Citing this review, the United Kingdom’s Royal College of Gynecologists had concluded that evidence was insufficient to support routine antibiotic prophylaxis in operative deliveries. The American College of Obstetricians and Gynecologists make no mention of antibiotic prophylaxis or postdelivery infection in its guidelines for operative delivery, Dr. Knight said.
Since confirmed or suspected infection was still seen in 11% of women who received antibiotics, further analysis “is needed to investigate whether early administration, prenatal administration, or repeated administration is more likely to be effective,” she said. Women in the ANODE trial received their dose at a median of 3 hours after delivery.
“Until these analyses are completed, there is no indication for administration of more than a single dose of prophylactic antibiotic, or for predelivery administration,” she said.
Dr. Knight reported that ANODE was funded by the U.K.’s National Institute for Health Research. She reported that she had no conflicts of interest.
SOURCE: Knight M et al. Am J Obstet Gynecol. 2019 Jan;220;1:S685. Abstract LB 3.
LAS VEGAS – A randomized controlled trial comparing a single postdelivery intravenous dose of antibiotic after operative delivery found that antibiotics nearly halved the risk for maternal infection.
For women who received a single dose of amoxicillin-clavulanic acid, the risk ratio was 0.58 for suspected or confirmed infection, compared with those who received an intravenous dose of saline solution (95% confidence interval, 0.49-0.69, P less than .001). Culture-confirmed systemic infections were similarly reduced by a risk ratio (RR) of 0.44 (95% CI, 0.22-0.89; P =.018).
Superficial and deep incisional infections were also significantly less likely in the women who had received antibiotics (RRs 0.53 and 0.46, respectively; P less than .001 for both). Although sepsis occurred in numerically fewer women who received antibiotics, the numbers were, overall, small and not statistically significant.
By 6 weeks after delivery, patients receiving antibiotics were less likely to have outpatient or home visits for perineal problems or concerns as well (P less than .001).
“This trial shows clear benefit of a single dose of prophylactic antibiotic after operative vaginal birth, and this should be introduced into routine practice,” said Marian Knight, MBChB, DPhil.
Dr. Knight presented findings of the randomized trial, dubbed ANODE, at a late-breaking abstract session of the meeting, which was sponsored by the Society for Maternal-Fetal Medicine. Dr. Knight, professor of maternal and child population health at the University of Oxford (England), explained that ANODE aimed to determine whether a single dose of prophylactic amoxicillin-clavulanic acid was clinically effective in preventing confirmed or suspected maternal infection after operative vaginal birth.
The study tips the scales in favor of the anti-infective properties of the single antibiotic dose after operative delivery, and comes at a time when unacceptable levels of maternal morbidity and mortality coexist with pressing worries about antibiotic resistance, Dr. Knight said.
The multicenter randomized, blinded, placebo-controlled trial was conducted at 27 sites in the United Kingdom between March 2016 and June 2018.
Women at the study sites who underwent operative delivery, whether by forceps or vacuum extraction, received either a single dose of intravenous amoxicillin-clavulanic acid (1 gm/200 mg), or a placebo dose of saline solution. Antibiotics were given in the window of 0 to 6 hours post-delivery.
The primary outcome measure was confirmed or suspected maternal infection within 6 weeks of delivery. Women were positive for infection if they were prescribed antibiotics for perineal wound infections, if they experienced endometrial or uterine infections, if they had urinary tract infections with “systemic features, or if they had other systemic infections. Other criteria for infection were culture-confirmed systemic infection, or endometritis by criteria established by the Centers for Disease Control and Prevention.
Dr. Knight and her colleagues used an intention-to-treat analysis that looked at the primary outcome as a risk ratio, with a 95% CI. Secondary outcomes, also presented as risk ratios, were considered with a 99% CI.
A total of 3,427 women were randomized. In all, 1,715 women in the active arm and 1,705 in the placebo arm were included in the outcomes analyses. Women were interviewed by telephone, they completed questionnaires, and they received a questionnaire by mail or completed one online. Slightly more than 1,500 women in each arm completed the phone interview, and nearly 1,300 in each arm completed the initial questionnaire.
The mean age was 30 years, and most of the participants (84%-87%) were white. Most were of normal weight, with a median body mass index at the initial prenatal visit of 25 kg/m2.
Though women with multiple pregnancies were included in the study, just 11 in the active arm and 9 in the placebo arm delivered twins. There were no triplets. Most women (76%-78%) were primiparous, and just 7%-8% of women had prior cesarean delivery.
The mode of operative delivery for most of the participants (63%-67%) was forceps, with all but 10 of the remaining women receiving vacuum extraction (the remaining 10 had spontaneous vaginal deliveries).
The reasons for instrumental delivery were approximately evenly divided between failure of labor to progress and fetal compromise.
Nearly 90% of the women – more than 1,500 in each study arm – received episiotomies, a figure that Dr. Knight said she found surprising. She noted that mediolateral incisions are the standard of care in the United Kingdom. Still, 29%-33% of the women experienced a tear, with most being second-degree tears. Third- and fourth-degree tears occurred in two women overall. Almost all of the women (99%) had their wounds sutured.
Three serious adverse events were reported. One woman in the placebo arm required intensive care unit admission for severe sepsis, and another placebo participant required a transfusion after postpartum hemorrhage. One patient who received antibiotic had immediate diffuse itching and a swollen throat. However, antibiotic side effects were reported in only 2 of the 1,715 active arm participants, Dr. Knight said.
The competing concerns of maternal safety and antibiotic stewardship are weighed against a global backdrop of high maternal infection rates, Dr. Knight said. Sepsis causes 11% of global maternal deaths, a rate that drops to about 5% in higher-income nations. However, she pointed out, that figure rises to about 13% in the United States.
“For every woman that dies from pregnancy-related infection, a further 70 have severe infection and survive,” she said.
Known risk factors for infection include operative vaginal delivery and cesarean deliveries. For cesareans performed after the onset of labor, the adjusted odds ratio reaches 6.7 for severe infection, Dr. Knight said (PLoS Med. 2014;11:e1001672). A systematic review estimated that the rate for any infection following cesarean delivery approaches one in four women, she said (Cochrane Database Syst Rev. 2014 Oct 28;[10]:CD007482).
The same systematic review found that prophylactic antibiotics reduced incidence of wound infection, endometritis, and serious maternal wound infection after cesarean delivery (RR 0.40, 0.38, and 0.31, respectively).
For operative vaginal deliveries, however, a Cochrane review found one study of 393 women. Although no women given antibiotics developed endometritis compared with seven cases of endometritis in the no-antibiotics group for a RR of .07, the 95% confidence interval in the Cochrane analysis included zero, so the findings weren’t statistically significant. Hospital length of stay didn’t differ between the two groups (Cochrane Database Syst Rev. 2014 Oct 13;[10]:CD004455).
Citing this review, the United Kingdom’s Royal College of Gynecologists had concluded that evidence was insufficient to support routine antibiotic prophylaxis in operative deliveries. The American College of Obstetricians and Gynecologists make no mention of antibiotic prophylaxis or postdelivery infection in its guidelines for operative delivery, Dr. Knight said.
Since confirmed or suspected infection was still seen in 11% of women who received antibiotics, further analysis “is needed to investigate whether early administration, prenatal administration, or repeated administration is more likely to be effective,” she said. Women in the ANODE trial received their dose at a median of 3 hours after delivery.
“Until these analyses are completed, there is no indication for administration of more than a single dose of prophylactic antibiotic, or for predelivery administration,” she said.
Dr. Knight reported that ANODE was funded by the U.K.’s National Institute for Health Research. She reported that she had no conflicts of interest.
SOURCE: Knight M et al. Am J Obstet Gynecol. 2019 Jan;220;1:S685. Abstract LB 3.
LAS VEGAS – A randomized controlled trial comparing a single postdelivery intravenous dose of antibiotic after operative delivery found that antibiotics nearly halved the risk for maternal infection.
For women who received a single dose of amoxicillin-clavulanic acid, the risk ratio was 0.58 for suspected or confirmed infection, compared with those who received an intravenous dose of saline solution (95% confidence interval, 0.49-0.69, P less than .001). Culture-confirmed systemic infections were similarly reduced by a risk ratio (RR) of 0.44 (95% CI, 0.22-0.89; P =.018).
Superficial and deep incisional infections were also significantly less likely in the women who had received antibiotics (RRs 0.53 and 0.46, respectively; P less than .001 for both). Although sepsis occurred in numerically fewer women who received antibiotics, the numbers were, overall, small and not statistically significant.
By 6 weeks after delivery, patients receiving antibiotics were less likely to have outpatient or home visits for perineal problems or concerns as well (P less than .001).
“This trial shows clear benefit of a single dose of prophylactic antibiotic after operative vaginal birth, and this should be introduced into routine practice,” said Marian Knight, MBChB, DPhil.
Dr. Knight presented findings of the randomized trial, dubbed ANODE, at a late-breaking abstract session of the meeting, which was sponsored by the Society for Maternal-Fetal Medicine. Dr. Knight, professor of maternal and child population health at the University of Oxford (England), explained that ANODE aimed to determine whether a single dose of prophylactic amoxicillin-clavulanic acid was clinically effective in preventing confirmed or suspected maternal infection after operative vaginal birth.
The study tips the scales in favor of the anti-infective properties of the single antibiotic dose after operative delivery, and comes at a time when unacceptable levels of maternal morbidity and mortality coexist with pressing worries about antibiotic resistance, Dr. Knight said.
The multicenter randomized, blinded, placebo-controlled trial was conducted at 27 sites in the United Kingdom between March 2016 and June 2018.
Women at the study sites who underwent operative delivery, whether by forceps or vacuum extraction, received either a single dose of intravenous amoxicillin-clavulanic acid (1 gm/200 mg), or a placebo dose of saline solution. Antibiotics were given in the window of 0 to 6 hours post-delivery.
The primary outcome measure was confirmed or suspected maternal infection within 6 weeks of delivery. Women were positive for infection if they were prescribed antibiotics for perineal wound infections, if they experienced endometrial or uterine infections, if they had urinary tract infections with “systemic features, or if they had other systemic infections. Other criteria for infection were culture-confirmed systemic infection, or endometritis by criteria established by the Centers for Disease Control and Prevention.
Dr. Knight and her colleagues used an intention-to-treat analysis that looked at the primary outcome as a risk ratio, with a 95% CI. Secondary outcomes, also presented as risk ratios, were considered with a 99% CI.
A total of 3,427 women were randomized. In all, 1,715 women in the active arm and 1,705 in the placebo arm were included in the outcomes analyses. Women were interviewed by telephone, they completed questionnaires, and they received a questionnaire by mail or completed one online. Slightly more than 1,500 women in each arm completed the phone interview, and nearly 1,300 in each arm completed the initial questionnaire.
The mean age was 30 years, and most of the participants (84%-87%) were white. Most were of normal weight, with a median body mass index at the initial prenatal visit of 25 kg/m2.
Though women with multiple pregnancies were included in the study, just 11 in the active arm and 9 in the placebo arm delivered twins. There were no triplets. Most women (76%-78%) were primiparous, and just 7%-8% of women had prior cesarean delivery.
The mode of operative delivery for most of the participants (63%-67%) was forceps, with all but 10 of the remaining women receiving vacuum extraction (the remaining 10 had spontaneous vaginal deliveries).
The reasons for instrumental delivery were approximately evenly divided between failure of labor to progress and fetal compromise.
Nearly 90% of the women – more than 1,500 in each study arm – received episiotomies, a figure that Dr. Knight said she found surprising. She noted that mediolateral incisions are the standard of care in the United Kingdom. Still, 29%-33% of the women experienced a tear, with most being second-degree tears. Third- and fourth-degree tears occurred in two women overall. Almost all of the women (99%) had their wounds sutured.
Three serious adverse events were reported. One woman in the placebo arm required intensive care unit admission for severe sepsis, and another placebo participant required a transfusion after postpartum hemorrhage. One patient who received antibiotic had immediate diffuse itching and a swollen throat. However, antibiotic side effects were reported in only 2 of the 1,715 active arm participants, Dr. Knight said.
The competing concerns of maternal safety and antibiotic stewardship are weighed against a global backdrop of high maternal infection rates, Dr. Knight said. Sepsis causes 11% of global maternal deaths, a rate that drops to about 5% in higher-income nations. However, she pointed out, that figure rises to about 13% in the United States.
“For every woman that dies from pregnancy-related infection, a further 70 have severe infection and survive,” she said.
Known risk factors for infection include operative vaginal delivery and cesarean deliveries. For cesareans performed after the onset of labor, the adjusted odds ratio reaches 6.7 for severe infection, Dr. Knight said (PLoS Med. 2014;11:e1001672). A systematic review estimated that the rate for any infection following cesarean delivery approaches one in four women, she said (Cochrane Database Syst Rev. 2014 Oct 28;[10]:CD007482).
The same systematic review found that prophylactic antibiotics reduced incidence of wound infection, endometritis, and serious maternal wound infection after cesarean delivery (RR 0.40, 0.38, and 0.31, respectively).
For operative vaginal deliveries, however, a Cochrane review found one study of 393 women. Although no women given antibiotics developed endometritis compared with seven cases of endometritis in the no-antibiotics group for a RR of .07, the 95% confidence interval in the Cochrane analysis included zero, so the findings weren’t statistically significant. Hospital length of stay didn’t differ between the two groups (Cochrane Database Syst Rev. 2014 Oct 13;[10]:CD004455).
Citing this review, the United Kingdom’s Royal College of Gynecologists had concluded that evidence was insufficient to support routine antibiotic prophylaxis in operative deliveries. The American College of Obstetricians and Gynecologists make no mention of antibiotic prophylaxis or postdelivery infection in its guidelines for operative delivery, Dr. Knight said.
Since confirmed or suspected infection was still seen in 11% of women who received antibiotics, further analysis “is needed to investigate whether early administration, prenatal administration, or repeated administration is more likely to be effective,” she said. Women in the ANODE trial received their dose at a median of 3 hours after delivery.
“Until these analyses are completed, there is no indication for administration of more than a single dose of prophylactic antibiotic, or for predelivery administration,” she said.
