ANSWER

The correct answer is to perform a punch biopsy (choice “b”). This will help establish the exact nature of the problem, which will dictate rational treatment.

The patient doesn’t have acne, so the suggested treatment options (choices “a,” “c,” and “d”) would be of no use. With cryotherapy, furthermore, there is a risk of leaving a permanent blemish on her skin.

DISCUSSION

A sample of one lesion was obtained via 3-mm punch biopsy and the resulting defect closed with a single suture. Pathologic examination showed the specimen to be a vellus hair cyst (VHC). In this case, it was one of many, making the diagnosis eruptive vellus hair cysts.

VHC, which can be acquired or inherited, typically manifests in the first two decades of life. In this developmental abnormality, a gradual disruption occurs between the proximal and distal portions of the vellus hair follicle, usually at the level of the infundibulum. As a result, the characteristic papule (which holds the retained hair) forms and the hair bulb atrophies.

The lesions may be solitary or appear in clusters on the body; they are easily mistaken for acne, milia, or even molluscum. As this case demonstrates, biopsy is often necessary to establish the correct diagnosis.

One final note about biopsy: It is best to incise each lesion with an 18-gauge needle tip or #11 blade and express the contents. This tedious process causes some discomfort for the patient, but it is quite effective and, if done correctly, should not leave a permanent mark on the skin.

ANSWER

The correct answer is to perform a punch biopsy (choice “b”). This will help establish the exact nature of the problem, which will dictate rational treatment.

The patient doesn’t have acne, so the suggested treatment options (choices “a,” “c,” and “d”) would be of no use. With cryotherapy, furthermore, there is a risk of leaving a permanent blemish on her skin.

DISCUSSION

A sample of one lesion was obtained via 3-mm punch biopsy and the resulting defect closed with a single suture. Pathologic examination showed the specimen to be a vellus hair cyst (VHC). In this case, it was one of many, making the diagnosis eruptive vellus hair cysts.

VHC, which can be acquired or inherited, typically manifests in the first two decades of life. In this developmental abnormality, a gradual disruption occurs between the proximal and distal portions of the vellus hair follicle, usually at the level of the infundibulum. As a result, the characteristic papule (which holds the retained hair) forms and the hair bulb atrophies.

The lesions may be solitary or appear in clusters on the body; they are easily mistaken for acne, milia, or even molluscum. As this case demonstrates, biopsy is often necessary to establish the correct diagnosis.

One final note about biopsy: It is best to incise each lesion with an 18-gauge needle tip or #11 blade and express the contents. This tedious process causes some discomfort for the patient, but it is quite effective and, if done correctly, should not leave a permanent mark on the skin.

ANSWER

The correct answer is to perform a punch biopsy (choice “b”). This will help establish the exact nature of the problem, which will dictate rational treatment.

The patient doesn’t have acne, so the suggested treatment options (choices “a,” “c,” and “d”) would be of no use. With cryotherapy, furthermore, there is a risk of leaving a permanent blemish on her skin.

DISCUSSION

A sample of one lesion was obtained via 3-mm punch biopsy and the resulting defect closed with a single suture. Pathologic examination showed the specimen to be a vellus hair cyst (VHC). In this case, it was one of many, making the diagnosis eruptive vellus hair cysts.

VHC, which can be acquired or inherited, typically manifests in the first two decades of life. In this developmental abnormality, a gradual disruption occurs between the proximal and distal portions of the vellus hair follicle, usually at the level of the infundibulum. As a result, the characteristic papule (which holds the retained hair) forms and the hair bulb atrophies.

The lesions may be solitary or appear in clusters on the body; they are easily mistaken for acne, milia, or even molluscum. As this case demonstrates, biopsy is often necessary to establish the correct diagnosis.

One final note about biopsy: It is best to incise each lesion with an 18-gauge needle tip or #11 blade and express the contents. This tedious process causes some discomfort for the patient, but it is quite effective and, if done correctly, should not leave a permanent mark on the skin.

Clinical question: Does bundled payment for lower extremity joint replacement (LEJR) reduce cost without compromising the quality of care?

There were no statistical differences in claims-based quality measures between the BPCI and comparison populations, which included 30- and 90-day unplanned readmissions, ED visits, and postdischarge mortality.

Bottom line: Bundled payments for joint replacements may have the potential to decrease cost while maintaining quality of care.

Citation: Dummit L, Kahvecioglu D, Marrufo G, et al. Association between hospital participation in a Medicare bundled payment initiative and payments and quality outcomes for lower extremity joint e replacement episodes. JAMA. 2016;316(12):1267-1278.

Dr. Briones is an assistant professor at the University of Miami Miller School of Medicine and medical director of the hospitalist service at the University of Miami Hospital.

Clinical question: Does bundled payment for lower extremity joint replacement (LEJR) reduce cost without compromising the quality of care?

There were no statistical differences in claims-based quality measures between the BPCI and comparison populations, which included 30- and 90-day unplanned readmissions, ED visits, and postdischarge mortality.

Bottom line: Bundled payments for joint replacements may have the potential to decrease cost while maintaining quality of care.

Citation: Dummit L, Kahvecioglu D, Marrufo G, et al. Association between hospital participation in a Medicare bundled payment initiative and payments and quality outcomes for lower extremity joint e replacement episodes. JAMA. 2016;316(12):1267-1278.

Dr. Briones is an assistant professor at the University of Miami Miller School of Medicine and medical director of the hospitalist service at the University of Miami Hospital.

Clinical question: Does bundled payment for lower extremity joint replacement (LEJR) reduce cost without compromising the quality of care?

There were no statistical differences in claims-based quality measures between the BPCI and comparison populations, which included 30- and 90-day unplanned readmissions, ED visits, and postdischarge mortality.

Bottom line: Bundled payments for joint replacements may have the potential to decrease cost while maintaining quality of care.

Citation: Dummit L, Kahvecioglu D, Marrufo G, et al. Association between hospital participation in a Medicare bundled payment initiative and payments and quality outcomes for lower extremity joint e replacement episodes. JAMA. 2016;316(12):1267-1278.

Dr. Briones is an assistant professor at the University of Miami Miller School of Medicine and medical director of the hospitalist service at the University of Miami Hospital.

A 28-year-old male presents to the emergency department with fever and severe headache. He has had a fever for 24 hours. Headache began that morning. On exam, he has marked nuchal rigidity, with a temperature of 103.5° F. He is fully oriented and has a nonfocal neurologic examination.

What would you do?

A) Lumbar puncture (LP).

B) CT scan, then LP.

C) Antibiotics, CT scan, then LP.

D) MRI, then LP.

E) Antibiotics, MRI, then LP.

The practice of obtaining a head CT scan (or MRI) before performing a lumbar puncture (LP) is commonplace in emergency departments. The concern is that if a lumbar puncture is done in a patient with increased intracranial pressure, then brain herniation could occur. How common is brain herniation, are there useful clinical indicators that make a CT scan not helpful, and does this concern reach myth status?

References

1. Br J Radiol. 1999 Mar;72(855):319.

2. J Emerg Med. 1994 Sep-Oct;12(5):597-601.

3. AMA Arch Neurol Psychiatry. 1954 Nov;72(5):568-72.

4. Postgrad Med J. 2006 Mar;82(965):162-5.

5. N Engl J Med. 2001 Dec 13;345(24):1727-33.
 

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

A 28-year-old male presents to the emergency department with fever and severe headache. He has had a fever for 24 hours. Headache began that morning. On exam, he has marked nuchal rigidity, with a temperature of 103.5° F. He is fully oriented and has a nonfocal neurologic examination.

What would you do?

A) Lumbar puncture (LP).

B) CT scan, then LP.

C) Antibiotics, CT scan, then LP.

D) MRI, then LP.

E) Antibiotics, MRI, then LP.

The practice of obtaining a head CT scan (or MRI) before performing a lumbar puncture (LP) is commonplace in emergency departments. The concern is that if a lumbar puncture is done in a patient with increased intracranial pressure, then brain herniation could occur. How common is brain herniation, are there useful clinical indicators that make a CT scan not helpful, and does this concern reach myth status?

References

1. Br J Radiol. 1999 Mar;72(855):319.

2. J Emerg Med. 1994 Sep-Oct;12(5):597-601.

3. AMA Arch Neurol Psychiatry. 1954 Nov;72(5):568-72.

4. Postgrad Med J. 2006 Mar;82(965):162-5.

5. N Engl J Med. 2001 Dec 13;345(24):1727-33.
 

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

A 28-year-old male presents to the emergency department with fever and severe headache. He has had a fever for 24 hours. Headache began that morning. On exam, he has marked nuchal rigidity, with a temperature of 103.5° F. He is fully oriented and has a nonfocal neurologic examination.

What would you do?

A) Lumbar puncture (LP).

B) CT scan, then LP.

C) Antibiotics, CT scan, then LP.

D) MRI, then LP.

E) Antibiotics, MRI, then LP.

The practice of obtaining a head CT scan (or MRI) before performing a lumbar puncture (LP) is commonplace in emergency departments. The concern is that if a lumbar puncture is done in a patient with increased intracranial pressure, then brain herniation could occur. How common is brain herniation, are there useful clinical indicators that make a CT scan not helpful, and does this concern reach myth status?

References

1. Br J Radiol. 1999 Mar;72(855):319.

2. J Emerg Med. 1994 Sep-Oct;12(5):597-601.

3. AMA Arch Neurol Psychiatry. 1954 Nov;72(5):568-72.

4. Postgrad Med J. 2006 Mar;82(965):162-5.

5. N Engl J Med. 2001 Dec 13;345(24):1727-33.
 

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

Triage to chemotherapy using a Ki67-based Preoperative Endocrine Prognostic Index (PEPI), which also integrates residual disease burden, appears useful for deescalating adjuvant treatment after neoadjuvant aromatase inhibitor (AI) therapy for breast cancer, investigators report in the Journal of Clinical Oncology.

Only 4 of 109 patients (3.7%) in the American College of Surgeons Oncology Group Z1031B trial with a PEPI score of 0 relapsed after a median of 5.5 years (and were therefore unlikely to benefit from adjuvant chemotherapy), compared with 49 (14.4%) of 341 patients with a PEPI score greater than 0 (recurrence hazard ratio, 0.27), reported Matthew J. Ellis, MD, of Baylor College of Medicine, Houston, and his associates.

[email protected]

Triage to chemotherapy using a Ki67-based Preoperative Endocrine Prognostic Index (PEPI), which also integrates residual disease burden, appears useful for deescalating adjuvant treatment after neoadjuvant aromatase inhibitor (AI) therapy for breast cancer, investigators report in the Journal of Clinical Oncology.

Only 4 of 109 patients (3.7%) in the American College of Surgeons Oncology Group Z1031B trial with a PEPI score of 0 relapsed after a median of 5.5 years (and were therefore unlikely to benefit from adjuvant chemotherapy), compared with 49 (14.4%) of 341 patients with a PEPI score greater than 0 (recurrence hazard ratio, 0.27), reported Matthew J. Ellis, MD, of Baylor College of Medicine, Houston, and his associates.

[email protected]

Triage to chemotherapy using a Ki67-based Preoperative Endocrine Prognostic Index (PEPI), which also integrates residual disease burden, appears useful for deescalating adjuvant treatment after neoadjuvant aromatase inhibitor (AI) therapy for breast cancer, investigators report in the Journal of Clinical Oncology.

