The Food and Drug Administration has announced the clearance of a modified multipatient-use endoscope connector, which was designed to reduce the risk of cross-contamination previously identified by the FDA.

Wikimedia Commons/FitzColinGerald/Creative Commons License

AGA Center for GI Innovation and Technology  will continue to monitor this issue and encourages all GIs to follow the most up-to-date FDA guidance.

lfranki@mdedge.com

The Food and Drug Administration has announced the clearance of a modified multipatient-use endoscope connector, which was designed to reduce the risk of cross-contamination previously identified by the FDA.

Wikimedia Commons/FitzColinGerald/Creative Commons License

AGA Center for GI Innovation and Technology  will continue to monitor this issue and encourages all GIs to follow the most up-to-date FDA guidance.

lfranki@mdedge.com

The Food and Drug Administration has announced the clearance of a modified multipatient-use endoscope connector, which was designed to reduce the risk of cross-contamination previously identified by the FDA.

Wikimedia Commons/FitzColinGerald/Creative Commons License

AGA Center for GI Innovation and Technology  will continue to monitor this issue and encourages all GIs to follow the most up-to-date FDA guidance.

lfranki@mdedge.com

Excessive postpartum bleeding is a major cause of maternal morbidity and mortality. Worldwide, obstetric hemorrhage is the most common cause of maternal death.^1,2 Medications reported to reduce postpartum bleeding include oxytocin, misoprostol, ergonovine, methylergonovine, carboprost, and tranexamic acid. A recent Cochrane network meta-analysis of 196 trials, including 135,559 women, distilled in 1,361 pages of analysis, reported on the medications associated with the greatest reduction in postpartum bleeding.³ Surprisingly, for preventing blood loss ≥ 500 mL, misoprostol plus oxytocin and ergonovine plus oxytocin were the highest ranked interventions. This evidence is summarized here.

Misoprostol plus oxytocin

After newborn delivery, active management of the third stage of labor, including uterotonic administration, is strongly recommended because it will reduce postpartum blood loss, decreasing the rate of postpartum hemorrhage (PPH).⁴ Both oxytocin and misoprostol are effective uterotonics. However, the combination of oxytocin plus misoprostol appears to be more effective than oxytocin alone in reducing the frequency of postpartum blood loss greater than 500 mL.³ To understand the clinical efficacy and adverse effects (AEs) of combined oxytocin plus misoprostol a meta-analysis was performed for both vaginal and cesarean deliveries (CDs).

Efficacy and AEs during vaginal delivery. In the meta-analysis, about 6,000 vaginal deliveries were analyzed, with no significant differences for misoprostol plus oxytocin versus oxytocin alone found for the following outcomes: maternal death, intensive care unit admissions, and rate of blood loss ≥ 1,000 mL (1.7% for both uterotonics vs 2.2% for oxytocin alone).³ Misoprostol plus oxytocin was significantly superior to oxytocin alone for the following outcomes: reduced risk of blood transfusion (0.95% vs 2.5%), reduced risk of blood loss ≥ 500 mL (5.9% vs 8.0%), reduced risk of requiring an additional uterotonic (3.6% vs 5.8%), and a smaller decrease in hemoglobin concentration from pre- to postdelivery (-0.89 g/L).³

In my opinion, the difference in hemoglobin concentration, although statistically significant, is not of clinical significance. However, compared with oxytocin alone, misoprostol plus oxytocin caused significantly more nausea (2.4% vs 0.66%), vomiting (3.1% vs 0.86%), and fever (21% vs 3.9%).³ A weakness of this meta-analysis is that the trials used a wide range of misoprostol dosages (200 to 600 µg) and multiple routes of administration, including sublingual (under the tongue), buccal, and rectal. This makes it impossible to identify a best misoprostol dosage and administration route.

Efficacy and AEs during CD. In the same meta-analysis about 2,000 CDs were analyzed, with no significant difference for misoprostol plus oxytocin versus oxytocin alone for the following outcomes: maternal death, intensive care unit admissions, and PPH ≥ 1,000 mL blood loss (6.2% vs 6.5%).³ Misoprostol plus oxytocin was significantly superior to oxytocin alone for the following outcomes: reduced risk of blood transfusion (2.6% vs 5.4%), reduced risk of blood loss ≥ 500 mL (32% vs 47%), reduced risk of requiring an additional uterotonic (14% vs 28%), and a smaller decrease in hemoglobin concentration from before to after delivery (-4.0 g/L).³ In my opinion, the statistically significant difference in hemoglobin concentration is not clinically significant. However, compared with oxytocin alone, misoprostol plus oxytocin caused significantly more nausea (12% vs 6.1%), vomiting (8.1% vs 5.4%), shivering (13% vs 7%), and fever (7.7% vs 4.0%).³

Continue to: Ergonovine plus oxytocin...

Ergonovine plus oxytocin

Ergonovine is an ergot derivative that causes uterine contractions and has been shown to effectively reduce blood loss at delivery. In the United States a methyl-derivative of ergonovine, methylergonovine, is widely available. In a meta-analysis with mostly vaginal deliveries, there were no significant differences for ergonovine plus oxytocin versus oxytocin alone for the following outcomes: death, intensive care unit admission, rate of blood loss ≥ 1,000 mL(2.0% vs 2.7%), blood transfusion, administration of an additional uterotonic, change in hemoglobin from pre- to postdelivery, nausea, hypertension, shivering, and fever.³ However, ergonovine plus oxytocin, compared with oxytocin alone, resulted in a significantly reduced rate of blood loss ≥ 500 mL (8.3% vs 10.2%) and an increased rate of vomiting (8.1% vs 1.6%).³ In these trials women with a blood pressure ≥ 150/100 mm Hg were generally excluded from receiving ergonovine because of its hypertensive effect.

Clinical practice options

Given the Cochrane meta-analysis results, ObGyns have two approaches for optimizing PPH reduction.

Option 1: Use a single uterotonic to reduce postpartum blood loss. If excess bleeding occurs, rapidly administer a second uterotonic agent. Currently, monotherapy with intravenous or intramuscular oxytocin is the standard for reducing postpartum blood loss.^5,6 Advantages of this approach compared with dual agent therapy include simplification of care and minimization of AEs. However, oxytocin monotherapy for minimizing postpartum bleeding may be suboptimal. In the largest trial ever performed (involving 29,645 women) when oxytocin was administered postpartum, the rates of estimated blood loss ≥ 500 mL and ≥ 1,000 mL were 9.1% and 1.45%, respectively.⁵ Is 9% an optimal rate for blood loss ≥ 500 mL following a vaginal delivery? Or should we try to achieve a lower rate?

Given the “high” rate of blood loss ≥ 500 mL with oxytocin alone, it is important for clinicians using the one-uterotonic approach to promptly recognize patients who have excessive bleeding and transition rapidly from prevention to treatment. When PPH cases are reviewed, a common finding is that the clinicians did not timely recognize excess bleeding, delaying transition to treatment with additional uterotonics and other interventions. When routinely using oxytocin monotherapy, lowering the threshold for administering a second uterotonic (methylergonovine, carboprost, misoprostol, or tranexamic acid) may help decrease the frequency of excess postpartum blood loss.

Option 2: Administer two uterotonics to reduce postpartum blood loss at all deliveries. Given the “high” rate of excess postpartum blood loss with oxytocin monotherapy, an alternative is to administer two uterotonics at all births or at births with a high risk of excess blood loss. As discussed, administering two uterotonics, oxytocin plus misoprostol or oxytocin plus ergonovine, has been reported to be more effective than oxytocin alone for reducing postpartum bleeding ≥ 500 mL.³ In the Cochrane meta-analysis, per 1,000 women given oxytocin following a vaginal birth, 122 would have blood loss ≥ 500 mL, compared with 85 given oxytocin plus misoprostol or oxytocin plus ergonovine.³

Misoprostol is administered sublingually, buccally, or rectally, and methylergonovine is administered by intramuscular injection. Although dual uterotonic therapy is more effective than monotherapy, dual therapy is associated with more AEs. As noted, compared with oxytocin monotherapy, the combination of oxytocin plus misoprostol is associated with more nausea, vomiting, shivering, and fever. Oxytocin plus ergonovine is associated with a higher rate of vomiting than oxytocin monotherapy. In my practice I prefer using intramuscular methylergonovine as the second agent to avoid the high rate of fever associated with misoprostol.

For dual agent therapy, one approach is to administer misoprostol 200 µg or 400 µg through the buccal^7,8 or sublingual^9,10 routes. Higher dosages of misoprostol (600 µg to 800 µg) have been used^11,12 but are likely associated with higher rates of nausea, vomiting,shivering, and fever than the lower dosages. Methylergonovine 0.2 mg is administered intramuscularly.

Continue to: The bottom line...

The bottom line

PPH is a major cause of maternal morbidity, and in low-resource settings, mortality. Oxytocin is the standard for reducing postpartum blood loss, but rates of blood loss ≥ 500 mL are high following this monotherapy. To reduce postpartum blood loss beyond what is possible with oxytocin alone, clinicians can more rapidly transition to administering a second uterotonic when they suspect blood loss is becoming excessive or they can use two uterotonic agents with all births or in those at high risk for excess bleeding. If blood loss does become excessive, clinicians need to pivot rapidly from prevention with oxytocin to treatment with our entire therapeutic armamentarium.

Excessive postpartum bleeding is a major cause of maternal morbidity and mortality. Worldwide, obstetric hemorrhage is the most common cause of maternal death.^1,2 Medications reported to reduce postpartum bleeding include oxytocin, misoprostol, ergonovine, methylergonovine, carboprost, and tranexamic acid. A recent Cochrane network meta-analysis of 196 trials, including 135,559 women, distilled in 1,361 pages of analysis, reported on the medications associated with the greatest reduction in postpartum bleeding.³ Surprisingly, for preventing blood loss ≥ 500 mL, misoprostol plus oxytocin and ergonovine plus oxytocin were the highest ranked interventions. This evidence is summarized here.

Misoprostol plus oxytocin

After newborn delivery, active management of the third stage of labor, including uterotonic administration, is strongly recommended because it will reduce postpartum blood loss, decreasing the rate of postpartum hemorrhage (PPH).⁴ Both oxytocin and misoprostol are effective uterotonics. However, the combination of oxytocin plus misoprostol appears to be more effective than oxytocin alone in reducing the frequency of postpartum blood loss greater than 500 mL.³ To understand the clinical efficacy and adverse effects (AEs) of combined oxytocin plus misoprostol a meta-analysis was performed for both vaginal and cesarean deliveries (CDs).

Efficacy and AEs during vaginal delivery. In the meta-analysis, about 6,000 vaginal deliveries were analyzed, with no significant differences for misoprostol plus oxytocin versus oxytocin alone found for the following outcomes: maternal death, intensive care unit admissions, and rate of blood loss ≥ 1,000 mL (1.7% for both uterotonics vs 2.2% for oxytocin alone).³ Misoprostol plus oxytocin was significantly superior to oxytocin alone for the following outcomes: reduced risk of blood transfusion (0.95% vs 2.5%), reduced risk of blood loss ≥ 500 mL (5.9% vs 8.0%), reduced risk of requiring an additional uterotonic (3.6% vs 5.8%), and a smaller decrease in hemoglobin concentration from pre- to postdelivery (-0.89 g/L).³

In my opinion, the difference in hemoglobin concentration, although statistically significant, is not of clinical significance. However, compared with oxytocin alone, misoprostol plus oxytocin caused significantly more nausea (2.4% vs 0.66%), vomiting (3.1% vs 0.86%), and fever (21% vs 3.9%).³ A weakness of this meta-analysis is that the trials used a wide range of misoprostol dosages (200 to 600 µg) and multiple routes of administration, including sublingual (under the tongue), buccal, and rectal. This makes it impossible to identify a best misoprostol dosage and administration route.

Efficacy and AEs during CD. In the same meta-analysis about 2,000 CDs were analyzed, with no significant difference for misoprostol plus oxytocin versus oxytocin alone for the following outcomes: maternal death, intensive care unit admissions, and PPH ≥ 1,000 mL blood loss (6.2% vs 6.5%).³ Misoprostol plus oxytocin was significantly superior to oxytocin alone for the following outcomes: reduced risk of blood transfusion (2.6% vs 5.4%), reduced risk of blood loss ≥ 500 mL (32% vs 47%), reduced risk of requiring an additional uterotonic (14% vs 28%), and a smaller decrease in hemoglobin concentration from before to after delivery (-4.0 g/L).³ In my opinion, the statistically significant difference in hemoglobin concentration is not clinically significant. However, compared with oxytocin alone, misoprostol plus oxytocin caused significantly more nausea (12% vs 6.1%), vomiting (8.1% vs 5.4%), shivering (13% vs 7%), and fever (7.7% vs 4.0%).³

Continue to: Ergonovine plus oxytocin...