Dr. Knight reported that ANODE was funded by the U.K.’s National Institute for Health Research. She reported that she had no conflicts of interest.
SOURCE: Knight M et al. Am J Obstet Gynecol. 2019 Jan;220;1:S685. Abstract LB 3.
REPORTING FROM THE PREGNANCY MEETING
Ehlers-Danlos syndrome: Increased IUGR risk reported
LAS VEGAS – Women with Ehlers-Danlos syndrome who became pregnant were more likely to experience antepartum hemorrhage, placenta previa, cervical incompetence, and preterm birth, according to a retrospective cohort study of national birth data. Long hospital stays also were more likely among these women.
Infants born to women with Ehlers-Danlos syndrome (EDS) were significantly more likely to have intrauterine growth retardation (IUGR) as well, an unexpected and as-yet unexplained finding, said the study’s first author, Laura Nicholls-Dempsey, MD, speaking at a poster session at the meeting sponsored by the Society for Maternal-Fetal Medicine.
Complications were infrequent overall, with a very low rate of intrauterine demise and no maternal mortality seen in the 910 women with EDS who were studied, said Dr. Nicholls-Dempsey, an ob.gyn. resident at McGill University, Montreal.
In counseling women with EDS, Dr. Nicholls-Dempsey said that she would advise them that “these are the types of things we’re going to watch out for, and we’ll see how the pregnancy goes. But we have to be careful about these: preterm birth, antepartum bleeding, placenta previa. We’ll watch the growth of the baby; we just have to be more careful about these specific things.”
Compared with women without EDS, those with the inherited connective tissue disorder had adjusted odds ratios (AORs) of 3.2 for cervical incompetence (95% confidence interval, 2.0-5.1) and 2.2 for placenta previa (95% CI, 1.3-3.9; P less than .01 for both). Absolute rates for these complications were 0.8% and 0.7% for women without EDS and 2.1% and 1.4% for women with EDS, respectively.
Women with EDS also had AORs of 1.8 for antepartum hemorrhage (2.8% versus 1.6%; 95% CI, 1.2-2.7; P less than .01). Cesarean delivery was more likely in women with EDS, with an AOR of 1.6 (37.4% versus 26.9%; 95% CI, 2.0-5.1); conversely, instrumental vaginal delivery was less likely in women with EDS (AOR = 0.5; 95% CI, 0.4-0.7; P less than .01 for both), meaning that spontaneous vaginal delivery was less likely in the EDS cohort.
The higher frequency of Cesarean deliveries may be attributable to anticipatory management by physicians seeking to avoid such complications as antepartum hemorrhage, as well as to the increased rate of placenta previa seen among the EDS cohort, Dr. Nicholls-Dempsey said.
After statistical adjustment, women in the EDS cohort were more than three times as likely to have hospital stays of both more than 7 days and 14 days (5.7% versus 2.1%, AOR = 3.1 for 7 days; 2.3% versus 0.7%, AOR = 3.8 for 14 days; P less than .01 for both).
Rates of some other maternal complications, such as pre-eclampsia, eclampsia, and gestational hypertension, were not elevated in the EDS cohort. Rates of premature rupture of membranes, chorioamnionitis, uterine rupture, postpartum hemorrhage, perineal laceration, and venous thromboembolism were also similar between groups.
However, not only was the AOR for preterm birth 1.5 for infants of women with EDS, but IUGR was more common in these neonates as well (AOR = 1.7, P less than .01 for both). The latter finding was unexpected, and Dr. Nicholls-Dempsey and her colleagues currently don’t have a mechanistic explanation for the higher IUGR rate.
Dr. Nicholls-Dempsey explained that she and her colleagues used data from the United States’ Health Care Cost and Utilization Project’s Nationwide Inpatient Sample (HCUP-NIS) to compare outcomes of women with EDS with the national sample as a whole.
Between 1999 and 2013, 13,881,592 births occurred in the HCUP-NIS cohort, with 910 deliveries to women who had EDS. These women were identified by ICD-9 codes, she said.
Comparing women with EDS to the non-EDS cohort, women with EDS were more likely to be Caucasian, have a higher income, and to be smokers; the cohorts were otherwise similar.
Ehlers-Danlos syndrome is a heterogeneous disorder involving abnormalities of collagen synthesis, with 13 known subtypes not captured in the HCUP-NIS data, Dr. Nicholls-Dempsey acknowledged. She characterized this as both a limitation but also a potential strength of the study.
“I really like this study because ... we know there’s 13 types of EDS that are genetically different ... They have their overlapping symptoms, but each one is different,” she said. “In an ideal world, we would have each subtype, and we would run this type of analysis on each subtype, to really be able to say to a patient, ‘You have this mutation, and this complication is going to be a big problem for you.’” The numbers of each subtype are so small that this is infeasible, she noted.
Still, the national sample acquired over many years offers real-world outcomes that clinicians can use in shared decision-making with EDS patients who are contemplating pregnancy or are already pregnant. Also, knowing which complications are more likely in patients with EDS can help plan optimal management of labor and delivery, Dr. Nicholls-Dempsey said.
Over the study’s 14-year span, the overall arc of EDS pregnancy outcomes is well captured regardless of mutation type. “It’s very applicable to the general population” of individuals with EDS, she noted. “Because it’s not type-specific, it’s really a good overview of what you can expect in EDS patients, regardless of the type.”
Dr. Nicholls-Dempsey reported no conflicts of interest and no outside sources of funding.
SOURCE: Nicholls-Dempsey L et al. Am J Obstet Gynecol. 2019 Jan;220(1):S381-382. Abstract 574
LAS VEGAS – Women with Ehlers-Danlos syndrome who became pregnant were more likely to experience antepartum hemorrhage, placenta previa, cervical incompetence, and preterm birth, according to a retrospective cohort study of national birth data. Long hospital stays also were more likely among these women.
Infants born to women with Ehlers-Danlos syndrome (EDS) were significantly more likely to have intrauterine growth retardation (IUGR) as well, an unexpected and as-yet unexplained finding, said the study’s first author, Laura Nicholls-Dempsey, MD, speaking at a poster session at the meeting sponsored by the Society for Maternal-Fetal Medicine.
Complications were infrequent overall, with a very low rate of intrauterine demise and no maternal mortality seen in the 910 women with EDS who were studied, said Dr. Nicholls-Dempsey, an ob.gyn. resident at McGill University, Montreal.
In counseling women with EDS, Dr. Nicholls-Dempsey said that she would advise them that “these are the types of things we’re going to watch out for, and we’ll see how the pregnancy goes. But we have to be careful about these: preterm birth, antepartum bleeding, placenta previa. We’ll watch the growth of the baby; we just have to be more careful about these specific things.”
Compared with women without EDS, those with the inherited connective tissue disorder had adjusted odds ratios (AORs) of 3.2 for cervical incompetence (95% confidence interval, 2.0-5.1) and 2.2 for placenta previa (95% CI, 1.3-3.9; P less than .01 for both). Absolute rates for these complications were 0.8% and 0.7% for women without EDS and 2.1% and 1.4% for women with EDS, respectively.
Women with EDS also had AORs of 1.8 for antepartum hemorrhage (2.8% versus 1.6%; 95% CI, 1.2-2.7; P less than .01). Cesarean delivery was more likely in women with EDS, with an AOR of 1.6 (37.4% versus 26.9%; 95% CI, 2.0-5.1); conversely, instrumental vaginal delivery was less likely in women with EDS (AOR = 0.5; 95% CI, 0.4-0.7; P less than .01 for both), meaning that spontaneous vaginal delivery was less likely in the EDS cohort.
The higher frequency of Cesarean deliveries may be attributable to anticipatory management by physicians seeking to avoid such complications as antepartum hemorrhage, as well as to the increased rate of placenta previa seen among the EDS cohort, Dr. Nicholls-Dempsey said.
After statistical adjustment, women in the EDS cohort were more than three times as likely to have hospital stays of both more than 7 days and 14 days (5.7% versus 2.1%, AOR = 3.1 for 7 days; 2.3% versus 0.7%, AOR = 3.8 for 14 days; P less than .01 for both).
Rates of some other maternal complications, such as pre-eclampsia, eclampsia, and gestational hypertension, were not elevated in the EDS cohort. Rates of premature rupture of membranes, chorioamnionitis, uterine rupture, postpartum hemorrhage, perineal laceration, and venous thromboembolism were also similar between groups.
However, not only was the AOR for preterm birth 1.5 for infants of women with EDS, but IUGR was more common in these neonates as well (AOR = 1.7, P less than .01 for both). The latter finding was unexpected, and Dr. Nicholls-Dempsey and her colleagues currently don’t have a mechanistic explanation for the higher IUGR rate.
Dr. Nicholls-Dempsey explained that she and her colleagues used data from the United States’ Health Care Cost and Utilization Project’s Nationwide Inpatient Sample (HCUP-NIS) to compare outcomes of women with EDS with the national sample as a whole.
Between 1999 and 2013, 13,881,592 births occurred in the HCUP-NIS cohort, with 910 deliveries to women who had EDS. These women were identified by ICD-9 codes, she said.
Comparing women with EDS to the non-EDS cohort, women with EDS were more likely to be Caucasian, have a higher income, and to be smokers; the cohorts were otherwise similar.
Ehlers-Danlos syndrome is a heterogeneous disorder involving abnormalities of collagen synthesis, with 13 known subtypes not captured in the HCUP-NIS data, Dr. Nicholls-Dempsey acknowledged. She characterized this as both a limitation but also a potential strength of the study.
“I really like this study because ... we know there’s 13 types of EDS that are genetically different ... They have their overlapping symptoms, but each one is different,” she said. “In an ideal world, we would have each subtype, and we would run this type of analysis on each subtype, to really be able to say to a patient, ‘You have this mutation, and this complication is going to be a big problem for you.’” The numbers of each subtype are so small that this is infeasible, she noted.
Still, the national sample acquired over many years offers real-world outcomes that clinicians can use in shared decision-making with EDS patients who are contemplating pregnancy or are already pregnant. Also, knowing which complications are more likely in patients with EDS can help plan optimal management of labor and delivery, Dr. Nicholls-Dempsey said.
Over the study’s 14-year span, the overall arc of EDS pregnancy outcomes is well captured regardless of mutation type. “It’s very applicable to the general population” of individuals with EDS, she noted. “Because it’s not type-specific, it’s really a good overview of what you can expect in EDS patients, regardless of the type.”
Dr. Nicholls-Dempsey reported no conflicts of interest and no outside sources of funding.
SOURCE: Nicholls-Dempsey L et al. Am J Obstet Gynecol. 2019 Jan;220(1):S381-382. Abstract 574
LAS VEGAS – Women with Ehlers-Danlos syndrome who became pregnant were more likely to experience antepartum hemorrhage, placenta previa, cervical incompetence, and preterm birth, according to a retrospective cohort study of national birth data. Long hospital stays also were more likely among these women.
Infants born to women with Ehlers-Danlos syndrome (EDS) were significantly more likely to have intrauterine growth retardation (IUGR) as well, an unexpected and as-yet unexplained finding, said the study’s first author, Laura Nicholls-Dempsey, MD, speaking at a poster session at the meeting sponsored by the Society for Maternal-Fetal Medicine.
Complications were infrequent overall, with a very low rate of intrauterine demise and no maternal mortality seen in the 910 women with EDS who were studied, said Dr. Nicholls-Dempsey, an ob.gyn. resident at McGill University, Montreal.
In counseling women with EDS, Dr. Nicholls-Dempsey said that she would advise them that “these are the types of things we’re going to watch out for, and we’ll see how the pregnancy goes. But we have to be careful about these: preterm birth, antepartum bleeding, placenta previa. We’ll watch the growth of the baby; we just have to be more careful about these specific things.”
Compared with women without EDS, those with the inherited connective tissue disorder had adjusted odds ratios (AORs) of 3.2 for cervical incompetence (95% confidence interval, 2.0-5.1) and 2.2 for placenta previa (95% CI, 1.3-3.9; P less than .01 for both). Absolute rates for these complications were 0.8% and 0.7% for women without EDS and 2.1% and 1.4% for women with EDS, respectively.
Women with EDS also had AORs of 1.8 for antepartum hemorrhage (2.8% versus 1.6%; 95% CI, 1.2-2.7; P less than .01). Cesarean delivery was more likely in women with EDS, with an AOR of 1.6 (37.4% versus 26.9%; 95% CI, 2.0-5.1); conversely, instrumental vaginal delivery was less likely in women with EDS (AOR = 0.5; 95% CI, 0.4-0.7; P less than .01 for both), meaning that spontaneous vaginal delivery was less likely in the EDS cohort.
The higher frequency of Cesarean deliveries may be attributable to anticipatory management by physicians seeking to avoid such complications as antepartum hemorrhage, as well as to the increased rate of placenta previa seen among the EDS cohort, Dr. Nicholls-Dempsey said.
After statistical adjustment, women in the EDS cohort were more than three times as likely to have hospital stays of both more than 7 days and 14 days (5.7% versus 2.1%, AOR = 3.1 for 7 days; 2.3% versus 0.7%, AOR = 3.8 for 14 days; P less than .01 for both).
Rates of some other maternal complications, such as pre-eclampsia, eclampsia, and gestational hypertension, were not elevated in the EDS cohort. Rates of premature rupture of membranes, chorioamnionitis, uterine rupture, postpartum hemorrhage, perineal laceration, and venous thromboembolism were also similar between groups.
However, not only was the AOR for preterm birth 1.5 for infants of women with EDS, but IUGR was more common in these neonates as well (AOR = 1.7, P less than .01 for both). The latter finding was unexpected, and Dr. Nicholls-Dempsey and her colleagues currently don’t have a mechanistic explanation for the higher IUGR rate.
Dr. Nicholls-Dempsey explained that she and her colleagues used data from the United States’ Health Care Cost and Utilization Project’s Nationwide Inpatient Sample (HCUP-NIS) to compare outcomes of women with EDS with the national sample as a whole.
Between 1999 and 2013, 13,881,592 births occurred in the HCUP-NIS cohort, with 910 deliveries to women who had EDS. These women were identified by ICD-9 codes, she said.