Only 4 of 109 patients (3.7%) in the American College of Surgeons Oncology Group Z1031B trial with a PEPI score of 0 relapsed after a median of 5.5 years (and were therefore unlikely to benefit from adjuvant chemotherapy), compared with 49 (14.4%) of 341 patients with a PEPI score greater than 0 (recurrence hazard ratio, 0.27), reported Matthew J. Ellis, MD, of Baylor College of Medicine, Houston, and his associates.

[email protected]

In this Update we discuss several exciting new recommendations for preventive treatments in pregnancy and prenatal diagnostic tests. Our A-to-Z coverage includes:

• antenatal steroids in late preterm pregnancy
• expanded list of high-risk conditions warranting low-dose aspirin for preeclampsia prevention
• chromosomal microarray analysis versus karyotype for specific clinical situations
• Zika virus infection evolving information.

Next: New recommendation for timing of late preterm antenatal steroids

New recommendation offered for timing of late preterm antenatal steroids

Gyamfi-Bannerman C, Thom EA, Blackwell SC, et al; for the NICHD Maternal-Fetal Medicine Units Network. Antenatal betamethasone for women at risk for late preterm delivery. N Engl J Med. 2016;374(14):1311-1320.

American College of Obstetricians and Gynecologists. Committee Opinion No. 677. Antenatal corticosteroidtherapy for fetal maturation. Obstet Gynecol. 2016;128(4):e187-e194.

Kamath-Rayne BD, Rozance PJ, Goldenberg RL, Jobe AH. Antenatal corticosteroids beyond 34 weeks gestation: what do we do now? Am J Obstet Gynecol. 2016;215(4):423-430.

A dramatic recommendation for obstetric practice change occurred in 2016: the option of administering antenatal steroids for fetal lung maturity after 34 weeks. In the Antenatal Late Preterm Steroids (ALPS) trial of betamethasone in the late preterm period in patients at "high risk" of imminent delivery, Gyamfi-Bannerman and colleagues demonstrated that the treated group had a significant decrease in the rate of neonatal respiratory complications.

The primary outcome, a composite of respiratory morbidities (including transient tachypnea of the newborn, surfactant use, and need for resuscitation at birth) within the first 72 hours of life, had significant differences between groups, occurring in 165 of 1,427 infants (11.6%) in the betamethasone-treated group and 202 of 1,400 (14.4%) in the placebo group (relative risk in the betamethasone group, 0.80; 95% confidence interval, 0.66-0.97; P = .02). However, there was no statistically significant difference in respiratory distress syndrome, apnea, or pneumonia between groups, and the significant difference noted in bronchopulmonary dysplasia was based on a total number of 11 cases.

In response to these findings, both the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) released practice advisories and interim updates, culminating in a final recommendation for a single course of betamethasone in patients at high risk of preterm delivery between 34 and 36 6/7 weeks who have not received a previous course.

Related article:
When could use of antenatal corticosteroids in the late preterm birth period be beneficial?

In a thorough review of the literature on antenatal steroid use, Kamath-Rayne and colleagues highlighted several factors that should be considered before adopting universal use of steroids at >34 weeks. These include:   

• The definition of "high risk of imminent delivery" as preterm labor with at least 3-cm dilation or 75% effacement, or spontaneous rupture of membranes. The effect of less stringent inclusion criteria in real-world clinical practice is not known, and many patients who will go on to deliver at term will receive steroids unnecessarily.
• Multiple gestation, patients with pre-existing diabetes, women who had previously received a course of steroids, and fetuses with anomalies were excluded from the ALPS study. Use of antenatal steroids in these groups at >34 weeks should be evaluated before universal adoption.

Related article:
What is the ideal gestational age for twin delivery to minimize perinatal deaths?

• The incidence of neonatal hypoglycemia in the treated group was significantly increased. This affects our colleagues in pediatrics considerably from a systems standpoint (need for changes to newborn protocols and communication between services).
• The long-term outcomes of patients exposed to steroids in the late preterm period are yet to be delineated, specifically, the potential neurodevelopmental effects of a medication known to alter preterm brain development as well as cardiovascular and metabolic consequences.

Next: Low-dose aspirin for reducing preeclampsia risk

Low-dose aspirin clearly is effective for reducing the risk of preeclampsia

American College of Obstetricians and Gynecologists. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013;122(5):1122-1131.

Henderson JT, Whitlock EP, O'Connor E, Senger CA, Thompson JH, Rowland MG. Low-dose aspirin for prevention of morbidity and mortality from preeclampsia: a systematic evidence review for the US Preventive Services Task Force. Ann Intern Med. 2014;160(10):695-703.

LeFevre ML; US Preventive Services Task Force. Low-dose aspirin use for the prevention of morbidity and mortality from preeclampsia: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;161(11):819-826.

American College of Obstetricians and Gynecologists. Practice advisory on low-dose aspirin and prevention of preeclampsia: updated recommendations. http://www.acog.org/About-ACOG/News-Room/Practice-Advisories/Practice-Advisory-Low-Dose-Aspirin-and-Prevention-of-Preeclampsia-Updated-Recommendations. Published July 11, 2016. Accessed December 6, 2016.

In the 2013 ACOG Task Force on Hypertension in Pregnancy report, low-dose aspirin (60-80 mg) was recommended to be initiated in the late first trimester to reduce preeclampsia risk for women with:

• prior early onset preeclampsia with preterm delivery at <34 weeks' gestation, or
• preeclampsia in more than one prior pregnancy.  

This recommendation was based on several meta-analyses that demonstrated a 10% to 17% reduction in risk with no increase in bleeding, placental abruption, or other adverse events.

In 2014, the US Preventive Services Task Force (USPSTF) conducted a systematic evidence review of low-dose aspirin use for prevention of morbidity and mortality from preeclampsia. That report revealed a 24% risk reduction of preeclampsia in high-risk women treated with low-dose aspirin, as well as a 14% reduction in preterm birth and a 20% reduction in fetal growth restriction. A final statement from the USPSTF in 2014 recommended low-dose aspirin (60-150 mg) starting between 12 and 28 weeks' gestation for women at "high" risk who have:

• a history of preeclampsia, especially if accompanied by an adverse outcome
• multifetal gestation
• chronic hypertension
• diabetes (type 1 or type 2)
• renal disease
• autoimmune disease (such as systematic lupus erythematosus, antiphospholipid syndrome).

Related article:
Start offering aspirin to pregnant women at high risk for preeclampsia

As of July 11, 2016, ACOG supports this expanded list of high-risk conditions. Additionally, the USPSTF identified a "moderate" risk group in which low-dose aspirin may be considered if a patient has several risk factors, such as obesity, nulliparity, family history of preeclampsia, age 35 years or older, or another poor pregnancy outcome. ACOG notes, however, that the evidence supporting this practice is uncertain and does not make a recommendation regarding aspirin use in this population. Further study should be conducted to determine the benefit of low-dose aspirin in these patients as well as the long-term effects of treatment on maternal and child outcomes.

Next: CMA for prenatal genetic diagnosis

Chromosomal microarray analysis is preferable to karyotype in certain situations  

Pauli JM, Repke JT. Update on obstetrics. OBG Manag. 2013;25(1):28-32.

Society for Maternal-Fetal Medicine (SMFM), Dugoff L, Norton ME, Kuller JA. The use of chromosomal microarray for prenatal diagnosis. Am J Obstet Gynecol. 2016;215(4):B2-B9.

American College of Obstetricians and Gynecologists. Committee Opinion No. 682. Microarrays and next- generation sequencing technology: the use of advanced genetic diagnostic tools in obstetrics and gynecology.Obstet  Gynecol. 2016;128(6):e262-e268.

We previously addressed the use of chromosomal microarray analysis (CMA) for prenatal diagnosis in our 2013 "Update on obstetrics," specifically, the question of whether CMA could replace karyotype. The main differences between karyotype and CMA are that 1) only karyotype can detect balanced translocations/inversions and 2) only CMA can detect copy number variants (CNV). There are some differences in the technology and capabilities of the 2 types of CMA currently available as well.

In our 2013 article we concluded that "The total costs of such an approach--test, interpretation, counseling, and long-term follow-up of uncertain results--are unknown at this time and may prove to be unaffordable on a population-wide basis." Today, the cost of CMA is still higher than karyotype, but it is expected to decrease and insurance coverage for this test is expected to increase.

Related article:
Cell-free DNA screening for women at low risk for fetal aneuploidy

Both SMFM and ACOG released recommendations in 2016 regarding the use of CMA in prenatal genetic diagnosis, summarized as follows:  

• CMA is recommended over karyotype for fetuses with structural abnormalities on ultrasound
  • The detection rate for clinically relevant abnormal CNVs in this population is about 6%
• CMA is recommended for diagnosis for stillbirth specimens
  • CMA does not require dividing cells and may be a quicker and more reliable test in this population
• Karotype or fluorescence in situ hybridization (FISH) is recommended for fetuses with ultrasound findings suggestive of aneuploidy
  • If it is negative, then CMA is recommended
• Karyotype or CMA is recommended for patients desiring prenatal diagnostic testing with a normal fetal ultrasound
  • The detection rate for clinically relevant CNVs in this population (advanced maternal age, abnormal serum screening, prior aneuploidy, parental anxiety) is about 1%
• Pretest and posttest counseling about the limitations of CMA and a 2% risk of detection of variants of unknown significance (VUS) should be performed by a provider who has expertise in CMA and who has access to databases with genotype/phenotype information for VUS
  • This counseling should also include the possibility of diagnosis of nonpaternity, consanguinity, and adult-onset disease
• Karyotype is recommended for couples with recurrent pregnancy loss
  • The identification of balanced translocations in this population is most relevant in this patient population
• Prenatal diagnosis with routine use of whole-genome or whole-exome sequencing is not recommended.

Next: Zika virus: Check for updates

Zika virus infection: Check often for the latest updates

American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine. Practice advisory on Zika virus. http://www.acog.org/About-ACOG/News-Room/Practice-Advisories/Practice-Advisory-Interim-Guidance-for-Care-of-Obstetric-Patients- During-a-Zika-Virus-Outbreak. Published December 5, 2016. Accessed December 6, 2016.

Centers for Disease Control and Prevention. Zika virus. http://www.cdc.gov/zika/pregnancy/index.html. Updated August 22, 2016. Accessed December 6, 2016.

Petersen EE, Meaney-Delman D, Neblett-Fanfair R, et al. Update: interim guidance for preconception counseling and prevention of sexual transmission of Zika virus for persons with possible Zika virus exposure--United States, September 2016. MMWR Morbid Mortal Wkly Rep. 2016;65(39):1077-1081.

A yearly update on obstetrics would be remiss without mention of the Zika virus and its impact on pregnancy and reproduction. That being said, any recommendations we offer may be out of date by the time this article is published given the rapidly changing picture of Zika virus since it first dominated the headlines in 2016. Here are the basics as summarized from ACOG and the Centers for Disease Control and Prevention (CDC):

Viral spread. Zika virus may be spread in several ways: by an infected Aedes species mosquito, mother to fetus, sexual contact, blood transfusion, or laboratory exposure.

Symptoms of infection include conjunctivitis, fever, rash, and arthralgia, but most patients (4/5) are asymptomatic.

Sequelae. Zika virus infection during pregnancy is believed to cause fetal and neonatal microcephaly, intracranial calcifications, and brain and eye abnormalities. The rate of these findings in infected individuals, as well as the rate of vertical transmission, is not known.

Travel advisory. Pregnant women should not travel to areas with active Zika infection (the CDC website regularly updates these restricted areas).

Preventive measures. If traveling to an area of active Zika infection, pregnant women should take preventative measures day and night against mosquito bites, such as use of insect repellents approved by the Environmental Protection Agency, clothing that covers exposed skin, and staying indoors.