Ergonovine plus oxytocin

Ergonovine is an ergot derivative that causes uterine contractions and has been shown to effectively reduce blood loss at delivery. In the United States a methyl-derivative of ergonovine, methylergonovine, is widely available. In a meta-analysis with mostly vaginal deliveries, there were no significant differences for ergonovine plus oxytocin versus oxytocin alone for the following outcomes: death, intensive care unit admission, rate of blood loss ≥ 1,000 mL(2.0% vs 2.7%), blood transfusion, administration of an additional uterotonic, change in hemoglobin from pre- to postdelivery, nausea, hypertension, shivering, and fever.³ However, ergonovine plus oxytocin, compared with oxytocin alone, resulted in a significantly reduced rate of blood loss ≥ 500 mL (8.3% vs 10.2%) and an increased rate of vomiting (8.1% vs 1.6%).³ In these trials women with a blood pressure ≥ 150/100 mm Hg were generally excluded from receiving ergonovine because of its hypertensive effect.

Clinical practice options

Given the Cochrane meta-analysis results, ObGyns have two approaches for optimizing PPH reduction.

Option 1: Use a single uterotonic to reduce postpartum blood loss. If excess bleeding occurs, rapidly administer a second uterotonic agent. Currently, monotherapy with intravenous or intramuscular oxytocin is the standard for reducing postpartum blood loss.^5,6 Advantages of this approach compared with dual agent therapy include simplification of care and minimization of AEs. However, oxytocin monotherapy for minimizing postpartum bleeding may be suboptimal. In the largest trial ever performed (involving 29,645 women) when oxytocin was administered postpartum, the rates of estimated blood loss ≥ 500 mL and ≥ 1,000 mL were 9.1% and 1.45%, respectively.⁵ Is 9% an optimal rate for blood loss ≥ 500 mL following a vaginal delivery? Or should we try to achieve a lower rate?

Given the “high” rate of blood loss ≥ 500 mL with oxytocin alone, it is important for clinicians using the one-uterotonic approach to promptly recognize patients who have excessive bleeding and transition rapidly from prevention to treatment. When PPH cases are reviewed, a common finding is that the clinicians did not timely recognize excess bleeding, delaying transition to treatment with additional uterotonics and other interventions. When routinely using oxytocin monotherapy, lowering the threshold for administering a second uterotonic (methylergonovine, carboprost, misoprostol, or tranexamic acid) may help decrease the frequency of excess postpartum blood loss.

Option 2: Administer two uterotonics to reduce postpartum blood loss at all deliveries. Given the “high” rate of excess postpartum blood loss with oxytocin monotherapy, an alternative is to administer two uterotonics at all births or at births with a high risk of excess blood loss. As discussed, administering two uterotonics, oxytocin plus misoprostol or oxytocin plus ergonovine, has been reported to be more effective than oxytocin alone for reducing postpartum bleeding ≥ 500 mL.³ In the Cochrane meta-analysis, per 1,000 women given oxytocin following a vaginal birth, 122 would have blood loss ≥ 500 mL, compared with 85 given oxytocin plus misoprostol or oxytocin plus ergonovine.³

Misoprostol is administered sublingually, buccally, or rectally, and methylergonovine is administered by intramuscular injection. Although dual uterotonic therapy is more effective than monotherapy, dual therapy is associated with more AEs. As noted, compared with oxytocin monotherapy, the combination of oxytocin plus misoprostol is associated with more nausea, vomiting, shivering, and fever. Oxytocin plus ergonovine is associated with a higher rate of vomiting than oxytocin monotherapy. In my practice I prefer using intramuscular methylergonovine as the second agent to avoid the high rate of fever associated with misoprostol.

For dual agent therapy, one approach is to administer misoprostol 200 µg or 400 µg through the buccal^7,8 or sublingual^9,10 routes. Higher dosages of misoprostol (600 µg to 800 µg) have been used^11,12 but are likely associated with higher rates of nausea, vomiting,shivering, and fever than the lower dosages. Methylergonovine 0.2 mg is administered intramuscularly.

Continue to: The bottom line...

The bottom line

PPH is a major cause of maternal morbidity, and in low-resource settings, mortality. Oxytocin is the standard for reducing postpartum blood loss, but rates of blood loss ≥ 500 mL are high following this monotherapy. To reduce postpartum blood loss beyond what is possible with oxytocin alone, clinicians can more rapidly transition to administering a second uterotonic when they suspect blood loss is becoming excessive or they can use two uterotonic agents with all births or in those at high risk for excess bleeding. If blood loss does become excessive, clinicians need to pivot rapidly from prevention with oxytocin to treatment with our entire therapeutic armamentarium.

Excessive postpartum bleeding is a major cause of maternal morbidity and mortality. Worldwide, obstetric hemorrhage is the most common cause of maternal death.^1,2 Medications reported to reduce postpartum bleeding include oxytocin, misoprostol, ergonovine, methylergonovine, carboprost, and tranexamic acid. A recent Cochrane network meta-analysis of 196 trials, including 135,559 women, distilled in 1,361 pages of analysis, reported on the medications associated with the greatest reduction in postpartum bleeding.³ Surprisingly, for preventing blood loss ≥ 500 mL, misoprostol plus oxytocin and ergonovine plus oxytocin were the highest ranked interventions. This evidence is summarized here.

Misoprostol plus oxytocin

After newborn delivery, active management of the third stage of labor, including uterotonic administration, is strongly recommended because it will reduce postpartum blood loss, decreasing the rate of postpartum hemorrhage (PPH).⁴ Both oxytocin and misoprostol are effective uterotonics. However, the combination of oxytocin plus misoprostol appears to be more effective than oxytocin alone in reducing the frequency of postpartum blood loss greater than 500 mL.³ To understand the clinical efficacy and adverse effects (AEs) of combined oxytocin plus misoprostol a meta-analysis was performed for both vaginal and cesarean deliveries (CDs).

Efficacy and AEs during vaginal delivery. In the meta-analysis, about 6,000 vaginal deliveries were analyzed, with no significant differences for misoprostol plus oxytocin versus oxytocin alone found for the following outcomes: maternal death, intensive care unit admissions, and rate of blood loss ≥ 1,000 mL (1.7% for both uterotonics vs 2.2% for oxytocin alone).³ Misoprostol plus oxytocin was significantly superior to oxytocin alone for the following outcomes: reduced risk of blood transfusion (0.95% vs 2.5%), reduced risk of blood loss ≥ 500 mL (5.9% vs 8.0%), reduced risk of requiring an additional uterotonic (3.6% vs 5.8%), and a smaller decrease in hemoglobin concentration from pre- to postdelivery (-0.89 g/L).³

In my opinion, the difference in hemoglobin concentration, although statistically significant, is not of clinical significance. However, compared with oxytocin alone, misoprostol plus oxytocin caused significantly more nausea (2.4% vs 0.66%), vomiting (3.1% vs 0.86%), and fever (21% vs 3.9%).³ A weakness of this meta-analysis is that the trials used a wide range of misoprostol dosages (200 to 600 µg) and multiple routes of administration, including sublingual (under the tongue), buccal, and rectal. This makes it impossible to identify a best misoprostol dosage and administration route.

Efficacy and AEs during CD. In the same meta-analysis about 2,000 CDs were analyzed, with no significant difference for misoprostol plus oxytocin versus oxytocin alone for the following outcomes: maternal death, intensive care unit admissions, and PPH ≥ 1,000 mL blood loss (6.2% vs 6.5%).³ Misoprostol plus oxytocin was significantly superior to oxytocin alone for the following outcomes: reduced risk of blood transfusion (2.6% vs 5.4%), reduced risk of blood loss ≥ 500 mL (32% vs 47%), reduced risk of requiring an additional uterotonic (14% vs 28%), and a smaller decrease in hemoglobin concentration from before to after delivery (-4.0 g/L).³ In my opinion, the statistically significant difference in hemoglobin concentration is not clinically significant. However, compared with oxytocin alone, misoprostol plus oxytocin caused significantly more nausea (12% vs 6.1%), vomiting (8.1% vs 5.4%), shivering (13% vs 7%), and fever (7.7% vs 4.0%).³

Continue to: Ergonovine plus oxytocin...

Ergonovine plus oxytocin

Ergonovine is an ergot derivative that causes uterine contractions and has been shown to effectively reduce blood loss at delivery. In the United States a methyl-derivative of ergonovine, methylergonovine, is widely available. In a meta-analysis with mostly vaginal deliveries, there were no significant differences for ergonovine plus oxytocin versus oxytocin alone for the following outcomes: death, intensive care unit admission, rate of blood loss ≥ 1,000 mL(2.0% vs 2.7%), blood transfusion, administration of an additional uterotonic, change in hemoglobin from pre- to postdelivery, nausea, hypertension, shivering, and fever.³ However, ergonovine plus oxytocin, compared with oxytocin alone, resulted in a significantly reduced rate of blood loss ≥ 500 mL (8.3% vs 10.2%) and an increased rate of vomiting (8.1% vs 1.6%).³ In these trials women with a blood pressure ≥ 150/100 mm Hg were generally excluded from receiving ergonovine because of its hypertensive effect.

Clinical practice options

Given the Cochrane meta-analysis results, ObGyns have two approaches for optimizing PPH reduction.

Option 1: Use a single uterotonic to reduce postpartum blood loss. If excess bleeding occurs, rapidly administer a second uterotonic agent. Currently, monotherapy with intravenous or intramuscular oxytocin is the standard for reducing postpartum blood loss.^5,6 Advantages of this approach compared with dual agent therapy include simplification of care and minimization of AEs. However, oxytocin monotherapy for minimizing postpartum bleeding may be suboptimal. In the largest trial ever performed (involving 29,645 women) when oxytocin was administered postpartum, the rates of estimated blood loss ≥ 500 mL and ≥ 1,000 mL were 9.1% and 1.45%, respectively.⁵ Is 9% an optimal rate for blood loss ≥ 500 mL following a vaginal delivery? Or should we try to achieve a lower rate?

Given the “high” rate of blood loss ≥ 500 mL with oxytocin alone, it is important for clinicians using the one-uterotonic approach to promptly recognize patients who have excessive bleeding and transition rapidly from prevention to treatment. When PPH cases are reviewed, a common finding is that the clinicians did not timely recognize excess bleeding, delaying transition to treatment with additional uterotonics and other interventions. When routinely using oxytocin monotherapy, lowering the threshold for administering a second uterotonic (methylergonovine, carboprost, misoprostol, or tranexamic acid) may help decrease the frequency of excess postpartum blood loss.

Option 2: Administer two uterotonics to reduce postpartum blood loss at all deliveries. Given the “high” rate of excess postpartum blood loss with oxytocin monotherapy, an alternative is to administer two uterotonics at all births or at births with a high risk of excess blood loss. As discussed, administering two uterotonics, oxytocin plus misoprostol or oxytocin plus ergonovine, has been reported to be more effective than oxytocin alone for reducing postpartum bleeding ≥ 500 mL.³ In the Cochrane meta-analysis, per 1,000 women given oxytocin following a vaginal birth, 122 would have blood loss ≥ 500 mL, compared with 85 given oxytocin plus misoprostol or oxytocin plus ergonovine.³

Misoprostol is administered sublingually, buccally, or rectally, and methylergonovine is administered by intramuscular injection. Although dual uterotonic therapy is more effective than monotherapy, dual therapy is associated with more AEs. As noted, compared with oxytocin monotherapy, the combination of oxytocin plus misoprostol is associated with more nausea, vomiting, shivering, and fever. Oxytocin plus ergonovine is associated with a higher rate of vomiting than oxytocin monotherapy. In my practice I prefer using intramuscular methylergonovine as the second agent to avoid the high rate of fever associated with misoprostol.

For dual agent therapy, one approach is to administer misoprostol 200 µg or 400 µg through the buccal^7,8 or sublingual^9,10 routes. Higher dosages of misoprostol (600 µg to 800 µg) have been used^11,12 but are likely associated with higher rates of nausea, vomiting,shivering, and fever than the lower dosages. Methylergonovine 0.2 mg is administered intramuscularly.

Continue to: The bottom line...

The bottom line

PPH is a major cause of maternal morbidity, and in low-resource settings, mortality. Oxytocin is the standard for reducing postpartum blood loss, but rates of blood loss ≥ 500 mL are high following this monotherapy. To reduce postpartum blood loss beyond what is possible with oxytocin alone, clinicians can more rapidly transition to administering a second uterotonic when they suspect blood loss is becoming excessive or they can use two uterotonic agents with all births or in those at high risk for excess bleeding. If blood loss does become excessive, clinicians need to pivot rapidly from prevention with oxytocin to treatment with our entire therapeutic armamentarium.