Comparing women with EDS to the non-EDS cohort, women with EDS were more likely to be Caucasian, have a higher income, and to be smokers; the cohorts were otherwise similar.
Ehlers-Danlos syndrome is a heterogeneous disorder involving abnormalities of collagen synthesis, with 13 known subtypes not captured in the HCUP-NIS data, Dr. Nicholls-Dempsey acknowledged. She characterized this as both a limitation but also a potential strength of the study.
“I really like this study because ... we know there’s 13 types of EDS that are genetically different ... They have their overlapping symptoms, but each one is different,” she said. “In an ideal world, we would have each subtype, and we would run this type of analysis on each subtype, to really be able to say to a patient, ‘You have this mutation, and this complication is going to be a big problem for you.’” The numbers of each subtype are so small that this is infeasible, she noted.
Still, the national sample acquired over many years offers real-world outcomes that clinicians can use in shared decision-making with EDS patients who are contemplating pregnancy or are already pregnant. Also, knowing which complications are more likely in patients with EDS can help plan optimal management of labor and delivery, Dr. Nicholls-Dempsey said.
Over the study’s 14-year span, the overall arc of EDS pregnancy outcomes is well captured regardless of mutation type. “It’s very applicable to the general population” of individuals with EDS, she noted. “Because it’s not type-specific, it’s really a good overview of what you can expect in EDS patients, regardless of the type.”
Dr. Nicholls-Dempsey reported no conflicts of interest and no outside sources of funding.
SOURCE: Nicholls-Dempsey L et al. Am J Obstet Gynecol. 2019 Jan;220(1):S381-382. Abstract 574
REPORTING FROM THE PREGNANCY MEETING
Obstetric patients with opioid use disorder fare well with medication-assisted treatment
LAS VEGAS – A prospective study of pregnant women with opioid use disorder showed good success with tapering or discontinuation of medication-assisted treatment (MAT) for women who wished to reduce or eliminate opioids while pregnant.
In related work, naltrexone showed promise for MAT in pregnancy, with rapid fetal clearance and no neonatal abstinence syndrome (NAS) seen in women who were adherent to naltrexone.
Presenting early experiences from an obstetric clinic dedicated to care of women with opioid use disorder (OUD), Craig Towers, MD, said that the clinic began seeing patients in November, 2016. “Eastern Tennessee has a high rate of opioid use disorder,” so the clinic at the University of Tennessee, Knoxville, fills an unmet need, he said, speaking during a poster session at the meeting sponsored by the Society for Maternal-Fetal Medicine.
Women who enroll at the clinic are offered MAT; those who are stable on MAT and adherent to prenatal care also are offered the choice to taper from MAT and detoxify, said Dr. Towers, professor in the division of maternal-fetal medicine in the department of obstetrics and gynecology at the University of Tennessee – Knoxville.
The prospective observational cohort study found that, of a total of 367 compliant patients, 286 (78%) chose opioid tapering/detoxification, and of these, 152 (53%) did detoxify fully. Of these patients, 126 (83%) were taking no opioids at delivery, and their infants experienced no NAS.
At the time of delivery, 26 patients (17%) were taking opioids at delivery; 18 were back on MAT, and 8 were using illicit opioids. A total of 116 patients chose to continue MAT, whether they stayed on the regimen or converted back to stable MAT doses after beginning to taper.
Another option offered women at the OUD-dedicated obstetric clinic is the use of the Bridge device, a percutaneous nerve field stimulator, for OUD. Dr. Tower said that, in early use in 14 patients, the Bridge was successful in helping women transition off opioids completely in 10 (71%) patients.
About the larger study, Dr. Towers said, “This is the first study to prospectively report outcome data on a designated OUD clinic that offers detoxification during pregnancy.
“With a structured program that includes behavioral health and offers the option of detoxification, fetal risks are negligible, relapse rates by delivery are low, and NAS rates are greatly decreased,” wrote Dr. Towers and colleagues in the abstract accompanying the study.
In a related poster presentation, Dr. Towers reported outcomes for a subset of pregnant women with OUD who received naltrexone as MAT. Previously, said Dr. Towers, retrospective work showed no significant harm using naltrexone, which is one of the three approved options for MAT to manage OUD, along with buprenorphine and methadone. Naltrexone has the advantage of helping reduce cravings.
Of the 108 patients, 82 (76%) remained on naltrexone until delivery; in these pregnancies, there were no cases of NAS. However, among the 26 pregnancies in which women stopped taking naltrexone before delivery, there were 6 (23%) NAS cases.
Fifty-one patients were started on naltrexone before 24 weeks’ gestation, and of those patients, no changes were seen with fetal monitoring. There were no instances of spontaneous abortion or intrauterine demise in any participants.
The investigators tracked gestational age at the point of full detoxification and gestational age at the point naltrexone was started. Additionally, fetal response to naltrexone and maternal and neonatal outcomes were recorded.
“This is the first prospective study and largest to date on the use of naltrexone in pregnancy,” Dr. Towers and his colleagues wrote in the poster accompanying the presentation. “These data demonstrate that naltrexone MAT is a viable option for managing OUD in pregnancy.”
Dr. Towers reported no conflicts of interest and no outside sources of funding.
LAS VEGAS – A prospective study of pregnant women with opioid use disorder showed good success with tapering or discontinuation of medication-assisted treatment (MAT) for women who wished to reduce or eliminate opioids while pregnant.
In related work, naltrexone showed promise for MAT in pregnancy, with rapid fetal clearance and no neonatal abstinence syndrome (NAS) seen in women who were adherent to naltrexone.
Presenting early experiences from an obstetric clinic dedicated to care of women with opioid use disorder (OUD), Craig Towers, MD, said that the clinic began seeing patients in November, 2016. “Eastern Tennessee has a high rate of opioid use disorder,” so the clinic at the University of Tennessee, Knoxville, fills an unmet need, he said, speaking during a poster session at the meeting sponsored by the Society for Maternal-Fetal Medicine.
Women who enroll at the clinic are offered MAT; those who are stable on MAT and adherent to prenatal care also are offered the choice to taper from MAT and detoxify, said Dr. Towers, professor in the division of maternal-fetal medicine in the department of obstetrics and gynecology at the University of Tennessee – Knoxville.
The prospective observational cohort study found that, of a total of 367 compliant patients, 286 (78%) chose opioid tapering/detoxification, and of these, 152 (53%) did detoxify fully. Of these patients, 126 (83%) were taking no opioids at delivery, and their infants experienced no NAS.
At the time of delivery, 26 patients (17%) were taking opioids at delivery; 18 were back on MAT, and 8 were using illicit opioids. A total of 116 patients chose to continue MAT, whether they stayed on the regimen or converted back to stable MAT doses after beginning to taper.
Another option offered women at the OUD-dedicated obstetric clinic is the use of the Bridge device, a percutaneous nerve field stimulator, for OUD. Dr. Tower said that, in early use in 14 patients, the Bridge was successful in helping women transition off opioids completely in 10 (71%) patients.
About the larger study, Dr. Towers said, “This is the first study to prospectively report outcome data on a designated OUD clinic that offers detoxification during pregnancy.
“With a structured program that includes behavioral health and offers the option of detoxification, fetal risks are negligible, relapse rates by delivery are low, and NAS rates are greatly decreased,” wrote Dr. Towers and colleagues in the abstract accompanying the study.
In a related poster presentation, Dr. Towers reported outcomes for a subset of pregnant women with OUD who received naltrexone as MAT. Previously, said Dr. Towers, retrospective work showed no significant harm using naltrexone, which is one of the three approved options for MAT to manage OUD, along with buprenorphine and methadone. Naltrexone has the advantage of helping reduce cravings.
Of the 108 patients, 82 (76%) remained on naltrexone until delivery; in these pregnancies, there were no cases of NAS. However, among the 26 pregnancies in which women stopped taking naltrexone before delivery, there were 6 (23%) NAS cases.
Fifty-one patients were started on naltrexone before 24 weeks’ gestation, and of those patients, no changes were seen with fetal monitoring. There were no instances of spontaneous abortion or intrauterine demise in any participants.
The investigators tracked gestational age at the point of full detoxification and gestational age at the point naltrexone was started. Additionally, fetal response to naltrexone and maternal and neonatal outcomes were recorded.
“This is the first prospective study and largest to date on the use of naltrexone in pregnancy,” Dr. Towers and his colleagues wrote in the poster accompanying the presentation. “These data demonstrate that naltrexone MAT is a viable option for managing OUD in pregnancy.”
Dr. Towers reported no conflicts of interest and no outside sources of funding.
LAS VEGAS – A prospective study of pregnant women with opioid use disorder showed good success with tapering or discontinuation of medication-assisted treatment (MAT) for women who wished to reduce or eliminate opioids while pregnant.
In related work, naltrexone showed promise for MAT in pregnancy, with rapid fetal clearance and no neonatal abstinence syndrome (NAS) seen in women who were adherent to naltrexone.
Presenting early experiences from an obstetric clinic dedicated to care of women with opioid use disorder (OUD), Craig Towers, MD, said that the clinic began seeing patients in November, 2016. “Eastern Tennessee has a high rate of opioid use disorder,” so the clinic at the University of Tennessee, Knoxville, fills an unmet need, he said, speaking during a poster session at the meeting sponsored by the Society for Maternal-Fetal Medicine.
Women who enroll at the clinic are offered MAT; those who are stable on MAT and adherent to prenatal care also are offered the choice to taper from MAT and detoxify, said Dr. Towers, professor in the division of maternal-fetal medicine in the department of obstetrics and gynecology at the University of Tennessee – Knoxville.
The prospective observational cohort study found that, of a total of 367 compliant patients, 286 (78%) chose opioid tapering/detoxification, and of these, 152 (53%) did detoxify fully. Of these patients, 126 (83%) were taking no opioids at delivery, and their infants experienced no NAS.
At the time of delivery, 26 patients (17%) were taking opioids at delivery; 18 were back on MAT, and 8 were using illicit opioids. A total of 116 patients chose to continue MAT, whether they stayed on the regimen or converted back to stable MAT doses after beginning to taper.
Another option offered women at the OUD-dedicated obstetric clinic is the use of the Bridge device, a percutaneous nerve field stimulator, for OUD. Dr. Tower said that, in early use in 14 patients, the Bridge was successful in helping women transition off opioids completely in 10 (71%) patients.
About the larger study, Dr. Towers said, “This is the first study to prospectively report outcome data on a designated OUD clinic that offers detoxification during pregnancy.
“With a structured program that includes behavioral health and offers the option of detoxification, fetal risks are negligible, relapse rates by delivery are low, and NAS rates are greatly decreased,” wrote Dr. Towers and colleagues in the abstract accompanying the study.
In a related poster presentation, Dr. Towers reported outcomes for a subset of pregnant women with OUD who received naltrexone as MAT. Previously, said Dr. Towers, retrospective work showed no significant harm using naltrexone, which is one of the three approved options for MAT to manage OUD, along with buprenorphine and methadone. Naltrexone has the advantage of helping reduce cravings.
Of the 108 patients, 82 (76%) remained on naltrexone until delivery; in these pregnancies, there were no cases of NAS. However, among the 26 pregnancies in which women stopped taking naltrexone before delivery, there were 6 (23%) NAS cases.
Fifty-one patients were started on naltrexone before 24 weeks’ gestation, and of those patients, no changes were seen with fetal monitoring. There were no instances of spontaneous abortion or intrauterine demise in any participants.
The investigators tracked gestational age at the point of full detoxification and gestational age at the point naltrexone was started. Additionally, fetal response to naltrexone and maternal and neonatal outcomes were recorded.
“This is the first prospective study and largest to date on the use of naltrexone in pregnancy,” Dr. Towers and his colleagues wrote in the poster accompanying the presentation. “These data demonstrate that naltrexone MAT is a viable option for managing OUD in pregnancy.”
Dr. Towers reported no conflicts of interest and no outside sources of funding.
REPORTING FROM THE PREGNANCY MEETING
Key clinical point: Over two-thirds of MAT-adherent patients chose detoxification.
Major finding:
Study details: Prospective single-center cohort study of 367 pregnant women with opioid use disorder.
Disclosures: Dr. Towers reported no outside sources of funding and no relevant conflicts of interest.
Source: Towers C. et al. SMFM 2019, Posters 141 & 142.
Short sleep linked with high homocysteine for some populations
Short sleep’s association with cardiovascular risk may be mediated in part by elevated homocysteine levels, suggests a new analysis of data from the 2005-2006 National Health and Nutrition Examination Survey (NHANES).
The study, published in the Journal of Clinical Sleep Medicine, found that elevated homocysteine levels were only associated with short sleep duration for some populations, including women, non-Hispanic white individuals, and participants with obesity.
A total of 4,480 NHANES participants had serum homocysteine levels on record and were included in the study; of these, those with self-reported sleep duration of 7 hours had the lowest serum homocysteine levels. Those with the shortest sleep duration – 5 hours or less per night – had the highest homocysteine levels.
When participants were broken into subgroups by such factors as sex, ethnicity/race, and body mass index, the association between extremely short sleep and elevated homocysteine levels was retained for three groups: women, non-Hispanic white participants, and those with BMIs of 30 kg/m2 and higher.
“[T]his finding might suggest increased vulnerability to cardiovascular risk or other atherothrombotic events in these groups in the context of short sleep,” wrote Tien-Yu Chen, MD, of Tri-Service General Hospital, Taipei, Taiwan, and coauthors in the abstract accompanying the study.
In the NHANES questionnaire, participants were asked how much sleep they usually got, in whole hours. Answers were grouped into 5 hours or less, 6 hours, 7 hours, or 8 hours, and 9 hours or more. Serum homocysteine was measured once for each study participant.
Using multivariate linear regression, homocysteine was considered the dependent, continuous variable, and the association between sleep duration and homocysteine was assessed using three models that accounted for confounders. The first and simplest model accounted for age, sex, and race/ethnicity. The second model added BMI, several cardiometabolic laboratory values, and vitamin B6, vitamin B12, and folate levels. The third model included all previous factors and added patient characteristics and comorbidities, such as sleep disorders, mental health service use, cardiovascular disease and cancer diagnoses, and alcohol and tobacco use.
