Flu season shows signs of peaking. Watch for depression symptom trajectory in high-risk young adults. ACOG: Avoid inductions before 39 weeks unless medically necessary. And malpractice suits are less frequent – but more costly.

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Flu season shows signs of peaking. Watch for depression symptom trajectory in high-risk young adults. ACOG: Avoid inductions before 39 weeks unless medically necessary. And malpractice suits are less frequent – but more costly.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify

Flu season shows signs of peaking. Watch for depression symptom trajectory in high-risk young adults. ACOG: Avoid inductions before 39 weeks unless medically necessary. And malpractice suits are less frequent – but more costly.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify

An intervention about the risks of teratogenic rheumatology medications has significantly increased education and pregnancy screening of pediatric patients.

Rawpixel/Thinkstock

While many medications in rheumatology are known or suspected to be teratogenic, there are no standards on educating rheumatology patients about this risk or on screening for pregnancy, wrote Ashley M. Cooper, MD, and her colleagues at Children’s Mercy Kansas City, Mo. Their report is in the April issue of Pediatrics.

“This is problematic in pediatric rheumatology because nearly half of adolescents report a history of sexual intercourse, but only 57% report condom use and 27% another form of contraception,” they wrote, pointing out that the United States also has one of the highest rates of teen pregnancy among industrialized nations; 80% are unplanned.

The intervention consisted of a number of approaches. Posters listing teratogenic medications were put in exam rooms, physicians received education about the Food and Drug Administration–mandated mycophenolate Risk Evaluation and Mitigation Strategy (REMS), and scripts were developed for staff to inform patients of teratogenic risks with medications, as well as prompts for referral to birth control clinics.

Researchers also implemented a standardized EHR template to allow clinical staff to review medication-specific teaching points and document the discussion with the patient. There also was a previsit planning process to review everything before the clinic day began, and identify patients for education or pregnancy screening.

After 8 months of the intervention – during which 1,366 eligible patient encounters occurred in rheumatology patients aged 10 years and older– researchers saw a significant increase in those encounters where teratogen education was recorded, from 25% before the intervention to 80% at 23 months after it. Pregnancy screening also increased among eligible patients, from 20% preintervention to 83% at 23 months after the first intervention.

Three patients became pregnant during the intervention period; all of the pregnancies were picked up by the screening process. In all cases, the teratogenic medication was immediately stopped; one patient underwent elective termination, one delivered a healthy term infant, and one patient was lost to follow-up. Two of the three had received education during the previous year.

“The strategies used in this project have implications that reach beyond rheumatology because teratogenic medications are commonly prescribed by other subspecialties,” the authors wrote.

Dr. Cooper and her associates noted that an original previsit checklist was later abandoned because it was viewed as being too much of a time imposition on staff at the beginning of a busy clinic day.

“The new process had higher staff buy-in because it was used to address multiple quality improvement projects and hospital requirements, some linked to provider remuneration,” they wrote.

No funding or conflicts of interest were declared.

SOURCE: Cooper AM et al. Pediatrics 2019; 143(4):e20180803. doi: 10.1542/peds.2018-0803.

An intervention about the risks of teratogenic rheumatology medications has significantly increased education and pregnancy screening of pediatric patients.

Rawpixel/Thinkstock

While many medications in rheumatology are known or suspected to be teratogenic, there are no standards on educating rheumatology patients about this risk or on screening for pregnancy, wrote Ashley M. Cooper, MD, and her colleagues at Children’s Mercy Kansas City, Mo. Their report is in the April issue of Pediatrics.

“This is problematic in pediatric rheumatology because nearly half of adolescents report a history of sexual intercourse, but only 57% report condom use and 27% another form of contraception,” they wrote, pointing out that the United States also has one of the highest rates of teen pregnancy among industrialized nations; 80% are unplanned.

The intervention consisted of a number of approaches. Posters listing teratogenic medications were put in exam rooms, physicians received education about the Food and Drug Administration–mandated mycophenolate Risk Evaluation and Mitigation Strategy (REMS), and scripts were developed for staff to inform patients of teratogenic risks with medications, as well as prompts for referral to birth control clinics.

Researchers also implemented a standardized EHR template to allow clinical staff to review medication-specific teaching points and document the discussion with the patient. There also was a previsit planning process to review everything before the clinic day began, and identify patients for education or pregnancy screening.

After 8 months of the intervention – during which 1,366 eligible patient encounters occurred in rheumatology patients aged 10 years and older– researchers saw a significant increase in those encounters where teratogen education was recorded, from 25% before the intervention to 80% at 23 months after it. Pregnancy screening also increased among eligible patients, from 20% preintervention to 83% at 23 months after the first intervention.

Three patients became pregnant during the intervention period; all of the pregnancies were picked up by the screening process. In all cases, the teratogenic medication was immediately stopped; one patient underwent elective termination, one delivered a healthy term infant, and one patient was lost to follow-up. Two of the three had received education during the previous year.

“The strategies used in this project have implications that reach beyond rheumatology because teratogenic medications are commonly prescribed by other subspecialties,” the authors wrote.

Dr. Cooper and her associates noted that an original previsit checklist was later abandoned because it was viewed as being too much of a time imposition on staff at the beginning of a busy clinic day.

“The new process had higher staff buy-in because it was used to address multiple quality improvement projects and hospital requirements, some linked to provider remuneration,” they wrote.

No funding or conflicts of interest were declared.

SOURCE: Cooper AM et al. Pediatrics 2019; 143(4):e20180803. doi: 10.1542/peds.2018-0803.

An intervention about the risks of teratogenic rheumatology medications has significantly increased education and pregnancy screening of pediatric patients.

Rawpixel/Thinkstock

While many medications in rheumatology are known or suspected to be teratogenic, there are no standards on educating rheumatology patients about this risk or on screening for pregnancy, wrote Ashley M. Cooper, MD, and her colleagues at Children’s Mercy Kansas City, Mo. Their report is in the April issue of Pediatrics.

“This is problematic in pediatric rheumatology because nearly half of adolescents report a history of sexual intercourse, but only 57% report condom use and 27% another form of contraception,” they wrote, pointing out that the United States also has one of the highest rates of teen pregnancy among industrialized nations; 80% are unplanned.

The intervention consisted of a number of approaches. Posters listing teratogenic medications were put in exam rooms, physicians received education about the Food and Drug Administration–mandated mycophenolate Risk Evaluation and Mitigation Strategy (REMS), and scripts were developed for staff to inform patients of teratogenic risks with medications, as well as prompts for referral to birth control clinics.

Researchers also implemented a standardized EHR template to allow clinical staff to review medication-specific teaching points and document the discussion with the patient. There also was a previsit planning process to review everything before the clinic day began, and identify patients for education or pregnancy screening.

After 8 months of the intervention – during which 1,366 eligible patient encounters occurred in rheumatology patients aged 10 years and older– researchers saw a significant increase in those encounters where teratogen education was recorded, from 25% before the intervention to 80% at 23 months after it. Pregnancy screening also increased among eligible patients, from 20% preintervention to 83% at 23 months after the first intervention.

Three patients became pregnant during the intervention period; all of the pregnancies were picked up by the screening process. In all cases, the teratogenic medication was immediately stopped; one patient underwent elective termination, one delivered a healthy term infant, and one patient was lost to follow-up. Two of the three had received education during the previous year.

“The strategies used in this project have implications that reach beyond rheumatology because teratogenic medications are commonly prescribed by other subspecialties,” the authors wrote.

Dr. Cooper and her associates noted that an original previsit checklist was later abandoned because it was viewed as being too much of a time imposition on staff at the beginning of a busy clinic day.

“The new process had higher staff buy-in because it was used to address multiple quality improvement projects and hospital requirements, some linked to provider remuneration,” they wrote.

No funding or conflicts of interest were declared.

SOURCE: Cooper AM et al. Pediatrics 2019; 143(4):e20180803. doi: 10.1542/peds.2018-0803.

EXPERT COMMENTARY

Sultan P, Bampoe S, Shah R, et al. Oral versus intravenous iron therapy for postpartum anemia: a systematic review and meta-analysis. Am J Obstet Gynecol. Published online December 19, 2018. DOI:10.1016/j.ajog.2018.12.016.

Iron deficiency anemia in pregnancy is associated with increased risk for adverse birth outcomes, including preterm delivery, cesarean delivery, and need for blood transfusion.^1,2 Although the outcomes with postpartum iron deficiency anemia are more difficult to study, this condition is associated with increased risk of maternal fatigue and depression, and it is often overlooked as a significant issue during the postpartum period.

In a recent systematic review, Sultan and colleagues sought to provide an updated assessment of IV versus oral iron treatment for postpartum anemia. The 6-week postpartum hemoglobin concentration was the primary outcome.

Details of the study

The authors screened 2,744 articles for randomized controlled trials (RCTs) comparing oral and IV iron in the treatment of postpartum anemia. Fifteen RCTs were included in the review, with 1,001 women receiving oral iron therapy and 1,181 women receiving IV iron. The baseline postpartum hemoglobin concentration in the 15 studies ranged from less than 8 g/dL to 10.5 g/dL.

In all but 1 study, the women in the IV treatment arm experienced a significant increase in postpartum hemoglobin concentration, with the mean difference being 1.0 g/dL at postpartum week 1 (95% confidence interval [CI], 0.5–1.5; P<.0001) and 0.9 g/dL at postpartum week 6 (95% CI, 0.4–1.3; P = .0003).

Only 4 studies were included in the meta-analysis; specifically, 6-week postpartum hemoglobin levels were measured in 251 women who received IV iron and in 134 who received oral iron. Significant differences were seen in the IV iron group compared with the oral iron group for 3 of the secondary outcomes evaluated: flushing (odds ratio [OR], 6.95), decreased constipation (OR, 0.08), and decreased dyspepsia (OR, 0.07).

None of the other secondary outcomes associated with IV iron (muscle cramps, headache, urticaria, rash, or anaphylaxis) occurred at statistically significant rates. Notably, adherence was not assessed in the majority of the studies. Although constipation was increased in the oral iron therapy group, it was reported at only 12%.

Study strengths and weaknesses

Results of this study support previous findings that IV iron is better tolerated, with fewer gastrointestinal adverse effects, than oral iron, and they re-emphasize that IV iron therapy is both safe (the authors identified only 2 cases of anaphylaxis) and effective in improving hematologic indices.

Continue to: The systematic review included...

The systematic review included studies, however, that excluded women treated for antepartum anemia, a group that may benefit from aggressive correction of iron deficiency. Another study weakness is that all the oral iron regimens used were dosed either daily or multiple times per day, which may lead to difficulty with adherence and can decrease overall iron absorption compared with an every-other-day regimen.³

Future studies are needed to determine 1) which women with what level of anemia will benefit the most from postpartum IV iron and 2) the hemoglobin level at which IV iron is a cost-effective therapy.

EXPERT COMMENTARY

Sultan P, Bampoe S, Shah R, et al. Oral versus intravenous iron therapy for postpartum anemia: a systematic review and meta-analysis. Am J Obstet Gynecol. Published online December 19, 2018. DOI:10.1016/j.ajog.2018.12.016.

Iron deficiency anemia in pregnancy is associated with increased risk for adverse birth outcomes, including preterm delivery, cesarean delivery, and need for blood transfusion.^1,2 Although the outcomes with postpartum iron deficiency anemia are more difficult to study, this condition is associated with increased risk of maternal fatigue and depression, and it is often overlooked as a significant issue during the postpartum period.

In a recent systematic review, Sultan and colleagues sought to provide an updated assessment of IV versus oral iron treatment for postpartum anemia. The 6-week postpartum hemoglobin concentration was the primary outcome.

Details of the study

The authors screened 2,744 articles for randomized controlled trials (RCTs) comparing oral and IV iron in the treatment of postpartum anemia. Fifteen RCTs were included in the review, with 1,001 women receiving oral iron therapy and 1,181 women receiving IV iron. The baseline postpartum hemoglobin concentration in the 15 studies ranged from less than 8 g/dL to 10.5 g/dL.