To the Editor:

A 17-year-old adolescent girl presented to the dermatology clinic with a tender pruritic rash on the left wrist that was spreading to the bilateral arms and legs of several years’ duration. An area of a prior biopsy on the left wrist was healing well with use of petroleum jelly and halcinonide cream. The patient denied any constitutional symptoms.

Physical examination revealed numerous erythematous papules coalescing into plaques on the bilateral anterior and posterior arms and legs, including some erythematous macules and papules on the palms and soles. The original area of involvement on the left dorsal medial wrist demonstrated a background of erythema with overlying peripheral scaling and resolving violaceous to erythematous papules with signs of serosanguineous crusting (Figure 1). Scattered perifollicular erythema was present on the posterior aspects of the bilateral thighs and arms (Figure 2). Baseline complete blood cell count and complete metabolic panel were within reference range.

To the Editor:

A 17-year-old adolescent girl presented to the dermatology clinic with a tender pruritic rash on the left wrist that was spreading to the bilateral arms and legs of several years’ duration. An area of a prior biopsy on the left wrist was healing well with use of petroleum jelly and halcinonide cream. The patient denied any constitutional symptoms.

Physical examination revealed numerous erythematous papules coalescing into plaques on the bilateral anterior and posterior arms and legs, including some erythematous macules and papules on the palms and soles. The original area of involvement on the left dorsal medial wrist demonstrated a background of erythema with overlying peripheral scaling and resolving violaceous to erythematous papules with signs of serosanguineous crusting (Figure 1). Scattered perifollicular erythema was present on the posterior aspects of the bilateral thighs and arms (Figure 2). Baseline complete blood cell count and complete metabolic panel were within reference range.

To the Editor:

A 17-year-old adolescent girl presented to the dermatology clinic with a tender pruritic rash on the left wrist that was spreading to the bilateral arms and legs of several years’ duration. An area of a prior biopsy on the left wrist was healing well with use of petroleum jelly and halcinonide cream. The patient denied any constitutional symptoms.

Physical examination revealed numerous erythematous papules coalescing into plaques on the bilateral anterior and posterior arms and legs, including some erythematous macules and papules on the palms and soles. The original area of involvement on the left dorsal medial wrist demonstrated a background of erythema with overlying peripheral scaling and resolving violaceous to erythematous papules with signs of serosanguineous crusting (Figure 1). Scattered perifollicular erythema was present on the posterior aspects of the bilateral thighs and arms (Figure 2). Baseline complete blood cell count and complete metabolic panel were within reference range.

Zwertbroek EF, Franssen MT, Broekhuijsen K, et al; HYPITAT-II Study Group. Neonatal developmental and behavioral outcomes of immediate delivery versus expectant monitoring of mild hypertensive disorders of pregnancy: 2-year outcomes of the HYPITAT-II trial. Am J Obstet Gynecol. doi:10.1016/j.ajog.2019.03.024.

EXPERT COMMENTARY

In women with mild hypertensive disorders in the preterm period, the maternal benefits of delivery should be weighed against the consequences of preterm birth for the neonate. In a recent study, Zwertbroek and colleagues sought to evaluate the long-term neurodevelopmental effects of this decision on the offspring.

Details of the study

The authors conducted a follow-up study of the randomized, controlled Hypertension and Preeclampsia Intervention Trial At Term II (HYPITAT-II), in which 704 women diagnosed with late preterm (34–37 weeks) hypertensive disorders in pregnancy (gestational hypertension, chronic hypertension, or mild preeclampsia) were randomly assigned to immediate delivery or expectant management.

Expectant management consisted of close monitoring until 37 weeks or until an indication for delivery occurred, whichever came first. Children born to those mothers were eligible for this study (women enrolled during 2011–2015) when they reached 2 years of age; 342 children were included in this analysis. Of note, children from the expectant management group had been delivered at a more advanced gestational age (median, 37.0 vs 36.1 weeks; P<.001) than those in the immediate-delivery group.

Survey tools. Parents completed 2 response surveys, the Ages and Stages Questionnaire (ASQ) and the Child Behavior Checklist (CBCL), between 23 and 26 months’ corrected age. The ASQ is designed to detect developmental delay, while the CBCL assesses behavioral and emotional problems. The primary outcome was an abnormal result on either screen.

Results. Based on 330 returned questionnaires, the authors found more abnormal ASQ scores (45 of 162 [28%] vs 27 of 148 [18%] children; P = .045) in the immediate-delivery group versus the expectant management group, most pronounced in the fine motor domain. They found no difference in the CBCL scores. The authors concluded that immediate delivery for women with late preterm mild hypertensive disorders in pregnancy increases the risk of developmental delay in the children.

Study strengths and limitations

This study is unique as a planned follow-up to a randomized, controlled trial, allowing for 2-year outcomes to be assessed on children of enrolled women with mild hypertensive disorders in the late preterm period. The authors used validated surveys that are known to predict long-term neurodevelopmental outcomes.

Continue to: This work has several limitations...

This work has several limitations, however. Randomization was not truly maintained given the less than 50% response rate of original participants. Additionally, parents completed the surveys and provider confirmation of developmental concerns or diagnoses was not obtained. Further, assessments at 2 years of age may be too early to detect subtle differences, with evaluations at 5 years more predictive of long-term outcomes; the authors stated that these data already are being collected.

Finally, while these data importantly reinforce the conclusions of the parent HYPITAT-II trial, which support expectant management for mild hypertensive disorders in the late preterm period,¹ clinicians must always take care to individualize decisions in the face of worsening maternal disease.

Zwertbroek EF, Franssen MT, Broekhuijsen K, et al; HYPITAT-II Study Group. Neonatal developmental and behavioral outcomes of immediate delivery versus expectant monitoring of mild hypertensive disorders of pregnancy: 2-year outcomes of the HYPITAT-II trial. Am J Obstet Gynecol. doi:10.1016/j.ajog.2019.03.024.

EXPERT COMMENTARY

In women with mild hypertensive disorders in the preterm period, the maternal benefits of delivery should be weighed against the consequences of preterm birth for the neonate. In a recent study, Zwertbroek and colleagues sought to evaluate the long-term neurodevelopmental effects of this decision on the offspring.

Details of the study

The authors conducted a follow-up study of the randomized, controlled Hypertension and Preeclampsia Intervention Trial At Term II (HYPITAT-II), in which 704 women diagnosed with late preterm (34–37 weeks) hypertensive disorders in pregnancy (gestational hypertension, chronic hypertension, or mild preeclampsia) were randomly assigned to immediate delivery or expectant management.

Expectant management consisted of close monitoring until 37 weeks or until an indication for delivery occurred, whichever came first. Children born to those mothers were eligible for this study (women enrolled during 2011–2015) when they reached 2 years of age; 342 children were included in this analysis. Of note, children from the expectant management group had been delivered at a more advanced gestational age (median, 37.0 vs 36.1 weeks; P<.001) than those in the immediate-delivery group.

Survey tools. Parents completed 2 response surveys, the Ages and Stages Questionnaire (ASQ) and the Child Behavior Checklist (CBCL), between 23 and 26 months’ corrected age. The ASQ is designed to detect developmental delay, while the CBCL assesses behavioral and emotional problems. The primary outcome was an abnormal result on either screen.

Results. Based on 330 returned questionnaires, the authors found more abnormal ASQ scores (45 of 162 [28%] vs 27 of 148 [18%] children; P = .045) in the immediate-delivery group versus the expectant management group, most pronounced in the fine motor domain. They found no difference in the CBCL scores. The authors concluded that immediate delivery for women with late preterm mild hypertensive disorders in pregnancy increases the risk of developmental delay in the children.

Study strengths and limitations

This study is unique as a planned follow-up to a randomized, controlled trial, allowing for 2-year outcomes to be assessed on children of enrolled women with mild hypertensive disorders in the late preterm period. The authors used validated surveys that are known to predict long-term neurodevelopmental outcomes.

Continue to: This work has several limitations...

This work has several limitations, however. Randomization was not truly maintained given the less than 50% response rate of original participants. Additionally, parents completed the surveys and provider confirmation of developmental concerns or diagnoses was not obtained. Further, assessments at 2 years of age may be too early to detect subtle differences, with evaluations at 5 years more predictive of long-term outcomes; the authors stated that these data already are being collected.

Finally, while these data importantly reinforce the conclusions of the parent HYPITAT-II trial, which support expectant management for mild hypertensive disorders in the late preterm period,¹ clinicians must always take care to individualize decisions in the face of worsening maternal disease.

Zwertbroek EF, Franssen MT, Broekhuijsen K, et al; HYPITAT-II Study Group. Neonatal developmental and behavioral outcomes of immediate delivery versus expectant monitoring of mild hypertensive disorders of pregnancy: 2-year outcomes of the HYPITAT-II trial. Am J Obstet Gynecol. doi:10.1016/j.ajog.2019.03.024.

EXPERT COMMENTARY

In women with mild hypertensive disorders in the preterm period, the maternal benefits of delivery should be weighed against the consequences of preterm birth for the neonate. In a recent study, Zwertbroek and colleagues sought to evaluate the long-term neurodevelopmental effects of this decision on the offspring.

Details of the study

The authors conducted a follow-up study of the randomized, controlled Hypertension and Preeclampsia Intervention Trial At Term II (HYPITAT-II), in which 704 women diagnosed with late preterm (34–37 weeks) hypertensive disorders in pregnancy (gestational hypertension, chronic hypertension, or mild preeclampsia) were randomly assigned to immediate delivery or expectant management.

Expectant management consisted of close monitoring until 37 weeks or until an indication for delivery occurred, whichever came first. Children born to those mothers were eligible for this study (women enrolled during 2011–2015) when they reached 2 years of age; 342 children were included in this analysis. Of note, children from the expectant management group had been delivered at a more advanced gestational age (median, 37.0 vs 36.1 weeks; P<.001) than those in the immediate-delivery group.

Survey tools. Parents completed 2 response surveys, the Ages and Stages Questionnaire (ASQ) and the Child Behavior Checklist (CBCL), between 23 and 26 months’ corrected age. The ASQ is designed to detect developmental delay, while the CBCL assesses behavioral and emotional problems. The primary outcome was an abnormal result on either screen.

Results. Based on 330 returned questionnaires, the authors found more abnormal ASQ scores (45 of 162 [28%] vs 27 of 148 [18%] children; P = .045) in the immediate-delivery group versus the expectant management group, most pronounced in the fine motor domain. They found no difference in the CBCL scores. The authors concluded that immediate delivery for women with late preterm mild hypertensive disorders in pregnancy increases the risk of developmental delay in the children.

Study strengths and limitations

This study is unique as a planned follow-up to a randomized, controlled trial, allowing for 2-year outcomes to be assessed on children of enrolled women with mild hypertensive disorders in the late preterm period. The authors used validated surveys that are known to predict long-term neurodevelopmental outcomes.

Continue to: This work has several limitations...

This work has several limitations, however. Randomization was not truly maintained given the less than 50% response rate of original participants. Additionally, parents completed the surveys and provider confirmation of developmental concerns or diagnoses was not obtained. Further, assessments at 2 years of age may be too early to detect subtle differences, with evaluations at 5 years more predictive of long-term outcomes; the authors stated that these data already are being collected.

Finally, while these data importantly reinforce the conclusions of the parent HYPITAT-II trial, which support expectant management for mild hypertensive disorders in the late preterm period,¹ clinicians must always take care to individualize decisions in the face of worsening maternal disease.

BALTIMORE – The biggest barrier to asthma care in public schools is students not having an albuterol inhaler with them, frequently because the parent did not provide an inhaler or did not provide a written order for one, according to new research. Only seven U.S. states have laws allowing schools to stock albuterol for students.

pelvidge/thinkstockphotos.com

“Most students only have access to this lifesaving medication when they bring a personal inhaler,” Alexandra M. Sims, MD, of Children’s National Hospital in Washington and colleagues wrote in their abstract at the annual meeting of Pediatric Academic Societies. “Interventions that address medication availability may be an important step in removing obstacles to asthma care in school.”

One such option is a stock inhaler available for any students to use. National guidelines from the Centers for Disease Control and Prevention recommend that students with asthma have access to inhaled albuterol at school, yet most states do not have legislation related to albuterol stocking in schools, according to the Asthma and Allergy Foundation of America.

Not having access to rescue inhaler medication at school contributes to lost class time and referrals to the emergency department, the authors note in their background information. Yet, “in most U.S. jurisdictions, including the school district we examined, students need both a personal albuterol inhaler and a physician order to receive medication at school.”