In their analysis, Dr. Chen and colleagues dichotomized homocysteine levels to above or below the 75th percentile of the log homocysteine level, which fell at 9.74 nmol/L.
After adjustment, women, but not men, had an association between short sleep and increased odds of elevated homocysteine (odds ratio, 2.691; P = .010). This association “persisted in fully adjusted models,” wrote Dr. Chen and coauthors.
For individuals with obesity (BMI of 30 or greater), the association between elevated homocysteine and extremely short sleep (5 hours or less) persisted in fully adjusted models (beta = .062; P = .039 for model 3).
When looking at ethnicity, the association between extremely short sleep and elevated homocysteine was only seen among non-Hispanic white participants; again, this association was seen after full adjustment for confounders (beta = .068; P = .032). Small sample sizes limited some of the racial/ethnic analyses, noted the investigators.
Homocysteine, explained Dr. Chen and coauthors, is associated with a variety atherogenic changes, and elevated levels are associated with increased risk for cardiovascular disease and mortality. Short sleep is also associated with increased cardiovascular risk, as is long sleep in some studies.
However, though preliminary work had shown that short sleep had an association with homocysteine levels, the relationship is unclear since that study had many potential cardiovascular confounders, said Dr. Chen and coauthors.
The association between extremely short sleep duration and cardiovascular events has been well established, with increased inflammation playing a potential role, although the reasons for the association are still being elucidated. “Because increased homocysteine levels are considered an independent risk factor for cardiovascular diseases, further studies are needed to better understand the relationships among short sleep duration, homocysteine levels, and cardiovascular events,” the investigators wrote.
Whether menstrual variations in serum homocysteine and sleep may have played a part in the significant association seen in women, but not men, was not ascertainable from the NHANES data, which introduces possible confounding, the authors noted.
Similarly, there may be ethnic differences in baseline serum homocysteine levels, said Dr. Chen and his colleagues.
The study’s strengths include the large sample size and ability to control for many demographic and individual characteristics, including comorbidities. However, sleep duration was based on self-report and did not include information about napping or sleep-wake times. Also, sleep quality was not assessed beyond a question about snoring or snorting and a question about a prior diagnosis of a sleep disorder.
“Further longitudinal investigations concerning the effect of sleep deprivation on homocysteine alteration might help provide a better understanding of the pathogenesis of cardiometabolic risk,” concluded Dr. Chen and colleagues.
One of the coauthors reported financial relationships with multiple pharmaceutical companies and UpToDate. The authors reported no external sources of funding.
SOURCE: Chen T-Y et al. J Clin Sleep Med. 2019;15(1):139-48.
Short sleep’s association with cardiovascular risk may be mediated in part by elevated homocysteine levels, suggests a new analysis of data from the 2005-2006 National Health and Nutrition Examination Survey (NHANES).
The study, published in the Journal of Clinical Sleep Medicine, found that elevated homocysteine levels were only associated with short sleep duration for some populations, including women, non-Hispanic white individuals, and participants with obesity.
A total of 4,480 NHANES participants had serum homocysteine levels on record and were included in the study; of these, those with self-reported sleep duration of 7 hours had the lowest serum homocysteine levels. Those with the shortest sleep duration – 5 hours or less per night – had the highest homocysteine levels.
When participants were broken into subgroups by such factors as sex, ethnicity/race, and body mass index, the association between extremely short sleep and elevated homocysteine levels was retained for three groups: women, non-Hispanic white participants, and those with BMIs of 30 kg/m2 and higher.
“[T]his finding might suggest increased vulnerability to cardiovascular risk or other atherothrombotic events in these groups in the context of short sleep,” wrote Tien-Yu Chen, MD, of Tri-Service General Hospital, Taipei, Taiwan, and coauthors in the abstract accompanying the study.
In the NHANES questionnaire, participants were asked how much sleep they usually got, in whole hours. Answers were grouped into 5 hours or less, 6 hours, 7 hours, or 8 hours, and 9 hours or more. Serum homocysteine was measured once for each study participant.
Using multivariate linear regression, homocysteine was considered the dependent, continuous variable, and the association between sleep duration and homocysteine was assessed using three models that accounted for confounders. The first and simplest model accounted for age, sex, and race/ethnicity. The second model added BMI, several cardiometabolic laboratory values, and vitamin B6, vitamin B12, and folate levels. The third model included all previous factors and added patient characteristics and comorbidities, such as sleep disorders, mental health service use, cardiovascular disease and cancer diagnoses, and alcohol and tobacco use.
In their analysis, Dr. Chen and colleagues dichotomized homocysteine levels to above or below the 75th percentile of the log homocysteine level, which fell at 9.74 nmol/L.
After adjustment, women, but not men, had an association between short sleep and increased odds of elevated homocysteine (odds ratio, 2.691; P = .010). This association “persisted in fully adjusted models,” wrote Dr. Chen and coauthors.
For individuals with obesity (BMI of 30 or greater), the association between elevated homocysteine and extremely short sleep (5 hours or less) persisted in fully adjusted models (beta = .062; P = .039 for model 3).
When looking at ethnicity, the association between extremely short sleep and elevated homocysteine was only seen among non-Hispanic white participants; again, this association was seen after full adjustment for confounders (beta = .068; P = .032). Small sample sizes limited some of the racial/ethnic analyses, noted the investigators.
Homocysteine, explained Dr. Chen and coauthors, is associated with a variety atherogenic changes, and elevated levels are associated with increased risk for cardiovascular disease and mortality. Short sleep is also associated with increased cardiovascular risk, as is long sleep in some studies.
However, though preliminary work had shown that short sleep had an association with homocysteine levels, the relationship is unclear since that study had many potential cardiovascular confounders, said Dr. Chen and coauthors.
The association between extremely short sleep duration and cardiovascular events has been well established, with increased inflammation playing a potential role, although the reasons for the association are still being elucidated. “Because increased homocysteine levels are considered an independent risk factor for cardiovascular diseases, further studies are needed to better understand the relationships among short sleep duration, homocysteine levels, and cardiovascular events,” the investigators wrote.
Whether menstrual variations in serum homocysteine and sleep may have played a part in the significant association seen in women, but not men, was not ascertainable from the NHANES data, which introduces possible confounding, the authors noted.
Similarly, there may be ethnic differences in baseline serum homocysteine levels, said Dr. Chen and his colleagues.
The study’s strengths include the large sample size and ability to control for many demographic and individual characteristics, including comorbidities. However, sleep duration was based on self-report and did not include information about napping or sleep-wake times. Also, sleep quality was not assessed beyond a question about snoring or snorting and a question about a prior diagnosis of a sleep disorder.
“Further longitudinal investigations concerning the effect of sleep deprivation on homocysteine alteration might help provide a better understanding of the pathogenesis of cardiometabolic risk,” concluded Dr. Chen and colleagues.
One of the coauthors reported financial relationships with multiple pharmaceutical companies and UpToDate. The authors reported no external sources of funding.
SOURCE: Chen T-Y et al. J Clin Sleep Med. 2019;15(1):139-48.
Short sleep’s association with cardiovascular risk may be mediated in part by elevated homocysteine levels, suggests a new analysis of data from the 2005-2006 National Health and Nutrition Examination Survey (NHANES).
The study, published in the Journal of Clinical Sleep Medicine, found that elevated homocysteine levels were only associated with short sleep duration for some populations, including women, non-Hispanic white individuals, and participants with obesity.
A total of 4,480 NHANES participants had serum homocysteine levels on record and were included in the study; of these, those with self-reported sleep duration of 7 hours had the lowest serum homocysteine levels. Those with the shortest sleep duration – 5 hours or less per night – had the highest homocysteine levels.
When participants were broken into subgroups by such factors as sex, ethnicity/race, and body mass index, the association between extremely short sleep and elevated homocysteine levels was retained for three groups: women, non-Hispanic white participants, and those with BMIs of 30 kg/m2 and higher.
“[T]his finding might suggest increased vulnerability to cardiovascular risk or other atherothrombotic events in these groups in the context of short sleep,” wrote Tien-Yu Chen, MD, of Tri-Service General Hospital, Taipei, Taiwan, and coauthors in the abstract accompanying the study.
In the NHANES questionnaire, participants were asked how much sleep they usually got, in whole hours. Answers were grouped into 5 hours or less, 6 hours, 7 hours, or 8 hours, and 9 hours or more. Serum homocysteine was measured once for each study participant.
Using multivariate linear regression, homocysteine was considered the dependent, continuous variable, and the association between sleep duration and homocysteine was assessed using three models that accounted for confounders. The first and simplest model accounted for age, sex, and race/ethnicity. The second model added BMI, several cardiometabolic laboratory values, and vitamin B6, vitamin B12, and folate levels. The third model included all previous factors and added patient characteristics and comorbidities, such as sleep disorders, mental health service use, cardiovascular disease and cancer diagnoses, and alcohol and tobacco use.
In their analysis, Dr. Chen and colleagues dichotomized homocysteine levels to above or below the 75th percentile of the log homocysteine level, which fell at 9.74 nmol/L.
After adjustment, women, but not men, had an association between short sleep and increased odds of elevated homocysteine (odds ratio, 2.691; P = .010). This association “persisted in fully adjusted models,” wrote Dr. Chen and coauthors.
For individuals with obesity (BMI of 30 or greater), the association between elevated homocysteine and extremely short sleep (5 hours or less) persisted in fully adjusted models (beta = .062; P = .039 for model 3).
When looking at ethnicity, the association between extremely short sleep and elevated homocysteine was only seen among non-Hispanic white participants; again, this association was seen after full adjustment for confounders (beta = .068; P = .032). Small sample sizes limited some of the racial/ethnic analyses, noted the investigators.
Homocysteine, explained Dr. Chen and coauthors, is associated with a variety atherogenic changes, and elevated levels are associated with increased risk for cardiovascular disease and mortality. Short sleep is also associated with increased cardiovascular risk, as is long sleep in some studies.
However, though preliminary work had shown that short sleep had an association with homocysteine levels, the relationship is unclear since that study had many potential cardiovascular confounders, said Dr. Chen and coauthors.
The association between extremely short sleep duration and cardiovascular events has been well established, with increased inflammation playing a potential role, although the reasons for the association are still being elucidated. “Because increased homocysteine levels are considered an independent risk factor for cardiovascular diseases, further studies are needed to better understand the relationships among short sleep duration, homocysteine levels, and cardiovascular events,” the investigators wrote.
Whether menstrual variations in serum homocysteine and sleep may have played a part in the significant association seen in women, but not men, was not ascertainable from the NHANES data, which introduces possible confounding, the authors noted.
Similarly, there may be ethnic differences in baseline serum homocysteine levels, said Dr. Chen and his colleagues.
The study’s strengths include the large sample size and ability to control for many demographic and individual characteristics, including comorbidities. However, sleep duration was based on self-report and did not include information about napping or sleep-wake times. Also, sleep quality was not assessed beyond a question about snoring or snorting and a question about a prior diagnosis of a sleep disorder.
“Further longitudinal investigations concerning the effect of sleep deprivation on homocysteine alteration might help provide a better understanding of the pathogenesis of cardiometabolic risk,” concluded Dr. Chen and colleagues.
One of the coauthors reported financial relationships with multiple pharmaceutical companies and UpToDate. The authors reported no external sources of funding.
SOURCE: Chen T-Y et al. J Clin Sleep Med. 2019;15(1):139-48.
FROM THE JOURNAL OF CLINICAL SLEEP MEDICINE
Key clinical point: Extreme short sleep was associated with high homocysteine levels.
Major finding: In women, extreme short sleep was associated with an odds ratio of 2.691 for elevated homocysteine.
Study details: Analysis of data from 4,480 NHANES participants.
Disclosures: One coauthor reported relationships with multiple pharmaceutical companies and UpToDate. The authors reported no outside sources of funding.
Source: Chen T-Y et al. J Clin Sleep Med. 2019;15(1):139-48.
Fine-tune staging for better SCC risk stratification
ORLANDO – When caring for individuals with sun-damaged skin, dermatologists need comfort with the full spectrum of photo-related skin disease. From assessment and treatment of actinic keratoses (AKs) and field cancerization, to long-term follow-up of cutaneous squamous cell carcinomas (SCCs), appropriate treatment and staging can improve patient quality of life and reduce health care costs, Vishal Patel, MD, said at the Orlando Dermatology Aesthetic and Clinical Conference.
said Dr. Patel, director of cutaneous oncology at George Washington University Cancer Center, Washington. On the other hand, he added, “field disease can be a marker for invasive squamous cell carcinoma risk, and it requires field treatment.” Treatment that reduces field disease is primary prevention because it decreases the formation of invasive SCC, he noted.
“But this level of disease – AKs and SCC in situ – doesn’t kill people,” he emphasized. “I want to leave you with an ability to stage this disease,” said Dr. Patel, noting that SCC mortality may eventually surpass melanoma mortality as deaths from the latter decline and numbers of older Americans with high ultraviolet light exposure and other risk factors climb.
While the majority of AKs regress within 5 years, he looks at the total burden of AKs as a marker for field cancerization “because having less than five in situ or actinic lesions puts you at less than a 1% risk of squamous cell carcinoma formation. Having more than 20 increases that risk 20-fold to 20%,” he said. “That’s the way we need to start thinking about this: Is this a disease – or a symptom?”
Rather than thinking of each AK or SCC in situ as a separate disease event, “the disease we need to be focusing on and treating is field cancerization,” he continued. Within this context, “we should not be thinking that … we need to be aggressive in our management,” which is what results in high costs.
“The reality is that this is a big quality of life issue for our patients. So what do we do?” Field treatment is appropriate for field disease, he said. Dr. Patel said that at GW only field treatment is used; destructive treatment for AKs and SCC in situ is not used. In the absence of patient and lesion characteristics that elevate risk,“surgery is really not the standard of care for in situ lesions for us,” he commented.
“We start by discerning the field disease from the invasive disease” with an initial round of field treatment and, if needed, adjunctive oral chemoprophylaxis. “We lather, rinse, and repeat” the field therapy, continuously if needed, Dr. Patel said.