Safe sex. Abstinence or consistent condom use is recommended for pregnant women with partners who travel to or live in areas of active Zika infection.

Delay conception. Conception should be postponed for at least 6 months in men with Zika infection and at least 8 weeks in women with Zika infection.

Testing recommendations. Pregnant women with Zika virus exposure should be tested, regardless of symptoms. Symptomatic exposed nonpregnant women and all men should be tested.

Prenatal surveillance. High-risk consultation and serial ultrasounds for fetal anatomy and growth should be considered in patients with Zika virus infection during pregnancy. Amniocentesis can be considered on a case-by-case basis.

Related article:
Zika virus update: A rapidly moving target

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

In this Update we discuss several exciting new recommendations for preventive treatments in pregnancy and prenatal diagnostic tests. Our A-to-Z coverage includes:

• antenatal steroids in late preterm pregnancy
• expanded list of high-risk conditions warranting low-dose aspirin for preeclampsia prevention
• chromosomal microarray analysis versus karyotype for specific clinical situations
• Zika virus infection evolving information.

Next: New recommendation for timing of late preterm antenatal steroids

New recommendation offered for timing of late preterm antenatal steroids

Gyamfi-Bannerman C, Thom EA, Blackwell SC, et al; for the NICHD Maternal-Fetal Medicine Units Network. Antenatal betamethasone for women at risk for late preterm delivery. N Engl J Med. 2016;374(14):1311-1320.

American College of Obstetricians and Gynecologists. Committee Opinion No. 677. Antenatal corticosteroidtherapy for fetal maturation. Obstet Gynecol. 2016;128(4):e187-e194.

Kamath-Rayne BD, Rozance PJ, Goldenberg RL, Jobe AH. Antenatal corticosteroids beyond 34 weeks gestation: what do we do now? Am J Obstet Gynecol. 2016;215(4):423-430.

A dramatic recommendation for obstetric practice change occurred in 2016: the option of administering antenatal steroids for fetal lung maturity after 34 weeks. In the Antenatal Late Preterm Steroids (ALPS) trial of betamethasone in the late preterm period in patients at "high risk" of imminent delivery, Gyamfi-Bannerman and colleagues demonstrated that the treated group had a significant decrease in the rate of neonatal respiratory complications.

The primary outcome, a composite of respiratory morbidities (including transient tachypnea of the newborn, surfactant use, and need for resuscitation at birth) within the first 72 hours of life, had significant differences between groups, occurring in 165 of 1,427 infants (11.6%) in the betamethasone-treated group and 202 of 1,400 (14.4%) in the placebo group (relative risk in the betamethasone group, 0.80; 95% confidence interval, 0.66-0.97; P = .02). However, there was no statistically significant difference in respiratory distress syndrome, apnea, or pneumonia between groups, and the significant difference noted in bronchopulmonary dysplasia was based on a total number of 11 cases.

In response to these findings, both the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) released practice advisories and interim updates, culminating in a final recommendation for a single course of betamethasone in patients at high risk of preterm delivery between 34 and 36 6/7 weeks who have not received a previous course.

Related article:
When could use of antenatal corticosteroids in the late preterm birth period be beneficial?

In a thorough review of the literature on antenatal steroid use, Kamath-Rayne and colleagues highlighted several factors that should be considered before adopting universal use of steroids at >34 weeks. These include:   

• The definition of "high risk of imminent delivery" as preterm labor with at least 3-cm dilation or 75% effacement, or spontaneous rupture of membranes. The effect of less stringent inclusion criteria in real-world clinical practice is not known, and many patients who will go on to deliver at term will receive steroids unnecessarily.
• Multiple gestation, patients with pre-existing diabetes, women who had previously received a course of steroids, and fetuses with anomalies were excluded from the ALPS study. Use of antenatal steroids in these groups at >34 weeks should be evaluated before universal adoption.

Related article:
What is the ideal gestational age for twin delivery to minimize perinatal deaths?

• The incidence of neonatal hypoglycemia in the treated group was significantly increased. This affects our colleagues in pediatrics considerably from a systems standpoint (need for changes to newborn protocols and communication between services).
• The long-term outcomes of patients exposed to steroids in the late preterm period are yet to be delineated, specifically, the potential neurodevelopmental effects of a medication known to alter preterm brain development as well as cardiovascular and metabolic consequences.

Next: Low-dose aspirin for reducing preeclampsia risk

Low-dose aspirin clearly is effective for reducing the risk of preeclampsia

American College of Obstetricians and Gynecologists. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013;122(5):1122-1131.

Henderson JT, Whitlock EP, O'Connor E, Senger CA, Thompson JH, Rowland MG. Low-dose aspirin for prevention of morbidity and mortality from preeclampsia: a systematic evidence review for the US Preventive Services Task Force. Ann Intern Med. 2014;160(10):695-703.

LeFevre ML; US Preventive Services Task Force. Low-dose aspirin use for the prevention of morbidity and mortality from preeclampsia: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;161(11):819-826.

American College of Obstetricians and Gynecologists. Practice advisory on low-dose aspirin and prevention of preeclampsia: updated recommendations. http://www.acog.org/About-ACOG/News-Room/Practice-Advisories/Practice-Advisory-Low-Dose-Aspirin-and-Prevention-of-Preeclampsia-Updated-Recommendations. Published July 11, 2016. Accessed December 6, 2016.

In the 2013 ACOG Task Force on Hypertension in Pregnancy report, low-dose aspirin (60-80 mg) was recommended to be initiated in the late first trimester to reduce preeclampsia risk for women with:

• prior early onset preeclampsia with preterm delivery at <34 weeks' gestation, or
• preeclampsia in more than one prior pregnancy.  

This recommendation was based on several meta-analyses that demonstrated a 10% to 17% reduction in risk with no increase in bleeding, placental abruption, or other adverse events.

In 2014, the US Preventive Services Task Force (USPSTF) conducted a systematic evidence review of low-dose aspirin use for prevention of morbidity and mortality from preeclampsia. That report revealed a 24% risk reduction of preeclampsia in high-risk women treated with low-dose aspirin, as well as a 14% reduction in preterm birth and a 20% reduction in fetal growth restriction. A final statement from the USPSTF in 2014 recommended low-dose aspirin (60-150 mg) starting between 12 and 28 weeks' gestation for women at "high" risk who have:

• a history of preeclampsia, especially if accompanied by an adverse outcome
• multifetal gestation
• chronic hypertension
• diabetes (type 1 or type 2)
• renal disease
• autoimmune disease (such as systematic lupus erythematosus, antiphospholipid syndrome).

Related article:
Start offering aspirin to pregnant women at high risk for preeclampsia

As of July 11, 2016, ACOG supports this expanded list of high-risk conditions. Additionally, the USPSTF identified a "moderate" risk group in which low-dose aspirin may be considered if a patient has several risk factors, such as obesity, nulliparity, family history of preeclampsia, age 35 years or older, or another poor pregnancy outcome. ACOG notes, however, that the evidence supporting this practice is uncertain and does not make a recommendation regarding aspirin use in this population. Further study should be conducted to determine the benefit of low-dose aspirin in these patients as well as the long-term effects of treatment on maternal and child outcomes.

Next: CMA for prenatal genetic diagnosis

Chromosomal microarray analysis is preferable to karyotype in certain situations  

Pauli JM, Repke JT. Update on obstetrics. OBG Manag. 2013;25(1):28-32.

Society for Maternal-Fetal Medicine (SMFM), Dugoff L, Norton ME, Kuller JA. The use of chromosomal microarray for prenatal diagnosis. Am J Obstet Gynecol. 2016;215(4):B2-B9.

American College of Obstetricians and Gynecologists. Committee Opinion No. 682. Microarrays and next- generation sequencing technology: the use of advanced genetic diagnostic tools in obstetrics and gynecology.Obstet  Gynecol. 2016;128(6):e262-e268.

We previously addressed the use of chromosomal microarray analysis (CMA) for prenatal diagnosis in our 2013 "Update on obstetrics," specifically, the question of whether CMA could replace karyotype. The main differences between karyotype and CMA are that 1) only karyotype can detect balanced translocations/inversions and 2) only CMA can detect copy number variants (CNV). There are some differences in the technology and capabilities of the 2 types of CMA currently available as well.

In our 2013 article we concluded that "The total costs of such an approach--test, interpretation, counseling, and long-term follow-up of uncertain results--are unknown at this time and may prove to be unaffordable on a population-wide basis." Today, the cost of CMA is still higher than karyotype, but it is expected to decrease and insurance coverage for this test is expected to increase.

Related article:
Cell-free DNA screening for women at low risk for fetal aneuploidy

Both SMFM and ACOG released recommendations in 2016 regarding the use of CMA in prenatal genetic diagnosis, summarized as follows:  

• CMA is recommended over karyotype for fetuses with structural abnormalities on ultrasound
  • The detection rate for clinically relevant abnormal CNVs in this population is about 6%
• CMA is recommended for diagnosis for stillbirth specimens
  • CMA does not require dividing cells and may be a quicker and more reliable test in this population
• Karotype or fluorescence in situ hybridization (FISH) is recommended for fetuses with ultrasound findings suggestive of aneuploidy
  • If it is negative, then CMA is recommended
• Karyotype or CMA is recommended for patients desiring prenatal diagnostic testing with a normal fetal ultrasound
  • The detection rate for clinically relevant CNVs in this population (advanced maternal age, abnormal serum screening, prior aneuploidy, parental anxiety) is about 1%
• Pretest and posttest counseling about the limitations of CMA and a 2% risk of detection of variants of unknown significance (VUS) should be performed by a provider who has expertise in CMA and who has access to databases with genotype/phenotype information for VUS
  • This counseling should also include the possibility of diagnosis of nonpaternity, consanguinity, and adult-onset disease
• Karyotype is recommended for couples with recurrent pregnancy loss
  • The identification of balanced translocations in this population is most relevant in this patient population
• Prenatal diagnosis with routine use of whole-genome or whole-exome sequencing is not recommended.

Next: Zika virus: Check for updates

Zika virus infection: Check often for the latest updates

American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine. Practice advisory on Zika virus. http://www.acog.org/About-ACOG/News-Room/Practice-Advisories/Practice-Advisory-Interim-Guidance-for-Care-of-Obstetric-Patients- During-a-Zika-Virus-Outbreak. Published December 5, 2016. Accessed December 6, 2016.

Centers for Disease Control and Prevention. Zika virus. http://www.cdc.gov/zika/pregnancy/index.html. Updated August 22, 2016. Accessed December 6, 2016.

Petersen EE, Meaney-Delman D, Neblett-Fanfair R, et al. Update: interim guidance for preconception counseling and prevention of sexual transmission of Zika virus for persons with possible Zika virus exposure--United States, September 2016. MMWR Morbid Mortal Wkly Rep. 2016;65(39):1077-1081.

A yearly update on obstetrics would be remiss without mention of the Zika virus and its impact on pregnancy and reproduction. That being said, any recommendations we offer may be out of date by the time this article is published given the rapidly changing picture of Zika virus since it first dominated the headlines in 2016. Here are the basics as summarized from ACOG and the Centers for Disease Control and Prevention (CDC):

Viral spread. Zika virus may be spread in several ways: by an infected Aedes species mosquito, mother to fetus, sexual contact, blood transfusion, or laboratory exposure.

Symptoms of infection include conjunctivitis, fever, rash, and arthralgia, but most patients (4/5) are asymptomatic.

Sequelae. Zika virus infection during pregnancy is believed to cause fetal and neonatal microcephaly, intracranial calcifications, and brain and eye abnormalities. The rate of these findings in infected individuals, as well as the rate of vertical transmission, is not known.