To determine what barriers exist regarding students’ asthma care in schools, the authors sent 166 school nurses in an urban school district an anonymous survey during the 2015-2016 school year. The survey asked about 21 factors that could delay or prevent students from returning to class and asked nurses’ agreement or disagreement with 25 additional statements.

The 130 respondents made up a 78% response rate. The institutions represented by the nurses included 44% elementary schools, 9% middle schools, 16% high schools, and 32% other (such as those who may serve multiple schools).

The majority of respondents (72%) agreed that asthma is one of the biggest health problems students face, particularly among middle and high school students (P less than .05). Most (74%) also said an albuterol inhaler at school could reduce the likelihood of students with asthma needing to leave school early.

The largest barrier to students returning to class was parents not providing an albuterol inhaler and/or a written order for an inhaler despite a request from the nurse, according to 69% of the respondents (P less than .05). In high schools in particular, another barrier was students simply not bringing their inhaler to school even though they usually carry one (P less than .01).

Only 15% of nurses saw disease severity as a significant barrier, and 17% cited the staff not adequately recognizing a student’s symptoms.

The researchers did not note use of external funding or author disclosures.

BALTIMORE – The biggest barrier to asthma care in public schools is students not having an albuterol inhaler with them, frequently because the parent did not provide an inhaler or did not provide a written order for one, according to new research. Only seven U.S. states have laws allowing schools to stock albuterol for students.

pelvidge/thinkstockphotos.com

“Most students only have access to this lifesaving medication when they bring a personal inhaler,” Alexandra M. Sims, MD, of Children’s National Hospital in Washington and colleagues wrote in their abstract at the annual meeting of Pediatric Academic Societies. “Interventions that address medication availability may be an important step in removing obstacles to asthma care in school.”

One such option is a stock inhaler available for any students to use. National guidelines from the Centers for Disease Control and Prevention recommend that students with asthma have access to inhaled albuterol at school, yet most states do not have legislation related to albuterol stocking in schools, according to the Asthma and Allergy Foundation of America.

Not having access to rescue inhaler medication at school contributes to lost class time and referrals to the emergency department, the authors note in their background information. Yet, “in most U.S. jurisdictions, including the school district we examined, students need both a personal albuterol inhaler and a physician order to receive medication at school.”

To determine what barriers exist regarding students’ asthma care in schools, the authors sent 166 school nurses in an urban school district an anonymous survey during the 2015-2016 school year. The survey asked about 21 factors that could delay or prevent students from returning to class and asked nurses’ agreement or disagreement with 25 additional statements.

The 130 respondents made up a 78% response rate. The institutions represented by the nurses included 44% elementary schools, 9% middle schools, 16% high schools, and 32% other (such as those who may serve multiple schools).

The majority of respondents (72%) agreed that asthma is one of the biggest health problems students face, particularly among middle and high school students (P less than .05). Most (74%) also said an albuterol inhaler at school could reduce the likelihood of students with asthma needing to leave school early.

The largest barrier to students returning to class was parents not providing an albuterol inhaler and/or a written order for an inhaler despite a request from the nurse, according to 69% of the respondents (P less than .05). In high schools in particular, another barrier was students simply not bringing their inhaler to school even though they usually carry one (P less than .01).

Only 15% of nurses saw disease severity as a significant barrier, and 17% cited the staff not adequately recognizing a student’s symptoms.

The researchers did not note use of external funding or author disclosures.

BALTIMORE – The biggest barrier to asthma care in public schools is students not having an albuterol inhaler with them, frequently because the parent did not provide an inhaler or did not provide a written order for one, according to new research. Only seven U.S. states have laws allowing schools to stock albuterol for students.

pelvidge/thinkstockphotos.com

“Most students only have access to this lifesaving medication when they bring a personal inhaler,” Alexandra M. Sims, MD, of Children’s National Hospital in Washington and colleagues wrote in their abstract at the annual meeting of Pediatric Academic Societies. “Interventions that address medication availability may be an important step in removing obstacles to asthma care in school.”

One such option is a stock inhaler available for any students to use. National guidelines from the Centers for Disease Control and Prevention recommend that students with asthma have access to inhaled albuterol at school, yet most states do not have legislation related to albuterol stocking in schools, according to the Asthma and Allergy Foundation of America.

Not having access to rescue inhaler medication at school contributes to lost class time and referrals to the emergency department, the authors note in their background information. Yet, “in most U.S. jurisdictions, including the school district we examined, students need both a personal albuterol inhaler and a physician order to receive medication at school.”

To determine what barriers exist regarding students’ asthma care in schools, the authors sent 166 school nurses in an urban school district an anonymous survey during the 2015-2016 school year. The survey asked about 21 factors that could delay or prevent students from returning to class and asked nurses’ agreement or disagreement with 25 additional statements.

The 130 respondents made up a 78% response rate. The institutions represented by the nurses included 44% elementary schools, 9% middle schools, 16% high schools, and 32% other (such as those who may serve multiple schools).

The majority of respondents (72%) agreed that asthma is one of the biggest health problems students face, particularly among middle and high school students (P less than .05). Most (74%) also said an albuterol inhaler at school could reduce the likelihood of students with asthma needing to leave school early.

The largest barrier to students returning to class was parents not providing an albuterol inhaler and/or a written order for an inhaler despite a request from the nurse, according to 69% of the respondents (P less than .05). In high schools in particular, another barrier was students simply not bringing their inhaler to school even though they usually carry one (P less than .01).

Only 15% of nurses saw disease severity as a significant barrier, and 17% cited the staff not adequately recognizing a student’s symptoms.

The researchers did not note use of external funding or author disclosures.

Breast pain is one of the most common breast-related patient complaints and is found to affect at least 50% of the female population.¹ Most cases are self-limiting and are related to hormonal and normal fibrocystic changes. The median age of onset of symptoms is 36 years, with most women experiencing pain for 5 to 12 years.² Because the cause of breast pain is not always clear, its presence can produce anxiety in patients and physicians over the possibility of underlying malignancy. Although breast cancer is not associated with breast pain, many patients presenting with pain are referred for diagnostic imaging (usually with negative results). The majority of women with mastalgia and normal clinical examination findings can be reassured with education about the many benign causes of breast pain.

What are causes of breast pain without an imaging abnormality?

Hormones. Mastalgia can be focal or generalized and is mostly due to hormonal changes. Elevated estrogen can stimulate the growth of breast tissue, which is known as epithelial hyperplasia.³ Fluctuations in hormone levels can occur in perimenopausal women in their forties and can result in new symptoms of breast pain.⁴ Sometimes starting a new contraceptive medication or hormone replacement therapy can exacerbate the pain. Switching brands or medications may help. Another cause of mastalgia may be elevated prolactin levels, with hypothalamic-pituitary dysfunction.^5,6

Diet. There is evidence to link a high-fat diet with breast pain. The pain has been shown to improve when lipid intake is reduced and high- and low-density lipoprotein cholesterol levels are normalized. As estrogen is a steroid hormone that can be synthesized from lipids and fatty acids, elevated lipid metabolism can increase estrogen levels and exacerbate breast pain symptoms.^7,8 Essential fatty acids, such as evening primrose oil and vitamin E, have been used to treat mastalgia because they reduce inflammation in fatty breast tissue through the prostaglandin pathway.^9,10

Caffeine. Methylxanthines can be found in coffee, tea, and chocolate and can aggravate mastalgia by enhancing the cyclin adenosine monophosphate (cAMP) pathway. This pathway stimulates cellular proliferation and fibrocystic changes which in turn can exacerbate breast pain.¹¹

Smoking. In my clinical practice I have clearly noted a higher incidence of breast pain in patients who smoke. The pain tends to improve significantly when the patient quits or even cuts back on smoking. The exact reasons for smoking’s effects on breast pain are not well known; however, they are thought to be related to acceleration of the cAMP pathway.

Large breast size. Very large breasts will strain and weaken the suspensory ligaments, leading to pain and discomfort. It has been shown that wearing a supportive sports bra during episodes of breast pain is effective.

Types of breast pain

Cyclical

Women with fibrocystic breasts tend to experience more breast pain. Breast sensitivity can be localized to the upper outer quadrants or to the nipple and sub-areolar area. It also can be generalized. The pain tends to peak with ovulation, improve with menses, and to recur every few weeks. Patients who have had partial hysterectomy (with ovaries in situ) or endometrial ablation will be unable to correlate their symptoms to menstruation. Therefore, women are encouraged to keep a diary or calendar of their symptoms to detect any correlation with their ovarian cycle. Such correlation is reassuring.

Continue to: Noncyclical...

Noncyclical

Noncyclical breast pain is not associated with the menstrual cycle and can be unilateral or bilateral. Providers should perform a good history of patients presenting with noncyclicalbreast pain, to include character, onset, duration, location, radiation, alleviating, and aggravating factors. A physical examination may elicit point tenderness at the chest by pushing the breast tissue off of the chest wall while the patient is in supine position and pressing directly over the ribs. Lack of tenderness on palpation of the breast parenchyma, but pain on the chest wall, points to a musculoskeletal etiology. Chest wall pain may be related to muscle spasm or muscle strain, trauma, rib fracture, or costochondritis (Tietze syndrome). Finally, based on history of review of systems and physical examination, referred pain from biliary or cardiac etiology should be considered.

When breast pain occurs with skin changes

Skin changes usually have an underlying pathology. Infectious processes, such as infected epidermal inclusion cyst, hidradenitis of the cleavage and inframammary crease, or breast abscess will present with pain and induration with an acute onset of 5 to 10 days. Large pendulous breasts may develop yeast infection at the inframammary crease. Chronic infectious irritation can lead to hyperpigmentation of that area. Eczema or contact dermatitis frequently can affect the areola and become confused with Paget disease (ductal carcinoma in situ of the nipple). With Paget, the excoriation always starts at the nipple and can then spread to the areola. However, with dermatitis, the rash begins on the peri-areolar skin, without affecting the nipple itself.

When breast pain occurs with nipple discharge

Breast pain with nipple discharge usually is bilateral and more common in patients with significant fibrocystic changes who smoke. If the nipple discharge is bilateral, serous and non-bloody, and multiduct, it is considered benign and physiologic. Physiologic nipple discharge can be multifactorial and hormonal. It may be related to thyroid disorders or medications such as antidepressants, selective serotonin reuptake inhibitors (SSRIs), mood stabilizers, or antipsychotics. The only nipple discharge that is considered pathologic is unilateral spontaneous bloody discharge for which diagnostic imaging and breast surgeon referral is indicated. Women should be discouraged from self-expressing their nipples, as 80% will experience serous nipple discharge upon manual self-expression.

Management of mastalgia

Appropriate breast pain management begins with a good history and physical examination. The decision to perform imaging should depend on clinical exam findings and not on symptoms of breast pain. If there is a palpable mass, then breast imaging and possible biopsy is appropriate. However, if clinical exam is normal, there is no indication for breast imaging in low-risk women under the age of 40 whose only symptom is breast pain. Women older than age 40 can undergo diagnostic imaging, if they have not had a negative screening mammogram in the past year.

Breast pain with abnormal clinical exam

In the patient who is younger than age 30 with a palpable mass. For this patient order targeted breast ultrasound (US) (FIGURE 1). If results are negative, repeat the clinical examination 1 week after menses. If the mass is persistent, refer the patient to a breast surgeon. If diagnostic imaging results are negative, consider breast MRI, especially if there is a strong family history of breast cancer.

In the patient who is aged 30 and older with a palpable mass. For this patient, bilateral diagnostic mammogram and US are in order. The testing is best performed 1 week after menses to reduce false-positive findings. If imaging is negative and the patient still has a clinically suspicious finding or mass, refer her to a breast surgeon and consider breast MRI. At this point if there is a persistent firm dominant mass, a biopsy is indicated as part of the triple test. If the mass resolves with menses, the patient can be reassured that the cause is most likely benign, with clinical examination repeated in 3 months.

Continue to: Breast pain and normal clinical exam...

Breast pain and normal clinical exam

When women who report breast pain have normal clinical examination findings (and have a negative screening mammogram in the past 12 months if older than age 40), there are several management strategies you can offer (FIGURE 2).

Reassurance and education. The majority of women with breast pain can be managed with reassurance and education, which are often sufficient to reduce their anxieties.

Supportive bra. The most effective intervention is to wear and sleep in a well-fitted supportive sports bra for 4 to 12 weeks. In a nonrandomized single-center trial of danazol versus sports bra, 85% of women reported relief of their breast pain with bra alone (vs 58% with danazol).¹² A supportive bra is the first-line management of mastalgia (Level II evidence).