“We like to do that because we can then identify those specific lesions we want to go after. No cryosurgery, no destructive therapy, because we run the risk of burying those tumors under the scar. They may recur and make it more difficult to accurately stage them in the future,” he noted.
“I like to be more sophisticated in thinking about our approach to the outcomes of these individual lesions,” he said. When it comes to excising lesions that have been biopsied and show invasive SCC, “disc excision may be a more cost-effective way to treat many low-risk SCCs,” he noted. In any case, “removal with clear surgical margins is key.”
Primary tumors with such low-risk attributes as diameter under a centimeter and thickness under 2 mm; well-defined borders; location on the trunk, neck, or extremities; well-differentiated histology; and lack of perineural invasion can all be considered for a disc technique, especially if the patient is immunocompetent without background chronic inflammation or a history of prior radiation therapy.
Staging SCCs, said Dr. Patel, is where things really get tricky. Older staging systems for SCC “led us to overtreat nonaggressive disease and undertreat aggressive disease. I think we have the responsibility to lead the charge to having a more sophisticated approach.” For example, patients whose tumors were staged T2 in the American Joint Commission on Cancer (AJCC) 7 classification system were most likely to have poor outcomes – in part because so few tumors were staged higher – which meant AJCC 7 didn’t provide adequate differentiation for useful risk prognostication.
A group of researchers at the Brigham and Women’s Hospital (BWH), Boston, “came up with a better system to better differentiate those T2 tumors into a high-risk and a low-risk subtype,” according to Dr. Patel.
With use of validated risk factors, the investigators applied a long list of risk factors to 2,000 tumors to see which risk factors, taken individually, were really contributing to poor outcomes. Eventually, four risk factors that made the most difference were identified: size greater than 2 cm, poor tumor differentiation, perineural invasion greater than 0.1 mm in diameter, and tumor invasion beyond subcutaneous fat. “I really want to highlight the size portion of those risk factors,” said Dr. Patel. “Something I’d like you to do in your clinical practice is to measure and document the size of the lesion. … That really, clearly helps” with risk prognostication.
These four factors were then used to break out a T2a stage for tumors with one risk factor and a T2b stage for tumors with two or three risk factors. Tumors with no risk factors are stage T1, and those with all four risk factors are stage T3. In situ SCC is T0.
Applying this new staging system to a 2,000-patient cohort with SCC yielded clear separation in outcomes including recurrence, nodal metastasis, disease-specific death, and overall survival between patients with the T2a and T2b tumors (P less than .001 for all; J Clin Oncol. 2014 Feb 1;32[4]:327-34).
While AJCC 8 is “significantly better” than AJCC 7 in its incorporation of meaningful risk factors into the SCC staging system, “it still underperforms in comparison” with the BWH staging system using the 2000 patient cohort, he said. Recent work has shown the BWH classification system to have superior specificity and positive predictive value in detecting nodal metastasis and disease-specific death in higher-grade tumors. But both BWH and AJCC 8 need further refinement.
“So what are the staging pearls to take home?” Dr. Patel asked. “First, utilize a staging system.” “Staging of SCC utilizing should be done routinely. Most data seems to suggest that the BWH system appears to outperform AJCC 8, and it is what we currently use routinely at GW,” he said.
Patients who are T1 by BWH criteria, with no risk factors, are at low or even no risk, he noted. He pointed out that of the nearly 1,400 patients who met T1 criteria, there were just eight local recurrences, one nodal metastasis, and no distant metastases or deaths. Knowing this should guide physicians on a treatment path that will reduce costs and provide patients with peace of mind, he said.
In the BWH schema, T2a patients fared almost as well, with a 2% risk of nodal metastasis and an overall 1% risk of disease-specific death. “T2a disease is low risk, in my mind. Most of these patients will go on to do well,” he said.
By contrast, “there may be a number of tumors that you are missing” that are candidates for close follow-up if the BWH criteria are not being used, said Dr. Patel. These are the T2b tumors. “For those patients, we want to aggressively follow them and think about a more aggressive management plan.”
The bottom line is that BWH T2b and T3 tumors are both high risk, and management needs to acknowledge this, he said. The current protocol in our cutaneous oncology program includes using routine radiologic nodal staging in patients with BWH stage 2b and above SCCs and considering sentinel lymph node biopsy for certain individuals.
For patients with BWH T2b and T3 tumors, dermatologists should give consideration to tertiary care or cancer center referrals so they have access to the full spectrum of diagnostic and therapeutic modalities and the opportunity to participate in clinical trials, Dr. Patel said.
Dr. Patel reported that he is a speaker for Regeneron/Sanofi and a cofounder of the Skin Cancer Outcomes (SCOUT) consortium.
This article was updated 2/9/2019
ORLANDO – When caring for individuals with sun-damaged skin, dermatologists need comfort with the full spectrum of photo-related skin disease. From assessment and treatment of actinic keratoses (AKs) and field cancerization, to long-term follow-up of cutaneous squamous cell carcinomas (SCCs), appropriate treatment and staging can improve patient quality of life and reduce health care costs, Vishal Patel, MD, said at the Orlando Dermatology Aesthetic and Clinical Conference.
said Dr. Patel, director of cutaneous oncology at George Washington University Cancer Center, Washington. On the other hand, he added, “field disease can be a marker for invasive squamous cell carcinoma risk, and it requires field treatment.” Treatment that reduces field disease is primary prevention because it decreases the formation of invasive SCC, he noted.
“But this level of disease – AKs and SCC in situ – doesn’t kill people,” he emphasized. “I want to leave you with an ability to stage this disease,” said Dr. Patel, noting that SCC mortality may eventually surpass melanoma mortality as deaths from the latter decline and numbers of older Americans with high ultraviolet light exposure and other risk factors climb.
While the majority of AKs regress within 5 years, he looks at the total burden of AKs as a marker for field cancerization “because having less than five in situ or actinic lesions puts you at less than a 1% risk of squamous cell carcinoma formation. Having more than 20 increases that risk 20-fold to 20%,” he said. “That’s the way we need to start thinking about this: Is this a disease – or a symptom?”
Rather than thinking of each AK or SCC in situ as a separate disease event, “the disease we need to be focusing on and treating is field cancerization,” he continued. Within this context, “we should not be thinking that … we need to be aggressive in our management,” which is what results in high costs.
“The reality is that this is a big quality of life issue for our patients. So what do we do?” Field treatment is appropriate for field disease, he said. Dr. Patel said that at GW only field treatment is used; destructive treatment for AKs and SCC in situ is not used. In the absence of patient and lesion characteristics that elevate risk,“surgery is really not the standard of care for in situ lesions for us,” he commented.
“We start by discerning the field disease from the invasive disease” with an initial round of field treatment and, if needed, adjunctive oral chemoprophylaxis. “We lather, rinse, and repeat” the field therapy, continuously if needed, Dr. Patel said.
“We like to do that because we can then identify those specific lesions we want to go after. No cryosurgery, no destructive therapy, because we run the risk of burying those tumors under the scar. They may recur and make it more difficult to accurately stage them in the future,” he noted.
“I like to be more sophisticated in thinking about our approach to the outcomes of these individual lesions,” he said. When it comes to excising lesions that have been biopsied and show invasive SCC, “disc excision may be a more cost-effective way to treat many low-risk SCCs,” he noted. In any case, “removal with clear surgical margins is key.”
Primary tumors with such low-risk attributes as diameter under a centimeter and thickness under 2 mm; well-defined borders; location on the trunk, neck, or extremities; well-differentiated histology; and lack of perineural invasion can all be considered for a disc technique, especially if the patient is immunocompetent without background chronic inflammation or a history of prior radiation therapy.
Staging SCCs, said Dr. Patel, is where things really get tricky. Older staging systems for SCC “led us to overtreat nonaggressive disease and undertreat aggressive disease. I think we have the responsibility to lead the charge to having a more sophisticated approach.” For example, patients whose tumors were staged T2 in the American Joint Commission on Cancer (AJCC) 7 classification system were most likely to have poor outcomes – in part because so few tumors were staged higher – which meant AJCC 7 didn’t provide adequate differentiation for useful risk prognostication.
A group of researchers at the Brigham and Women’s Hospital (BWH), Boston, “came up with a better system to better differentiate those T2 tumors into a high-risk and a low-risk subtype,” according to Dr. Patel.
With use of validated risk factors, the investigators applied a long list of risk factors to 2,000 tumors to see which risk factors, taken individually, were really contributing to poor outcomes. Eventually, four risk factors that made the most difference were identified: size greater than 2 cm, poor tumor differentiation, perineural invasion greater than 0.1 mm in diameter, and tumor invasion beyond subcutaneous fat. “I really want to highlight the size portion of those risk factors,” said Dr. Patel. “Something I’d like you to do in your clinical practice is to measure and document the size of the lesion. … That really, clearly helps” with risk prognostication.
These four factors were then used to break out a T2a stage for tumors with one risk factor and a T2b stage for tumors with two or three risk factors. Tumors with no risk factors are stage T1, and those with all four risk factors are stage T3. In situ SCC is T0.
Applying this new staging system to a 2,000-patient cohort with SCC yielded clear separation in outcomes including recurrence, nodal metastasis, disease-specific death, and overall survival between patients with the T2a and T2b tumors (P less than .001 for all; J Clin Oncol. 2014 Feb 1;32[4]:327-34).
While AJCC 8 is “significantly better” than AJCC 7 in its incorporation of meaningful risk factors into the SCC staging system, “it still underperforms in comparison” with the BWH staging system using the 2000 patient cohort, he said. Recent work has shown the BWH classification system to have superior specificity and positive predictive value in detecting nodal metastasis and disease-specific death in higher-grade tumors. But both BWH and AJCC 8 need further refinement.
“So what are the staging pearls to take home?” Dr. Patel asked. “First, utilize a staging system.” “Staging of SCC utilizing should be done routinely. Most data seems to suggest that the BWH system appears to outperform AJCC 8, and it is what we currently use routinely at GW,” he said.
Patients who are T1 by BWH criteria, with no risk factors, are at low or even no risk, he noted. He pointed out that of the nearly 1,400 patients who met T1 criteria, there were just eight local recurrences, one nodal metastasis, and no distant metastases or deaths. Knowing this should guide physicians on a treatment path that will reduce costs and provide patients with peace of mind, he said.
In the BWH schema, T2a patients fared almost as well, with a 2% risk of nodal metastasis and an overall 1% risk of disease-specific death. “T2a disease is low risk, in my mind. Most of these patients will go on to do well,” he said.
By contrast, “there may be a number of tumors that you are missing” that are candidates for close follow-up if the BWH criteria are not being used, said Dr. Patel. These are the T2b tumors. “For those patients, we want to aggressively follow them and think about a more aggressive management plan.”
The bottom line is that BWH T2b and T3 tumors are both high risk, and management needs to acknowledge this, he said. The current protocol in our cutaneous oncology program includes using routine radiologic nodal staging in patients with BWH stage 2b and above SCCs and considering sentinel lymph node biopsy for certain individuals.
For patients with BWH T2b and T3 tumors, dermatologists should give consideration to tertiary care or cancer center referrals so they have access to the full spectrum of diagnostic and therapeutic modalities and the opportunity to participate in clinical trials, Dr. Patel said.
Dr. Patel reported that he is a speaker for Regeneron/Sanofi and a cofounder of the Skin Cancer Outcomes (SCOUT) consortium.
This article was updated 2/9/2019
ORLANDO – When caring for individuals with sun-damaged skin, dermatologists need comfort with the full spectrum of photo-related skin disease. From assessment and treatment of actinic keratoses (AKs) and field cancerization, to long-term follow-up of cutaneous squamous cell carcinomas (SCCs), appropriate treatment and staging can improve patient quality of life and reduce health care costs, Vishal Patel, MD, said at the Orlando Dermatology Aesthetic and Clinical Conference.
said Dr. Patel, director of cutaneous oncology at George Washington University Cancer Center, Washington. On the other hand, he added, “field disease can be a marker for invasive squamous cell carcinoma risk, and it requires field treatment.” Treatment that reduces field disease is primary prevention because it decreases the formation of invasive SCC, he noted.
“But this level of disease – AKs and SCC in situ – doesn’t kill people,” he emphasized. “I want to leave you with an ability to stage this disease,” said Dr. Patel, noting that SCC mortality may eventually surpass melanoma mortality as deaths from the latter decline and numbers of older Americans with high ultraviolet light exposure and other risk factors climb.
While the majority of AKs regress within 5 years, he looks at the total burden of AKs as a marker for field cancerization “because having less than five in situ or actinic lesions puts you at less than a 1% risk of squamous cell carcinoma formation. Having more than 20 increases that risk 20-fold to 20%,” he said. “That’s the way we need to start thinking about this: Is this a disease – or a symptom?”
Rather than thinking of each AK or SCC in situ as a separate disease event, “the disease we need to be focusing on and treating is field cancerization,” he continued. Within this context, “we should not be thinking that … we need to be aggressive in our management,” which is what results in high costs.
“The reality is that this is a big quality of life issue for our patients. So what do we do?” Field treatment is appropriate for field disease, he said. Dr. Patel said that at GW only field treatment is used; destructive treatment for AKs and SCC in situ is not used. In the absence of patient and lesion characteristics that elevate risk,“surgery is really not the standard of care for in situ lesions for us,” he commented.
“We start by discerning the field disease from the invasive disease” with an initial round of field treatment and, if needed, adjunctive oral chemoprophylaxis. “We lather, rinse, and repeat” the field therapy, continuously if needed, Dr. Patel said.
“We like to do that because we can then identify those specific lesions we want to go after. No cryosurgery, no destructive therapy, because we run the risk of burying those tumors under the scar. They may recur and make it more difficult to accurately stage them in the future,” he noted.
“I like to be more sophisticated in thinking about our approach to the outcomes of these individual lesions,” he said. When it comes to excising lesions that have been biopsied and show invasive SCC, “disc excision may be a more cost-effective way to treat many low-risk SCCs,” he noted. In any case, “removal with clear surgical margins is key.”