In all but 1 study, the women in the IV treatment arm experienced a significant increase in postpartum hemoglobin concentration, with the mean difference being 1.0 g/dL at postpartum week 1 (95% confidence interval [CI], 0.5–1.5; P<.0001) and 0.9 g/dL at postpartum week 6 (95% CI, 0.4–1.3; P = .0003).

Only 4 studies were included in the meta-analysis; specifically, 6-week postpartum hemoglobin levels were measured in 251 women who received IV iron and in 134 who received oral iron. Significant differences were seen in the IV iron group compared with the oral iron group for 3 of the secondary outcomes evaluated: flushing (odds ratio [OR], 6.95), decreased constipation (OR, 0.08), and decreased dyspepsia (OR, 0.07).

None of the other secondary outcomes associated with IV iron (muscle cramps, headache, urticaria, rash, or anaphylaxis) occurred at statistically significant rates. Notably, adherence was not assessed in the majority of the studies. Although constipation was increased in the oral iron therapy group, it was reported at only 12%.

Study strengths and weaknesses

Results of this study support previous findings that IV iron is better tolerated, with fewer gastrointestinal adverse effects, than oral iron, and they re-emphasize that IV iron therapy is both safe (the authors identified only 2 cases of anaphylaxis) and effective in improving hematologic indices.

Continue to: The systematic review included...

The systematic review included studies, however, that excluded women treated for antepartum anemia, a group that may benefit from aggressive correction of iron deficiency. Another study weakness is that all the oral iron regimens used were dosed either daily or multiple times per day, which may lead to difficulty with adherence and can decrease overall iron absorption compared with an every-other-day regimen.³

Future studies are needed to determine 1) which women with what level of anemia will benefit the most from postpartum IV iron and 2) the hemoglobin level at which IV iron is a cost-effective therapy.

EXPERT COMMENTARY

Sultan P, Bampoe S, Shah R, et al. Oral versus intravenous iron therapy for postpartum anemia: a systematic review and meta-analysis. Am J Obstet Gynecol. Published online December 19, 2018. DOI:10.1016/j.ajog.2018.12.016.

Iron deficiency anemia in pregnancy is associated with increased risk for adverse birth outcomes, including preterm delivery, cesarean delivery, and need for blood transfusion.^1,2 Although the outcomes with postpartum iron deficiency anemia are more difficult to study, this condition is associated with increased risk of maternal fatigue and depression, and it is often overlooked as a significant issue during the postpartum period.

In a recent systematic review, Sultan and colleagues sought to provide an updated assessment of IV versus oral iron treatment for postpartum anemia. The 6-week postpartum hemoglobin concentration was the primary outcome.

Details of the study

The authors screened 2,744 articles for randomized controlled trials (RCTs) comparing oral and IV iron in the treatment of postpartum anemia. Fifteen RCTs were included in the review, with 1,001 women receiving oral iron therapy and 1,181 women receiving IV iron. The baseline postpartum hemoglobin concentration in the 15 studies ranged from less than 8 g/dL to 10.5 g/dL.

In all but 1 study, the women in the IV treatment arm experienced a significant increase in postpartum hemoglobin concentration, with the mean difference being 1.0 g/dL at postpartum week 1 (95% confidence interval [CI], 0.5–1.5; P<.0001) and 0.9 g/dL at postpartum week 6 (95% CI, 0.4–1.3; P = .0003).

Only 4 studies were included in the meta-analysis; specifically, 6-week postpartum hemoglobin levels were measured in 251 women who received IV iron and in 134 who received oral iron. Significant differences were seen in the IV iron group compared with the oral iron group for 3 of the secondary outcomes evaluated: flushing (odds ratio [OR], 6.95), decreased constipation (OR, 0.08), and decreased dyspepsia (OR, 0.07).

None of the other secondary outcomes associated with IV iron (muscle cramps, headache, urticaria, rash, or anaphylaxis) occurred at statistically significant rates. Notably, adherence was not assessed in the majority of the studies. Although constipation was increased in the oral iron therapy group, it was reported at only 12%.

Study strengths and weaknesses

Results of this study support previous findings that IV iron is better tolerated, with fewer gastrointestinal adverse effects, than oral iron, and they re-emphasize that IV iron therapy is both safe (the authors identified only 2 cases of anaphylaxis) and effective in improving hematologic indices.

Continue to: The systematic review included...

The systematic review included studies, however, that excluded women treated for antepartum anemia, a group that may benefit from aggressive correction of iron deficiency. Another study weakness is that all the oral iron regimens used were dosed either daily or multiple times per day, which may lead to difficulty with adherence and can decrease overall iron absorption compared with an every-other-day regimen.³

Future studies are needed to determine 1) which women with what level of anemia will benefit the most from postpartum IV iron and 2) the hemoglobin level at which IV iron is a cost-effective therapy.

CASE 7- to 8-lb baby suspected to be in occiput posterior (OP) position

A certified nurse midwife (CNM) asks you to consult on a 37-year-old woman (G1P0) at 41 weeks’ gestation who was admitted to labor and delivery for a late-term induction. The patient had a normal first stage of labor with placement of a combined spinal-epidural anesthetic at a cervical dilation of 4 cm. She has been fully dilated for 3.5 hours and pushing for 2.5 hours with a Category 1 fetal heart rate tracing. The CNM reports that the estimated fetal weight is 7 to 8 lb and the station is +3/5. She suspects that the fetus is in the left OP position. She asks for your advice on how to best deliver the fetus. The patient strongly prefers not to have a cesarean delivery (CD).

What is your recommended approach?
 

The cardinal movements of labor include cephalic engagement, descent, flexion, internal rotation, extension and rotation of the head at delivery, internal rotation of the shoulders, and expulsion of the body. In the first stage of labor many fetuses are in the OP position. Flexion and internal rotation of the fetal head in a mother with a gynecoid pelvis results in most fetuses assuming an occiput anterior (OA) position with the presenting diameter of the head (occipitobregmatic) being optimal for spontaneous vaginal delivery. Late in the second stage of labor only about 5% of fetuses are in the OP position with the presenting diameter of the head being large (occipitofrontal) with an extended head attitude, thereby reducing the probability of a rapid spontaneous vaginal delivery.

Risk factors for OP position late in the second stage of labor include^1,2:

• nulliparity
• body mass index > 29 kg/m²
• gestation age ≥ 41 weeks
• birth weight > 4 kg
• regional anesthesia.

Maternal outcomes associated with persistent OP position include protracted first and second stage of labor, arrest of second stage of labor, and increased rates of operative vaginal delivery, anal sphincter injury, CD, postpartum hemorrhage, chorioamnionitis, and endomyometritis.^1,3,4 The neonatal complications of persistent OP position include increased rates of shoulder dystocia, low Apgar score, umbilical artery acidemia, meconium, and admission to a neonatal intensive care unit.^1,5

Diagnosis

Many obstetricians report that they can reliably detect a fetus in the OP position based upon abdominal palpation of the fetal spine and digital vaginal examination of the fetal sutures, fontanels, and ears. Such self-confidence may not be wholly warranted, however. Most contemporary data indicate that digital vaginal examination has an error rate of approximately 20% for identifying the position of the cephalic fetus, especially in the presence of fetal caput succedaneum and asynclitism.^6-10

The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) recommends that cephalic position be determined by transabdominal imaging.¹¹ By placing the ultrasound probe on the maternal abdomen, a view of the fetal body at the level of the chest helps determine the position of the fetal spine. When the probe is placed in a suprapubic position, the observation of the fetal orbits facing the probe indicates an OP position.

When the presenting part is at a very low station, a transperineal ultrasound may be helpful to determine the position of the occiput. The ISUOG recommends that position be defined using a clock face, with positions from 330 h to 830 h being indicative of OP and positions from 930 h to 230 h being indicative of OA.¹¹ The small remaining slivers on the clock face indicate an occiput transverse position (FIGURE).¹¹

Continue to: Approaches to managing the OP position

Approaches to managing the OP position

First stage of labor

Identification of a cephalic-presenting fetus in the OP position in the first stage of labor might warrant increased attention to fetal position in the second stage of labor, but does not usually alter management of the first stage.

Second stage of labor

If an OP position is identified in the second stage of labor, many obstetricians will consider manual rotation of the fetal occiput to an anterior pelvic quadrant to facilitate labor progress. Because a fetus in the OP position may spontaneously rotate to the OA position at any point during the second stage, a judicious interval of waiting is reasonable before attempting a manual rotation in the second stage. For example, allowing the second stage to progress for 60 to 90 min in a nulliparous woman or 30 to 60 min in a multiparous woman will permit some fetuses to rotate to the OA position without intervention.

If the OP position persists beyond these time points, a manual rotation could be considered. There are no high-quality clinical trials to support this maneuver,¹² but observational reports suggest that this low-risk maneuver may help reduce the rate of CD and anal sphincter trauma.^13-15

Manual rotation from OP to OA. Prior to performing the rotation, the maternal bladder should be emptied and an adequate anesthetic provided. One technique is to use the 4 fingers of the hand as a “spatula” to turn the head. If the fetus is in a left OP position, the operator’s right hand is pronated and inserted into the vagina, palm up. Four fingers are placed under the posterior parietal bone with the thumb over the anterior parietal bone (ILLUSTRATION).⁴ The operator uses the fingers and thumb to flex and rotate the head to the right, moving the fetal occiput into an anterior pelvic quadrant.⁴ If the head is in the right OP position, the left hand is used to rotate the head. The nonvaginal hand can be placed on the maternal abdominal wall to assess the fetal spine position as the fetal head is rotated. The fetal head may need to be held in the anterior pelvic quadrant during a few maternal pushes to prevent the head from rotating back into the OP position.

Approaching delivery late in the second stage

If the second stage has progressed for 3 or 4 hours, as in the case described above, and the fetus remains in the OP position, delivery may be indicated to avoid the maternal and fetal complications of an even more prolonged second stage. At some point in a prolonged second stage, expectant management carries more maternal and fetal risks than intervention.

Late in the second stage, options for delivery of the fetus in the OP include: CD, rotational forceps delivery, direct forceps delivery from the OP position, and vacuum delivery.

Cesarean delivery. CD of the fetus in the OP position may be indicated when the fetus is estimated to be macrosomic, the station is high (biparietal diameter palpable on abdominal examination), or when the parturient has an android pelvis (narrow fore-pelvis and anterior convergence of the pelvic bone structures in a wedge shape). During CD, if difficulty is encountered in delivering the fetal head, a hand from below, extension of the uterine incision, or reverse breech extraction may be necessary to complete the delivery. If the clinical situation is conducive to operative vaginal delivery, forceps or vacuum can be used.

Continue to: Rotational forceps delivery...

Rotational forceps delivery. During residency I was told to always use rotational forceps to deliver a fetus in the persistently OP position if the parturient had a gynecoid pelvis (wide oval shape of pelvic bones, wide subpubic arch). Dr. Frederick Irving wrote¹⁶:

“Although textbooks almost universally advocate the extraction of the occiput directly posterior without rotation we do not advise it.... Such an extraction maneuver is inartistic and show[s] a lack of regard for the mechanical factors involved in the mechanism of labor. The method used at the Boston Lying-In Hospital presupposes an accurate diagnosis of the primary position. If the fetal back is on the right the head should be rotated to the right; if on the left, toward the left. The head is always rotated in the direction in which the back lies. The forceps are applied as if the occiput was directly anterior. Carrying the forceps handles in a wide sweep the occiput is now rotated to the anterior quadrant of the pelvis or 135 degrees. It will be found that the head turns easily in the way it should go but that it is difficult or impossible to rotate it in the improper direction. The instrument is then reapplied as in the second part of the Scanzoni maneuver.”

Rotation of the fetus from the OP to the OA position may reduce the risk of sphincter injury with vaginal birth. With the waning of rotational forceps skills, many obstetricians prefer a nonrotational approach with direct forceps or vacuum delivery from the OP position.

Direct forceps delivery from the OP position. A fetus in the OP position for 3 to 4 hours of the second stage of labor will often have a significant degree of head molding. The Simpson forceps, with its shallow and longer cephalic curve, accommodates significant fetal head molding and is a good forceps choice in this situation.