Symptom diary/calendar. Many women do not know whether or not their symptoms correspond to their ovarian cycle or are related to hormonal fluctuations. Therefore, it is reassuring and informative for them to keep a calendar or a diary of their symptoms to determine whether their symptoms occur or are exacerbated in a cyclical pattern.

Diet and lifestyle modification. Women should avoid caffeine (especially when having pain). Studies on methylxanthines have demonstrated some symptom relief with reducing caffeine intake.^11,13 One cup of coffee or tea per day most likely will not make a difference. However, if a woman is drinking large quantities of caffeinated beverages throughout the day, it will very likely improve her breast pain if she cuts back. This is especially true during the times of exacerbated pain prior to her menses.

In addition, recommend reduced dietary fat (overall good health). This is good advice for any patient. There were 2 small studies that showed improvement in breast pain with a 15% reduction in dietary fat.^7,8

Finally, advise that patients stop smoking. Smoking aggravates and exacerbates fibrocystic changes, and these will lead to more breast pain.

Medical management. Over-the-counter medications that are found in the vitamin section of a local drug store are vitamin E and evening primrose oil. There are no significant adverse effects with these treatments. Their efficacy is theoretical, however; 3 randomized controlled trials demonstrated no significant clinical benefit with evening primrose oil versus placebo for treatment of mastalgia.¹⁴

Topical or oral nonsteroidal anti-inflammatory drugs (NSAIDs; Voltaren gel, topical compound pain creams) are useful as second-line management after using a supportive bra. Three randomized controlled trials have demonstrated up to 90% improvement of mastalgia with topical NSAIDs.^15-17

Tamoxifen is a selective estrogen-receptor modulator (SERM), which is an antagonist to the estrogen receptor (ER) in the breast and an agonist to the ER in the endometrium. Tamoxifen has been found to reduce symptoms of mastalgia by 70% even at a lower dosage of 10-mg per day (for 6 months), or as a topical gel (afimoxifene). The oral form can have some adverse effects, including hot flashes, and has a low risk for thromboembolic events and endometrial neoplasia.^18-20

Danazol is very effective in reducing breast pain symptoms (by 80%), with a higher relapse after stopping the medication. Danazol is less tolerated due to its androgenic effects, such as hirsutism, acne, menorrhagia, and voice changes. Both danazol and tamoxifen can be teratogenic and should be used with caution in women of child-bearing age.²¹

Finally, bromocriptine inhibits serum prolactin and has been reported to provide 65% improvement in breast pain. Its use for breast pain is not US Food and Drug Administration–approved and adverse effects include nausea, dizziness, and hypotension.²²

Tamoxifen, danazol, and bromocriptine can be considered as third-line management options for severe treatment-resistant mastalgia.

Continue to: FIGURE 2 Treatment algorithm for breast pain...

In summary

Evaluation and counseling for breast pain should be managed by women’s health care providers in a primary care setting. Most patients need reassurance and medical explanation of their symptoms. They should be educated that more than 95% of the time breast pain is not caused by an underlying malignancy but rather due to hormonal and fibrocystic changes, which can be managed conservatively. If the clinical breast examination and recent screening mammogram (in women over age 40) results are negative, patients should be educated that their pain is benign and undergo a trial of conservative measures: wear and sleep in a supporting bra; keep a calendar of symptoms to determine any relation to cyclical changes; and avoid nicotine, caffeine, and fatty food. Topical pain creams with diclofenac and evening primrose oil also can be effective in ameliorating the symptoms. Breast pain is not a surgical disease; referral to a surgical specialist and diagnostic imaging can be unnecessary and expensive.

Breast pain is one of the most common breast-related patient complaints and is found to affect at least 50% of the female population.¹ Most cases are self-limiting and are related to hormonal and normal fibrocystic changes. The median age of onset of symptoms is 36 years, with most women experiencing pain for 5 to 12 years.² Because the cause of breast pain is not always clear, its presence can produce anxiety in patients and physicians over the possibility of underlying malignancy. Although breast cancer is not associated with breast pain, many patients presenting with pain are referred for diagnostic imaging (usually with negative results). The majority of women with mastalgia and normal clinical examination findings can be reassured with education about the many benign causes of breast pain.

What are causes of breast pain without an imaging abnormality?

Hormones. Mastalgia can be focal or generalized and is mostly due to hormonal changes. Elevated estrogen can stimulate the growth of breast tissue, which is known as epithelial hyperplasia.³ Fluctuations in hormone levels can occur in perimenopausal women in their forties and can result in new symptoms of breast pain.⁴ Sometimes starting a new contraceptive medication or hormone replacement therapy can exacerbate the pain. Switching brands or medications may help. Another cause of mastalgia may be elevated prolactin levels, with hypothalamic-pituitary dysfunction.^5,6

Diet. There is evidence to link a high-fat diet with breast pain. The pain has been shown to improve when lipid intake is reduced and high- and low-density lipoprotein cholesterol levels are normalized. As estrogen is a steroid hormone that can be synthesized from lipids and fatty acids, elevated lipid metabolism can increase estrogen levels and exacerbate breast pain symptoms.^7,8 Essential fatty acids, such as evening primrose oil and vitamin E, have been used to treat mastalgia because they reduce inflammation in fatty breast tissue through the prostaglandin pathway.^9,10

Caffeine. Methylxanthines can be found in coffee, tea, and chocolate and can aggravate mastalgia by enhancing the cyclin adenosine monophosphate (cAMP) pathway. This pathway stimulates cellular proliferation and fibrocystic changes which in turn can exacerbate breast pain.¹¹

Smoking. In my clinical practice I have clearly noted a higher incidence of breast pain in patients who smoke. The pain tends to improve significantly when the patient quits or even cuts back on smoking. The exact reasons for smoking’s effects on breast pain are not well known; however, they are thought to be related to acceleration of the cAMP pathway.

Large breast size. Very large breasts will strain and weaken the suspensory ligaments, leading to pain and discomfort. It has been shown that wearing a supportive sports bra during episodes of breast pain is effective.

Types of breast pain

Cyclical

Women with fibrocystic breasts tend to experience more breast pain. Breast sensitivity can be localized to the upper outer quadrants or to the nipple and sub-areolar area. It also can be generalized. The pain tends to peak with ovulation, improve with menses, and to recur every few weeks. Patients who have had partial hysterectomy (with ovaries in situ) or endometrial ablation will be unable to correlate their symptoms to menstruation. Therefore, women are encouraged to keep a diary or calendar of their symptoms to detect any correlation with their ovarian cycle. Such correlation is reassuring.

Continue to: Noncyclical...

Noncyclical

Noncyclical breast pain is not associated with the menstrual cycle and can be unilateral or bilateral. Providers should perform a good history of patients presenting with noncyclicalbreast pain, to include character, onset, duration, location, radiation, alleviating, and aggravating factors. A physical examination may elicit point tenderness at the chest by pushing the breast tissue off of the chest wall while the patient is in supine position and pressing directly over the ribs. Lack of tenderness on palpation of the breast parenchyma, but pain on the chest wall, points to a musculoskeletal etiology. Chest wall pain may be related to muscle spasm or muscle strain, trauma, rib fracture, or costochondritis (Tietze syndrome). Finally, based on history of review of systems and physical examination, referred pain from biliary or cardiac etiology should be considered.

When breast pain occurs with skin changes

Skin changes usually have an underlying pathology. Infectious processes, such as infected epidermal inclusion cyst, hidradenitis of the cleavage and inframammary crease, or breast abscess will present with pain and induration with an acute onset of 5 to 10 days. Large pendulous breasts may develop yeast infection at the inframammary crease. Chronic infectious irritation can lead to hyperpigmentation of that area. Eczema or contact dermatitis frequently can affect the areola and become confused with Paget disease (ductal carcinoma in situ of the nipple). With Paget, the excoriation always starts at the nipple and can then spread to the areola. However, with dermatitis, the rash begins on the peri-areolar skin, without affecting the nipple itself.

When breast pain occurs with nipple discharge

Breast pain with nipple discharge usually is bilateral and more common in patients with significant fibrocystic changes who smoke. If the nipple discharge is bilateral, serous and non-bloody, and multiduct, it is considered benign and physiologic. Physiologic nipple discharge can be multifactorial and hormonal. It may be related to thyroid disorders or medications such as antidepressants, selective serotonin reuptake inhibitors (SSRIs), mood stabilizers, or antipsychotics. The only nipple discharge that is considered pathologic is unilateral spontaneous bloody discharge for which diagnostic imaging and breast surgeon referral is indicated. Women should be discouraged from self-expressing their nipples, as 80% will experience serous nipple discharge upon manual self-expression.

Management of mastalgia

Appropriate breast pain management begins with a good history and physical examination. The decision to perform imaging should depend on clinical exam findings and not on symptoms of breast pain. If there is a palpable mass, then breast imaging and possible biopsy is appropriate. However, if clinical exam is normal, there is no indication for breast imaging in low-risk women under the age of 40 whose only symptom is breast pain. Women older than age 40 can undergo diagnostic imaging, if they have not had a negative screening mammogram in the past year.

Breast pain with abnormal clinical exam

In the patient who is younger than age 30 with a palpable mass. For this patient order targeted breast ultrasound (US) (FIGURE 1). If results are negative, repeat the clinical examination 1 week after menses. If the mass is persistent, refer the patient to a breast surgeon. If diagnostic imaging results are negative, consider breast MRI, especially if there is a strong family history of breast cancer.

In the patient who is aged 30 and older with a palpable mass. For this patient, bilateral diagnostic mammogram and US are in order. The testing is best performed 1 week after menses to reduce false-positive findings. If imaging is negative and the patient still has a clinically suspicious finding or mass, refer her to a breast surgeon and consider breast MRI. At this point if there is a persistent firm dominant mass, a biopsy is indicated as part of the triple test. If the mass resolves with menses, the patient can be reassured that the cause is most likely benign, with clinical examination repeated in 3 months.

Continue to: Breast pain and normal clinical exam...

Breast pain and normal clinical exam

When women who report breast pain have normal clinical examination findings (and have a negative screening mammogram in the past 12 months if older than age 40), there are several management strategies you can offer (FIGURE 2).

Reassurance and education. The majority of women with breast pain can be managed with reassurance and education, which are often sufficient to reduce their anxieties.

Supportive bra. The most effective intervention is to wear and sleep in a well-fitted supportive sports bra for 4 to 12 weeks. In a nonrandomized single-center trial of danazol versus sports bra, 85% of women reported relief of their breast pain with bra alone (vs 58% with danazol).¹² A supportive bra is the first-line management of mastalgia (Level II evidence).

Symptom diary/calendar. Many women do not know whether or not their symptoms correspond to their ovarian cycle or are related to hormonal fluctuations. Therefore, it is reassuring and informative for them to keep a calendar or a diary of their symptoms to determine whether their symptoms occur or are exacerbated in a cyclical pattern.

Diet and lifestyle modification. Women should avoid caffeine (especially when having pain). Studies on methylxanthines have demonstrated some symptom relief with reducing caffeine intake.^11,13 One cup of coffee or tea per day most likely will not make a difference. However, if a woman is drinking large quantities of caffeinated beverages throughout the day, it will very likely improve her breast pain if she cuts back. This is especially true during the times of exacerbated pain prior to her menses.

In addition, recommend reduced dietary fat (overall good health). This is good advice for any patient. There were 2 small studies that showed improvement in breast pain with a 15% reduction in dietary fat.^7,8

Finally, advise that patients stop smoking. Smoking aggravates and exacerbates fibrocystic changes, and these will lead to more breast pain.

Medical management. Over-the-counter medications that are found in the vitamin section of a local drug store are vitamin E and evening primrose oil. There are no significant adverse effects with these treatments. Their efficacy is theoretical, however; 3 randomized controlled trials demonstrated no significant clinical benefit with evening primrose oil versus placebo for treatment of mastalgia.¹⁴

Topical or oral nonsteroidal anti-inflammatory drugs (NSAIDs; Voltaren gel, topical compound pain creams) are useful as second-line management after using a supportive bra. Three randomized controlled trials have demonstrated up to 90% improvement of mastalgia with topical NSAIDs.^15-17

Tamoxifen is a selective estrogen-receptor modulator (SERM), which is an antagonist to the estrogen receptor (ER) in the breast and an agonist to the ER in the endometrium. Tamoxifen has been found to reduce symptoms of mastalgia by 70% even at a lower dosage of 10-mg per day (for 6 months), or as a topical gel (afimoxifene). The oral form can have some adverse effects, including hot flashes, and has a low risk for thromboembolic events and endometrial neoplasia.^18-20

Danazol is very effective in reducing breast pain symptoms (by 80%), with a higher relapse after stopping the medication. Danazol is less tolerated due to its androgenic effects, such as hirsutism, acne, menorrhagia, and voice changes. Both danazol and tamoxifen can be teratogenic and should be used with caution in women of child-bearing age.²¹

Finally, bromocriptine inhibits serum prolactin and has been reported to provide 65% improvement in breast pain. Its use for breast pain is not US Food and Drug Administration–approved and adverse effects include nausea, dizziness, and hypotension.²²

Tamoxifen, danazol, and bromocriptine can be considered as third-line management options for severe treatment-resistant mastalgia.