Primary tumors with such low-risk attributes as diameter under a centimeter and thickness under 2 mm; well-defined borders; location on the trunk, neck, or extremities; well-differentiated histology; and lack of perineural invasion can all be considered for a disc technique, especially if the patient is immunocompetent without background chronic inflammation or a history of prior radiation therapy.
Staging SCCs, said Dr. Patel, is where things really get tricky. Older staging systems for SCC “led us to overtreat nonaggressive disease and undertreat aggressive disease. I think we have the responsibility to lead the charge to having a more sophisticated approach.” For example, patients whose tumors were staged T2 in the American Joint Commission on Cancer (AJCC) 7 classification system were most likely to have poor outcomes – in part because so few tumors were staged higher – which meant AJCC 7 didn’t provide adequate differentiation for useful risk prognostication.
A group of researchers at the Brigham and Women’s Hospital (BWH), Boston, “came up with a better system to better differentiate those T2 tumors into a high-risk and a low-risk subtype,” according to Dr. Patel.
With use of validated risk factors, the investigators applied a long list of risk factors to 2,000 tumors to see which risk factors, taken individually, were really contributing to poor outcomes. Eventually, four risk factors that made the most difference were identified: size greater than 2 cm, poor tumor differentiation, perineural invasion greater than 0.1 mm in diameter, and tumor invasion beyond subcutaneous fat. “I really want to highlight the size portion of those risk factors,” said Dr. Patel. “Something I’d like you to do in your clinical practice is to measure and document the size of the lesion. … That really, clearly helps” with risk prognostication.
These four factors were then used to break out a T2a stage for tumors with one risk factor and a T2b stage for tumors with two or three risk factors. Tumors with no risk factors are stage T1, and those with all four risk factors are stage T3. In situ SCC is T0.
Applying this new staging system to a 2,000-patient cohort with SCC yielded clear separation in outcomes including recurrence, nodal metastasis, disease-specific death, and overall survival between patients with the T2a and T2b tumors (P less than .001 for all; J Clin Oncol. 2014 Feb 1;32[4]:327-34).
While AJCC 8 is “significantly better” than AJCC 7 in its incorporation of meaningful risk factors into the SCC staging system, “it still underperforms in comparison” with the BWH staging system using the 2000 patient cohort, he said. Recent work has shown the BWH classification system to have superior specificity and positive predictive value in detecting nodal metastasis and disease-specific death in higher-grade tumors. But both BWH and AJCC 8 need further refinement.
“So what are the staging pearls to take home?” Dr. Patel asked. “First, utilize a staging system.” “Staging of SCC utilizing should be done routinely. Most data seems to suggest that the BWH system appears to outperform AJCC 8, and it is what we currently use routinely at GW,” he said.
Patients who are T1 by BWH criteria, with no risk factors, are at low or even no risk, he noted. He pointed out that of the nearly 1,400 patients who met T1 criteria, there were just eight local recurrences, one nodal metastasis, and no distant metastases or deaths. Knowing this should guide physicians on a treatment path that will reduce costs and provide patients with peace of mind, he said.
In the BWH schema, T2a patients fared almost as well, with a 2% risk of nodal metastasis and an overall 1% risk of disease-specific death. “T2a disease is low risk, in my mind. Most of these patients will go on to do well,” he said.
By contrast, “there may be a number of tumors that you are missing” that are candidates for close follow-up if the BWH criteria are not being used, said Dr. Patel. These are the T2b tumors. “For those patients, we want to aggressively follow them and think about a more aggressive management plan.”
The bottom line is that BWH T2b and T3 tumors are both high risk, and management needs to acknowledge this, he said. The current protocol in our cutaneous oncology program includes using routine radiologic nodal staging in patients with BWH stage 2b and above SCCs and considering sentinel lymph node biopsy for certain individuals.
For patients with BWH T2b and T3 tumors, dermatologists should give consideration to tertiary care or cancer center referrals so they have access to the full spectrum of diagnostic and therapeutic modalities and the opportunity to participate in clinical trials, Dr. Patel said.
Dr. Patel reported that he is a speaker for Regeneron/Sanofi and a cofounder of the Skin Cancer Outcomes (SCOUT) consortium.
This article was updated 2/9/2019
EXPERT ANALYSIS FROM ODAC 2019
HHS effort aims to end new HIV cases within 10 years
WASHINGTON – Leaders from five federal agencies came together to announce the framework for a bold new national initiative that aims to eliminate new cases of HIV infection in the United States within 10 years. The announcement came the day after President Trump’s State of the Union address, which highlighted the new effort.
“HIV has cost America too much for too long,” said Adm. Brett Giroir, MD, assistant secretary for health at the Department of Health & Human Services, in a press briefing. In addition to the 700,000 U.S. lives the disease has claimed since 1981, “We are at high risk of another 400,000 becoming infected over the next decade,” with about 40,000 new infections still occurring every year, he said.
Dr. Giroir will lead a coordinated effort among HHS, the Centers for Disease Control, the National Institutes of Health, the Health Resources and Services Administration, and the Indian Health Service. The goals are to reduce new cases of HIV by 50% within 5 years, and by 90% within 10 years.
These 48 counties, together with Washington and San Juan, Puerto Rico, accounted for more than half of the new HIV diagnoses in 2016 and 2017, said Dr. Giroir.
“This is a laser-focused program targeting counties where infection is the highest,” said CDC Director Robert R. Redfield, MD. “We propose to deploy personnel, resources, and strategies” in these targeted areas to maximize not just diagnosis and treatment but also to reach those at risk for HIV to enroll them in preexposure prophylaxis (PrEP) regimens, he said.
In addition to the targeted counties, seven states in the rural South as well as Native American and Alaskan Native populations also will receive intensified education, diagnostic, and treatment services. The targeted states are Alabama, Arkansas, Kentucky, Mississippi, Missouri, Oklahoma, and South Carolina.
George Sigounas, PhD, administrator or the Health Resources and Services Administration, said that existing community health centers will be especially important in reaching rural underserved and marginalized populations. Currently, he said, HRSA supports 12,000 service delivery sites across the country that are already delivering care to 27 million individuals. “These sites will play a major expanded role in providing PrEP to those who are at the greatest risk of contracting HIV,” said Dr. Sigounas.
Among the currently existing resources that will be leveraged are services provided by the Ryan White HIV/AIDS program, which already provides HIV primary medical care and support services through a network of grants to states and local government and community organizations. About half of the people currently diagnosed with HIV in the United States receive services through this program now.
The NIH maintains a geographically distributed network of Centers for AIDS Research that also will be folded into the new initiative.
In his remarks, Anthony S. Fauci, MD, director of the NIH’s National Center for Allergy and Infectious Diseases, pointed out that, “Treatment and detection are wrapped together, because treated individuals can’t transmit HIV” if they are adherent to antiretroviral medication use and achieve an undetectable viral load, he said. “If you get everyone who’s infected on antiretrovirals and give those who need it PrEP, you can theoretically end the epidemic as we know it – and that is our goal.”
Dr. Fauci went on to say that implementation science will play a key role in achieving a targeted and coordinated approach. “We will work closely with our colleagues to make sure the implementation is done well. We have lessons learned; we will do better and better,” he said.
The nuts and bolts of the program include a four-pronged strategy to diagnose individuals as early as possible after infection, to initiate prompt, effective, and sustained treatment, to protect those at risk for HIV by proven means including PrEP, and to provide rapid response when new HIV clusters are identified. A reimagining of current and future personnel into an “HIV health force” will put teams on the ground in each jurisdiction to carry out the initiative.
Though the goal is to provide PrEP to every at-risk individual, Dr. Fauci said that current modeling shows that if PrEP reaches 50%-60% in the at-risk population, new infections can be reduced by 90%. He added, “PrEP works. The efficacy is well over 90%.”
Funding details were not released at the press briefing; Dr. Giroir said that figures will be released by the Office of Management and Budget as part of the 2020 budget cycle. He confirmed, however, that new funds will be allocated for the effort, rather than a mere reshuffling of existing fund and resources.
Several of the leaders acknowledged the problem of stigma and marginalization that many individuals living with or at risk for HIV face, since men who have sex with men, transgender people, sex workers, and those with opioid use disorder all fall into this category.
“Every American deserves to be treated with respect and dignity. We will vigorously enforce all laws on the books about discrimination,” said Rear Adm. Michael Weahkee, MD, principal deputy director of the Indian Health Service. This is especially important in Native American communities “where everybody knows everybody,” he said, and it’s vitally important to include individual and community education in the efforts.
Dr. Redfield concurred, adding that “Dr. Fauci and I have been engaged in HIV since 1981. We have witnessed firsthand the negative impact that stigma can have on our capacity to practice public health. The transgender population, in particular, needs to be reached out to. We need to be able to address in a comprehensive way how to destigmatize the HIV population.”
WASHINGTON – Leaders from five federal agencies came together to announce the framework for a bold new national initiative that aims to eliminate new cases of HIV infection in the United States within 10 years. The announcement came the day after President Trump’s State of the Union address, which highlighted the new effort.
“HIV has cost America too much for too long,” said Adm. Brett Giroir, MD, assistant secretary for health at the Department of Health & Human Services, in a press briefing. In addition to the 700,000 U.S. lives the disease has claimed since 1981, “We are at high risk of another 400,000 becoming infected over the next decade,” with about 40,000 new infections still occurring every year, he said.
Dr. Giroir will lead a coordinated effort among HHS, the Centers for Disease Control, the National Institutes of Health, the Health Resources and Services Administration, and the Indian Health Service. The goals are to reduce new cases of HIV by 50% within 5 years, and by 90% within 10 years.
These 48 counties, together with Washington and San Juan, Puerto Rico, accounted for more than half of the new HIV diagnoses in 2016 and 2017, said Dr. Giroir.
“This is a laser-focused program targeting counties where infection is the highest,” said CDC Director Robert R. Redfield, MD. “We propose to deploy personnel, resources, and strategies” in these targeted areas to maximize not just diagnosis and treatment but also to reach those at risk for HIV to enroll them in preexposure prophylaxis (PrEP) regimens, he said.
In addition to the targeted counties, seven states in the rural South as well as Native American and Alaskan Native populations also will receive intensified education, diagnostic, and treatment services. The targeted states are Alabama, Arkansas, Kentucky, Mississippi, Missouri, Oklahoma, and South Carolina.
George Sigounas, PhD, administrator or the Health Resources and Services Administration, said that existing community health centers will be especially important in reaching rural underserved and marginalized populations. Currently, he said, HRSA supports 12,000 service delivery sites across the country that are already delivering care to 27 million individuals. “These sites will play a major expanded role in providing PrEP to those who are at the greatest risk of contracting HIV,” said Dr. Sigounas.
Among the currently existing resources that will be leveraged are services provided by the Ryan White HIV/AIDS program, which already provides HIV primary medical care and support services through a network of grants to states and local government and community organizations. About half of the people currently diagnosed with HIV in the United States receive services through this program now.
The NIH maintains a geographically distributed network of Centers for AIDS Research that also will be folded into the new initiative.
In his remarks, Anthony S. Fauci, MD, director of the NIH’s National Center for Allergy and Infectious Diseases, pointed out that, “Treatment and detection are wrapped together, because treated individuals can’t transmit HIV” if they are adherent to antiretroviral medication use and achieve an undetectable viral load, he said. “If you get everyone who’s infected on antiretrovirals and give those who need it PrEP, you can theoretically end the epidemic as we know it – and that is our goal.”
Dr. Fauci went on to say that implementation science will play a key role in achieving a targeted and coordinated approach. “We will work closely with our colleagues to make sure the implementation is done well. We have lessons learned; we will do better and better,” he said.
The nuts and bolts of the program include a four-pronged strategy to diagnose individuals as early as possible after infection, to initiate prompt, effective, and sustained treatment, to protect those at risk for HIV by proven means including PrEP, and to provide rapid response when new HIV clusters are identified. A reimagining of current and future personnel into an “HIV health force” will put teams on the ground in each jurisdiction to carry out the initiative.
Though the goal is to provide PrEP to every at-risk individual, Dr. Fauci said that current modeling shows that if PrEP reaches 50%-60% in the at-risk population, new infections can be reduced by 90%. He added, “PrEP works. The efficacy is well over 90%.”
Funding details were not released at the press briefing; Dr. Giroir said that figures will be released by the Office of Management and Budget as part of the 2020 budget cycle. He confirmed, however, that new funds will be allocated for the effort, rather than a mere reshuffling of existing fund and resources.
Several of the leaders acknowledged the problem of stigma and marginalization that many individuals living with or at risk for HIV face, since men who have sex with men, transgender people, sex workers, and those with opioid use disorder all fall into this category.
“Every American deserves to be treated with respect and dignity. We will vigorously enforce all laws on the books about discrimination,” said Rear Adm. Michael Weahkee, MD, principal deputy director of the Indian Health Service. This is especially important in Native American communities “where everybody knows everybody,” he said, and it’s vitally important to include individual and community education in the efforts.
Dr. Redfield concurred, adding that “Dr. Fauci and I have been engaged in HIV since 1981. We have witnessed firsthand the negative impact that stigma can have on our capacity to practice public health. The transgender population, in particular, needs to be reached out to. We need to be able to address in a comprehensive way how to destigmatize the HIV population.”
WASHINGTON – Leaders from five federal agencies came together to announce the framework for a bold new national initiative that aims to eliminate new cases of HIV infection in the United States within 10 years. The announcement came the day after President Trump’s State of the Union address, which highlighted the new effort.
“HIV has cost America too much for too long,” said Adm. Brett Giroir, MD, assistant secretary for health at the Department of Health & Human Services, in a press briefing. In addition to the 700,000 U.S. lives the disease has claimed since 1981, “We are at high risk of another 400,000 becoming infected over the next decade,” with about 40,000 new infections still occurring every year, he said.
Dr. Giroir will lead a coordinated effort among HHS, the Centers for Disease Control, the National Institutes of Health, the Health Resources and Services Administration, and the Indian Health Service. The goals are to reduce new cases of HIV by 50% within 5 years, and by 90% within 10 years.
These 48 counties, together with Washington and San Juan, Puerto Rico, accounted for more than half of the new HIV diagnoses in 2016 and 2017, said Dr. Giroir.