Vacuum delivery. In the United States, approximately 5% of vaginal deliveries are performed with a vacuum device, and 1% with forceps.¹⁷ Consequently, many obstetricians frequently perform operative vaginal delivery with a vacuum device and infrequently or never perform operative vaginal delivery with forceps. Vacuum vaginal delivery may be the instrument of choice for many obstetricians performing an operative delivery of a fetus in the OP position. However, the vacuum has a higher rate of failure, especially if the OP fetus is at a higher station.¹⁸

In some centers, direct forceps delivery from the OP position is preferred over an attempt at vacuum delivery, because in contemporary obstetric practice most centers do not permit the sequential use of vacuum followed by forceps (due to the higher rate of fetal trauma of combination operative delivery). Since vacuum delivery of the fetus in the OP position has a greater rate of failure than forceps, it may be best to initiate operative vaginal delivery of the fetus in the OP position with forceps. If vacuum is used to attempt a vaginal delivery and fails due to too many pop-offs, a CD would be the next step.

Take action when needed to optimize outcomes

The persistent OP position is associated with a longer second stage of labor. It is common during a change of shift for an obstetrician to sign out to the on-coming clinician a case of a prolonged second stage with the fetus in the OP position. In this situation, the on-coming clinician cannot wait hour after hour after hour hoping for a spontaneous delivery. If the on-coming clinician has a clear plan of how to deal with the persistent OP position—including ultrasound confirmation of position and physical examination to determine station, fetal size and adequacy of the pelvis, and timely selection of a delivery technique—the adverse maternal and neonatal outcomes sometimes caused by the persistent OP position will be minimized.

Continue to: CASE Resolved...

CASE Resolved

The consulting obstetrician performed a transabdominal ultrasound and observed the fetal orbits were facing the transducer, confirming an OP position. On physical examination, the station was +3/5, and the fetal weight was confirmed to be approximately 8 lb. The obstetrician recommended a direct forceps delivery from the OP position. The patient and CNM agreed with the plan.

The obstetrician applied Simpson forceps and performed a mediolateral episiotomy just prior to delivery of the head. Following delivery, the rectal sphincter and anal mucosa were intact and the episiotomy was repaired. The newborn, safely delivered, and the mother, having avoided a CD, were transferred to the postpartum floor later in the day.

CASE 7- to 8-lb baby suspected to be in occiput posterior (OP) position

A certified nurse midwife (CNM) asks you to consult on a 37-year-old woman (G1P0) at 41 weeks’ gestation who was admitted to labor and delivery for a late-term induction. The patient had a normal first stage of labor with placement of a combined spinal-epidural anesthetic at a cervical dilation of 4 cm. She has been fully dilated for 3.5 hours and pushing for 2.5 hours with a Category 1 fetal heart rate tracing. The CNM reports that the estimated fetal weight is 7 to 8 lb and the station is +3/5. She suspects that the fetus is in the left OP position. She asks for your advice on how to best deliver the fetus. The patient strongly prefers not to have a cesarean delivery (CD).

What is your recommended approach?
 

The cardinal movements of labor include cephalic engagement, descent, flexion, internal rotation, extension and rotation of the head at delivery, internal rotation of the shoulders, and expulsion of the body. In the first stage of labor many fetuses are in the OP position. Flexion and internal rotation of the fetal head in a mother with a gynecoid pelvis results in most fetuses assuming an occiput anterior (OA) position with the presenting diameter of the head (occipitobregmatic) being optimal for spontaneous vaginal delivery. Late in the second stage of labor only about 5% of fetuses are in the OP position with the presenting diameter of the head being large (occipitofrontal) with an extended head attitude, thereby reducing the probability of a rapid spontaneous vaginal delivery.

Risk factors for OP position late in the second stage of labor include^1,2:

• nulliparity
• body mass index > 29 kg/m²
• gestation age ≥ 41 weeks
• birth weight > 4 kg
• regional anesthesia.

Maternal outcomes associated with persistent OP position include protracted first and second stage of labor, arrest of second stage of labor, and increased rates of operative vaginal delivery, anal sphincter injury, CD, postpartum hemorrhage, chorioamnionitis, and endomyometritis.^1,3,4 The neonatal complications of persistent OP position include increased rates of shoulder dystocia, low Apgar score, umbilical artery acidemia, meconium, and admission to a neonatal intensive care unit.^1,5

Diagnosis

Many obstetricians report that they can reliably detect a fetus in the OP position based upon abdominal palpation of the fetal spine and digital vaginal examination of the fetal sutures, fontanels, and ears. Such self-confidence may not be wholly warranted, however. Most contemporary data indicate that digital vaginal examination has an error rate of approximately 20% for identifying the position of the cephalic fetus, especially in the presence of fetal caput succedaneum and asynclitism.^6-10

The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) recommends that cephalic position be determined by transabdominal imaging.¹¹ By placing the ultrasound probe on the maternal abdomen, a view of the fetal body at the level of the chest helps determine the position of the fetal spine. When the probe is placed in a suprapubic position, the observation of the fetal orbits facing the probe indicates an OP position.

When the presenting part is at a very low station, a transperineal ultrasound may be helpful to determine the position of the occiput. The ISUOG recommends that position be defined using a clock face, with positions from 330 h to 830 h being indicative of OP and positions from 930 h to 230 h being indicative of OA.¹¹ The small remaining slivers on the clock face indicate an occiput transverse position (FIGURE).¹¹

Continue to: Approaches to managing the OP position

Approaches to managing the OP position

First stage of labor

Identification of a cephalic-presenting fetus in the OP position in the first stage of labor might warrant increased attention to fetal position in the second stage of labor, but does not usually alter management of the first stage.

Second stage of labor

If an OP position is identified in the second stage of labor, many obstetricians will consider manual rotation of the fetal occiput to an anterior pelvic quadrant to facilitate labor progress. Because a fetus in the OP position may spontaneously rotate to the OA position at any point during the second stage, a judicious interval of waiting is reasonable before attempting a manual rotation in the second stage. For example, allowing the second stage to progress for 60 to 90 min in a nulliparous woman or 30 to 60 min in a multiparous woman will permit some fetuses to rotate to the OA position without intervention.

If the OP position persists beyond these time points, a manual rotation could be considered. There are no high-quality clinical trials to support this maneuver,¹² but observational reports suggest that this low-risk maneuver may help reduce the rate of CD and anal sphincter trauma.^13-15

Manual rotation from OP to OA. Prior to performing the rotation, the maternal bladder should be emptied and an adequate anesthetic provided. One technique is to use the 4 fingers of the hand as a “spatula” to turn the head. If the fetus is in a left OP position, the operator’s right hand is pronated and inserted into the vagina, palm up. Four fingers are placed under the posterior parietal bone with the thumb over the anterior parietal bone (ILLUSTRATION).⁴ The operator uses the fingers and thumb to flex and rotate the head to the right, moving the fetal occiput into an anterior pelvic quadrant.⁴ If the head is in the right OP position, the left hand is used to rotate the head. The nonvaginal hand can be placed on the maternal abdominal wall to assess the fetal spine position as the fetal head is rotated. The fetal head may need to be held in the anterior pelvic quadrant during a few maternal pushes to prevent the head from rotating back into the OP position.

Approaching delivery late in the second stage

If the second stage has progressed for 3 or 4 hours, as in the case described above, and the fetus remains in the OP position, delivery may be indicated to avoid the maternal and fetal complications of an even more prolonged second stage. At some point in a prolonged second stage, expectant management carries more maternal and fetal risks than intervention.

Late in the second stage, options for delivery of the fetus in the OP include: CD, rotational forceps delivery, direct forceps delivery from the OP position, and vacuum delivery.

Cesarean delivery. CD of the fetus in the OP position may be indicated when the fetus is estimated to be macrosomic, the station is high (biparietal diameter palpable on abdominal examination), or when the parturient has an android pelvis (narrow fore-pelvis and anterior convergence of the pelvic bone structures in a wedge shape). During CD, if difficulty is encountered in delivering the fetal head, a hand from below, extension of the uterine incision, or reverse breech extraction may be necessary to complete the delivery. If the clinical situation is conducive to operative vaginal delivery, forceps or vacuum can be used.

Continue to: Rotational forceps delivery...

Rotational forceps delivery. During residency I was told to always use rotational forceps to deliver a fetus in the persistently OP position if the parturient had a gynecoid pelvis (wide oval shape of pelvic bones, wide subpubic arch). Dr. Frederick Irving wrote¹⁶:

“Although textbooks almost universally advocate the extraction of the occiput directly posterior without rotation we do not advise it.... Such an extraction maneuver is inartistic and show[s] a lack of regard for the mechanical factors involved in the mechanism of labor. The method used at the Boston Lying-In Hospital presupposes an accurate diagnosis of the primary position. If the fetal back is on the right the head should be rotated to the right; if on the left, toward the left. The head is always rotated in the direction in which the back lies. The forceps are applied as if the occiput was directly anterior. Carrying the forceps handles in a wide sweep the occiput is now rotated to the anterior quadrant of the pelvis or 135 degrees. It will be found that the head turns easily in the way it should go but that it is difficult or impossible to rotate it in the improper direction. The instrument is then reapplied as in the second part of the Scanzoni maneuver.”

Rotation of the fetus from the OP to the OA position may reduce the risk of sphincter injury with vaginal birth. With the waning of rotational forceps skills, many obstetricians prefer a nonrotational approach with direct forceps or vacuum delivery from the OP position.

Direct forceps delivery from the OP position. A fetus in the OP position for 3 to 4 hours of the second stage of labor will often have a significant degree of head molding. The Simpson forceps, with its shallow and longer cephalic curve, accommodates significant fetal head molding and is a good forceps choice in this situation.

Vacuum delivery. In the United States, approximately 5% of vaginal deliveries are performed with a vacuum device, and 1% with forceps.¹⁷ Consequently, many obstetricians frequently perform operative vaginal delivery with a vacuum device and infrequently or never perform operative vaginal delivery with forceps. Vacuum vaginal delivery may be the instrument of choice for many obstetricians performing an operative delivery of a fetus in the OP position. However, the vacuum has a higher rate of failure, especially if the OP fetus is at a higher station.¹⁸

In some centers, direct forceps delivery from the OP position is preferred over an attempt at vacuum delivery, because in contemporary obstetric practice most centers do not permit the sequential use of vacuum followed by forceps (due to the higher rate of fetal trauma of combination operative delivery). Since vacuum delivery of the fetus in the OP position has a greater rate of failure than forceps, it may be best to initiate operative vaginal delivery of the fetus in the OP position with forceps. If vacuum is used to attempt a vaginal delivery and fails due to too many pop-offs, a CD would be the next step.

Take action when needed to optimize outcomes

The persistent OP position is associated with a longer second stage of labor. It is common during a change of shift for an obstetrician to sign out to the on-coming clinician a case of a prolonged second stage with the fetus in the OP position. In this situation, the on-coming clinician cannot wait hour after hour after hour hoping for a spontaneous delivery. If the on-coming clinician has a clear plan of how to deal with the persistent OP position—including ultrasound confirmation of position and physical examination to determine station, fetal size and adequacy of the pelvis, and timely selection of a delivery technique—the adverse maternal and neonatal outcomes sometimes caused by the persistent OP position will be minimized.

Continue to: CASE Resolved...

CASE Resolved

The consulting obstetrician performed a transabdominal ultrasound and observed the fetal orbits were facing the transducer, confirming an OP position. On physical examination, the station was +3/5, and the fetal weight was confirmed to be approximately 8 lb. The obstetrician recommended a direct forceps delivery from the OP position. The patient and CNM agreed with the plan.

The obstetrician applied Simpson forceps and performed a mediolateral episiotomy just prior to delivery of the head. Following delivery, the rectal sphincter and anal mucosa were intact and the episiotomy was repaired. The newborn, safely delivered, and the mother, having avoided a CD, were transferred to the postpartum floor later in the day.