Continue to: FIGURE 2 Treatment algorithm for breast pain...

In summary

Evaluation and counseling for breast pain should be managed by women’s health care providers in a primary care setting. Most patients need reassurance and medical explanation of their symptoms. They should be educated that more than 95% of the time breast pain is not caused by an underlying malignancy but rather due to hormonal and fibrocystic changes, which can be managed conservatively. If the clinical breast examination and recent screening mammogram (in women over age 40) results are negative, patients should be educated that their pain is benign and undergo a trial of conservative measures: wear and sleep in a supporting bra; keep a calendar of symptoms to determine any relation to cyclical changes; and avoid nicotine, caffeine, and fatty food. Topical pain creams with diclofenac and evening primrose oil also can be effective in ameliorating the symptoms. Breast pain is not a surgical disease; referral to a surgical specialist and diagnostic imaging can be unnecessary and expensive.

Breast pain is one of the most common breast-related patient complaints and is found to affect at least 50% of the female population.¹ Most cases are self-limiting and are related to hormonal and normal fibrocystic changes. The median age of onset of symptoms is 36 years, with most women experiencing pain for 5 to 12 years.² Because the cause of breast pain is not always clear, its presence can produce anxiety in patients and physicians over the possibility of underlying malignancy. Although breast cancer is not associated with breast pain, many patients presenting with pain are referred for diagnostic imaging (usually with negative results). The majority of women with mastalgia and normal clinical examination findings can be reassured with education about the many benign causes of breast pain.

What are causes of breast pain without an imaging abnormality?

Hormones. Mastalgia can be focal or generalized and is mostly due to hormonal changes. Elevated estrogen can stimulate the growth of breast tissue, which is known as epithelial hyperplasia.³ Fluctuations in hormone levels can occur in perimenopausal women in their forties and can result in new symptoms of breast pain.⁴ Sometimes starting a new contraceptive medication or hormone replacement therapy can exacerbate the pain. Switching brands or medications may help. Another cause of mastalgia may be elevated prolactin levels, with hypothalamic-pituitary dysfunction.^5,6

Diet. There is evidence to link a high-fat diet with breast pain. The pain has been shown to improve when lipid intake is reduced and high- and low-density lipoprotein cholesterol levels are normalized. As estrogen is a steroid hormone that can be synthesized from lipids and fatty acids, elevated lipid metabolism can increase estrogen levels and exacerbate breast pain symptoms.^7,8 Essential fatty acids, such as evening primrose oil and vitamin E, have been used to treat mastalgia because they reduce inflammation in fatty breast tissue through the prostaglandin pathway.^9,10

Caffeine. Methylxanthines can be found in coffee, tea, and chocolate and can aggravate mastalgia by enhancing the cyclin adenosine monophosphate (cAMP) pathway. This pathway stimulates cellular proliferation and fibrocystic changes which in turn can exacerbate breast pain.¹¹

Smoking. In my clinical practice I have clearly noted a higher incidence of breast pain in patients who smoke. The pain tends to improve significantly when the patient quits or even cuts back on smoking. The exact reasons for smoking’s effects on breast pain are not well known; however, they are thought to be related to acceleration of the cAMP pathway.

Large breast size. Very large breasts will strain and weaken the suspensory ligaments, leading to pain and discomfort. It has been shown that wearing a supportive sports bra during episodes of breast pain is effective.

Types of breast pain

Cyclical

Women with fibrocystic breasts tend to experience more breast pain. Breast sensitivity can be localized to the upper outer quadrants or to the nipple and sub-areolar area. It also can be generalized. The pain tends to peak with ovulation, improve with menses, and to recur every few weeks. Patients who have had partial hysterectomy (with ovaries in situ) or endometrial ablation will be unable to correlate their symptoms to menstruation. Therefore, women are encouraged to keep a diary or calendar of their symptoms to detect any correlation with their ovarian cycle. Such correlation is reassuring.

Continue to: Noncyclical...

Noncyclical

Noncyclical breast pain is not associated with the menstrual cycle and can be unilateral or bilateral. Providers should perform a good history of patients presenting with noncyclicalbreast pain, to include character, onset, duration, location, radiation, alleviating, and aggravating factors. A physical examination may elicit point tenderness at the chest by pushing the breast tissue off of the chest wall while the patient is in supine position and pressing directly over the ribs. Lack of tenderness on palpation of the breast parenchyma, but pain on the chest wall, points to a musculoskeletal etiology. Chest wall pain may be related to muscle spasm or muscle strain, trauma, rib fracture, or costochondritis (Tietze syndrome). Finally, based on history of review of systems and physical examination, referred pain from biliary or cardiac etiology should be considered.

When breast pain occurs with skin changes

Skin changes usually have an underlying pathology. Infectious processes, such as infected epidermal inclusion cyst, hidradenitis of the cleavage and inframammary crease, or breast abscess will present with pain and induration with an acute onset of 5 to 10 days. Large pendulous breasts may develop yeast infection at the inframammary crease. Chronic infectious irritation can lead to hyperpigmentation of that area. Eczema or contact dermatitis frequently can affect the areola and become confused with Paget disease (ductal carcinoma in situ of the nipple). With Paget, the excoriation always starts at the nipple and can then spread to the areola. However, with dermatitis, the rash begins on the peri-areolar skin, without affecting the nipple itself.

When breast pain occurs with nipple discharge

Breast pain with nipple discharge usually is bilateral and more common in patients with significant fibrocystic changes who smoke. If the nipple discharge is bilateral, serous and non-bloody, and multiduct, it is considered benign and physiologic. Physiologic nipple discharge can be multifactorial and hormonal. It may be related to thyroid disorders or medications such as antidepressants, selective serotonin reuptake inhibitors (SSRIs), mood stabilizers, or antipsychotics. The only nipple discharge that is considered pathologic is unilateral spontaneous bloody discharge for which diagnostic imaging and breast surgeon referral is indicated. Women should be discouraged from self-expressing their nipples, as 80% will experience serous nipple discharge upon manual self-expression.

Management of mastalgia

Appropriate breast pain management begins with a good history and physical examination. The decision to perform imaging should depend on clinical exam findings and not on symptoms of breast pain. If there is a palpable mass, then breast imaging and possible biopsy is appropriate. However, if clinical exam is normal, there is no indication for breast imaging in low-risk women under the age of 40 whose only symptom is breast pain. Women older than age 40 can undergo diagnostic imaging, if they have not had a negative screening mammogram in the past year.

Breast pain with abnormal clinical exam

In the patient who is younger than age 30 with a palpable mass. For this patient order targeted breast ultrasound (US) (FIGURE 1). If results are negative, repeat the clinical examination 1 week after menses. If the mass is persistent, refer the patient to a breast surgeon. If diagnostic imaging results are negative, consider breast MRI, especially if there is a strong family history of breast cancer.

In the patient who is aged 30 and older with a palpable mass. For this patient, bilateral diagnostic mammogram and US are in order. The testing is best performed 1 week after menses to reduce false-positive findings. If imaging is negative and the patient still has a clinically suspicious finding or mass, refer her to a breast surgeon and consider breast MRI. At this point if there is a persistent firm dominant mass, a biopsy is indicated as part of the triple test. If the mass resolves with menses, the patient can be reassured that the cause is most likely benign, with clinical examination repeated in 3 months.

Continue to: Breast pain and normal clinical exam...

Breast pain and normal clinical exam

When women who report breast pain have normal clinical examination findings (and have a negative screening mammogram in the past 12 months if older than age 40), there are several management strategies you can offer (FIGURE 2).

Reassurance and education. The majority of women with breast pain can be managed with reassurance and education, which are often sufficient to reduce their anxieties.

Supportive bra. The most effective intervention is to wear and sleep in a well-fitted supportive sports bra for 4 to 12 weeks. In a nonrandomized single-center trial of danazol versus sports bra, 85% of women reported relief of their breast pain with bra alone (vs 58% with danazol).¹² A supportive bra is the first-line management of mastalgia (Level II evidence).

Symptom diary/calendar. Many women do not know whether or not their symptoms correspond to their ovarian cycle or are related to hormonal fluctuations. Therefore, it is reassuring and informative for them to keep a calendar or a diary of their symptoms to determine whether their symptoms occur or are exacerbated in a cyclical pattern.

Diet and lifestyle modification. Women should avoid caffeine (especially when having pain). Studies on methylxanthines have demonstrated some symptom relief with reducing caffeine intake.^11,13 One cup of coffee or tea per day most likely will not make a difference. However, if a woman is drinking large quantities of caffeinated beverages throughout the day, it will very likely improve her breast pain if she cuts back. This is especially true during the times of exacerbated pain prior to her menses.

In addition, recommend reduced dietary fat (overall good health). This is good advice for any patient. There were 2 small studies that showed improvement in breast pain with a 15% reduction in dietary fat.^7,8

Finally, advise that patients stop smoking. Smoking aggravates and exacerbates fibrocystic changes, and these will lead to more breast pain.

Medical management. Over-the-counter medications that are found in the vitamin section of a local drug store are vitamin E and evening primrose oil. There are no significant adverse effects with these treatments. Their efficacy is theoretical, however; 3 randomized controlled trials demonstrated no significant clinical benefit with evening primrose oil versus placebo for treatment of mastalgia.¹⁴

Topical or oral nonsteroidal anti-inflammatory drugs (NSAIDs; Voltaren gel, topical compound pain creams) are useful as second-line management after using a supportive bra. Three randomized controlled trials have demonstrated up to 90% improvement of mastalgia with topical NSAIDs.^15-17

Tamoxifen is a selective estrogen-receptor modulator (SERM), which is an antagonist to the estrogen receptor (ER) in the breast and an agonist to the ER in the endometrium. Tamoxifen has been found to reduce symptoms of mastalgia by 70% even at a lower dosage of 10-mg per day (for 6 months), or as a topical gel (afimoxifene). The oral form can have some adverse effects, including hot flashes, and has a low risk for thromboembolic events and endometrial neoplasia.^18-20

Danazol is very effective in reducing breast pain symptoms (by 80%), with a higher relapse after stopping the medication. Danazol is less tolerated due to its androgenic effects, such as hirsutism, acne, menorrhagia, and voice changes. Both danazol and tamoxifen can be teratogenic and should be used with caution in women of child-bearing age.²¹

Finally, bromocriptine inhibits serum prolactin and has been reported to provide 65% improvement in breast pain. Its use for breast pain is not US Food and Drug Administration–approved and adverse effects include nausea, dizziness, and hypotension.²²

Tamoxifen, danazol, and bromocriptine can be considered as third-line management options for severe treatment-resistant mastalgia.

Continue to: FIGURE 2 Treatment algorithm for breast pain...

In summary

Evaluation and counseling for breast pain should be managed by women’s health care providers in a primary care setting. Most patients need reassurance and medical explanation of their symptoms. They should be educated that more than 95% of the time breast pain is not caused by an underlying malignancy but rather due to hormonal and fibrocystic changes, which can be managed conservatively. If the clinical breast examination and recent screening mammogram (in women over age 40) results are negative, patients should be educated that their pain is benign and undergo a trial of conservative measures: wear and sleep in a supporting bra; keep a calendar of symptoms to determine any relation to cyclical changes; and avoid nicotine, caffeine, and fatty food. Topical pain creams with diclofenac and evening primrose oil also can be effective in ameliorating the symptoms. Breast pain is not a surgical disease; referral to a surgical specialist and diagnostic imaging can be unnecessary and expensive.

This article is part of a series that illustrates strategies intended to redesign primary care education at the Veterans Health Administration (VHA), using interprofessional workplace learning. All have been implemented in the VA Centers of Excellence in Primary Care Education (CoEPCE). These models embody visionary transformation of clinical and educational environments that have potential for replication and dissemination throughout VA and other primary care clinical educational environments. For an introduction to the series see Klink K. Transforming primary care clinical learning environments to optimize education, outcomes, and satisfaction. Fed Pract. 2018;35(9):8-10.