Travel advisory. Pregnant women should not travel to areas with active Zika infection (the CDC website regularly updates these restricted areas).

Preventive measures. If traveling to an area of active Zika infection, pregnant women should take preventative measures day and night against mosquito bites, such as use of insect repellents approved by the Environmental Protection Agency, clothing that covers exposed skin, and staying indoors.

Safe sex. Abstinence or consistent condom use is recommended for pregnant women with partners who travel to or live in areas of active Zika infection.

Delay conception. Conception should be postponed for at least 6 months in men with Zika infection and at least 8 weeks in women with Zika infection.

Testing recommendations. Pregnant women with Zika virus exposure should be tested, regardless of symptoms. Symptomatic exposed nonpregnant women and all men should be tested.

Prenatal surveillance. High-risk consultation and serial ultrasounds for fetal anatomy and growth should be considered in patients with Zika virus infection during pregnancy. Amniocentesis can be considered on a case-by-case basis.

Related article:
Zika virus update: A rapidly moving target

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

In this Update we discuss several exciting new recommendations for preventive treatments in pregnancy and prenatal diagnostic tests. Our A-to-Z coverage includes:

• antenatal steroids in late preterm pregnancy
• expanded list of high-risk conditions warranting low-dose aspirin for preeclampsia prevention
• chromosomal microarray analysis versus karyotype for specific clinical situations
• Zika virus infection evolving information.

Next: New recommendation for timing of late preterm antenatal steroids

New recommendation offered for timing of late preterm antenatal steroids

Gyamfi-Bannerman C, Thom EA, Blackwell SC, et al; for the NICHD Maternal-Fetal Medicine Units Network. Antenatal betamethasone for women at risk for late preterm delivery. N Engl J Med. 2016;374(14):1311-1320.

American College of Obstetricians and Gynecologists. Committee Opinion No. 677. Antenatal corticosteroidtherapy for fetal maturation. Obstet Gynecol. 2016;128(4):e187-e194.

Kamath-Rayne BD, Rozance PJ, Goldenberg RL, Jobe AH. Antenatal corticosteroids beyond 34 weeks gestation: what do we do now? Am J Obstet Gynecol. 2016;215(4):423-430.

A dramatic recommendation for obstetric practice change occurred in 2016: the option of administering antenatal steroids for fetal lung maturity after 34 weeks. In the Antenatal Late Preterm Steroids (ALPS) trial of betamethasone in the late preterm period in patients at "high risk" of imminent delivery, Gyamfi-Bannerman and colleagues demonstrated that the treated group had a significant decrease in the rate of neonatal respiratory complications.

The primary outcome, a composite of respiratory morbidities (including transient tachypnea of the newborn, surfactant use, and need for resuscitation at birth) within the first 72 hours of life, had significant differences between groups, occurring in 165 of 1,427 infants (11.6%) in the betamethasone-treated group and 202 of 1,400 (14.4%) in the placebo group (relative risk in the betamethasone group, 0.80; 95% confidence interval, 0.66-0.97; P = .02). However, there was no statistically significant difference in respiratory distress syndrome, apnea, or pneumonia between groups, and the significant difference noted in bronchopulmonary dysplasia was based on a total number of 11 cases.

In response to these findings, both the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) released practice advisories and interim updates, culminating in a final recommendation for a single course of betamethasone in patients at high risk of preterm delivery between 34 and 36 6/7 weeks who have not received a previous course.

Related article:
When could use of antenatal corticosteroids in the late preterm birth period be beneficial?

In a thorough review of the literature on antenatal steroid use, Kamath-Rayne and colleagues highlighted several factors that should be considered before adopting universal use of steroids at >34 weeks. These include:   

• The definition of "high risk of imminent delivery" as preterm labor with at least 3-cm dilation or 75% effacement, or spontaneous rupture of membranes. The effect of less stringent inclusion criteria in real-world clinical practice is not known, and many patients who will go on to deliver at term will receive steroids unnecessarily.
• Multiple gestation, patients with pre-existing diabetes, women who had previously received a course of steroids, and fetuses with anomalies were excluded from the ALPS study. Use of antenatal steroids in these groups at >34 weeks should be evaluated before universal adoption.

Related article:
What is the ideal gestational age for twin delivery to minimize perinatal deaths?

• The incidence of neonatal hypoglycemia in the treated group was significantly increased. This affects our colleagues in pediatrics considerably from a systems standpoint (need for changes to newborn protocols and communication between services).
• The long-term outcomes of patients exposed to steroids in the late preterm period are yet to be delineated, specifically, the potential neurodevelopmental effects of a medication known to alter preterm brain development as well as cardiovascular and metabolic consequences.

Next: Low-dose aspirin for reducing preeclampsia risk

Low-dose aspirin clearly is effective for reducing the risk of preeclampsia

American College of Obstetricians and Gynecologists. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013;122(5):1122-1131.

Henderson JT, Whitlock EP, O'Connor E, Senger CA, Thompson JH, Rowland MG. Low-dose aspirin for prevention of morbidity and mortality from preeclampsia: a systematic evidence review for the US Preventive Services Task Force. Ann Intern Med. 2014;160(10):695-703.

LeFevre ML; US Preventive Services Task Force. Low-dose aspirin use for the prevention of morbidity and mortality from preeclampsia: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;161(11):819-826.

American College of Obstetricians and Gynecologists. Practice advisory on low-dose aspirin and prevention of preeclampsia: updated recommendations. http://www.acog.org/About-ACOG/News-Room/Practice-Advisories/Practice-Advisory-Low-Dose-Aspirin-and-Prevention-of-Preeclampsia-Updated-Recommendations. Published July 11, 2016. Accessed December 6, 2016.

In the 2013 ACOG Task Force on Hypertension in Pregnancy report, low-dose aspirin (60-80 mg) was recommended to be initiated in the late first trimester to reduce preeclampsia risk for women with:

• prior early onset preeclampsia with preterm delivery at <34 weeks' gestation, or
• preeclampsia in more than one prior pregnancy.  

This recommendation was based on several meta-analyses that demonstrated a 10% to 17% reduction in risk with no increase in bleeding, placental abruption, or other adverse events.

In 2014, the US Preventive Services Task Force (USPSTF) conducted a systematic evidence review of low-dose aspirin use for prevention of morbidity and mortality from preeclampsia. That report revealed a 24% risk reduction of preeclampsia in high-risk women treated with low-dose aspirin, as well as a 14% reduction in preterm birth and a 20% reduction in fetal growth restriction. A final statement from the USPSTF in 2014 recommended low-dose aspirin (60-150 mg) starting between 12 and 28 weeks' gestation for women at "high" risk who have:

• a history of preeclampsia, especially if accompanied by an adverse outcome
• multifetal gestation
• chronic hypertension
• diabetes (type 1 or type 2)
• renal disease
• autoimmune disease (such as systematic lupus erythematosus, antiphospholipid syndrome).

Related article:
Start offering aspirin to pregnant women at high risk for preeclampsia

As of July 11, 2016, ACOG supports this expanded list of high-risk conditions. Additionally, the USPSTF identified a "moderate" risk group in which low-dose aspirin may be considered if a patient has several risk factors, such as obesity, nulliparity, family history of preeclampsia, age 35 years or older, or another poor pregnancy outcome. ACOG notes, however, that the evidence supporting this practice is uncertain and does not make a recommendation regarding aspirin use in this population. Further study should be conducted to determine the benefit of low-dose aspirin in these patients as well as the long-term effects of treatment on maternal and child outcomes.

Next: CMA for prenatal genetic diagnosis

Chromosomal microarray analysis is preferable to karyotype in certain situations  

Pauli JM, Repke JT. Update on obstetrics. OBG Manag. 2013;25(1):28-32.

Society for Maternal-Fetal Medicine (SMFM), Dugoff L, Norton ME, Kuller JA. The use of chromosomal microarray for prenatal diagnosis. Am J Obstet Gynecol. 2016;215(4):B2-B9.

American College of Obstetricians and Gynecologists. Committee Opinion No. 682. Microarrays and next- generation sequencing technology: the use of advanced genetic diagnostic tools in obstetrics and gynecology.Obstet  Gynecol. 2016;128(6):e262-e268.

We previously addressed the use of chromosomal microarray analysis (CMA) for prenatal diagnosis in our 2013 "Update on obstetrics," specifically, the question of whether CMA could replace karyotype. The main differences between karyotype and CMA are that 1) only karyotype can detect balanced translocations/inversions and 2) only CMA can detect copy number variants (CNV). There are some differences in the technology and capabilities of the 2 types of CMA currently available as well.

In our 2013 article we concluded that "The total costs of such an approach--test, interpretation, counseling, and long-term follow-up of uncertain results--are unknown at this time and may prove to be unaffordable on a population-wide basis." Today, the cost of CMA is still higher than karyotype, but it is expected to decrease and insurance coverage for this test is expected to increase.

Related article:
Cell-free DNA screening for women at low risk for fetal aneuploidy

Both SMFM and ACOG released recommendations in 2016 regarding the use of CMA in prenatal genetic diagnosis, summarized as follows:  

• CMA is recommended over karyotype for fetuses with structural abnormalities on ultrasound
  • The detection rate for clinically relevant abnormal CNVs in this population is about 6%
• CMA is recommended for diagnosis for stillbirth specimens
  • CMA does not require dividing cells and may be a quicker and more reliable test in this population
• Karotype or fluorescence in situ hybridization (FISH) is recommended for fetuses with ultrasound findings suggestive of aneuploidy
  • If it is negative, then CMA is recommended
• Karyotype or CMA is recommended for patients desiring prenatal diagnostic testing with a normal fetal ultrasound
  • The detection rate for clinically relevant CNVs in this population (advanced maternal age, abnormal serum screening, prior aneuploidy, parental anxiety) is about 1%
• Pretest and posttest counseling about the limitations of CMA and a 2% risk of detection of variants of unknown significance (VUS) should be performed by a provider who has expertise in CMA and who has access to databases with genotype/phenotype information for VUS
  • This counseling should also include the possibility of diagnosis of nonpaternity, consanguinity, and adult-onset disease
• Karyotype is recommended for couples with recurrent pregnancy loss
  • The identification of balanced translocations in this population is most relevant in this patient population
• Prenatal diagnosis with routine use of whole-genome or whole-exome sequencing is not recommended.

Next: Zika virus: Check for updates

Zika virus infection: Check often for the latest updates

American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine. Practice advisory on Zika virus. http://www.acog.org/About-ACOG/News-Room/Practice-Advisories/Practice-Advisory-Interim-Guidance-for-Care-of-Obstetric-Patients- During-a-Zika-Virus-Outbreak. Published December 5, 2016. Accessed December 6, 2016.

Centers for Disease Control and Prevention. Zika virus. http://www.cdc.gov/zika/pregnancy/index.html. Updated August 22, 2016. Accessed December 6, 2016.

Petersen EE, Meaney-Delman D, Neblett-Fanfair R, et al. Update: interim guidance for preconception counseling and prevention of sexual transmission of Zika virus for persons with possible Zika virus exposure--United States, September 2016. MMWR Morbid Mortal Wkly Rep. 2016;65(39):1077-1081.

A yearly update on obstetrics would be remiss without mention of the Zika virus and its impact on pregnancy and reproduction. That being said, any recommendations we offer may be out of date by the time this article is published given the rapidly changing picture of Zika virus since it first dominated the headlines in 2016. Here are the basics as summarized from ACOG and the Centers for Disease Control and Prevention (CDC):

Viral spread. Zika virus may be spread in several ways: by an infected Aedes species mosquito, mother to fetus, sexual contact, blood transfusion, or laboratory exposure.