CASE 7- to 8-lb baby suspected to be in occiput posterior (OP) position

A certified nurse midwife (CNM) asks you to consult on a 37-year-old woman (G1P0) at 41 weeks’ gestation who was admitted to labor and delivery for a late-term induction. The patient had a normal first stage of labor with placement of a combined spinal-epidural anesthetic at a cervical dilation of 4 cm. She has been fully dilated for 3.5 hours and pushing for 2.5 hours with a Category 1 fetal heart rate tracing. The CNM reports that the estimated fetal weight is 7 to 8 lb and the station is +3/5. She suspects that the fetus is in the left OP position. She asks for your advice on how to best deliver the fetus. The patient strongly prefers not to have a cesarean delivery (CD).

What is your recommended approach?
 

The cardinal movements of labor include cephalic engagement, descent, flexion, internal rotation, extension and rotation of the head at delivery, internal rotation of the shoulders, and expulsion of the body. In the first stage of labor many fetuses are in the OP position. Flexion and internal rotation of the fetal head in a mother with a gynecoid pelvis results in most fetuses assuming an occiput anterior (OA) position with the presenting diameter of the head (occipitobregmatic) being optimal for spontaneous vaginal delivery. Late in the second stage of labor only about 5% of fetuses are in the OP position with the presenting diameter of the head being large (occipitofrontal) with an extended head attitude, thereby reducing the probability of a rapid spontaneous vaginal delivery.

Risk factors for OP position late in the second stage of labor include^1,2:

• nulliparity
• body mass index > 29 kg/m²
• gestation age ≥ 41 weeks
• birth weight > 4 kg
• regional anesthesia.

Maternal outcomes associated with persistent OP position include protracted first and second stage of labor, arrest of second stage of labor, and increased rates of operative vaginal delivery, anal sphincter injury, CD, postpartum hemorrhage, chorioamnionitis, and endomyometritis.^1,3,4 The neonatal complications of persistent OP position include increased rates of shoulder dystocia, low Apgar score, umbilical artery acidemia, meconium, and admission to a neonatal intensive care unit.^1,5

Diagnosis

Many obstetricians report that they can reliably detect a fetus in the OP position based upon abdominal palpation of the fetal spine and digital vaginal examination of the fetal sutures, fontanels, and ears. Such self-confidence may not be wholly warranted, however. Most contemporary data indicate that digital vaginal examination has an error rate of approximately 20% for identifying the position of the cephalic fetus, especially in the presence of fetal caput succedaneum and asynclitism.^6-10

The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) recommends that cephalic position be determined by transabdominal imaging.¹¹ By placing the ultrasound probe on the maternal abdomen, a view of the fetal body at the level of the chest helps determine the position of the fetal spine. When the probe is placed in a suprapubic position, the observation of the fetal orbits facing the probe indicates an OP position.

When the presenting part is at a very low station, a transperineal ultrasound may be helpful to determine the position of the occiput. The ISUOG recommends that position be defined using a clock face, with positions from 330 h to 830 h being indicative of OP and positions from 930 h to 230 h being indicative of OA.¹¹ The small remaining slivers on the clock face indicate an occiput transverse position (FIGURE).¹¹

Continue to: Approaches to managing the OP position

Approaches to managing the OP position

First stage of labor

Identification of a cephalic-presenting fetus in the OP position in the first stage of labor might warrant increased attention to fetal position in the second stage of labor, but does not usually alter management of the first stage.

Second stage of labor

If an OP position is identified in the second stage of labor, many obstetricians will consider manual rotation of the fetal occiput to an anterior pelvic quadrant to facilitate labor progress. Because a fetus in the OP position may spontaneously rotate to the OA position at any point during the second stage, a judicious interval of waiting is reasonable before attempting a manual rotation in the second stage. For example, allowing the second stage to progress for 60 to 90 min in a nulliparous woman or 30 to 60 min in a multiparous woman will permit some fetuses to rotate to the OA position without intervention.

If the OP position persists beyond these time points, a manual rotation could be considered. There are no high-quality clinical trials to support this maneuver,¹² but observational reports suggest that this low-risk maneuver may help reduce the rate of CD and anal sphincter trauma.^13-15

Manual rotation from OP to OA. Prior to performing the rotation, the maternal bladder should be emptied and an adequate anesthetic provided. One technique is to use the 4 fingers of the hand as a “spatula” to turn the head. If the fetus is in a left OP position, the operator’s right hand is pronated and inserted into the vagina, palm up. Four fingers are placed under the posterior parietal bone with the thumb over the anterior parietal bone (ILLUSTRATION).⁴ The operator uses the fingers and thumb to flex and rotate the head to the right, moving the fetal occiput into an anterior pelvic quadrant.⁴ If the head is in the right OP position, the left hand is used to rotate the head. The nonvaginal hand can be placed on the maternal abdominal wall to assess the fetal spine position as the fetal head is rotated. The fetal head may need to be held in the anterior pelvic quadrant during a few maternal pushes to prevent the head from rotating back into the OP position.

Approaching delivery late in the second stage

If the second stage has progressed for 3 or 4 hours, as in the case described above, and the fetus remains in the OP position, delivery may be indicated to avoid the maternal and fetal complications of an even more prolonged second stage. At some point in a prolonged second stage, expectant management carries more maternal and fetal risks than intervention.

Late in the second stage, options for delivery of the fetus in the OP include: CD, rotational forceps delivery, direct forceps delivery from the OP position, and vacuum delivery.

Cesarean delivery. CD of the fetus in the OP position may be indicated when the fetus is estimated to be macrosomic, the station is high (biparietal diameter palpable on abdominal examination), or when the parturient has an android pelvis (narrow fore-pelvis and anterior convergence of the pelvic bone structures in a wedge shape). During CD, if difficulty is encountered in delivering the fetal head, a hand from below, extension of the uterine incision, or reverse breech extraction may be necessary to complete the delivery. If the clinical situation is conducive to operative vaginal delivery, forceps or vacuum can be used.

Continue to: Rotational forceps delivery...

Rotational forceps delivery. During residency I was told to always use rotational forceps to deliver a fetus in the persistently OP position if the parturient had a gynecoid pelvis (wide oval shape of pelvic bones, wide subpubic arch). Dr. Frederick Irving wrote¹⁶:

“Although textbooks almost universally advocate the extraction of the occiput directly posterior without rotation we do not advise it.... Such an extraction maneuver is inartistic and show[s] a lack of regard for the mechanical factors involved in the mechanism of labor. The method used at the Boston Lying-In Hospital presupposes an accurate diagnosis of the primary position. If the fetal back is on the right the head should be rotated to the right; if on the left, toward the left. The head is always rotated in the direction in which the back lies. The forceps are applied as if the occiput was directly anterior. Carrying the forceps handles in a wide sweep the occiput is now rotated to the anterior quadrant of the pelvis or 135 degrees. It will be found that the head turns easily in the way it should go but that it is difficult or impossible to rotate it in the improper direction. The instrument is then reapplied as in the second part of the Scanzoni maneuver.”

Rotation of the fetus from the OP to the OA position may reduce the risk of sphincter injury with vaginal birth. With the waning of rotational forceps skills, many obstetricians prefer a nonrotational approach with direct forceps or vacuum delivery from the OP position.

Direct forceps delivery from the OP position. A fetus in the OP position for 3 to 4 hours of the second stage of labor will often have a significant degree of head molding. The Simpson forceps, with its shallow and longer cephalic curve, accommodates significant fetal head molding and is a good forceps choice in this situation.

Vacuum delivery. In the United States, approximately 5% of vaginal deliveries are performed with a vacuum device, and 1% with forceps.¹⁷ Consequently, many obstetricians frequently perform operative vaginal delivery with a vacuum device and infrequently or never perform operative vaginal delivery with forceps. Vacuum vaginal delivery may be the instrument of choice for many obstetricians performing an operative delivery of a fetus in the OP position. However, the vacuum has a higher rate of failure, especially if the OP fetus is at a higher station.¹⁸

In some centers, direct forceps delivery from the OP position is preferred over an attempt at vacuum delivery, because in contemporary obstetric practice most centers do not permit the sequential use of vacuum followed by forceps (due to the higher rate of fetal trauma of combination operative delivery). Since vacuum delivery of the fetus in the OP position has a greater rate of failure than forceps, it may be best to initiate operative vaginal delivery of the fetus in the OP position with forceps. If vacuum is used to attempt a vaginal delivery and fails due to too many pop-offs, a CD would be the next step.

Take action when needed to optimize outcomes

The persistent OP position is associated with a longer second stage of labor. It is common during a change of shift for an obstetrician to sign out to the on-coming clinician a case of a prolonged second stage with the fetus in the OP position. In this situation, the on-coming clinician cannot wait hour after hour after hour hoping for a spontaneous delivery. If the on-coming clinician has a clear plan of how to deal with the persistent OP position—including ultrasound confirmation of position and physical examination to determine station, fetal size and adequacy of the pelvis, and timely selection of a delivery technique—the adverse maternal and neonatal outcomes sometimes caused by the persistent OP position will be minimized.

Continue to: CASE Resolved...

CASE Resolved

The consulting obstetrician performed a transabdominal ultrasound and observed the fetal orbits were facing the transducer, confirming an OP position. On physical examination, the station was +3/5, and the fetal weight was confirmed to be approximately 8 lb. The obstetrician recommended a direct forceps delivery from the OP position. The patient and CNM agreed with the plan.

The obstetrician applied Simpson forceps and performed a mediolateral episiotomy just prior to delivery of the head. Following delivery, the rectal sphincter and anal mucosa were intact and the episiotomy was repaired. The newborn, safely delivered, and the mother, having avoided a CD, were transferred to the postpartum floor later in the day.

The estimated prevalence of multiple sclerosis (MS) as of 2010 is the highest to date, according to an analysis of administrative health claims (AHC) datasets and 2010 U.S. Census data.

“Our findings suggest that there has been a steady rise in the prevalence of MS over the past 5 decades, that the prevalence of MS remains higher for women than men, and that a north-south geographic gradient still persists,” wrote lead author Mitchell T. Wallin, MD, of Georgetown University, Washington, and his coauthors. The study was published in Neurology.

To determine adult cases of MS, Dr. Wallin and colleagues applied a validated algorithm to private, military, and public AHC datasets. Data from the 2010 U.S. Census were also used to standardize age and sex. In total, 125 million people over 18 years of age were captured in the study, nearly 45% of the U.S. population.

After adjustment, the 2010 prevalence for MS cumulated over 10 years was 309.2 per 100,000 adults (95% confidence interval, 308.1-310.1). This represented a total of 727,344 people with MS. The female to male ratio was 2.8, with a prevalence of 450.1 per 100,000 (95% CI, 448.1-451.6) for women versus a prevalence of 159.7 (95% CI, 158.7-160.6) for men. The age group with the highest estimated prevalence was 55-64 years old, and the prevalence in northern regions of the United States was statistically significantly higher than in southern regions.

The limitations of this study included not including children, the Indian Health Service, the U.S. prison system, or undocumented U.S. residents in the prevalence estimates. However, the authors did note that “these segments of the population are relatively small or, in the case of children, would contribute few cases.” In addition, they were unable to acquire more than 3 years of data for all insurance pools because of high costs.

The study was funded by a grant from the National Multiple Sclerosis Society. The authors reported numerous disclosures, including receiving consulting fees, researching funding, and grant support from various government agencies, foundations, and pharmaceutical companies.

SOURCE: Wallin MT et al. Neurology. 2019 Feb 15. doi: 10.1212/WNL.0000000000007035.

The estimated prevalence of multiple sclerosis (MS) as of 2010 is the highest to date, according to an analysis of administrative health claims (AHC) datasets and 2010 U.S. Census data.

“Our findings suggest that there has been a steady rise in the prevalence of MS over the past 5 decades, that the prevalence of MS remains higher for women than men, and that a north-south geographic gradient still persists,” wrote lead author Mitchell T. Wallin, MD, of Georgetown University, Washington, and his coauthors. The study was published in Neurology.