Background

In 2011, 5 US Department of Veterans Affairs (VA) medical centers were selected by the VA Office of Academic Affiliations (OAA) to establish Centers of Excellence in Primary Care Education (CoEPCE). Part of the New Models of Care initiative, the 5 CoEPCEs use VA primary care settings to develop and test innovative approaches to prepare physician residents, medical students, advanced practice registered nurses, undergraduate nursing students, and other health professions’ trainees, such as social workers, pharmacists, psychologists, and physician assistants, for improved primary care practice. The CoEPCEs are interprofessional Academic PACTs (iAPACTs) with ≥ 2 professions of trainees engaged in learning on the PACT team.

The VA Puget Sound Seattle CoEPCE curriculum is embedded in a well-established academic VA primary care training site.¹ Trainees include doctor of nursing practice (DNP) students in adult, family, and psychiatric mental health nurse practitioner (NP) programs; NP residents; internal medicine physician residents; postgraduate pharmacy residents; and other health professions’ trainees. A Seattle CoEPCE priority is to provide DNP students, DNP residents, and physician residents with a longitudinal experience in team-based care as well as interprofessional education and collaborative practice (IPECP). Learners spend the majority of CoEPCE time in supervised, direct patient care, including primary care, women’s health, deployment health, homeless care, and home care. Formal IPECP activities comprise about 20% of time, supported by 3 educational strategies: (1) Panel management (PM)/quality improvement (QI); (2) Team building/ communications; and (3) Clinical content seminars to expand trainee clinical knowledge and skills and curriculum developed with the CoEPCE enterprise core domains in mind (Table).

Panel Management

Clinicians are increasingly being required to proactively optimize the health of an assigned population of patients in addition to assessing and managing the health of individual patients presenting for care. To address the objectives of increased accountability for population health outcomes and improved face-to-face care, Seattle CoEPCE developed curriculum for trainees to learn PM, a set of tools and processes that can be applied in the primary care setting.

PM clinical providers use data to proactively provide care to their patients between traditional clinic visits. The process is proactive in that gaps are identified whether or not an in-person visit occurs and involves an outreach mechanism to increase continuity of care, such as follow-up communications with the patients.² PM also has been associated with improvements in chronic disease care.^3-5

The Seattle CoEPCE developed an interprofessional team approach to PM that teaches trainees about the tools and resources used to close the gaps in care, including the use of clinical team members as health care systems subject matter experts. CoEPCE trainees are taught to analyze the care they provide to their panel of veterans (eg, identifying patients who have not refilled chronic medications or those who use the emergency department [ED] for nonacute conditions) and take action to improve care. PM yields rich discussions on systems resources and processes and is easily applied to a range of health conditions as well as delivery system issues. PM gives learners the tools they can use to close these gaps, such as the expertise of their peers, clinical team, and specialists.⁶

Planning and Implementation

In addition to completing a literature review to determine the state of PM practice and models, CoEPCE faculty polled recent graduates inquiring about strategies they did not learn prior to graduation. Based on their responses, CoEPCE faculty identified 2 skill deficits: management of chronic diseases and proficiency with data and statistics about performance improvement in panel patient care over time. Addressing these unmet needs became the impetus for developing curriculum for conducting PM. Planning and launching the CoEPCE approach to PM took about 3 months and involved CoEPCE faculty, a data manager, and administrative support. The learning objectives of Seattle’s PM initiative are to:

• Promote preventive health and chronic disease care by use performance data;
• Develop individual- and populationfocused action plans;
• Work collaboratively, strategically, and effectively with an interprofessional care team; and
• Learn how to effectively use system resources.

Curriculum

The PM curriculum is a longitudinal, experiential approach to learning how to manage chronic diseases between visits by using patient data. It is designed for trainees in a continuity clinic to review the care of their patients on a regular basis. Seattle CoEPCE medicine residents are assigned patient panels, which increase from 70 patients in the first year to about 140 patients by the end of the third year. DNP postgraduate trainees are assigned an initial panel of 50 patients that increases incrementally over the year-long residency.

CoEPCE faculty determined the focus of PM sessions to be diabetes mellitus (DM), hypertension, obesity, chronic opioid therapy, and low-acuity ED use. Because PM sessions are designed to allow participants to identify systems issues that may affect multiple patients, some of these topics have expanded into QI projects. PM sessions run 2 to 3 hours per session and are held 4 to 6 times a year. Each session is repeated twice to accommodate diverse trainee schedules. PM participants must have their patient visit time blocked for each session (Appendix).

Faculty Roles and Development

PM faculty involved in any individual session may include a combination of a CoEPCE clinical pharmacy specialist, a registered nurse (RN) care manager, a social worker, a NP, a physician, a clinical psychologist, and a medicine outpatient chief resident (PGY4, termed clinician-teacher fellow at Seattle VA medical center). The chief resident is a medicine residency graduate and takes on teaching responsibilities depending on the topic of the session. The CoEPCE clinical pharmacist role varies depending on the session topic: They may facilitate the session or provide recommendations for medication management for individual cases. The RN care manager often knows the patients and brings a unique perspective that complements that of the primary care providers and ideally participates in every session. The patients of multiple RN care managers may be presented at each session, and it was not feasible to include all RN care managers in every session. After case discussions, trainees often communicated with the RN care managers about the case, using instant messaging, and CoEPCE provides other avenues for patient care discussion through huddles involving the provider, RN care manager, clinical pharmacist, and other clinical professions.

Resources

The primary resource required to support PM is an information technology (IT) system that provides relevant health outcome and health care utilization data on patients assigned to trainees. PM sessions include teaching trainees how to access patient data. Since discussion about the care of panel patients during the learning sessions often results in real-time adjustments in the care plan, modest administrative support required post-PM sessions, such as clerical scheduling of the requested clinic or telephone follow-up with the physician, nurse, or pharmacist.

Monitoring and Assessment

Panel performance is evaluated at each educational session. To assess the CoEPCE PM curriculum, participants provide feedback in 8 questions over 3 domains: trainee perception of curriculum content, confidence in performing PM involving completion of a PM workshop, and likelihood of using PM techniques in the future. CoEPCE faculty use the feedback to improve their instruction of panel management skill and develop new sessions that target additional population groups. Evaluation of the curriculum also includes monitoring of panel patients’ chronic disease measures.

Several partnerships have contributed to the success and integrations of PM into facility activities. First, having the primary care clinic director as a member of the Co- EPCE faculty has encouraged faculty and staff to operationalize and implement PM broadly by distributing data monthly to all clinic staff. Second, high facility staff interest outside the CoEPCE and primary care clinic has facilitated establishing communications outside the CoEPCE regarding clinic data.

Challenges and Solutions

Trainees at earlier academic levels often desire more instruction in clinical knowledge, such as treatment options for DM or goals of therapy in hypertension. In contrast, advanced trainees are able to review patient data, brainstorm, and optimize solutions. Seattle CoEPCE balances these different learning needs via a flexible approach to the 3-hour sessions. For example, advanced trainees progress from structured short lectures to informal sessions, which train them to perform PM on their own. In addition, the flexible design integrates trainees with diverse schedules, particularly among DNP students and residents, pharmacy residents, and physician residents. Some of this work falls on the RN care management team and administrative support staff.

Competing Priorities

The demand for direct patient care points to the importance of indirect patient care activities like PM to demonstrate improved results. Managing chronic conditions and matching appropriate services and resources should improve clinical outcomes and efficiency longterm. In the interim, it is important to note that PM demonstrates the continuous aspect of clinical care, particularly for trainees who have strict guidelines defining clinical care for the experiences to count toward eligibility for licensure. Additionally, PM results in trainees who are making decisions with VA patients and are more efficiently providing and supporting patient care. Therefore, it is critical to secure important resources, such as provider time for conducting PM.

Data Access

No single data system in VA covers the broad range of topics covered in the PM sessions, and not all trainees have their own assigned panels. For example, health professions students are not assigned a panel of patients. While they do not have access to panel data such as those generated by Primary Care Almanac in VSSC (a data source in the VA Support Service Center database),the Seattle CoEPCE data manager pulls a set of patient data from the students’ paired faculty preceptors’ panels for review. Thus they learn PM principles and strategies for improving patient care via PM as part of the unique VA longitudinal clinic experience and the opportunity to learn from a multidisciplinary team that is not available at other clinical sites. Postgraduate NP residents in CoEPCE training have their own panels of patients and thus the ability to directly access their panel performance data.

Success Factors

A key success factor includes CoEPCE faculty’s ability to develop and operationalize a panel management model that simultaneously aligns with the educational goals of an interprofessional education training program and supports VA adoption of the medical home or patient aligned care teams (PACT). The CoEPCE contributes staff expertise in accessing and reporting patient data, accessing appropriate teaching space, managing panels of patients with chronic diseases, and facilitating a team-based approach to care. Additionally, the CoEPCE brand is helpful for getting buy-in from the clinical and academic stakeholders necessary for moving PM forward.

Colocating CoEPCE trainees and faculty in the primary care clinic promotes team identity around the RN care managers and facilitated communications with non-CoEPCE clinical teams that have trainees from other professions. RN care managers serve as the locus of highquality PM since they share patient panels with the trainees and already track admissions, ED visits, and numerous chronic health care metrics. RN care managers offer a level of insight into chronic disease that other providers may not possess, such as the specific details on medication adherence and the impact of adverse effects (AEs) for that particular patient. RN care managers are able to teach about their team role and responsibilities, strengthening the model.

PM is an opportunity to expand CoEPCE interprofessional education capacity by creating colocation of different trainee and faculty professions during the PM sessions; the sharing of data with trainees; and sharing and reflecting on data, strengthening communications between professions and within the PACT. The Seattle CoEPCE now has systems in place that allow the RN care manager to send notes to a physician and DNP resident, and the resident is expected to respond. In addition, the PM approach provides experience with analyzing data to improve care in an interprofessional team setting, which is a requirement of the Accreditation Council for Graduate Medical Education.

Interprofessional Collaboration

PM sessions are intentionally designed to improve communication among team members and foster a team approach to care. PM sessions provide an opportunity for trainees and clinician faculty to be together and learn about each profession’s perspectives. For example, early in the process physician and DNP trainees learn about the importance of clinical pharmacists to the team who prescribe and make medication adjustments within their scope of practice as well as the importance of making appropriate pharmacy referrals. Additionally, the RN care manager and clinical pharmacy specialists who serve as faculty in the CoEPCE provide pertinent information on individual patients, increasing integration with the PACT. Finally, there is anecdotal evidence that faculty also are learning more about interprofessional education and expanding their own skills.

Clinical Performance

CoEPCE trainees, non-CoEPCE physician residents, and CoEPCE faculty participants regularly receive patient data with which they can proactively develop or amend a treatment plan between visits. PM has resulted in improved data sharing with providers. Instead of once a year, providers and clinic staff now receive patient data monthly on chronic conditions from the clinic director. Trainees on ambulatory rotations are expected to review their panel data at least a half day per week. CoEPCE staff evaluate trainee likelihood to use PM and ability to identify patients who benefit from team-based care.

At the population level of chronic disease management, preliminary evidence demonstrates that primary care clinic patient panels are increasingly within target for DM and blood pressure measures, as assessed by periodic clinical reports to providers. Some of the PM topics have resulted in systems-level improvements, such as reducing unnecessary ED use for nonacute conditions and better opioid prescription monitoring. Moreover, PM supports everyone working at the top of his/her professional capability. For example, the RN care manager has the impetus to initiate DM education with a particular patient.

Since CoEPCE began teaching PM, the Seattle primary care clinic has committed to the regular access and review of data. This has encouraged the alignment of standards of care for chronic disease management so that all care providers are working toward the same benchmark goals.

Patient Outcomes

At the individual level, PM provide a mechanism to systemically review trainee panel patients with out-of-target clinical measures, and develop new care approaches involving interprofessional strategies and problem solving. PM also helps identify patients who have missed follow-up, reducing the risk that patients with chronic care needs will be lost to clinical engagement if they are not reminded or do not pursue appointments. The PM-trained PACT reaches out to patients who might not otherwise get care before the next clinic visit and provides new care plans. Second, patients have the benefit of a team that manages their health needs. For example, including the clinical pharmacists in the PM sessions ensures timely identification of medication interactions and the potential AEs. Additionally, PM contributes to the care coordination model by involving individuals on the primary care team who know the patient. These members review the patient’s data between visits and initiate team-based changes to the care plan to improve care. More team members connect with a patient, resulting in more intense care and quicker follow-up to determine the effectiveness of a treatment plan.

PM topics have spun off QI projects resulting in new clinic processes and programs, including processes for managing wounds in primary care and to assure timely post-ED visit follow-ups. Areas for expansion include a follow-up QI project to reduce nonacute ED visits by patients on the homeless PACT panel and interventions for better management of care for women veterans with mental health needs. PM also has extended to non-Co- EPCE teams and to other clinic activities, such as strengthening huddles of team members specifically related to panel data and addressing selected patient cases between visits. Pharmacy residents and faculty are more involved in reviewing the panel before patients are seen to review medication lists and identify duplications.