Symptoms of infection include conjunctivitis, fever, rash, and arthralgia, but most patients (4/5) are asymptomatic.

Sequelae. Zika virus infection during pregnancy is believed to cause fetal and neonatal microcephaly, intracranial calcifications, and brain and eye abnormalities. The rate of these findings in infected individuals, as well as the rate of vertical transmission, is not known.

Travel advisory. Pregnant women should not travel to areas with active Zika infection (the CDC website regularly updates these restricted areas).

Preventive measures. If traveling to an area of active Zika infection, pregnant women should take preventative measures day and night against mosquito bites, such as use of insect repellents approved by the Environmental Protection Agency, clothing that covers exposed skin, and staying indoors.

Safe sex. Abstinence or consistent condom use is recommended for pregnant women with partners who travel to or live in areas of active Zika infection.

Delay conception. Conception should be postponed for at least 6 months in men with Zika infection and at least 8 weeks in women with Zika infection.

Testing recommendations. Pregnant women with Zika virus exposure should be tested, regardless of symptoms. Symptomatic exposed nonpregnant women and all men should be tested.

Prenatal surveillance. High-risk consultation and serial ultrasounds for fetal anatomy and growth should be considered in patients with Zika virus infection during pregnancy. Amniocentesis can be considered on a case-by-case basis.

Related article:
Zika virus update: A rapidly moving target

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

It is that time of year again. We are in the midst of flu season, which means that it is time to remind our patients’ parents about the importance of using acetaminophen instead of aspirin. This fact became evident when several guardians of our patients came in within a few days of each other in late November to early December unaware of the dangers of giving their children aspirin and other salicylate medications.

Case 1: A 4-year-old boy presented with mild diarrhea, but otherwise was clinically well. The diarrhea started while visiting family in Mexico. The mother took out a small bottle of Pepto-Bismol (bismuth subsalicylate) liquid, which she gave him 2 days previously. The bottle did have, in small font, a warning about Reye’s syndrome on the label, which the mother did not notice. She also did not think it pertained to her son anyway. During the visit, she was counseled on this being early influenza season and the avoidance of salicylate products since the 1980s in children, with the exception of cardiac uses.

References

1. Pediatrics. 1980 Dec;66(6):859-64.

2. J Gen Intern Med. 2012 Dec;27(12):1697-703.

Rachel Masia is a third-year medical student at Rowan University School of Osteopathic Medicine, Stratford, N.J. Dr. Alan Masia, Ms. Masia’s father, has a practice in Toms River, N.J. They said they had no relevant financial disclosures.

It is that time of year again. We are in the midst of flu season, which means that it is time to remind our patients’ parents about the importance of using acetaminophen instead of aspirin. This fact became evident when several guardians of our patients came in within a few days of each other in late November to early December unaware of the dangers of giving their children aspirin and other salicylate medications.

Case 1: A 4-year-old boy presented with mild diarrhea, but otherwise was clinically well. The diarrhea started while visiting family in Mexico. The mother took out a small bottle of Pepto-Bismol (bismuth subsalicylate) liquid, which she gave him 2 days previously. The bottle did have, in small font, a warning about Reye’s syndrome on the label, which the mother did not notice. She also did not think it pertained to her son anyway. During the visit, she was counseled on this being early influenza season and the avoidance of salicylate products since the 1980s in children, with the exception of cardiac uses.

References

1. Pediatrics. 1980 Dec;66(6):859-64.

2. J Gen Intern Med. 2012 Dec;27(12):1697-703.

Rachel Masia is a third-year medical student at Rowan University School of Osteopathic Medicine, Stratford, N.J. Dr. Alan Masia, Ms. Masia’s father, has a practice in Toms River, N.J. They said they had no relevant financial disclosures.

It is that time of year again. We are in the midst of flu season, which means that it is time to remind our patients’ parents about the importance of using acetaminophen instead of aspirin. This fact became evident when several guardians of our patients came in within a few days of each other in late November to early December unaware of the dangers of giving their children aspirin and other salicylate medications.

Case 1: A 4-year-old boy presented with mild diarrhea, but otherwise was clinically well. The diarrhea started while visiting family in Mexico. The mother took out a small bottle of Pepto-Bismol (bismuth subsalicylate) liquid, which she gave him 2 days previously. The bottle did have, in small font, a warning about Reye’s syndrome on the label, which the mother did not notice. She also did not think it pertained to her son anyway. During the visit, she was counseled on this being early influenza season and the avoidance of salicylate products since the 1980s in children, with the exception of cardiac uses.

References

1. Pediatrics. 1980 Dec;66(6):859-64.

2. J Gen Intern Med. 2012 Dec;27(12):1697-703.

Rachel Masia is a third-year medical student at Rowan University School of Osteopathic Medicine, Stratford, N.J. Dr. Alan Masia, Ms. Masia’s father, has a practice in Toms River, N.J. They said they had no relevant financial disclosures.

Four years ago, I left my career at a large urban VA hospital due to cancer; residual effects of my treatment have prevented my return. I share this as it reflects my personal experience with pain management.

As a Certified Addiction Registered Nurse–Advance Practice, I worked in a substance abuse clinic for 15 years, providing everything from primary care to detoxification and opiate replacement maintenance. I also consulted on cases throughout the facility and advocated for patients with substance abuse histories in regard to care management concerns, including pain. I spent a great deal of time educating staff from all areas on proper care for patients with a variety of substance abuse and addiction concerns.

In order to better address the conundrum of appropriate pain management, a fine distinction needs to be made between dependence and addiction. Chemical dependence is a physiologic status and a medical diagnosis; reduction or discontinuation of a culprit drug will result in symptoms of physiologic withdrawal. Addiction, on the other hand, is a legitimate brain disease that might be better thought of as a mental health disorder. It manifests signs and symptoms very similar to those of chemical dependence.

Perhaps the distinction is best revealed by example: A 65-year-old woman who is on opioid-based pain management for two weeks due to a complicated orthopedic injury will need to be tapered off to avoid physiologic symptoms of withdrawal. Yet, she is not considered a drug addict.

The behavioral characteristics of addiction are familiar: drug-seeking, illicit use, presentation with unexplained withdrawal symptoms, etc. Additionally, process addictions involve the same neurochemical pathways as chemical addictions. When they abstain, gamblers, sex addicts, and television addicts manifest the same anxiety and psychologic or even physical symptoms of withdrawal. The pathophysiology of the addiction process is established in addiction medicine literature.

The problem is that this knowledge has not been extended to practice. In my experience, poorly managed pain has a much greater risk for unintended negative consequences than aggressive management with opiods and adjuncts in a patient with a history of heroin addiction. Pseudo-addiction is real, and patients present with signs and symptoms similar to those of addiction: demanding, making specific requests, history of multiple providers (doctor shopping), and elevated anxiety.

Anyone who has experienced poorly managed severe pain will share stories of the drive to get relief at almost any cost. These people are not drug addicts. They are patients in need of informed, aggressive, and compassionate care.

Fear-based inadequate pain management creates instability and desperation in patients. Their intensive search for relief is nothing but rational. A clinician’s withholding of adequate care due to social prejudice, fear (of the DEA), and/or ignorance in a field where knowledge and tools are widely available is bad care at best and negligent incompetence at worst. Ultimately, it is the patient who suffers the consequences.

The well-known but often denied chasm between medicine and mental health has gone on too long. Medical practitioners need to

• Be better able to identify and distinguish between potential and current chemical dependence and true addiction.
• Be willing to treat pain aggressively in patients with a known history of addiction in order to prevent relapse or exacerbation of their addictive use.
• Develop a working knowledge of strategies to treat pain while minimizing risk for addiction and dependence.
• Commit to the intensity of practice that is required for effective pain management in any population.

Yes, my suggestions imply a labor-intensive approach. But there are no 20-minute appointments with a heroin addict. And time spent appropriately assessing patient risk for substance abuse, treating legitimate pain management needs, and intensively following up will reduce the medical and mental health costs associated with poorly managed pain in low-risk patients, and the hugely expensive and potentially tragic outcomes associated with poorly treated drug addicts.

L. Henry Beazlie, RN, CCRN, CARN-AP, MSN, MA (retired)

Akron, OH

Four years ago, I left my career at a large urban VA hospital due to cancer; residual effects of my treatment have prevented my return. I share this as it reflects my personal experience with pain management.

As a Certified Addiction Registered Nurse–Advance Practice, I worked in a substance abuse clinic for 15 years, providing everything from primary care to detoxification and opiate replacement maintenance. I also consulted on cases throughout the facility and advocated for patients with substance abuse histories in regard to care management concerns, including pain. I spent a great deal of time educating staff from all areas on proper care for patients with a variety of substance abuse and addiction concerns.

In order to better address the conundrum of appropriate pain management, a fine distinction needs to be made between dependence and addiction. Chemical dependence is a physiologic status and a medical diagnosis; reduction or discontinuation of a culprit drug will result in symptoms of physiologic withdrawal. Addiction, on the other hand, is a legitimate brain disease that might be better thought of as a mental health disorder. It manifests signs and symptoms very similar to those of chemical dependence.

Perhaps the distinction is best revealed by example: A 65-year-old woman who is on opioid-based pain management for two weeks due to a complicated orthopedic injury will need to be tapered off to avoid physiologic symptoms of withdrawal. Yet, she is not considered a drug addict.

The behavioral characteristics of addiction are familiar: drug-seeking, illicit use, presentation with unexplained withdrawal symptoms, etc. Additionally, process addictions involve the same neurochemical pathways as chemical addictions. When they abstain, gamblers, sex addicts, and television addicts manifest the same anxiety and psychologic or even physical symptoms of withdrawal. The pathophysiology of the addiction process is established in addiction medicine literature.

The problem is that this knowledge has not been extended to practice. In my experience, poorly managed pain has a much greater risk for unintended negative consequences than aggressive management with opiods and adjuncts in a patient with a history of heroin addiction. Pseudo-addiction is real, and patients present with signs and symptoms similar to those of addiction: demanding, making specific requests, history of multiple providers (doctor shopping), and elevated anxiety.

Anyone who has experienced poorly managed severe pain will share stories of the drive to get relief at almost any cost. These people are not drug addicts. They are patients in need of informed, aggressive, and compassionate care.

Fear-based inadequate pain management creates instability and desperation in patients. Their intensive search for relief is nothing but rational. A clinician’s withholding of adequate care due to social prejudice, fear (of the DEA), and/or ignorance in a field where knowledge and tools are widely available is bad care at best and negligent incompetence at worst. Ultimately, it is the patient who suffers the consequences.

The well-known but often denied chasm between medicine and mental health has gone on too long. Medical practitioners need to

• Be better able to identify and distinguish between potential and current chemical dependence and true addiction.
• Be willing to treat pain aggressively in patients with a known history of addiction in order to prevent relapse or exacerbation of their addictive use.
• Develop a working knowledge of strategies to treat pain while minimizing risk for addiction and dependence.
• Commit to the intensity of practice that is required for effective pain management in any population.

Yes, my suggestions imply a labor-intensive approach. But there are no 20-minute appointments with a heroin addict. And time spent appropriately assessing patient risk for substance abuse, treating legitimate pain management needs, and intensively following up will reduce the medical and mental health costs associated with poorly managed pain in low-risk patients, and the hugely expensive and potentially tragic outcomes associated with poorly treated drug addicts.