To determine adult cases of MS, Dr. Wallin and colleagues applied a validated algorithm to private, military, and public AHC datasets. Data from the 2010 U.S. Census were also used to standardize age and sex. In total, 125 million people over 18 years of age were captured in the study, nearly 45% of the U.S. population.

After adjustment, the 2010 prevalence for MS cumulated over 10 years was 309.2 per 100,000 adults (95% confidence interval, 308.1-310.1). This represented a total of 727,344 people with MS. The female to male ratio was 2.8, with a prevalence of 450.1 per 100,000 (95% CI, 448.1-451.6) for women versus a prevalence of 159.7 (95% CI, 158.7-160.6) for men. The age group with the highest estimated prevalence was 55-64 years old, and the prevalence in northern regions of the United States was statistically significantly higher than in southern regions.

The limitations of this study included not including children, the Indian Health Service, the U.S. prison system, or undocumented U.S. residents in the prevalence estimates. However, the authors did note that “these segments of the population are relatively small or, in the case of children, would contribute few cases.” In addition, they were unable to acquire more than 3 years of data for all insurance pools because of high costs.

The study was funded by a grant from the National Multiple Sclerosis Society. The authors reported numerous disclosures, including receiving consulting fees, researching funding, and grant support from various government agencies, foundations, and pharmaceutical companies.

SOURCE: Wallin MT et al. Neurology. 2019 Feb 15. doi: 10.1212/WNL.0000000000007035.

The estimated prevalence of multiple sclerosis (MS) as of 2010 is the highest to date, according to an analysis of administrative health claims (AHC) datasets and 2010 U.S. Census data.

“Our findings suggest that there has been a steady rise in the prevalence of MS over the past 5 decades, that the prevalence of MS remains higher for women than men, and that a north-south geographic gradient still persists,” wrote lead author Mitchell T. Wallin, MD, of Georgetown University, Washington, and his coauthors. The study was published in Neurology.

To determine adult cases of MS, Dr. Wallin and colleagues applied a validated algorithm to private, military, and public AHC datasets. Data from the 2010 U.S. Census were also used to standardize age and sex. In total, 125 million people over 18 years of age were captured in the study, nearly 45% of the U.S. population.

After adjustment, the 2010 prevalence for MS cumulated over 10 years was 309.2 per 100,000 adults (95% confidence interval, 308.1-310.1). This represented a total of 727,344 people with MS. The female to male ratio was 2.8, with a prevalence of 450.1 per 100,000 (95% CI, 448.1-451.6) for women versus a prevalence of 159.7 (95% CI, 158.7-160.6) for men. The age group with the highest estimated prevalence was 55-64 years old, and the prevalence in northern regions of the United States was statistically significantly higher than in southern regions.

The limitations of this study included not including children, the Indian Health Service, the U.S. prison system, or undocumented U.S. residents in the prevalence estimates. However, the authors did note that “these segments of the population are relatively small or, in the case of children, would contribute few cases.” In addition, they were unable to acquire more than 3 years of data for all insurance pools because of high costs.

The study was funded by a grant from the National Multiple Sclerosis Society. The authors reported numerous disclosures, including receiving consulting fees, researching funding, and grant support from various government agencies, foundations, and pharmaceutical companies.

SOURCE: Wallin MT et al. Neurology. 2019 Feb 15. doi: 10.1212/WNL.0000000000007035.

SAN DIEGO – A simplified version of the Sequential Organ Failure Assessment (SOFA) criteria, known as eSOFA, has the potential to make it easier for hospitals to benchmark sepsis outcomes and quality of care, and could propel new sepsis research. The new method replaces some of SOFA’s more subjective criteria with objective measures.

eSOFA relies on electronic health records to reduce reliance on administrative records, which suffer from cross-hospital variability in diagnosis and coding practices, as well as changes in these practices over time. The diagnosis of sepsis itself is also highly subjective. Instead, eSOFA determines dysfunction in six organ systems, indicated by use of vasopressors and mechanical ventilation, and the presence of abnormal laboratory values.

“The SOFA score includes measures like the Glasgow Coma Scale, which undoubtedly at the bedside is a very important clinical sign, but when trying to implement something that is objective for purposes of retrospective case counting and standardization, it can be problematic. The measures we chose [for eSOFA] are concrete, important maneuvers that were initiated by clinicians,” Chanu Rhee, MD, said in an interview.

Dr. Rhee is assistant professor of population medicine at Harvard Medical School and Brigham and Women’s Hospital, Boston. He presented the results of the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine, and the work was simultaneously published online in Critical Care Medicine.

Key elements of SOFA that pose challenges for administrative data include: PaO₂/FiO₂, which are not routinely measured, and can be difficult to assign to arterial or venous samples; inconsistency in blood pressure and transient increases in vasopressor dose; the subjectivity of the Glasgow Coma Scale, which is also difficult to assess in sedated patients; and inconsistent urine output.

eSOFA introduced new measures for various organ functions, including cardiovascular (vasopressor initiation), pulmonary (mechanical ventilation initiation), renal (doubling of creatinine levels or a 50% or greater decrease in estimated glomerular filtration rate, compared with baseline), hepatic (bilirubin levels greater than or equal to 2.0 mg/dL and at least doubled from baseline), coagulation (platelet count less than 100 cells/mcL and at least a 50% decrease from a baseline of at least 100 cells/mcL), and neurological (lactate greater than or equal to 2.0 mmol/L).

“[eSOFA] opens a window into inter-facility comparisons that has not been possible to do. It’s really critical to ask, ‘How am I doing compared to my peer institutions?’ If you’re doing worse, you can look at the whole spectrum of things to try to drive improvements in care,” said Dr. Rhee.

The new tool isn’t just limited to quality improvement research. Shaeesta Khan, MD, assistant professor of critical care medicine at Geisinger Medical Center,Danville, Pa., has found eSOFA to be useful in her research into how genetic polymorphisms play a role in sepsis outcomes. Geisinger has a large population of patients with completed whole genome sequencing, and Dr. Khan began by trying to glean sepsis outcomes from administrative data.

“I explained SOFA scores to our data broker, and he pulled up 3,000 patients and gave everybody a SOFA score based on the algorithm he created, and it was all over the chart. Once I started doing chart review and phenotype verification, it was just a nightmare,” Dr. Khan said in an interview.

After struggling with the project, one of her mentors put her in touch with one of Dr. Rhee’s colleagues, and she asked the data broker to modify the eSOFA algorithm to fit her specific criteria. “It was a blessing,” she said.

Now, she has data from 5,000 patients with sepsis and sequenced DNA, and can begin comparing outcomes and genetic variants. About 20 candidate genes for sepsis outcomes have been identified to date, but she has a particular interest in PCSK9, which is an innate immune system regulator. She hopes to present results at CCC49 in 2020.
 

Validating mortality prediction

The researchers compared eSOFA and SOFA in a sample from 111 U.S. acute care hospitals to see if eSOFA had a comparable predictive validity for mortality. The analysis included 942,360 adults seen between 2013 and 2015. A total of 11.1% (104,903) had a presumed serious infection based on a blood culture order and at least 4 consecutive days of antibiotic use.

The analysis showed that 6.1% of those with infections had a sepsis event based on at least a 2-point increase in SOFA score from baseline (Sepsis-3 criteria), compared with 4.4% identified by at least a 1-point increase in eSOFA score. A total of 34,174 patients (3.6%) overlapped between SOFA and eSOFA, which represented good agreement (Cronbach’s alpha, 0.81). Compared with SOFA/Sepsis-3, eSOFA had a sensitivity of 60%, and a positive predictive value of 82%.

Patients identified by eSOFA were slightly more ill, with more requiring ICU admission (41% vs. 35%), and a greater frequency of in-hospital mortality (17% vs. 14%). Those patients who were identified by SOFA/Sepsis-3, but missed by eSOFA, had an overall lower mortality (6%).

There was a similar risk of mortality across deciles between SOFA- and eSOFA-identified sepsis patients. In an independent analysis of four hospitals from the Emory system, the area under the receiver operating characteristics was 0.77 for eSOFA and 0.76 for SOFA (P less than .001).

The Centers for Disease Control and Prevention and the Agency for Healthcare Research and Quality funded the study. Dr. Rhee and Dr. Khan have no relevant financial conflicts.
 

SOURCE: Rhee C et al. Crit Care Med. 2019;47(3):307-14.

SAN DIEGO – A simplified version of the Sequential Organ Failure Assessment (SOFA) criteria, known as eSOFA, has the potential to make it easier for hospitals to benchmark sepsis outcomes and quality of care, and could propel new sepsis research. The new method replaces some of SOFA’s more subjective criteria with objective measures.

eSOFA relies on electronic health records to reduce reliance on administrative records, which suffer from cross-hospital variability in diagnosis and coding practices, as well as changes in these practices over time. The diagnosis of sepsis itself is also highly subjective. Instead, eSOFA determines dysfunction in six organ systems, indicated by use of vasopressors and mechanical ventilation, and the presence of abnormal laboratory values.

“The SOFA score includes measures like the Glasgow Coma Scale, which undoubtedly at the bedside is a very important clinical sign, but when trying to implement something that is objective for purposes of retrospective case counting and standardization, it can be problematic. The measures we chose [for eSOFA] are concrete, important maneuvers that were initiated by clinicians,” Chanu Rhee, MD, said in an interview.

Dr. Rhee is assistant professor of population medicine at Harvard Medical School and Brigham and Women’s Hospital, Boston. He presented the results of the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine, and the work was simultaneously published online in Critical Care Medicine.

Key elements of SOFA that pose challenges for administrative data include: PaO₂/FiO₂, which are not routinely measured, and can be difficult to assign to arterial or venous samples; inconsistency in blood pressure and transient increases in vasopressor dose; the subjectivity of the Glasgow Coma Scale, which is also difficult to assess in sedated patients; and inconsistent urine output.

eSOFA introduced new measures for various organ functions, including cardiovascular (vasopressor initiation), pulmonary (mechanical ventilation initiation), renal (doubling of creatinine levels or a 50% or greater decrease in estimated glomerular filtration rate, compared with baseline), hepatic (bilirubin levels greater than or equal to 2.0 mg/dL and at least doubled from baseline), coagulation (platelet count less than 100 cells/mcL and at least a 50% decrease from a baseline of at least 100 cells/mcL), and neurological (lactate greater than or equal to 2.0 mmol/L).

“[eSOFA] opens a window into inter-facility comparisons that has not been possible to do. It’s really critical to ask, ‘How am I doing compared to my peer institutions?’ If you’re doing worse, you can look at the whole spectrum of things to try to drive improvements in care,” said Dr. Rhee.

The new tool isn’t just limited to quality improvement research. Shaeesta Khan, MD, assistant professor of critical care medicine at Geisinger Medical Center,Danville, Pa., has found eSOFA to be useful in her research into how genetic polymorphisms play a role in sepsis outcomes. Geisinger has a large population of patients with completed whole genome sequencing, and Dr. Khan began by trying to glean sepsis outcomes from administrative data.

“I explained SOFA scores to our data broker, and he pulled up 3,000 patients and gave everybody a SOFA score based on the algorithm he created, and it was all over the chart. Once I started doing chart review and phenotype verification, it was just a nightmare,” Dr. Khan said in an interview.

After struggling with the project, one of her mentors put her in touch with one of Dr. Rhee’s colleagues, and she asked the data broker to modify the eSOFA algorithm to fit her specific criteria. “It was a blessing,” she said.

Now, she has data from 5,000 patients with sepsis and sequenced DNA, and can begin comparing outcomes and genetic variants. About 20 candidate genes for sepsis outcomes have been identified to date, but she has a particular interest in PCSK9, which is an innate immune system regulator. She hopes to present results at CCC49 in 2020.
 

Validating mortality prediction

The researchers compared eSOFA and SOFA in a sample from 111 U.S. acute care hospitals to see if eSOFA had a comparable predictive validity for mortality. The analysis included 942,360 adults seen between 2013 and 2015. A total of 11.1% (104,903) had a presumed serious infection based on a blood culture order and at least 4 consecutive days of antibiotic use.