“This is a laser-focused program targeting counties where infection is the highest,” said CDC Director Robert R. Redfield, MD. “We propose to deploy personnel, resources, and strategies” in these targeted areas to maximize not just diagnosis and treatment but also to reach those at risk for HIV to enroll them in preexposure prophylaxis (PrEP) regimens, he said.
In addition to the targeted counties, seven states in the rural South as well as Native American and Alaskan Native populations also will receive intensified education, diagnostic, and treatment services. The targeted states are Alabama, Arkansas, Kentucky, Mississippi, Missouri, Oklahoma, and South Carolina.
George Sigounas, PhD, administrator or the Health Resources and Services Administration, said that existing community health centers will be especially important in reaching rural underserved and marginalized populations. Currently, he said, HRSA supports 12,000 service delivery sites across the country that are already delivering care to 27 million individuals. “These sites will play a major expanded role in providing PrEP to those who are at the greatest risk of contracting HIV,” said Dr. Sigounas.
Among the currently existing resources that will be leveraged are services provided by the Ryan White HIV/AIDS program, which already provides HIV primary medical care and support services through a network of grants to states and local government and community organizations. About half of the people currently diagnosed with HIV in the United States receive services through this program now.
The NIH maintains a geographically distributed network of Centers for AIDS Research that also will be folded into the new initiative.
In his remarks, Anthony S. Fauci, MD, director of the NIH’s National Center for Allergy and Infectious Diseases, pointed out that, “Treatment and detection are wrapped together, because treated individuals can’t transmit HIV” if they are adherent to antiretroviral medication use and achieve an undetectable viral load, he said. “If you get everyone who’s infected on antiretrovirals and give those who need it PrEP, you can theoretically end the epidemic as we know it – and that is our goal.”
Dr. Fauci went on to say that implementation science will play a key role in achieving a targeted and coordinated approach. “We will work closely with our colleagues to make sure the implementation is done well. We have lessons learned; we will do better and better,” he said.
The nuts and bolts of the program include a four-pronged strategy to diagnose individuals as early as possible after infection, to initiate prompt, effective, and sustained treatment, to protect those at risk for HIV by proven means including PrEP, and to provide rapid response when new HIV clusters are identified. A reimagining of current and future personnel into an “HIV health force” will put teams on the ground in each jurisdiction to carry out the initiative.
Though the goal is to provide PrEP to every at-risk individual, Dr. Fauci said that current modeling shows that if PrEP reaches 50%-60% in the at-risk population, new infections can be reduced by 90%. He added, “PrEP works. The efficacy is well over 90%.”
Funding details were not released at the press briefing; Dr. Giroir said that figures will be released by the Office of Management and Budget as part of the 2020 budget cycle. He confirmed, however, that new funds will be allocated for the effort, rather than a mere reshuffling of existing fund and resources.
Several of the leaders acknowledged the problem of stigma and marginalization that many individuals living with or at risk for HIV face, since men who have sex with men, transgender people, sex workers, and those with opioid use disorder all fall into this category.
“Every American deserves to be treated with respect and dignity. We will vigorously enforce all laws on the books about discrimination,” said Rear Adm. Michael Weahkee, MD, principal deputy director of the Indian Health Service. This is especially important in Native American communities “where everybody knows everybody,” he said, and it’s vitally important to include individual and community education in the efforts.
Dr. Redfield concurred, adding that “Dr. Fauci and I have been engaged in HIV since 1981. We have witnessed firsthand the negative impact that stigma can have on our capacity to practice public health. The transgender population, in particular, needs to be reached out to. We need to be able to address in a comprehensive way how to destigmatize the HIV population.”
FROM A HEALTH AND HUMAN SERVICES BRIEFING
2019 ID update for dermatologists: Ticks are the “ride of choice” for arthropods
ORLANDO – New tricks from ticks, near-zero Zika, and the perils of personal grooming: Dermatologists have a lot to think about along the infectious disease spectrum in 2019, according to Justin Finch, MD, speaking at the Orlando Dermatology Aesthetic and Clinical Conference.
Anaphylaxis from alpha-gal syndrome is on the rise, caused in part by the geographic spread of the Lone Star tick. Beginning in 2006, isolated cases of an anaphylactic reaction to cetuximab, the epidermal growth factor receptor antagonist used to treat certain cancers, began to be seen in a curious geographic distribution. “The anaphylaxis cases were restricted to the southeastern United States, the home of the Lone Star tick,” said Dr. Finch, of the department of dermatology at the University of Connecticut, Farmington.
With some detective work, physicians and epidemiologists eventually determined that patients were reacting to an oligosaccharide called galactose-alpha–1,3-galactose (alpha-gal) found in cetuximab. This protein is also found in the meat of nonprimate mammals; individuals in the southeastern United States, where the Lone Star tick is endemic, had been sensitized via exposure to alpha-gal from Lone Star tick bites.
“Alpha-gal syndrome is on the rise,” said Dr. Finch, driven by the increased spread of this tick. Individuals who are sensitized develop delayed anaphylaxis 2-7 hours after ingesting red meat such as beef, pork, or lamb. “Ask about it,” said Dr. Finch, in patients who develop urticaria, dyspnea, angioedema, or hypotension without a clear offender. Because of the delay between allergen ingestion and anaphylaxis, it can be hard to connect the dots.
A number of drugs other than cetuximab contain alpha-gal, so patients must also be told to avoid these agents, said Dr. Finch, who noted that alpha-gal syndrome isn’t the only emerging culprit for tick-borne diseases. “The tick is the ride of choice for arthropod-borne diseases in the U.S.,” he added. “Year after year, tick-borne diseases top mosquito-borne diseases in the U.S.” Zika’s explosion in 2016 made that year the exception to the rule.
Now, Zika virus may be on the wane – the number of case reports have plummeted both in the United States and in Central and South America this past year – but it hasn’t completely gone away. “It looks like it fell off all the maps,” but the virus is still present at low levels, he said.
When Zika virus is symptomatic, there’s often a nonspecific maculopapular rash. Critically, Dr. Finch said, “women with a rash are four times as likely to have adverse congenital outcomes. This is the important point for us to take home as dermatologists. ... It’s really important to have a high index of suspicion and to screen these women as they are coming into our clinic.”
Turning back to ticks, Lyme disease continues to be a problem in endemic areas in the Northeast, the mid-Atlantic region, and the Midwest, said Dr. Finch, so it’s a perennial on the differential diagnosis for dermatologists.
An Asian tick new to North America was seen for the first time in New Jersey in the summer of 2017. The Asian longhorned tick carries a phlebovirus that causes severe fever with thrombocytopenia syndrome, a disease with a 15% fatality rate. The reservoir host of this virus in Asia isn’t known, said Dr. Finch, adding that no cases of the virus have yet been seen in the United States. As of November 2018, according to the Centers for Disease Control and Prevention, the tick had been found in nine states (Arkansas, Connecticut, Maryland, North Carolina, New Jersey, New York, Pennsylvania, Virginia, and West Virginia).
“What’s not on the rise? Pubic lice. We are destroying their natural habitat!” said Dr. Finch, citing surveys about personal grooming that show that more than 90% of women remove at least some of their pubic hair. Most college campuses are currently reporting essentially no cases of pubic lice, he noted.
However, the same personal grooming practices may be contributing to increases in molluscum contagiosum, herpes simplex virus, some strains of human papillomavirus, and cutaneous Streptococcus pyogenes infections, he said.
Another STI has had a resurgence in geographic pockets around the nation and among specific populations, said Dr. Finch. Syphilis is on the rise among gay and bisexual men and African Americans. Known as the “great imitator,” syphilis should be on the differential for dermatologists when the clinical picture isn’t quite adding up. “Think of this, and screen with an RPR [rapid plasma reagin],” he said.
Finally, an old enemy is back: A total of 11 measles outbreaks were reported in 2018. “We need to know about measles because of the complications,” said Dr. Finch. Even years later, such dire sequelae as subacute sclerosing panencephalitis can crop up, he added.
After a 2-week incubation period, measles begins with a fever and cough, congestion, and conjunctivitis. The rash begins on the head and spreads inferiorly by day 3. As the rash blooms, the classic morbilliform eruption becomes apparent. A biopsy of affected skin will be nonspecific; measles is diagnosed with a nasopharyngeal culture and serologic assay. Dr. Finch pointed out that dermatologists are unlikely to see measles in its earliest stages because their expertise will be called on only after it becomes clear that the patient is not experiencing just a mild illness with a viral exanthem.
When there’s suspicion for measles, a full-body skin exam is needed. “Koplik’s spots – the gray white papules on the buccal mucosa – are not pathognomonic in themselves, but in the clinical scenario of a person with measles” they can help the dermatologist make a definitive call, he said.
Vitamin A can be given to a patient with active measles, but prevention via immunization at age 12 months and 5 years is the only way to stop the disease, Dr. Finch noted.
Dr. Finch reported that he has no relevant conflicts of interest.
ORLANDO – New tricks from ticks, near-zero Zika, and the perils of personal grooming: Dermatologists have a lot to think about along the infectious disease spectrum in 2019, according to Justin Finch, MD, speaking at the Orlando Dermatology Aesthetic and Clinical Conference.
Anaphylaxis from alpha-gal syndrome is on the rise, caused in part by the geographic spread of the Lone Star tick. Beginning in 2006, isolated cases of an anaphylactic reaction to cetuximab, the epidermal growth factor receptor antagonist used to treat certain cancers, began to be seen in a curious geographic distribution. “The anaphylaxis cases were restricted to the southeastern United States, the home of the Lone Star tick,” said Dr. Finch, of the department of dermatology at the University of Connecticut, Farmington.
With some detective work, physicians and epidemiologists eventually determined that patients were reacting to an oligosaccharide called galactose-alpha–1,3-galactose (alpha-gal) found in cetuximab. This protein is also found in the meat of nonprimate mammals; individuals in the southeastern United States, where the Lone Star tick is endemic, had been sensitized via exposure to alpha-gal from Lone Star tick bites.
“Alpha-gal syndrome is on the rise,” said Dr. Finch, driven by the increased spread of this tick. Individuals who are sensitized develop delayed anaphylaxis 2-7 hours after ingesting red meat such as beef, pork, or lamb. “Ask about it,” said Dr. Finch, in patients who develop urticaria, dyspnea, angioedema, or hypotension without a clear offender. Because of the delay between allergen ingestion and anaphylaxis, it can be hard to connect the dots.
A number of drugs other than cetuximab contain alpha-gal, so patients must also be told to avoid these agents, said Dr. Finch, who noted that alpha-gal syndrome isn’t the only emerging culprit for tick-borne diseases. “The tick is the ride of choice for arthropod-borne diseases in the U.S.,” he added. “Year after year, tick-borne diseases top mosquito-borne diseases in the U.S.” Zika’s explosion in 2016 made that year the exception to the rule.
Now, Zika virus may be on the wane – the number of case reports have plummeted both in the United States and in Central and South America this past year – but it hasn’t completely gone away. “It looks like it fell off all the maps,” but the virus is still present at low levels, he said.
When Zika virus is symptomatic, there’s often a nonspecific maculopapular rash. Critically, Dr. Finch said, “women with a rash are four times as likely to have adverse congenital outcomes. This is the important point for us to take home as dermatologists. ... It’s really important to have a high index of suspicion and to screen these women as they are coming into our clinic.”
Turning back to ticks, Lyme disease continues to be a problem in endemic areas in the Northeast, the mid-Atlantic region, and the Midwest, said Dr. Finch, so it’s a perennial on the differential diagnosis for dermatologists.
An Asian tick new to North America was seen for the first time in New Jersey in the summer of 2017. The Asian longhorned tick carries a phlebovirus that causes severe fever with thrombocytopenia syndrome, a disease with a 15% fatality rate. The reservoir host of this virus in Asia isn’t known, said Dr. Finch, adding that no cases of the virus have yet been seen in the United States. As of November 2018, according to the Centers for Disease Control and Prevention, the tick had been found in nine states (Arkansas, Connecticut, Maryland, North Carolina, New Jersey, New York, Pennsylvania, Virginia, and West Virginia).
“What’s not on the rise? Pubic lice. We are destroying their natural habitat!” said Dr. Finch, citing surveys about personal grooming that show that more than 90% of women remove at least some of their pubic hair. Most college campuses are currently reporting essentially no cases of pubic lice, he noted.
However, the same personal grooming practices may be contributing to increases in molluscum contagiosum, herpes simplex virus, some strains of human papillomavirus, and cutaneous Streptococcus pyogenes infections, he said.
Another STI has had a resurgence in geographic pockets around the nation and among specific populations, said Dr. Finch. Syphilis is on the rise among gay and bisexual men and African Americans. Known as the “great imitator,” syphilis should be on the differential for dermatologists when the clinical picture isn’t quite adding up. “Think of this, and screen with an RPR [rapid plasma reagin],” he said.
Finally, an old enemy is back: A total of 11 measles outbreaks were reported in 2018. “We need to know about measles because of the complications,” said Dr. Finch. Even years later, such dire sequelae as subacute sclerosing panencephalitis can crop up, he added.
After a 2-week incubation period, measles begins with a fever and cough, congestion, and conjunctivitis. The rash begins on the head and spreads inferiorly by day 3. As the rash blooms, the classic morbilliform eruption becomes apparent. A biopsy of affected skin will be nonspecific; measles is diagnosed with a nasopharyngeal culture and serologic assay. Dr. Finch pointed out that dermatologists are unlikely to see measles in its earliest stages because their expertise will be called on only after it becomes clear that the patient is not experiencing just a mild illness with a viral exanthem.
When there’s suspicion for measles, a full-body skin exam is needed. “Koplik’s spots – the gray white papules on the buccal mucosa – are not pathognomonic in themselves, but in the clinical scenario of a person with measles” they can help the dermatologist make a definitive call, he said.
Vitamin A can be given to a patient with active measles, but prevention via immunization at age 12 months and 5 years is the only way to stop the disease, Dr. Finch noted.
Dr. Finch reported that he has no relevant conflicts of interest.
ORLANDO – New tricks from ticks, near-zero Zika, and the perils of personal grooming: Dermatologists have a lot to think about along the infectious disease spectrum in 2019, according to Justin Finch, MD, speaking at the Orlando Dermatology Aesthetic and Clinical Conference.