L. Henry Beazlie, RN, CCRN, CARN-AP, MSN, MA (retired)

Akron, OH

Four years ago, I left my career at a large urban VA hospital due to cancer; residual effects of my treatment have prevented my return. I share this as it reflects my personal experience with pain management.

As a Certified Addiction Registered Nurse–Advance Practice, I worked in a substance abuse clinic for 15 years, providing everything from primary care to detoxification and opiate replacement maintenance. I also consulted on cases throughout the facility and advocated for patients with substance abuse histories in regard to care management concerns, including pain. I spent a great deal of time educating staff from all areas on proper care for patients with a variety of substance abuse and addiction concerns.

In order to better address the conundrum of appropriate pain management, a fine distinction needs to be made between dependence and addiction. Chemical dependence is a physiologic status and a medical diagnosis; reduction or discontinuation of a culprit drug will result in symptoms of physiologic withdrawal. Addiction, on the other hand, is a legitimate brain disease that might be better thought of as a mental health disorder. It manifests signs and symptoms very similar to those of chemical dependence.

Perhaps the distinction is best revealed by example: A 65-year-old woman who is on opioid-based pain management for two weeks due to a complicated orthopedic injury will need to be tapered off to avoid physiologic symptoms of withdrawal. Yet, she is not considered a drug addict.

The behavioral characteristics of addiction are familiar: drug-seeking, illicit use, presentation with unexplained withdrawal symptoms, etc. Additionally, process addictions involve the same neurochemical pathways as chemical addictions. When they abstain, gamblers, sex addicts, and television addicts manifest the same anxiety and psychologic or even physical symptoms of withdrawal. The pathophysiology of the addiction process is established in addiction medicine literature.

The problem is that this knowledge has not been extended to practice. In my experience, poorly managed pain has a much greater risk for unintended negative consequences than aggressive management with opiods and adjuncts in a patient with a history of heroin addiction. Pseudo-addiction is real, and patients present with signs and symptoms similar to those of addiction: demanding, making specific requests, history of multiple providers (doctor shopping), and elevated anxiety.

Anyone who has experienced poorly managed severe pain will share stories of the drive to get relief at almost any cost. These people are not drug addicts. They are patients in need of informed, aggressive, and compassionate care.

Fear-based inadequate pain management creates instability and desperation in patients. Their intensive search for relief is nothing but rational. A clinician’s withholding of adequate care due to social prejudice, fear (of the DEA), and/or ignorance in a field where knowledge and tools are widely available is bad care at best and negligent incompetence at worst. Ultimately, it is the patient who suffers the consequences.

The well-known but often denied chasm between medicine and mental health has gone on too long. Medical practitioners need to

• Be better able to identify and distinguish between potential and current chemical dependence and true addiction.
• Be willing to treat pain aggressively in patients with a known history of addiction in order to prevent relapse or exacerbation of their addictive use.
• Develop a working knowledge of strategies to treat pain while minimizing risk for addiction and dependence.
• Commit to the intensity of practice that is required for effective pain management in any population.

Yes, my suggestions imply a labor-intensive approach. But there are no 20-minute appointments with a heroin addict. And time spent appropriately assessing patient risk for substance abuse, treating legitimate pain management needs, and intensively following up will reduce the medical and mental health costs associated with poorly managed pain in low-risk patients, and the hugely expensive and potentially tragic outcomes associated with poorly treated drug addicts.

L. Henry Beazlie, RN, CCRN, CARN-AP, MSN, MA (retired)

Akron, OH

Before pain was introduced as the “fifth vital sign” and the Joint Commission issued its standards, more than a decade’s worth of international research indicated that pain was largely ignored, untreated, or undertreated. The best tools available to treat pain (opioids) were reserved for patients on their deathbed. The horrific results of the SUPPORT study at the nation’s leading hospitals revealed that most patients had severe, uncontrolled pain up until their final days of life.¹ Unfortunately, research suggests we are still reserving opioids for the last days or weeks of life.²

In 1992 and 1994, the Department of Health and Human Services issued clinical practice guidelines highlighting the huge gap between the availability of evidence-based pain control methods and the lack of pain assessment and treatment in practice.³ When these guidelines failed to change practice, the Joint Commission added “attending to pain” to its standards—the first effort to require that evidence-based practices be utilized. Twenty years later, the National Academy of Science issued a report stating that, despite transient improvements, the current state is inadequate since pain is the leading reason people seek health care. Patients with pain report an inability to get help, which is “viewed worldwide as poor medicine, unethical practice, and an abrogation of a fundamental human right.”⁴ Since I started working as an NP in 1983, I have never seen as many patients with pain stigmatized, ignored, labeled, and denied access to treatment as I have in the past year.

Pain afflicts more than 100 million Americans and is the leading cause of disability worldwide.⁵ Acute pain that is not effectively treated progresses to chronic pain in 51% of cases.⁶ An estimated 23 million Americans report frequent intense pain, 25 million endure daily chronic pain, and 40 million adults have high-impact, disabling, chronic pain that degrades health and requires health care intervention.^6,7 The most notable damage is to the structure and function of the central nervous system.⁸ Brain remodeling and loss of gray matter occurs, producing changes in the brain similar to those observed with 10 to 20 years of aging; this explains why some of the learning, memory, and emotional difficulties endured by many with ongoing pain can be partially reversed with effective treatment.⁹ Left untreated, pain can result in significant biopsychosocial problems, frailty, financial ruin, and premature death.^10-14

Prescription drug misuse and addiction also affect millions and have been a largely ignored public health problem for decades. Trying to fix the pain problem without attending equally to the problems of nonmedical drug use, addiction, and overdose deaths has contributed to the escalation of health problems to “epidemic” and “crisis” proportions. Although most patients who are prescribed medically indicated opioids for pain do not misuse their medications or become addicted, the failure to subsequently identify and properly treat an emergent substance use disorder is a problem in our current system.¹⁵ Unfortunately, making prescription opioids inaccessible to patients forces some to abuse alcohol or seek drugs from illicit sources, which only exacerbates the situation.¹⁶ A national study performed over a five-year period revealed that only 10% of patients admitted for prescription opioid treatment were referred from their health care providers.¹⁷ So, health care providers may have been part of the problem but have not been fully engaged in the solution.

Although opioids are neither the firstline, nor only, treatment option in our current evidence-based treatment toolbox, their prudent use does not cause addiction. Only 1% of patients who receive postoperative opioids go on to develop chronic opioid use, and adolescents treated with medically necessary opioids have no greater risk for future addiction than unexposed children. It is the nonmedical use of opioids, rather than proper medical use, that predisposes people to addiction.^18,19 Discharging or not treating patients suspected of “drug-seeking” exacerbates the problem. Rates of opioid prescription have declined, while overdoses of illicitly manufactured fentanyl increased by 79% in 27 states from 2013 to 2014.²⁰ In Massachusetts, only 8% of people who fatally overdosed had a prescription, while illicit fentanyl accounted for 54% of overdose deaths in 2015 and more than 74% in the third quarter of 2016.²¹ We need to screen for nonmedical use, drug misuse, and addiction before, during, and after we treat with this particular tool.

Unfortunately, the prevalence of pain and addiction are both increasing, especially for women and minorities—but there are safe, effective medications and non-drug approaches available to combat this.^22-24 These problems will not go away on their own, and every health care professional must choose to be part of the solution rather than perpetuate the problem. A good place to start is to become familiar with the Surgeon General’s Report and the National Pain Strategy. Educate your patients, colleagues, and policy makers about the true nature of these problems. Take a public health approach to primary, secondary, and tertiary prevention by recognizing and treating these conditions in an expedient and effective matter. When problems persist, expand the treatment team to include specialists who can develop a patient-centered, multimodal treatment plan that treats co-occurring conditions. If we continue to ignore these problems, or focus on one at the expense of the other, both problems will worsen and our patients will suffer serious consequences.

Paul Arnstein, PhD, NP-C, FAAN, FNP-C

Boston, MA

Before pain was introduced as the “fifth vital sign” and the Joint Commission issued its standards, more than a decade’s worth of international research indicated that pain was largely ignored, untreated, or undertreated. The best tools available to treat pain (opioids) were reserved for patients on their deathbed. The horrific results of the SUPPORT study at the nation’s leading hospitals revealed that most patients had severe, uncontrolled pain up until their final days of life.¹ Unfortunately, research suggests we are still reserving opioids for the last days or weeks of life.²

In 1992 and 1994, the Department of Health and Human Services issued clinical practice guidelines highlighting the huge gap between the availability of evidence-based pain control methods and the lack of pain assessment and treatment in practice.³ When these guidelines failed to change practice, the Joint Commission added “attending to pain” to its standards—the first effort to require that evidence-based practices be utilized. Twenty years later, the National Academy of Science issued a report stating that, despite transient improvements, the current state is inadequate since pain is the leading reason people seek health care. Patients with pain report an inability to get help, which is “viewed worldwide as poor medicine, unethical practice, and an abrogation of a fundamental human right.”⁴ Since I started working as an NP in 1983, I have never seen as many patients with pain stigmatized, ignored, labeled, and denied access to treatment as I have in the past year.

Pain afflicts more than 100 million Americans and is the leading cause of disability worldwide.⁵ Acute pain that is not effectively treated progresses to chronic pain in 51% of cases.⁶ An estimated 23 million Americans report frequent intense pain, 25 million endure daily chronic pain, and 40 million adults have high-impact, disabling, chronic pain that degrades health and requires health care intervention.^6,7 The most notable damage is to the structure and function of the central nervous system.⁸ Brain remodeling and loss of gray matter occurs, producing changes in the brain similar to those observed with 10 to 20 years of aging; this explains why some of the learning, memory, and emotional difficulties endured by many with ongoing pain can be partially reversed with effective treatment.⁹ Left untreated, pain can result in significant biopsychosocial problems, frailty, financial ruin, and premature death.^10-14

Prescription drug misuse and addiction also affect millions and have been a largely ignored public health problem for decades. Trying to fix the pain problem without attending equally to the problems of nonmedical drug use, addiction, and overdose deaths has contributed to the escalation of health problems to “epidemic” and “crisis” proportions. Although most patients who are prescribed medically indicated opioids for pain do not misuse their medications or become addicted, the failure to subsequently identify and properly treat an emergent substance use disorder is a problem in our current system.¹⁵ Unfortunately, making prescription opioids inaccessible to patients forces some to abuse alcohol or seek drugs from illicit sources, which only exacerbates the situation.¹⁶ A national study performed over a five-year period revealed that only 10% of patients admitted for prescription opioid treatment were referred from their health care providers.¹⁷ So, health care providers may have been part of the problem but have not been fully engaged in the solution.

Although opioids are neither the firstline, nor only, treatment option in our current evidence-based treatment toolbox, their prudent use does not cause addiction. Only 1% of patients who receive postoperative opioids go on to develop chronic opioid use, and adolescents treated with medically necessary opioids have no greater risk for future addiction than unexposed children. It is the nonmedical use of opioids, rather than proper medical use, that predisposes people to addiction.^18,19 Discharging or not treating patients suspected of “drug-seeking” exacerbates the problem. Rates of opioid prescription have declined, while overdoses of illicitly manufactured fentanyl increased by 79% in 27 states from 2013 to 2014.²⁰ In Massachusetts, only 8% of people who fatally overdosed had a prescription, while illicit fentanyl accounted for 54% of overdose deaths in 2015 and more than 74% in the third quarter of 2016.²¹ We need to screen for nonmedical use, drug misuse, and addiction before, during, and after we treat with this particular tool.