The analysis showed that 6.1% of those with infections had a sepsis event based on at least a 2-point increase in SOFA score from baseline (Sepsis-3 criteria), compared with 4.4% identified by at least a 1-point increase in eSOFA score. A total of 34,174 patients (3.6%) overlapped between SOFA and eSOFA, which represented good agreement (Cronbach’s alpha, 0.81). Compared with SOFA/Sepsis-3, eSOFA had a sensitivity of 60%, and a positive predictive value of 82%.

Patients identified by eSOFA were slightly more ill, with more requiring ICU admission (41% vs. 35%), and a greater frequency of in-hospital mortality (17% vs. 14%). Those patients who were identified by SOFA/Sepsis-3, but missed by eSOFA, had an overall lower mortality (6%).

There was a similar risk of mortality across deciles between SOFA- and eSOFA-identified sepsis patients. In an independent analysis of four hospitals from the Emory system, the area under the receiver operating characteristics was 0.77 for eSOFA and 0.76 for SOFA (P less than .001).

The Centers for Disease Control and Prevention and the Agency for Healthcare Research and Quality funded the study. Dr. Rhee and Dr. Khan have no relevant financial conflicts.
 

SOURCE: Rhee C et al. Crit Care Med. 2019;47(3):307-14.

SAN DIEGO – A simplified version of the Sequential Organ Failure Assessment (SOFA) criteria, known as eSOFA, has the potential to make it easier for hospitals to benchmark sepsis outcomes and quality of care, and could propel new sepsis research. The new method replaces some of SOFA’s more subjective criteria with objective measures.

eSOFA relies on electronic health records to reduce reliance on administrative records, which suffer from cross-hospital variability in diagnosis and coding practices, as well as changes in these practices over time. The diagnosis of sepsis itself is also highly subjective. Instead, eSOFA determines dysfunction in six organ systems, indicated by use of vasopressors and mechanical ventilation, and the presence of abnormal laboratory values.

“The SOFA score includes measures like the Glasgow Coma Scale, which undoubtedly at the bedside is a very important clinical sign, but when trying to implement something that is objective for purposes of retrospective case counting and standardization, it can be problematic. The measures we chose [for eSOFA] are concrete, important maneuvers that were initiated by clinicians,” Chanu Rhee, MD, said in an interview.

Dr. Rhee is assistant professor of population medicine at Harvard Medical School and Brigham and Women’s Hospital, Boston. He presented the results of the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine, and the work was simultaneously published online in Critical Care Medicine.

Key elements of SOFA that pose challenges for administrative data include: PaO₂/FiO₂, which are not routinely measured, and can be difficult to assign to arterial or venous samples; inconsistency in blood pressure and transient increases in vasopressor dose; the subjectivity of the Glasgow Coma Scale, which is also difficult to assess in sedated patients; and inconsistent urine output.

eSOFA introduced new measures for various organ functions, including cardiovascular (vasopressor initiation), pulmonary (mechanical ventilation initiation), renal (doubling of creatinine levels or a 50% or greater decrease in estimated glomerular filtration rate, compared with baseline), hepatic (bilirubin levels greater than or equal to 2.0 mg/dL and at least doubled from baseline), coagulation (platelet count less than 100 cells/mcL and at least a 50% decrease from a baseline of at least 100 cells/mcL), and neurological (lactate greater than or equal to 2.0 mmol/L).

“[eSOFA] opens a window into inter-facility comparisons that has not been possible to do. It’s really critical to ask, ‘How am I doing compared to my peer institutions?’ If you’re doing worse, you can look at the whole spectrum of things to try to drive improvements in care,” said Dr. Rhee.

The new tool isn’t just limited to quality improvement research. Shaeesta Khan, MD, assistant professor of critical care medicine at Geisinger Medical Center,Danville, Pa., has found eSOFA to be useful in her research into how genetic polymorphisms play a role in sepsis outcomes. Geisinger has a large population of patients with completed whole genome sequencing, and Dr. Khan began by trying to glean sepsis outcomes from administrative data.

“I explained SOFA scores to our data broker, and he pulled up 3,000 patients and gave everybody a SOFA score based on the algorithm he created, and it was all over the chart. Once I started doing chart review and phenotype verification, it was just a nightmare,” Dr. Khan said in an interview.

After struggling with the project, one of her mentors put her in touch with one of Dr. Rhee’s colleagues, and she asked the data broker to modify the eSOFA algorithm to fit her specific criteria. “It was a blessing,” she said.

Now, she has data from 5,000 patients with sepsis and sequenced DNA, and can begin comparing outcomes and genetic variants. About 20 candidate genes for sepsis outcomes have been identified to date, but she has a particular interest in PCSK9, which is an innate immune system regulator. She hopes to present results at CCC49 in 2020.
 

Validating mortality prediction

The researchers compared eSOFA and SOFA in a sample from 111 U.S. acute care hospitals to see if eSOFA had a comparable predictive validity for mortality. The analysis included 942,360 adults seen between 2013 and 2015. A total of 11.1% (104,903) had a presumed serious infection based on a blood culture order and at least 4 consecutive days of antibiotic use.

The analysis showed that 6.1% of those with infections had a sepsis event based on at least a 2-point increase in SOFA score from baseline (Sepsis-3 criteria), compared with 4.4% identified by at least a 1-point increase in eSOFA score. A total of 34,174 patients (3.6%) overlapped between SOFA and eSOFA, which represented good agreement (Cronbach’s alpha, 0.81). Compared with SOFA/Sepsis-3, eSOFA had a sensitivity of 60%, and a positive predictive value of 82%.

Patients identified by eSOFA were slightly more ill, with more requiring ICU admission (41% vs. 35%), and a greater frequency of in-hospital mortality (17% vs. 14%). Those patients who were identified by SOFA/Sepsis-3, but missed by eSOFA, had an overall lower mortality (6%).

There was a similar risk of mortality across deciles between SOFA- and eSOFA-identified sepsis patients. In an independent analysis of four hospitals from the Emory system, the area under the receiver operating characteristics was 0.77 for eSOFA and 0.76 for SOFA (P less than .001).

The Centers for Disease Control and Prevention and the Agency for Healthcare Research and Quality funded the study. Dr. Rhee and Dr. Khan have no relevant financial conflicts.
 

SOURCE: Rhee C et al. Crit Care Med. 2019;47(3):307-14.

It appears to be safe to hold the anthracycline in patients with HER2-negative early breast cancer who are at intermediate-to-high genomic risk, results of a large randomized trial suggest.

Among both pre- and postmenopausal women with pathologic stage T1 to T4c with positive nodes or node-negative but high-risk early breast cancer, there were no significant differences in 5-year outcomes for patients treated with six cycles of docetaxel and cyclophosphamide (TC) or four cycles of epirubicin and cyclophosphamide followed by four cycles of docetaxel (EC-T), reported Ulrike Nitz, MD, from the West German Study Group in Mönchengladbach, Germany, and her colleagues in the West German Study PlanB Trial.

Disease-free survival (DFS, the primary endpoint), distant recurrence-free interval (dRFI), and overall survival (OS) “were excellent and virtually identical in patients who received the anthracycline-containing or the anthracycline-free regimen. Subgroups that benefited from the anthracycline-containing regimen were not identified by interaction analysis, although a potentially clinically relevant benefit in particular (e.g., high-risk) subgroups cannot be ruled out,” they wrote. The report is in Journal of Clinical Oncology.

The investigators noted that anthracyclines are associated with increased risk for cardiac disease and hematologic malignancies, prompting investigators in other trials to consider anthracycline-free regimens.

“As the number of long-term survivors, elderly patients, and patients with preexisting cardiac risk factors increases, the toxicity profile becomes a more important discriminator in adjuvant treatment selection,” they wrote.

The investigators enrolled and randomized 2,449 women (median age 55, range 25-77 years) who had histologically confirmed, unilateral primary invasive breast cancer, adequate surgical treatment, and no evidence of metastatic disease. The patients all had HER2-negative disease, pT1 to pT4c, known hormone receptor status, and either pN+ or pN0 with one or more risk factors.

The intention-to-treat analysis included 1,227 patients assigned to EC-T and 1,222 assigned to TC in the efficacy population, and 1,167 and 1,178 patients, respectively, in the safety population.

After a median follow-up of 60 months, the 5-year DFS rate in the TC-treated group was 89.6%, compared with 89.9% in the EC-T–treated group. The estimated 5-year dRFI rates were 94.1% vs. 93.4%, and the estimated 5-year OS rates were 94.7% vs. 94.5%, respectively. None of the comparisons were statistically significant.

There were five treatment-related deaths in the TC arm, (one each from urosepsis, Streptococcus septicemia, peritonitis/diverticulitis, Staphylococcus epidermidis septicemia, and pulmonary embolism), and one in the EC-T arm (from septicemia).

In an interim safety analysis, the rate of febrile neutropenia was 6.1% in the TC arm and 3.9% in the EC-T arm, leading to a recommendation for “generous” prophylaxis with granulocyte-colony stimulating factor, and ciprofloxacine for patients with a history of diverticulitis or chronic infectious GI disease, or expected duration of neutropenia greater than 1 week.

Rates of grade 3 or 4 leukopenia, neutropenia, nausea, vomiting, peripheral polyneuropathy, hand-foot syndrome, mucositis/stomatitis, arthralgia, myalgia, and fatigue were significantly higher among patients treated with EC-T. There were numerically more grade 3-4 infections and febrile neutropenia within the TC arm, but this trend did not reach statistical significance.

The investigators noted that the results of their trial provide the strongest evidence for patients with pathologic NO or N1 disease, and that the trial did not examine the question of dose-dense chemotherapy in patients with high-risk early breast cancer.

Genomic Health, Sanofi, and Amgen supported the study. Dr. Nitz and multiple coauthors disclosed financial relationships with these companies and others.

SOURCE: Nitz U et al. J Clin Oncol. 2019 Feb 20. doi: 10.1200/JCO.18.00028.

It appears to be safe to hold the anthracycline in patients with HER2-negative early breast cancer who are at intermediate-to-high genomic risk, results of a large randomized trial suggest.

Among both pre- and postmenopausal women with pathologic stage T1 to T4c with positive nodes or node-negative but high-risk early breast cancer, there were no significant differences in 5-year outcomes for patients treated with six cycles of docetaxel and cyclophosphamide (TC) or four cycles of epirubicin and cyclophosphamide followed by four cycles of docetaxel (EC-T), reported Ulrike Nitz, MD, from the West German Study Group in Mönchengladbach, Germany, and her colleagues in the West German Study PlanB Trial.

Disease-free survival (DFS, the primary endpoint), distant recurrence-free interval (dRFI), and overall survival (OS) “were excellent and virtually identical in patients who received the anthracycline-containing or the anthracycline-free regimen. Subgroups that benefited from the anthracycline-containing regimen were not identified by interaction analysis, although a potentially clinically relevant benefit in particular (e.g., high-risk) subgroups cannot be ruled out,” they wrote. The report is in Journal of Clinical Oncology.

The investigators noted that anthracyclines are associated with increased risk for cardiac disease and hematologic malignancies, prompting investigators in other trials to consider anthracycline-free regimens.

“As the number of long-term survivors, elderly patients, and patients with preexisting cardiac risk factors increases, the toxicity profile becomes a more important discriminator in adjuvant treatment selection,” they wrote.

The investigators enrolled and randomized 2,449 women (median age 55, range 25-77 years) who had histologically confirmed, unilateral primary invasive breast cancer, adequate surgical treatment, and no evidence of metastatic disease. The patients all had HER2-negative disease, pT1 to pT4c, known hormone receptor status, and either pN+ or pN0 with one or more risk factors.

The intention-to-treat analysis included 1,227 patients assigned to EC-T and 1,222 assigned to TC in the efficacy population, and 1,167 and 1,178 patients, respectively, in the safety population.

After a median follow-up of 60 months, the 5-year DFS rate in the TC-treated group was 89.6%, compared with 89.9% in the EC-T–treated group. The estimated 5-year dRFI rates were 94.1% vs. 93.4%, and the estimated 5-year OS rates were 94.7% vs. 94.5%, respectively. None of the comparisons were statistically significant.