Anaphylaxis from alpha-gal syndrome is on the rise, caused in part by the geographic spread of the Lone Star tick. Beginning in 2006, isolated cases of an anaphylactic reaction to cetuximab, the epidermal growth factor receptor antagonist used to treat certain cancers, began to be seen in a curious geographic distribution. “The anaphylaxis cases were restricted to the southeastern United States, the home of the Lone Star tick,” said Dr. Finch, of the department of dermatology at the University of Connecticut, Farmington.
With some detective work, physicians and epidemiologists eventually determined that patients were reacting to an oligosaccharide called galactose-alpha–1,3-galactose (alpha-gal) found in cetuximab. This protein is also found in the meat of nonprimate mammals; individuals in the southeastern United States, where the Lone Star tick is endemic, had been sensitized via exposure to alpha-gal from Lone Star tick bites.
“Alpha-gal syndrome is on the rise,” said Dr. Finch, driven by the increased spread of this tick. Individuals who are sensitized develop delayed anaphylaxis 2-7 hours after ingesting red meat such as beef, pork, or lamb. “Ask about it,” said Dr. Finch, in patients who develop urticaria, dyspnea, angioedema, or hypotension without a clear offender. Because of the delay between allergen ingestion and anaphylaxis, it can be hard to connect the dots.
A number of drugs other than cetuximab contain alpha-gal, so patients must also be told to avoid these agents, said Dr. Finch, who noted that alpha-gal syndrome isn’t the only emerging culprit for tick-borne diseases. “The tick is the ride of choice for arthropod-borne diseases in the U.S.,” he added. “Year after year, tick-borne diseases top mosquito-borne diseases in the U.S.” Zika’s explosion in 2016 made that year the exception to the rule.
Now, Zika virus may be on the wane – the number of case reports have plummeted both in the United States and in Central and South America this past year – but it hasn’t completely gone away. “It looks like it fell off all the maps,” but the virus is still present at low levels, he said.
When Zika virus is symptomatic, there’s often a nonspecific maculopapular rash. Critically, Dr. Finch said, “women with a rash are four times as likely to have adverse congenital outcomes. This is the important point for us to take home as dermatologists. ... It’s really important to have a high index of suspicion and to screen these women as they are coming into our clinic.”
Turning back to ticks, Lyme disease continues to be a problem in endemic areas in the Northeast, the mid-Atlantic region, and the Midwest, said Dr. Finch, so it’s a perennial on the differential diagnosis for dermatologists.
An Asian tick new to North America was seen for the first time in New Jersey in the summer of 2017. The Asian longhorned tick carries a phlebovirus that causes severe fever with thrombocytopenia syndrome, a disease with a 15% fatality rate. The reservoir host of this virus in Asia isn’t known, said Dr. Finch, adding that no cases of the virus have yet been seen in the United States. As of November 2018, according to the Centers for Disease Control and Prevention, the tick had been found in nine states (Arkansas, Connecticut, Maryland, North Carolina, New Jersey, New York, Pennsylvania, Virginia, and West Virginia).
“What’s not on the rise? Pubic lice. We are destroying their natural habitat!” said Dr. Finch, citing surveys about personal grooming that show that more than 90% of women remove at least some of their pubic hair. Most college campuses are currently reporting essentially no cases of pubic lice, he noted.
However, the same personal grooming practices may be contributing to increases in molluscum contagiosum, herpes simplex virus, some strains of human papillomavirus, and cutaneous Streptococcus pyogenes infections, he said.
Another STI has had a resurgence in geographic pockets around the nation and among specific populations, said Dr. Finch. Syphilis is on the rise among gay and bisexual men and African Americans. Known as the “great imitator,” syphilis should be on the differential for dermatologists when the clinical picture isn’t quite adding up. “Think of this, and screen with an RPR [rapid plasma reagin],” he said.
Finally, an old enemy is back: A total of 11 measles outbreaks were reported in 2018. “We need to know about measles because of the complications,” said Dr. Finch. Even years later, such dire sequelae as subacute sclerosing panencephalitis can crop up, he added.
After a 2-week incubation period, measles begins with a fever and cough, congestion, and conjunctivitis. The rash begins on the head and spreads inferiorly by day 3. As the rash blooms, the classic morbilliform eruption becomes apparent. A biopsy of affected skin will be nonspecific; measles is diagnosed with a nasopharyngeal culture and serologic assay. Dr. Finch pointed out that dermatologists are unlikely to see measles in its earliest stages because their expertise will be called on only after it becomes clear that the patient is not experiencing just a mild illness with a viral exanthem.
When there’s suspicion for measles, a full-body skin exam is needed. “Koplik’s spots – the gray white papules on the buccal mucosa – are not pathognomonic in themselves, but in the clinical scenario of a person with measles” they can help the dermatologist make a definitive call, he said.
Vitamin A can be given to a patient with active measles, but prevention via immunization at age 12 months and 5 years is the only way to stop the disease, Dr. Finch noted.
Dr. Finch reported that he has no relevant conflicts of interest.
EXPERT ANALYSIS FROM ODAC 2019
Will microneedling enhance the impact of photodynamic therapy?
ORLANDO –
Dr. Spencer, who practices in St. Petersburg, Fla., and is cochair of the conference, gave attendees a roundup of what’s new in adjuncts and delivery methods for photodynamic therapy (PDT). Among the updates is the promise of PDT delivered by means of an ultrashort incubation time of 10-20 minutes, followed by prolonged blue light exposure time of 1 hour. “The idea is that the enzymatic conversion is occurring during the light exposure,” Dr. Spencer said, adding that reports of this approach are mostly anecdotal.
A variation on the ultrashort incubation adds microneedling, he said. In one recent study, 33 patients who had facial actinic keratoses (AKs) were randomized to 10 or 20 minutes of incubation after application of aminolevulinic acid (ALA), followed by 1,000 seconds of exposure to blue light. However, in this split-face study, participants each had one side of their faces treated with microneedling and the other half with a sham treatment before ALA was applied.
Those who had the shorter incubation time had 43% of AKs cleared on the side that received microneedling, compared with 38% on the sham side. For those who received 20 minutes of ALA incubation, rates were higher, with 76% AK clearance on the treated side and 58% on the sham side. “Patients reported that the procedure was virtually painless on both sides,” said Dr. Spencer.
Though the addition of microneedling to PDT is a newer trend, there’s one that’s been a mainstay in Europe for some time: daylight PDT. He cited a review article published in 2016, which identified 17 studies on the use of daylight PDT (Dermatol Surg. 2016 Mar;42[3]:286-95).
Advantages of daylight PDT, he said, include less time in the office for patients and “supposedly less pain.” European protocols vary, but most use methyl aminolevulinate, which he said is a “little more lipophilic than ALA,” with incubation times ranging from 0 to 30 minutes. Exposure time is also variable, but will usually range from 1.5 to 2.5 hours. Most patients receive just one treatment, but some protocols will include up to three treatments.
Overall, studies show a range from 46% to almost 90% complete response rates when AKs are treated with daylight PDT. One study that looked at daylight PDT for small basal cell carcinomas showed that 94% of patients had clinical clearance of their lesions after two treatment sessions; however, the recurrence rate at 12 months post therapy was 21%, Dr. Spencer said.
He shared results of a recent head-to-head study of conventional and daylight PDT; conducted in Greece, the study enrolled patients with “high sun exposure” and used a split-face design.
Of the 46 patients who received MAL on both sides of their faces, response rates were similar at both 3 and 12 months, with slightly numerically higher clearance rates for conventional versus daylight PDT. The 3-month clearance rate for conventional PDT was 80.6%, compared with 78.0% for daylight PDT. At 12 months, the respective clearance rates were 73.7% and 71.8% (J Eur Acad Dermatol Venereol. 2018 Apr;32[4]:595-600). However, “significantly less pain was reported with daylight PDT,” Dr. Spencer said.
Daylight PDT hasn’t caught on the United States. Physicians have concern about the lack of control of UV dosing, and, he pointed out, “this, of course, is not billable.”
Dr. Spencer reported that he serves on the speakers bureau for Genentech.
ORLANDO –
Dr. Spencer, who practices in St. Petersburg, Fla., and is cochair of the conference, gave attendees a roundup of what’s new in adjuncts and delivery methods for photodynamic therapy (PDT). Among the updates is the promise of PDT delivered by means of an ultrashort incubation time of 10-20 minutes, followed by prolonged blue light exposure time of 1 hour. “The idea is that the enzymatic conversion is occurring during the light exposure,” Dr. Spencer said, adding that reports of this approach are mostly anecdotal.
A variation on the ultrashort incubation adds microneedling, he said. In one recent study, 33 patients who had facial actinic keratoses (AKs) were randomized to 10 or 20 minutes of incubation after application of aminolevulinic acid (ALA), followed by 1,000 seconds of exposure to blue light. However, in this split-face study, participants each had one side of their faces treated with microneedling and the other half with a sham treatment before ALA was applied.
Those who had the shorter incubation time had 43% of AKs cleared on the side that received microneedling, compared with 38% on the sham side. For those who received 20 minutes of ALA incubation, rates were higher, with 76% AK clearance on the treated side and 58% on the sham side. “Patients reported that the procedure was virtually painless on both sides,” said Dr. Spencer.
Though the addition of microneedling to PDT is a newer trend, there’s one that’s been a mainstay in Europe for some time: daylight PDT. He cited a review article published in 2016, which identified 17 studies on the use of daylight PDT (Dermatol Surg. 2016 Mar;42[3]:286-95).
Advantages of daylight PDT, he said, include less time in the office for patients and “supposedly less pain.” European protocols vary, but most use methyl aminolevulinate, which he said is a “little more lipophilic than ALA,” with incubation times ranging from 0 to 30 minutes. Exposure time is also variable, but will usually range from 1.5 to 2.5 hours. Most patients receive just one treatment, but some protocols will include up to three treatments.
Overall, studies show a range from 46% to almost 90% complete response rates when AKs are treated with daylight PDT. One study that looked at daylight PDT for small basal cell carcinomas showed that 94% of patients had clinical clearance of their lesions after two treatment sessions; however, the recurrence rate at 12 months post therapy was 21%, Dr. Spencer said.
He shared results of a recent head-to-head study of conventional and daylight PDT; conducted in Greece, the study enrolled patients with “high sun exposure” and used a split-face design.
Of the 46 patients who received MAL on both sides of their faces, response rates were similar at both 3 and 12 months, with slightly numerically higher clearance rates for conventional versus daylight PDT. The 3-month clearance rate for conventional PDT was 80.6%, compared with 78.0% for daylight PDT. At 12 months, the respective clearance rates were 73.7% and 71.8% (J Eur Acad Dermatol Venereol. 2018 Apr;32[4]:595-600). However, “significantly less pain was reported with daylight PDT,” Dr. Spencer said.
Daylight PDT hasn’t caught on the United States. Physicians have concern about the lack of control of UV dosing, and, he pointed out, “this, of course, is not billable.”
Dr. Spencer reported that he serves on the speakers bureau for Genentech.
ORLANDO –
Dr. Spencer, who practices in St. Petersburg, Fla., and is cochair of the conference, gave attendees a roundup of what’s new in adjuncts and delivery methods for photodynamic therapy (PDT). Among the updates is the promise of PDT delivered by means of an ultrashort incubation time of 10-20 minutes, followed by prolonged blue light exposure time of 1 hour. “The idea is that the enzymatic conversion is occurring during the light exposure,” Dr. Spencer said, adding that reports of this approach are mostly anecdotal.
A variation on the ultrashort incubation adds microneedling, he said. In one recent study, 33 patients who had facial actinic keratoses (AKs) were randomized to 10 or 20 minutes of incubation after application of aminolevulinic acid (ALA), followed by 1,000 seconds of exposure to blue light. However, in this split-face study, participants each had one side of their faces treated with microneedling and the other half with a sham treatment before ALA was applied.
Those who had the shorter incubation time had 43% of AKs cleared on the side that received microneedling, compared with 38% on the sham side. For those who received 20 minutes of ALA incubation, rates were higher, with 76% AK clearance on the treated side and 58% on the sham side. “Patients reported that the procedure was virtually painless on both sides,” said Dr. Spencer.
Though the addition of microneedling to PDT is a newer trend, there’s one that’s been a mainstay in Europe for some time: daylight PDT. He cited a review article published in 2016, which identified 17 studies on the use of daylight PDT (Dermatol Surg. 2016 Mar;42[3]:286-95).
Advantages of daylight PDT, he said, include less time in the office for patients and “supposedly less pain.” European protocols vary, but most use methyl aminolevulinate, which he said is a “little more lipophilic than ALA,” with incubation times ranging from 0 to 30 minutes. Exposure time is also variable, but will usually range from 1.5 to 2.5 hours. Most patients receive just one treatment, but some protocols will include up to three treatments.
Overall, studies show a range from 46% to almost 90% complete response rates when AKs are treated with daylight PDT. One study that looked at daylight PDT for small basal cell carcinomas showed that 94% of patients had clinical clearance of their lesions after two treatment sessions; however, the recurrence rate at 12 months post therapy was 21%, Dr. Spencer said.
He shared results of a recent head-to-head study of conventional and daylight PDT; conducted in Greece, the study enrolled patients with “high sun exposure” and used a split-face design.
Of the 46 patients who received MAL on both sides of their faces, response rates were similar at both 3 and 12 months, with slightly numerically higher clearance rates for conventional versus daylight PDT. The 3-month clearance rate for conventional PDT was 80.6%, compared with 78.0% for daylight PDT. At 12 months, the respective clearance rates were 73.7% and 71.8% (J Eur Acad Dermatol Venereol. 2018 Apr;32[4]:595-600). However, “significantly less pain was reported with daylight PDT,” Dr. Spencer said.
Daylight PDT hasn’t caught on the United States. Physicians have concern about the lack of control of UV dosing, and, he pointed out, “this, of course, is not billable.”
Dr. Spencer reported that he serves on the speakers bureau for Genentech.
EXPERT ANALYSIS FROM ODAC 2019