Unfortunately, the prevalence of pain and addiction are both increasing, especially for women and minorities—but there are safe, effective medications and non-drug approaches available to combat this.^22-24 These problems will not go away on their own, and every health care professional must choose to be part of the solution rather than perpetuate the problem. A good place to start is to become familiar with the Surgeon General’s Report and the National Pain Strategy. Educate your patients, colleagues, and policy makers about the true nature of these problems. Take a public health approach to primary, secondary, and tertiary prevention by recognizing and treating these conditions in an expedient and effective matter. When problems persist, expand the treatment team to include specialists who can develop a patient-centered, multimodal treatment plan that treats co-occurring conditions. If we continue to ignore these problems, or focus on one at the expense of the other, both problems will worsen and our patients will suffer serious consequences.

Paul Arnstein, PhD, NP-C, FAAN, FNP-C

Boston, MA

Before pain was introduced as the “fifth vital sign” and the Joint Commission issued its standards, more than a decade’s worth of international research indicated that pain was largely ignored, untreated, or undertreated. The best tools available to treat pain (opioids) were reserved for patients on their deathbed. The horrific results of the SUPPORT study at the nation’s leading hospitals revealed that most patients had severe, uncontrolled pain up until their final days of life.¹ Unfortunately, research suggests we are still reserving opioids for the last days or weeks of life.²

In 1992 and 1994, the Department of Health and Human Services issued clinical practice guidelines highlighting the huge gap between the availability of evidence-based pain control methods and the lack of pain assessment and treatment in practice.³ When these guidelines failed to change practice, the Joint Commission added “attending to pain” to its standards—the first effort to require that evidence-based practices be utilized. Twenty years later, the National Academy of Science issued a report stating that, despite transient improvements, the current state is inadequate since pain is the leading reason people seek health care. Patients with pain report an inability to get help, which is “viewed worldwide as poor medicine, unethical practice, and an abrogation of a fundamental human right.”⁴ Since I started working as an NP in 1983, I have never seen as many patients with pain stigmatized, ignored, labeled, and denied access to treatment as I have in the past year.

Pain afflicts more than 100 million Americans and is the leading cause of disability worldwide.⁵ Acute pain that is not effectively treated progresses to chronic pain in 51% of cases.⁶ An estimated 23 million Americans report frequent intense pain, 25 million endure daily chronic pain, and 40 million adults have high-impact, disabling, chronic pain that degrades health and requires health care intervention.^6,7 The most notable damage is to the structure and function of the central nervous system.⁸ Brain remodeling and loss of gray matter occurs, producing changes in the brain similar to those observed with 10 to 20 years of aging; this explains why some of the learning, memory, and emotional difficulties endured by many with ongoing pain can be partially reversed with effective treatment.⁹ Left untreated, pain can result in significant biopsychosocial problems, frailty, financial ruin, and premature death.^10-14

Prescription drug misuse and addiction also affect millions and have been a largely ignored public health problem for decades. Trying to fix the pain problem without attending equally to the problems of nonmedical drug use, addiction, and overdose deaths has contributed to the escalation of health problems to “epidemic” and “crisis” proportions. Although most patients who are prescribed medically indicated opioids for pain do not misuse their medications or become addicted, the failure to subsequently identify and properly treat an emergent substance use disorder is a problem in our current system.¹⁵ Unfortunately, making prescription opioids inaccessible to patients forces some to abuse alcohol or seek drugs from illicit sources, which only exacerbates the situation.¹⁶ A national study performed over a five-year period revealed that only 10% of patients admitted for prescription opioid treatment were referred from their health care providers.¹⁷ So, health care providers may have been part of the problem but have not been fully engaged in the solution.

Although opioids are neither the firstline, nor only, treatment option in our current evidence-based treatment toolbox, their prudent use does not cause addiction. Only 1% of patients who receive postoperative opioids go on to develop chronic opioid use, and adolescents treated with medically necessary opioids have no greater risk for future addiction than unexposed children. It is the nonmedical use of opioids, rather than proper medical use, that predisposes people to addiction.^18,19 Discharging or not treating patients suspected of “drug-seeking” exacerbates the problem. Rates of opioid prescription have declined, while overdoses of illicitly manufactured fentanyl increased by 79% in 27 states from 2013 to 2014.²⁰ In Massachusetts, only 8% of people who fatally overdosed had a prescription, while illicit fentanyl accounted for 54% of overdose deaths in 2015 and more than 74% in the third quarter of 2016.²¹ We need to screen for nonmedical use, drug misuse, and addiction before, during, and after we treat with this particular tool.

Unfortunately, the prevalence of pain and addiction are both increasing, especially for women and minorities—but there are safe, effective medications and non-drug approaches available to combat this.^22-24 These problems will not go away on their own, and every health care professional must choose to be part of the solution rather than perpetuate the problem. A good place to start is to become familiar with the Surgeon General’s Report and the National Pain Strategy. Educate your patients, colleagues, and policy makers about the true nature of these problems. Take a public health approach to primary, secondary, and tertiary prevention by recognizing and treating these conditions in an expedient and effective matter. When problems persist, expand the treatment team to include specialists who can develop a patient-centered, multimodal treatment plan that treats co-occurring conditions. If we continue to ignore these problems, or focus on one at the expense of the other, both problems will worsen and our patients will suffer serious consequences.

Paul Arnstein, PhD, NP-C, FAAN, FNP-C

Boston, MA

SAN ANTONIO – PARPi 7, BRCAness, and MammaPrint high1/(ultra)high2 signatures could help predict response to combination therapy with the poly ADP ribose polymerase (PARP) inhibitors veliparib and carboplatin among high-risk breast cancer patients and thereby improve patient care, according to findings from the I-SPY 2 clinical trial.

“I-SPY 2 is a phase II adaptively randomized neoadjuvant clinical trial with a shared control arm where patients receive standard neoadjuvant chemotherapy, and up to 4 simultaneous investigational arms. The primary endpoint of the trial is pathologic complete response, or pCR. The goal is to match therapies with the most responsive breast cancer subtypes,” Denise M. Wolf, PhD, of the University of California, San Francisco, explained at the San Antonio Breast Cancer Symposium.

The current analysis of I-Spy 2 data focuses on veliparib/carboplatin (VC), and the subtypes Dr. Wolf mentioned are defined by hormone receptor (HR) and HER2 expression, and by MammaPrint high1 or (ultra)high2 risk status, which, “roughly speaking, is a further stratification of the poor prognosis group into high- and extra-high-risk groups,” she said.

“This arm was open to HER2-negative patients, and graduated successfully in the triple-negative subset,” she noted, explaining that “agents or combinations graduate for efficacy if they reach 85% predicted probability of success in a subsequent phase III trial in the most responsive patient subset.”

The biomarker component of the trial aimed to evaluate biomarkers associated with the mechanisms of action of each investigational agent along with the predefined subsets.

Although the findings require verification in a larger trial, Dr. Wolf and her colleagues found that three biomarkers – the PARPi 7 gene signature, the 77-gene BRCAness signature (which both relate to DNA damage repair deficiency), and the MammaPrint high1 and (ultra)high2 risk categories – were each moderately correlated with treatment response in 72 patients receiving veliparib/carboplatin (VC), but not in 44 controls, and that the treatment-biomarker interactions retained statistical significance after adjusting for hormone receptor status.

“And so we asked the question, ‘Are these signatures identifying the same patients – and if not, might there be a way to combine them to identify a subset of patients who are especially likely to respond to VC?’” she said.

Further analysis showed that even though each of the biomarkers was a predictor of response, the biomarkers did not appear to identify exactly the same patients, therefore combining them might be of benefit.

“We did this using a simple voting scheme to combine pairs of biomarkers,” she said, adding that if the two paired biomarkers predicted resistance, the biomarker also predicted resistance. If only 1 predicted resistance, the combination predicted resistance, and only if both biomarkers predicted sensitivity did the combination predict sensitivity.

In the graduated triple-negative subset, for example, the 40% of patients who were PARPi 7–high and MammaPrint high2 (the two biomarkers most predictive of response) a dramatic separation was seen in the pCR probability curves, with an estimated pCR of 79% with VC treatment vs. 23% in the control arm.

“In contrast, triple-negative patients who were negative for one or more of the sensitivity markers had nearly overlapping probability response curves, from which we conclude that nearly all of the specific sensitivity to VC seen in the triple-negative patients is found in that subset who are positive for both sensitivity markers,” she said.

Additionally, although only 9% of HR-positive/HER2-negative patients were PARPi 7-high and MammaPrint high2, those patients also appeared to be more responsive to VC vs. the control arm (49% vs. 15%).

The results also demonstrate the value of an exploratory voting method for combining multiple biomarkers for the same treatment, Dr. Wolf noted.

However, the findings are limited by the small sample size and need to be evaluated in larger trials, and the biomarkers also need to be evaluated in carboplatin-only arms in order to “tease out whether the biomarkers are really specific to a PARP inhibitor with carboplatin or whether they might also apply to carboplatin alone.

“Our ongoing and future work is to develop predictive biomarkers for other I-Spy 2 agents,” she said.

Dr. Wolf reported having no disclosures.

[email protected]

SAN ANTONIO – PARPi 7, BRCAness, and MammaPrint high1/(ultra)high2 signatures could help predict response to combination therapy with the poly ADP ribose polymerase (PARP) inhibitors veliparib and carboplatin among high-risk breast cancer patients and thereby improve patient care, according to findings from the I-SPY 2 clinical trial.

“I-SPY 2 is a phase II adaptively randomized neoadjuvant clinical trial with a shared control arm where patients receive standard neoadjuvant chemotherapy, and up to 4 simultaneous investigational arms. The primary endpoint of the trial is pathologic complete response, or pCR. The goal is to match therapies with the most responsive breast cancer subtypes,” Denise M. Wolf, PhD, of the University of California, San Francisco, explained at the San Antonio Breast Cancer Symposium.

The current analysis of I-Spy 2 data focuses on veliparib/carboplatin (VC), and the subtypes Dr. Wolf mentioned are defined by hormone receptor (HR) and HER2 expression, and by MammaPrint high1 or (ultra)high2 risk status, which, “roughly speaking, is a further stratification of the poor prognosis group into high- and extra-high-risk groups,” she said.

“This arm was open to HER2-negative patients, and graduated successfully in the triple-negative subset,” she noted, explaining that “agents or combinations graduate for efficacy if they reach 85% predicted probability of success in a subsequent phase III trial in the most responsive patient subset.”

The biomarker component of the trial aimed to evaluate biomarkers associated with the mechanisms of action of each investigational agent along with the predefined subsets.

Although the findings require verification in a larger trial, Dr. Wolf and her colleagues found that three biomarkers – the PARPi 7 gene signature, the 77-gene BRCAness signature (which both relate to DNA damage repair deficiency), and the MammaPrint high1 and (ultra)high2 risk categories – were each moderately correlated with treatment response in 72 patients receiving veliparib/carboplatin (VC), but not in 44 controls, and that the treatment-biomarker interactions retained statistical significance after adjusting for hormone receptor status.

“And so we asked the question, ‘Are these signatures identifying the same patients – and if not, might there be a way to combine them to identify a subset of patients who are especially likely to respond to VC?’” she said.

Further analysis showed that even though each of the biomarkers was a predictor of response, the biomarkers did not appear to identify exactly the same patients, therefore combining them might be of benefit.

“We did this using a simple voting scheme to combine pairs of biomarkers,” she said, adding that if the two paired biomarkers predicted resistance, the biomarker also predicted resistance. If only 1 predicted resistance, the combination predicted resistance, and only if both biomarkers predicted sensitivity did the combination predict sensitivity.