There were five treatment-related deaths in the TC arm, (one each from urosepsis, Streptococcus septicemia, peritonitis/diverticulitis, Staphylococcus epidermidis septicemia, and pulmonary embolism), and one in the EC-T arm (from septicemia).

In an interim safety analysis, the rate of febrile neutropenia was 6.1% in the TC arm and 3.9% in the EC-T arm, leading to a recommendation for “generous” prophylaxis with granulocyte-colony stimulating factor, and ciprofloxacine for patients with a history of diverticulitis or chronic infectious GI disease, or expected duration of neutropenia greater than 1 week.

Rates of grade 3 or 4 leukopenia, neutropenia, nausea, vomiting, peripheral polyneuropathy, hand-foot syndrome, mucositis/stomatitis, arthralgia, myalgia, and fatigue were significantly higher among patients treated with EC-T. There were numerically more grade 3-4 infections and febrile neutropenia within the TC arm, but this trend did not reach statistical significance.

The investigators noted that the results of their trial provide the strongest evidence for patients with pathologic NO or N1 disease, and that the trial did not examine the question of dose-dense chemotherapy in patients with high-risk early breast cancer.

Genomic Health, Sanofi, and Amgen supported the study. Dr. Nitz and multiple coauthors disclosed financial relationships with these companies and others.

SOURCE: Nitz U et al. J Clin Oncol. 2019 Feb 20. doi: 10.1200/JCO.18.00028.

It appears to be safe to hold the anthracycline in patients with HER2-negative early breast cancer who are at intermediate-to-high genomic risk, results of a large randomized trial suggest.

Among both pre- and postmenopausal women with pathologic stage T1 to T4c with positive nodes or node-negative but high-risk early breast cancer, there were no significant differences in 5-year outcomes for patients treated with six cycles of docetaxel and cyclophosphamide (TC) or four cycles of epirubicin and cyclophosphamide followed by four cycles of docetaxel (EC-T), reported Ulrike Nitz, MD, from the West German Study Group in Mönchengladbach, Germany, and her colleagues in the West German Study PlanB Trial.

Disease-free survival (DFS, the primary endpoint), distant recurrence-free interval (dRFI), and overall survival (OS) “were excellent and virtually identical in patients who received the anthracycline-containing or the anthracycline-free regimen. Subgroups that benefited from the anthracycline-containing regimen were not identified by interaction analysis, although a potentially clinically relevant benefit in particular (e.g., high-risk) subgroups cannot be ruled out,” they wrote. The report is in Journal of Clinical Oncology.

The investigators noted that anthracyclines are associated with increased risk for cardiac disease and hematologic malignancies, prompting investigators in other trials to consider anthracycline-free regimens.

“As the number of long-term survivors, elderly patients, and patients with preexisting cardiac risk factors increases, the toxicity profile becomes a more important discriminator in adjuvant treatment selection,” they wrote.

The investigators enrolled and randomized 2,449 women (median age 55, range 25-77 years) who had histologically confirmed, unilateral primary invasive breast cancer, adequate surgical treatment, and no evidence of metastatic disease. The patients all had HER2-negative disease, pT1 to pT4c, known hormone receptor status, and either pN+ or pN0 with one or more risk factors.

The intention-to-treat analysis included 1,227 patients assigned to EC-T and 1,222 assigned to TC in the efficacy population, and 1,167 and 1,178 patients, respectively, in the safety population.

After a median follow-up of 60 months, the 5-year DFS rate in the TC-treated group was 89.6%, compared with 89.9% in the EC-T–treated group. The estimated 5-year dRFI rates were 94.1% vs. 93.4%, and the estimated 5-year OS rates were 94.7% vs. 94.5%, respectively. None of the comparisons were statistically significant.

There were five treatment-related deaths in the TC arm, (one each from urosepsis, Streptococcus septicemia, peritonitis/diverticulitis, Staphylococcus epidermidis septicemia, and pulmonary embolism), and one in the EC-T arm (from septicemia).

In an interim safety analysis, the rate of febrile neutropenia was 6.1% in the TC arm and 3.9% in the EC-T arm, leading to a recommendation for “generous” prophylaxis with granulocyte-colony stimulating factor, and ciprofloxacine for patients with a history of diverticulitis or chronic infectious GI disease, or expected duration of neutropenia greater than 1 week.

Rates of grade 3 or 4 leukopenia, neutropenia, nausea, vomiting, peripheral polyneuropathy, hand-foot syndrome, mucositis/stomatitis, arthralgia, myalgia, and fatigue were significantly higher among patients treated with EC-T. There were numerically more grade 3-4 infections and febrile neutropenia within the TC arm, but this trend did not reach statistical significance.

The investigators noted that the results of their trial provide the strongest evidence for patients with pathologic NO or N1 disease, and that the trial did not examine the question of dose-dense chemotherapy in patients with high-risk early breast cancer.

Genomic Health, Sanofi, and Amgen supported the study. Dr. Nitz and multiple coauthors disclosed financial relationships with these companies and others.

SOURCE: Nitz U et al. J Clin Oncol. 2019 Feb 20. doi: 10.1200/JCO.18.00028.

The American Society of Clinical Oncology has issued a new guideline on the early detection and management of colorectal cancer in people at average risk for colorectal cancer, which was written by Gilberto Lopes, MD, of the University of Miami and his associates on an ASCO expert panel.

The panel assembled by ASCO to write the guideline consisted of medical oncology, surgical oncology, surgery, gastroenterology, health technology assessment, cancer epidemiology, pathology, radiology, radiation oncology, and patient advocacy experts. Guidelines from eight different developers were examined, and recommendations from those guidelines were adapted to form the new ASCO guideline. The guideline was published in the Journal of Global Oncology.

In people who are asymptomatic, are aged 50-75 years, have no family history of colorectal cancer, are at average risk, and are in settings with high incidences of colorectal cancer, the expert panel recommends guaiac fecal occult blood test or fecal immunochemical testing every 1-2 years, flexible sigmoidoscopy every 5 years, a combination of flexible sigmoidoscopy every 10 years and annual stool-based testing, or colonoscopy every 10 years, depending on available resources. The testing strategy for those with positive stool-based testing or flexible sigmoidoscopy is colonoscopy or a double-contrast barium enema if colonoscopy is unavailable.

For patients who have polyps, polypectomy at the time of colonoscopy is recommended, with the option of referral for surgical resection if not suitable for endoscopic resection. When symptoms (iron-deficiency anemia, bleeding, abdominal pain, and/or change in bowel habits) are present, a colonoscopy should be performed if available. If colonoscopy is contraindicated, a double-contrast barium enema can be performed; if endoscopy is contraindicated, CT colonography can be performed.

More information, including a data supplement with additional evidence tables, a methodology supplement with information about evidence quality and strength of recommendations, slide sets, and clinical tools and resources is available at www.asco.org/resource-stratified-guidelines, the guideline noted.

Several members of the expert panel reported conflicts of interest.

lfranki@mdedge.com

SOURCE: Lopes G et al. J Glob Oncol. 2019 Feb 25. doi: 10.1200/JGO.18.00213.

This story was updated on March 4, 2019.

The American Society of Clinical Oncology has issued a new guideline on the early detection and management of colorectal cancer in people at average risk for colorectal cancer, which was written by Gilberto Lopes, MD, of the University of Miami and his associates on an ASCO expert panel.

The panel assembled by ASCO to write the guideline consisted of medical oncology, surgical oncology, surgery, gastroenterology, health technology assessment, cancer epidemiology, pathology, radiology, radiation oncology, and patient advocacy experts. Guidelines from eight different developers were examined, and recommendations from those guidelines were adapted to form the new ASCO guideline. The guideline was published in the Journal of Global Oncology.

In people who are asymptomatic, are aged 50-75 years, have no family history of colorectal cancer, are at average risk, and are in settings with high incidences of colorectal cancer, the expert panel recommends guaiac fecal occult blood test or fecal immunochemical testing every 1-2 years, flexible sigmoidoscopy every 5 years, a combination of flexible sigmoidoscopy every 10 years and annual stool-based testing, or colonoscopy every 10 years, depending on available resources. The testing strategy for those with positive stool-based testing or flexible sigmoidoscopy is colonoscopy or a double-contrast barium enema if colonoscopy is unavailable.

For patients who have polyps, polypectomy at the time of colonoscopy is recommended, with the option of referral for surgical resection if not suitable for endoscopic resection. When symptoms (iron-deficiency anemia, bleeding, abdominal pain, and/or change in bowel habits) are present, a colonoscopy should be performed if available. If colonoscopy is contraindicated, a double-contrast barium enema can be performed; if endoscopy is contraindicated, CT colonography can be performed.

More information, including a data supplement with additional evidence tables, a methodology supplement with information about evidence quality and strength of recommendations, slide sets, and clinical tools and resources is available at www.asco.org/resource-stratified-guidelines, the guideline noted.

Several members of the expert panel reported conflicts of interest.

lfranki@mdedge.com

SOURCE: Lopes G et al. J Glob Oncol. 2019 Feb 25. doi: 10.1200/JGO.18.00213.

This story was updated on March 4, 2019.

The American Society of Clinical Oncology has issued a new guideline on the early detection and management of colorectal cancer in people at average risk for colorectal cancer, which was written by Gilberto Lopes, MD, of the University of Miami and his associates on an ASCO expert panel.

The panel assembled by ASCO to write the guideline consisted of medical oncology, surgical oncology, surgery, gastroenterology, health technology assessment, cancer epidemiology, pathology, radiology, radiation oncology, and patient advocacy experts. Guidelines from eight different developers were examined, and recommendations from those guidelines were adapted to form the new ASCO guideline. The guideline was published in the Journal of Global Oncology.

In people who are asymptomatic, are aged 50-75 years, have no family history of colorectal cancer, are at average risk, and are in settings with high incidences of colorectal cancer, the expert panel recommends guaiac fecal occult blood test or fecal immunochemical testing every 1-2 years, flexible sigmoidoscopy every 5 years, a combination of flexible sigmoidoscopy every 10 years and annual stool-based testing, or colonoscopy every 10 years, depending on available resources. The testing strategy for those with positive stool-based testing or flexible sigmoidoscopy is colonoscopy or a double-contrast barium enema if colonoscopy is unavailable.

For patients who have polyps, polypectomy at the time of colonoscopy is recommended, with the option of referral for surgical resection if not suitable for endoscopic resection. When symptoms (iron-deficiency anemia, bleeding, abdominal pain, and/or change in bowel habits) are present, a colonoscopy should be performed if available. If colonoscopy is contraindicated, a double-contrast barium enema can be performed; if endoscopy is contraindicated, CT colonography can be performed.

More information, including a data supplement with additional evidence tables, a methodology supplement with information about evidence quality and strength of recommendations, slide sets, and clinical tools and resources is available at www.asco.org/resource-stratified-guidelines, the guideline noted.

Several members of the expert panel reported conflicts of interest.

lfranki@mdedge.com

SOURCE: Lopes G et al. J Glob Oncol. 2019 Feb 25. doi: 10.1200/JGO.18.00213.

This story was updated on March 4, 2019.

SAN FRANCISCO – A peanut or egg allergy diagnosed when infants were 1 year of age often resolved by the time they turned 6, in a longitudinal, population-based study of more than 5,000 Australian children.

Mitchel L. Zoler/MDedge News

Among 131 infants diagnosed with a peanut allergy when they were 1 year old and then followed with repeat testing 5 years later, 41 (31%) had complete resolution of their peanut allergy, while the allergy persisted in the other 90 children, Rachel L. Peters, PhD, said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. The study also followed 404 infants diagnosed with an egg allergy at 1 year of age and found that by age 6 the allergy had resolved in 368 (91%), while persisting in 36 children, said Dr. Peters, an epidemiologist at Murdoch Children’s Research Institute in Parkville, Australia.


The analysis also identified risk factors that linked with an increased rate of allergy persistence. For peanut allergy persistence beyond the first year, the correlating factors were early-onset eczema, tree nut allergy, and a stronger peanut allergy identified by a greater than 4-mm reaction to a peanut skin-prick test. Factors that linked with an increased rate of persistent egg allergy were eczema, peanut allergy, gastrointestinal or respiratory reaction symptoms to milk, and reaction on an oral food challenge elicited by a low dose (less than 0.5 mL) of milk.

A consequence of the frequent resolution of these food allergies was that a positive skin-prick test reaction to either peanut or egg at 1 year old was poorly predictive of allergy status at age 6, while skin-prick tests at age 6 worked well for identifying a persistent food allergy at that age.

The analyses that Dr. Peters and her associates ran used data collected in the HealthNuts study, a comprehensive, prospective, population-based study of food allergies in children that enrolled 5,276 infants at 1 year old. The HealthNuts researchers enrolled infants at immunization clinics in the Melbourne area, with enrollment stratified to represent the people who live in that region (Clin Exp Allergy. 2010 Oct;40[10]:1516-22).

mzoler@mdedge.com

On Twitter @mitchelzoler

SOURCE: Peters R et al. J Allergy Clin Immunol. 2019 Feb;143[2]:AB421.

SAN FRANCISCO – A peanut or egg allergy diagnosed when infants were 1 year of age often resolved by the time they turned 6, in a longitudinal, population-based study of more than 5,000 Australian children.

Mitchel L. Zoler/MDedge News

Among 131 infants diagnosed with a peanut allergy when they were 1 year old and then followed with repeat testing 5 years later, 41 (31%) had complete resolution of their peanut allergy, while the allergy persisted in the other 90 children, Rachel L. Peters, PhD, said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. The study also followed 404 infants diagnosed with an egg allergy at 1 year of age and found that by age 6 the allergy had resolved in 368 (91%), while persisting in 36 children, said Dr. Peters, an epidemiologist at Murdoch Children’s Research Institute in Parkville, Australia.


The analysis also identified risk factors that linked with an increased rate of allergy persistence. For peanut allergy persistence beyond the first year, the correlating factors were early-onset eczema, tree nut allergy, and a stronger peanut allergy identified by a greater than 4-mm reaction to a peanut skin-prick test. Factors that linked with an increased rate of persistent egg allergy were eczema, peanut allergy, gastrointestinal or respiratory reaction symptoms to milk, and reaction on an oral food challenge elicited by a low dose (less than 0.5 mL) of milk.

A consequence of the frequent resolution of these food allergies was that a positive skin-prick test reaction to either peanut or egg at 1 year old was poorly predictive of allergy status at age 6, while skin-prick tests at age 6 worked well for identifying a persistent food allergy at that age.

The analyses that Dr. Peters and her associates ran used data collected in the HealthNuts study, a comprehensive, prospective, population-based study of food allergies in children that enrolled 5,276 infants at 1 year old. The HealthNuts researchers enrolled infants at immunization clinics in the Melbourne area, with enrollment stratified to represent the people who live in that region (Clin Exp Allergy. 2010 Oct;40[10]:1516-22).

mzoler@mdedge.com

On Twitter @mitchelzoler

SOURCE: Peters R et al. J Allergy Clin Immunol. 2019 Feb;143[2]:AB421.

SAN FRANCISCO – A peanut or egg allergy diagnosed when infants were 1 year of age often resolved by the time they turned 6, in a longitudinal, population-based study of more than 5,000 Australian children.

Mitchel L. Zoler/MDedge News

Among 131 infants diagnosed with a peanut allergy when they were 1 year old and then followed with repeat testing 5 years later, 41 (31%) had complete resolution of their peanut allergy, while the allergy persisted in the other 90 children, Rachel L. Peters, PhD, said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. The study also followed 404 infants diagnosed with an egg allergy at 1 year of age and found that by age 6 the allergy had resolved in 368 (91%), while persisting in 36 children, said Dr. Peters, an epidemiologist at Murdoch Children’s Research Institute in Parkville, Australia.


The analysis also identified risk factors that linked with an increased rate of allergy persistence. For peanut allergy persistence beyond the first year, the correlating factors were early-onset eczema, tree nut allergy, and a stronger peanut allergy identified by a greater than 4-mm reaction to a peanut skin-prick test. Factors that linked with an increased rate of persistent egg allergy were eczema, peanut allergy, gastrointestinal or respiratory reaction symptoms to milk, and reaction on an oral food challenge elicited by a low dose (less than 0.5 mL) of milk.

A consequence of the frequent resolution of these food allergies was that a positive skin-prick test reaction to either peanut or egg at 1 year old was poorly predictive of allergy status at age 6, while skin-prick tests at age 6 worked well for identifying a persistent food allergy at that age.

The analyses that Dr. Peters and her associates ran used data collected in the HealthNuts study, a comprehensive, prospective, population-based study of food allergies in children that enrolled 5,276 infants at 1 year old. The HealthNuts researchers enrolled infants at immunization clinics in the Melbourne area, with enrollment stratified to represent the people who live in that region (Clin Exp Allergy. 2010 Oct;40[10]:1516-22).

mzoler@mdedge.com

On Twitter @mitchelzoler

SOURCE: Peters R et al. J Allergy Clin Immunol. 2019 Feb;143[2]:AB421.

Single-patient use (SPU) of investigational therapies via the Food and Drug Administration’s Expanded Access program is an option worth considering for heavily pretreated cancer patients, according to a retrospective analysis of SPUs at Memorial Sloan Kettering Cancer Center.

Although approximately 2% of cancer cases at Kettering are pediatric, 34.1% of SPUs were for children, reported lead author Noah Z. Feit of Cornell University, New York, and his colleagues.

Therefore, “SPUs may provide an important means of pediatric drug access,” the investigators wrote in a JAMA Oncology letter.

The analysis involved 179 patients with 43 cancer types; these were more often solid tumors than hematologic malignancies (57.9% vs. 42.1%). The most common solid tumor type was neuroblastoma (15.3%), followed by lung (7.9%), primary brain (7.9%), and breast (5.9%). Sixty-six investigational products were given; the top three types were kinase inhibitors (28.8%), naked antibodies (12.5%), and allogeneic cell therapy (12.0%). Therapies were in various stages of development, including phase 3 (39.4%), phase 2 (36.1%), and phase 1 (18.8%). SPU approval was most often based on previous clinical experience (61.5%), although genomic data (38.0%) and preclinical evidence (30.8%) were also cited. The median number of prior treatments was four, suggesting a heavily pretreated patient population.

Analysis showed that the overall response rate to SPU agents was 20.1%, and patients with hematologic cancers responded more often than did those with solid tumors (30.4% vs. 12.2%). Median progression-free survival and overall survival were 3.9 months and 11.4 months, respectively. About one-third of patients (29.7%) had at least one serious treatment-related adverse event, with adults more often affected than children (35.3% vs. 19.1%). No treatment-related deaths occurred.

“In summary, our data provide an initial evidence basis to evaluate the FDA Expanded Access mechanism. We find its use is broad, involving a wide variety of patients and products, and clinical benefit was observed,” the investigators concluded. “Routine prospective collection of key safety and efficacy metrics should be considered moving forward.”

The study was funded by National Institutes of Health, the St. Baldrick’s Foundation, and the Nonna’s Garden Foundation Initiative in Precision Oncology. The investigators reported financial relationships with Mylan, Atara Biotherapeutics, Chugai Pharma, Boehringer Ingelheim, and others.

SOURCE: Feit et al. JAMA Onc. 2019 Feb 28. doi: 10.1001/jamaoncol.2018.7002.

Single-patient use (SPU) of investigational therapies via the Food and Drug Administration’s Expanded Access program is an option worth considering for heavily pretreated cancer patients, according to a retrospective analysis of SPUs at Memorial Sloan Kettering Cancer Center.

Although approximately 2% of cancer cases at Kettering are pediatric, 34.1% of SPUs were for children, reported lead author Noah Z. Feit of Cornell University, New York, and his colleagues.

Therefore, “SPUs may provide an important means of pediatric drug access,” the investigators wrote in a JAMA Oncology letter.

The analysis involved 179 patients with 43 cancer types; these were more often solid tumors than hematologic malignancies (57.9% vs. 42.1%). The most common solid tumor type was neuroblastoma (15.3%), followed by lung (7.9%), primary brain (7.9%), and breast (5.9%). Sixty-six investigational products were given; the top three types were kinase inhibitors (28.8%), naked antibodies (12.5%), and allogeneic cell therapy (12.0%). Therapies were in various stages of development, including phase 3 (39.4%), phase 2 (36.1%), and phase 1 (18.8%). SPU approval was most often based on previous clinical experience (61.5%), although genomic data (38.0%) and preclinical evidence (30.8%) were also cited. The median number of prior treatments was four, suggesting a heavily pretreated patient population.

Analysis showed that the overall response rate to SPU agents was 20.1%, and patients with hematologic cancers responded more often than did those with solid tumors (30.4% vs. 12.2%). Median progression-free survival and overall survival were 3.9 months and 11.4 months, respectively. About one-third of patients (29.7%) had at least one serious treatment-related adverse event, with adults more often affected than children (35.3% vs. 19.1%). No treatment-related deaths occurred.

“In summary, our data provide an initial evidence basis to evaluate the FDA Expanded Access mechanism. We find its use is broad, involving a wide variety of patients and products, and clinical benefit was observed,” the investigators concluded. “Routine prospective collection of key safety and efficacy metrics should be considered moving forward.”

The study was funded by National Institutes of Health, the St. Baldrick’s Foundation, and the Nonna’s Garden Foundation Initiative in Precision Oncology. The investigators reported financial relationships with Mylan, Atara Biotherapeutics, Chugai Pharma, Boehringer Ingelheim, and others.

SOURCE: Feit et al. JAMA Onc. 2019 Feb 28. doi: 10.1001/jamaoncol.2018.7002.

Single-patient use (SPU) of investigational therapies via the Food and Drug Administration’s Expanded Access program is an option worth considering for heavily pretreated cancer patients, according to a retrospective analysis of SPUs at Memorial Sloan Kettering Cancer Center.

Although approximately 2% of cancer cases at Kettering are pediatric, 34.1% of SPUs were for children, reported lead author Noah Z. Feit of Cornell University, New York, and his colleagues.

Therefore, “SPUs may provide an important means of pediatric drug access,” the investigators wrote in a JAMA Oncology letter.

The analysis involved 179 patients with 43 cancer types; these were more often solid tumors than hematologic malignancies (57.9% vs. 42.1%). The most common solid tumor type was neuroblastoma (15.3%), followed by lung (7.9%), primary brain (7.9%), and breast (5.9%). Sixty-six investigational products were given; the top three types were kinase inhibitors (28.8%), naked antibodies (12.5%), and allogeneic cell therapy (12.0%). Therapies were in various stages of development, including phase 3 (39.4%), phase 2 (36.1%), and phase 1 (18.8%). SPU approval was most often based on previous clinical experience (61.5%), although genomic data (38.0%) and preclinical evidence (30.8%) were also cited. The median number of prior treatments was four, suggesting a heavily pretreated patient population.

Analysis showed that the overall response rate to SPU agents was 20.1%, and patients with hematologic cancers responded more often than did those with solid tumors (30.4% vs. 12.2%). Median progression-free survival and overall survival were 3.9 months and 11.4 months, respectively. About one-third of patients (29.7%) had at least one serious treatment-related adverse event, with adults more often affected than children (35.3% vs. 19.1%). No treatment-related deaths occurred.

“In summary, our data provide an initial evidence basis to evaluate the FDA Expanded Access mechanism. We find its use is broad, involving a wide variety of patients and products, and clinical benefit was observed,” the investigators concluded. “Routine prospective collection of key safety and efficacy metrics should be considered moving forward.”

The study was funded by National Institutes of Health, the St. Baldrick’s Foundation, and the Nonna’s Garden Foundation Initiative in Precision Oncology. The investigators reported financial relationships with Mylan, Atara Biotherapeutics, Chugai Pharma, Boehringer Ingelheim, and others.

SOURCE: Feit et al. JAMA Onc. 2019 Feb 28. doi: 10.1001/jamaoncol.2018.7002.