In the graduated triple-negative subset, for example, the 40% of patients who were PARPi 7–high and MammaPrint high2 (the two biomarkers most predictive of response) a dramatic separation was seen in the pCR probability curves, with an estimated pCR of 79% with VC treatment vs. 23% in the control arm.

“In contrast, triple-negative patients who were negative for one or more of the sensitivity markers had nearly overlapping probability response curves, from which we conclude that nearly all of the specific sensitivity to VC seen in the triple-negative patients is found in that subset who are positive for both sensitivity markers,” she said.

Additionally, although only 9% of HR-positive/HER2-negative patients were PARPi 7-high and MammaPrint high2, those patients also appeared to be more responsive to VC vs. the control arm (49% vs. 15%).

The results also demonstrate the value of an exploratory voting method for combining multiple biomarkers for the same treatment, Dr. Wolf noted.

However, the findings are limited by the small sample size and need to be evaluated in larger trials, and the biomarkers also need to be evaluated in carboplatin-only arms in order to “tease out whether the biomarkers are really specific to a PARP inhibitor with carboplatin or whether they might also apply to carboplatin alone.

“Our ongoing and future work is to develop predictive biomarkers for other I-Spy 2 agents,” she said.

Dr. Wolf reported having no disclosures.

[email protected]

SAN ANTONIO – PARPi 7, BRCAness, and MammaPrint high1/(ultra)high2 signatures could help predict response to combination therapy with the poly ADP ribose polymerase (PARP) inhibitors veliparib and carboplatin among high-risk breast cancer patients and thereby improve patient care, according to findings from the I-SPY 2 clinical trial.

“I-SPY 2 is a phase II adaptively randomized neoadjuvant clinical trial with a shared control arm where patients receive standard neoadjuvant chemotherapy, and up to 4 simultaneous investigational arms. The primary endpoint of the trial is pathologic complete response, or pCR. The goal is to match therapies with the most responsive breast cancer subtypes,” Denise M. Wolf, PhD, of the University of California, San Francisco, explained at the San Antonio Breast Cancer Symposium.

The current analysis of I-Spy 2 data focuses on veliparib/carboplatin (VC), and the subtypes Dr. Wolf mentioned are defined by hormone receptor (HR) and HER2 expression, and by MammaPrint high1 or (ultra)high2 risk status, which, “roughly speaking, is a further stratification of the poor prognosis group into high- and extra-high-risk groups,” she said.

“This arm was open to HER2-negative patients, and graduated successfully in the triple-negative subset,” she noted, explaining that “agents or combinations graduate for efficacy if they reach 85% predicted probability of success in a subsequent phase III trial in the most responsive patient subset.”

The biomarker component of the trial aimed to evaluate biomarkers associated with the mechanisms of action of each investigational agent along with the predefined subsets.

Although the findings require verification in a larger trial, Dr. Wolf and her colleagues found that three biomarkers – the PARPi 7 gene signature, the 77-gene BRCAness signature (which both relate to DNA damage repair deficiency), and the MammaPrint high1 and (ultra)high2 risk categories – were each moderately correlated with treatment response in 72 patients receiving veliparib/carboplatin (VC), but not in 44 controls, and that the treatment-biomarker interactions retained statistical significance after adjusting for hormone receptor status.

“And so we asked the question, ‘Are these signatures identifying the same patients – and if not, might there be a way to combine them to identify a subset of patients who are especially likely to respond to VC?’” she said.

Further analysis showed that even though each of the biomarkers was a predictor of response, the biomarkers did not appear to identify exactly the same patients, therefore combining them might be of benefit.

“We did this using a simple voting scheme to combine pairs of biomarkers,” she said, adding that if the two paired biomarkers predicted resistance, the biomarker also predicted resistance. If only 1 predicted resistance, the combination predicted resistance, and only if both biomarkers predicted sensitivity did the combination predict sensitivity.

In the graduated triple-negative subset, for example, the 40% of patients who were PARPi 7–high and MammaPrint high2 (the two biomarkers most predictive of response) a dramatic separation was seen in the pCR probability curves, with an estimated pCR of 79% with VC treatment vs. 23% in the control arm.

“In contrast, triple-negative patients who were negative for one or more of the sensitivity markers had nearly overlapping probability response curves, from which we conclude that nearly all of the specific sensitivity to VC seen in the triple-negative patients is found in that subset who are positive for both sensitivity markers,” she said.

Additionally, although only 9% of HR-positive/HER2-negative patients were PARPi 7-high and MammaPrint high2, those patients also appeared to be more responsive to VC vs. the control arm (49% vs. 15%).

The results also demonstrate the value of an exploratory voting method for combining multiple biomarkers for the same treatment, Dr. Wolf noted.

However, the findings are limited by the small sample size and need to be evaluated in larger trials, and the biomarkers also need to be evaluated in carboplatin-only arms in order to “tease out whether the biomarkers are really specific to a PARP inhibitor with carboplatin or whether they might also apply to carboplatin alone.

“Our ongoing and future work is to develop predictive biomarkers for other I-Spy 2 agents,” she said.

Dr. Wolf reported having no disclosures.

[email protected]

HOUSTON – The incidence of fractures in pediatric patients taking antiepileptic medication stands at an estimated 1.1%, according to results from a 4-year period at a children’s hospital.

“Understanding the prevalence of fractures in pediatric patients on an AED [antiepileptic drug] will allow clinicians to weigh the risk versus benefit of therapy,” researchers led by Shannon DiCarlo, MD, wrote in an abstract presented during a poster session at the annual meeting of the American Epilepsy Society. “Recognizing a risk of fractures with AEDs will permit clinicians to provide appropriate supportive care and monitoring from the initiation of therapy.”

Dr. DiCarlo of Texas Children’s Hospital, Houston, and her associates went on to note that adults with epilepsy have a twofold to sixfold greater risk of experiencing fractures, compared with the general population, and that fractures secondary to seizures “are a major concern in pediatrics.” In fact, one survey of 404 pediatric neurologists found that only 41% of respondents were aware of the association between AEDs and reduced bone mass (Arch Neurol. 2001;58[9]:1369-74).

In an effort to evaluate the prevalence of fractures in pediatric patients on an antiepileptic drug, the researchers conducted a cohort study of 10,153 patients younger than 18 years of age who received an AED at Texas Children’s Hospital from 2011 to 2014. Half of the study population were female, and the most common concomitant disease was epilepsy (52.6%), followed by cerebral palsy (8.3%), epilepsy plus cerebral palsy (6.9%), osteoporosis (0.2%), and osteopenia (0.3%). In all, 113 patients (1.1%) experienced a fracture while on an antiepileptic drug, and the mean time from initiation of an AED to time of fracture was 1.6 years. Patients on enzyme-inducing AEDs were two times more likely to experience a fracture, while those with cerebral palsy and epilepsy were three times more likely to experience a fracture. Proton pump inhibitors and corticosteroids were the most common concomitant drugs. The researchers also found that less than 10% of patients were on calcium or vitamin D supplementation.

“Vigilant monitoring should be employed for at-risk patients,” the researchers concluded. “Regular monitoring of calcium and vitamin D levels may be warranted; further studies are needed to evaluate the roll of prophylactic calcium and vitamin D supplements.”

The researchers reported having no relevant financial disclosures.

[email protected]

HOUSTON – The incidence of fractures in pediatric patients taking antiepileptic medication stands at an estimated 1.1%, according to results from a 4-year period at a children’s hospital.

“Understanding the prevalence of fractures in pediatric patients on an AED [antiepileptic drug] will allow clinicians to weigh the risk versus benefit of therapy,” researchers led by Shannon DiCarlo, MD, wrote in an abstract presented during a poster session at the annual meeting of the American Epilepsy Society. “Recognizing a risk of fractures with AEDs will permit clinicians to provide appropriate supportive care and monitoring from the initiation of therapy.”

Dr. DiCarlo of Texas Children’s Hospital, Houston, and her associates went on to note that adults with epilepsy have a twofold to sixfold greater risk of experiencing fractures, compared with the general population, and that fractures secondary to seizures “are a major concern in pediatrics.” In fact, one survey of 404 pediatric neurologists found that only 41% of respondents were aware of the association between AEDs and reduced bone mass (Arch Neurol. 2001;58[9]:1369-74).

In an effort to evaluate the prevalence of fractures in pediatric patients on an antiepileptic drug, the researchers conducted a cohort study of 10,153 patients younger than 18 years of age who received an AED at Texas Children’s Hospital from 2011 to 2014. Half of the study population were female, and the most common concomitant disease was epilepsy (52.6%), followed by cerebral palsy (8.3%), epilepsy plus cerebral palsy (6.9%), osteoporosis (0.2%), and osteopenia (0.3%). In all, 113 patients (1.1%) experienced a fracture while on an antiepileptic drug, and the mean time from initiation of an AED to time of fracture was 1.6 years. Patients on enzyme-inducing AEDs were two times more likely to experience a fracture, while those with cerebral palsy and epilepsy were three times more likely to experience a fracture. Proton pump inhibitors and corticosteroids were the most common concomitant drugs. The researchers also found that less than 10% of patients were on calcium or vitamin D supplementation.

“Vigilant monitoring should be employed for at-risk patients,” the researchers concluded. “Regular monitoring of calcium and vitamin D levels may be warranted; further studies are needed to evaluate the roll of prophylactic calcium and vitamin D supplements.”

The researchers reported having no relevant financial disclosures.

[email protected]

HOUSTON – The incidence of fractures in pediatric patients taking antiepileptic medication stands at an estimated 1.1%, according to results from a 4-year period at a children’s hospital.

“Understanding the prevalence of fractures in pediatric patients on an AED [antiepileptic drug] will allow clinicians to weigh the risk versus benefit of therapy,” researchers led by Shannon DiCarlo, MD, wrote in an abstract presented during a poster session at the annual meeting of the American Epilepsy Society. “Recognizing a risk of fractures with AEDs will permit clinicians to provide appropriate supportive care and monitoring from the initiation of therapy.”

Dr. DiCarlo of Texas Children’s Hospital, Houston, and her associates went on to note that adults with epilepsy have a twofold to sixfold greater risk of experiencing fractures, compared with the general population, and that fractures secondary to seizures “are a major concern in pediatrics.” In fact, one survey of 404 pediatric neurologists found that only 41% of respondents were aware of the association between AEDs and reduced bone mass (Arch Neurol. 2001;58[9]:1369-74).

In an effort to evaluate the prevalence of fractures in pediatric patients on an antiepileptic drug, the researchers conducted a cohort study of 10,153 patients younger than 18 years of age who received an AED at Texas Children’s Hospital from 2011 to 2014. Half of the study population were female, and the most common concomitant disease was epilepsy (52.6%), followed by cerebral palsy (8.3%), epilepsy plus cerebral palsy (6.9%), osteoporosis (0.2%), and osteopenia (0.3%). In all, 113 patients (1.1%) experienced a fracture while on an antiepileptic drug, and the mean time from initiation of an AED to time of fracture was 1.6 years. Patients on enzyme-inducing AEDs were two times more likely to experience a fracture, while those with cerebral palsy and epilepsy were three times more likely to experience a fracture. Proton pump inhibitors and corticosteroids were the most common concomitant drugs. The researchers also found that less than 10% of patients were on calcium or vitamin D supplementation.

“Vigilant monitoring should be employed for at-risk patients,” the researchers concluded. “Regular monitoring of calcium and vitamin D levels may be warranted; further studies are needed to evaluate the roll of prophylactic calcium and vitamin D supplements.”

The researchers reported having no relevant financial disclosures.

[email protected]