The Future

Under stage 2 of the program, the Seattle CoEPCE intends to lead in the creation of a PM toolkit as well as a data access guide that will allow VA facilities with limited data management expertise to access chronic disease metrics. Second, the CoEPCE will continue its dissemination efforts locally to other residents in the internal medicine residency program in all of its continuity clinics. Additionally, there is high interest by DNP training programs to expand and export longitudinal training experience PM curriculum to non-VA based students.

This article is part of a series that illustrates strategies intended to redesign primary care education at the Veterans Health Administration (VHA), using interprofessional workplace learning. All have been implemented in the VA Centers of Excellence in Primary Care Education (CoEPCE). These models embody visionary transformation of clinical and educational environments that have potential for replication and dissemination throughout VA and other primary care clinical educational environments. For an introduction to the series see Klink K. Transforming primary care clinical learning environments to optimize education, outcomes, and satisfaction. Fed Pract. 2018;35(9):8-10.

Background

In 2011, 5 US Department of Veterans Affairs (VA) medical centers were selected by the VA Office of Academic Affiliations (OAA) to establish Centers of Excellence in Primary Care Education (CoEPCE). Part of the New Models of Care initiative, the 5 CoEPCEs use VA primary care settings to develop and test innovative approaches to prepare physician residents, medical students, advanced practice registered nurses, undergraduate nursing students, and other health professions’ trainees, such as social workers, pharmacists, psychologists, and physician assistants, for improved primary care practice. The CoEPCEs are interprofessional Academic PACTs (iAPACTs) with ≥ 2 professions of trainees engaged in learning on the PACT team.

The VA Puget Sound Seattle CoEPCE curriculum is embedded in a well-established academic VA primary care training site.¹ Trainees include doctor of nursing practice (DNP) students in adult, family, and psychiatric mental health nurse practitioner (NP) programs; NP residents; internal medicine physician residents; postgraduate pharmacy residents; and other health professions’ trainees. A Seattle CoEPCE priority is to provide DNP students, DNP residents, and physician residents with a longitudinal experience in team-based care as well as interprofessional education and collaborative practice (IPECP). Learners spend the majority of CoEPCE time in supervised, direct patient care, including primary care, women’s health, deployment health, homeless care, and home care. Formal IPECP activities comprise about 20% of time, supported by 3 educational strategies: (1) Panel management (PM)/quality improvement (QI); (2) Team building/ communications; and (3) Clinical content seminars to expand trainee clinical knowledge and skills and curriculum developed with the CoEPCE enterprise core domains in mind (Table).

Panel Management

Clinicians are increasingly being required to proactively optimize the health of an assigned population of patients in addition to assessing and managing the health of individual patients presenting for care. To address the objectives of increased accountability for population health outcomes and improved face-to-face care, Seattle CoEPCE developed curriculum for trainees to learn PM, a set of tools and processes that can be applied in the primary care setting.

PM clinical providers use data to proactively provide care to their patients between traditional clinic visits. The process is proactive in that gaps are identified whether or not an in-person visit occurs and involves an outreach mechanism to increase continuity of care, such as follow-up communications with the patients.² PM also has been associated with improvements in chronic disease care.^3-5

The Seattle CoEPCE developed an interprofessional team approach to PM that teaches trainees about the tools and resources used to close the gaps in care, including the use of clinical team members as health care systems subject matter experts. CoEPCE trainees are taught to analyze the care they provide to their panel of veterans (eg, identifying patients who have not refilled chronic medications or those who use the emergency department [ED] for nonacute conditions) and take action to improve care. PM yields rich discussions on systems resources and processes and is easily applied to a range of health conditions as well as delivery system issues. PM gives learners the tools they can use to close these gaps, such as the expertise of their peers, clinical team, and specialists.⁶

Planning and Implementation

In addition to completing a literature review to determine the state of PM practice and models, CoEPCE faculty polled recent graduates inquiring about strategies they did not learn prior to graduation. Based on their responses, CoEPCE faculty identified 2 skill deficits: management of chronic diseases and proficiency with data and statistics about performance improvement in panel patient care over time. Addressing these unmet needs became the impetus for developing curriculum for conducting PM. Planning and launching the CoEPCE approach to PM took about 3 months and involved CoEPCE faculty, a data manager, and administrative support. The learning objectives of Seattle’s PM initiative are to:

• Promote preventive health and chronic disease care by use performance data;
• Develop individual- and populationfocused action plans;
• Work collaboratively, strategically, and effectively with an interprofessional care team; and
• Learn how to effectively use system resources.

Curriculum

The PM curriculum is a longitudinal, experiential approach to learning how to manage chronic diseases between visits by using patient data. It is designed for trainees in a continuity clinic to review the care of their patients on a regular basis. Seattle CoEPCE medicine residents are assigned patient panels, which increase from 70 patients in the first year to about 140 patients by the end of the third year. DNP postgraduate trainees are assigned an initial panel of 50 patients that increases incrementally over the year-long residency.

CoEPCE faculty determined the focus of PM sessions to be diabetes mellitus (DM), hypertension, obesity, chronic opioid therapy, and low-acuity ED use. Because PM sessions are designed to allow participants to identify systems issues that may affect multiple patients, some of these topics have expanded into QI projects. PM sessions run 2 to 3 hours per session and are held 4 to 6 times a year. Each session is repeated twice to accommodate diverse trainee schedules. PM participants must have their patient visit time blocked for each session (Appendix).

Faculty Roles and Development

PM faculty involved in any individual session may include a combination of a CoEPCE clinical pharmacy specialist, a registered nurse (RN) care manager, a social worker, a NP, a physician, a clinical psychologist, and a medicine outpatient chief resident (PGY4, termed clinician-teacher fellow at Seattle VA medical center). The chief resident is a medicine residency graduate and takes on teaching responsibilities depending on the topic of the session. The CoEPCE clinical pharmacist role varies depending on the session topic: They may facilitate the session or provide recommendations for medication management for individual cases. The RN care manager often knows the patients and brings a unique perspective that complements that of the primary care providers and ideally participates in every session. The patients of multiple RN care managers may be presented at each session, and it was not feasible to include all RN care managers in every session. After case discussions, trainees often communicated with the RN care managers about the case, using instant messaging, and CoEPCE provides other avenues for patient care discussion through huddles involving the provider, RN care manager, clinical pharmacist, and other clinical professions.

Resources

The primary resource required to support PM is an information technology (IT) system that provides relevant health outcome and health care utilization data on patients assigned to trainees. PM sessions include teaching trainees how to access patient data. Since discussion about the care of panel patients during the learning sessions often results in real-time adjustments in the care plan, modest administrative support required post-PM sessions, such as clerical scheduling of the requested clinic or telephone follow-up with the physician, nurse, or pharmacist.

Monitoring and Assessment

Panel performance is evaluated at each educational session. To assess the CoEPCE PM curriculum, participants provide feedback in 8 questions over 3 domains: trainee perception of curriculum content, confidence in performing PM involving completion of a PM workshop, and likelihood of using PM techniques in the future. CoEPCE faculty use the feedback to improve their instruction of panel management skill and develop new sessions that target additional population groups. Evaluation of the curriculum also includes monitoring of panel patients’ chronic disease measures.

Several partnerships have contributed to the success and integrations of PM into facility activities. First, having the primary care clinic director as a member of the Co- EPCE faculty has encouraged faculty and staff to operationalize and implement PM broadly by distributing data monthly to all clinic staff. Second, high facility staff interest outside the CoEPCE and primary care clinic has facilitated establishing communications outside the CoEPCE regarding clinic data.

Challenges and Solutions

Trainees at earlier academic levels often desire more instruction in clinical knowledge, such as treatment options for DM or goals of therapy in hypertension. In contrast, advanced trainees are able to review patient data, brainstorm, and optimize solutions. Seattle CoEPCE balances these different learning needs via a flexible approach to the 3-hour sessions. For example, advanced trainees progress from structured short lectures to informal sessions, which train them to perform PM on their own. In addition, the flexible design integrates trainees with diverse schedules, particularly among DNP students and residents, pharmacy residents, and physician residents. Some of this work falls on the RN care management team and administrative support staff.

Competing Priorities

The demand for direct patient care points to the importance of indirect patient care activities like PM to demonstrate improved results. Managing chronic conditions and matching appropriate services and resources should improve clinical outcomes and efficiency longterm. In the interim, it is important to note that PM demonstrates the continuous aspect of clinical care, particularly for trainees who have strict guidelines defining clinical care for the experiences to count toward eligibility for licensure. Additionally, PM results in trainees who are making decisions with VA patients and are more efficiently providing and supporting patient care. Therefore, it is critical to secure important resources, such as provider time for conducting PM.

Data Access

No single data system in VA covers the broad range of topics covered in the PM sessions, and not all trainees have their own assigned panels. For example, health professions students are not assigned a panel of patients. While they do not have access to panel data such as those generated by Primary Care Almanac in VSSC (a data source in the VA Support Service Center database),the Seattle CoEPCE data manager pulls a set of patient data from the students’ paired faculty preceptors’ panels for review. Thus they learn PM principles and strategies for improving patient care via PM as part of the unique VA longitudinal clinic experience and the opportunity to learn from a multidisciplinary team that is not available at other clinical sites. Postgraduate NP residents in CoEPCE training have their own panels of patients and thus the ability to directly access their panel performance data.

Success Factors

A key success factor includes CoEPCE faculty’s ability to develop and operationalize a panel management model that simultaneously aligns with the educational goals of an interprofessional education training program and supports VA adoption of the medical home or patient aligned care teams (PACT). The CoEPCE contributes staff expertise in accessing and reporting patient data, accessing appropriate teaching space, managing panels of patients with chronic diseases, and facilitating a team-based approach to care. Additionally, the CoEPCE brand is helpful for getting buy-in from the clinical and academic stakeholders necessary for moving PM forward.

Colocating CoEPCE trainees and faculty in the primary care clinic promotes team identity around the RN care managers and facilitated communications with non-CoEPCE clinical teams that have trainees from other professions. RN care managers serve as the locus of highquality PM since they share patient panels with the trainees and already track admissions, ED visits, and numerous chronic health care metrics. RN care managers offer a level of insight into chronic disease that other providers may not possess, such as the specific details on medication adherence and the impact of adverse effects (AEs) for that particular patient. RN care managers are able to teach about their team role and responsibilities, strengthening the model.

PM is an opportunity to expand CoEPCE interprofessional education capacity by creating colocation of different trainee and faculty professions during the PM sessions; the sharing of data with trainees; and sharing and reflecting on data, strengthening communications between professions and within the PACT. The Seattle CoEPCE now has systems in place that allow the RN care manager to send notes to a physician and DNP resident, and the resident is expected to respond. In addition, the PM approach provides experience with analyzing data to improve care in an interprofessional team setting, which is a requirement of the Accreditation Council for Graduate Medical Education.

Interprofessional Collaboration

PM sessions are intentionally designed to improve communication among team members and foster a team approach to care. PM sessions provide an opportunity for trainees and clinician faculty to be together and learn about each profession’s perspectives. For example, early in the process physician and DNP trainees learn about the importance of clinical pharmacists to the team who prescribe and make medication adjustments within their scope of practice as well as the importance of making appropriate pharmacy referrals. Additionally, the RN care manager and clinical pharmacy specialists who serve as faculty in the CoEPCE provide pertinent information on individual patients, increasing integration with the PACT. Finally, there is anecdotal evidence that faculty also are learning more about interprofessional education and expanding their own skills.

Clinical Performance

CoEPCE trainees, non-CoEPCE physician residents, and CoEPCE faculty participants regularly receive patient data with which they can proactively develop or amend a treatment plan between visits. PM has resulted in improved data sharing with providers. Instead of once a year, providers and clinic staff now receive patient data monthly on chronic conditions from the clinic director. Trainees on ambulatory rotations are expected to review their panel data at least a half day per week. CoEPCE staff evaluate trainee likelihood to use PM and ability to identify patients who benefit from team-based care.

At the population level of chronic disease management, preliminary evidence demonstrates that primary care clinic patient panels are increasingly within target for DM and blood pressure measures, as assessed by periodic clinical reports to providers. Some of the PM topics have resulted in systems-level improvements, such as reducing unnecessary ED use for nonacute conditions and better opioid prescription monitoring. Moreover, PM supports everyone working at the top of his/her professional capability. For example, the RN care manager has the impetus to initiate DM education with a particular patient.

Since CoEPCE began teaching PM, the Seattle primary care clinic has committed to the regular access and review of data. This has encouraged the alignment of standards of care for chronic disease management so that all care providers are working toward the same benchmark goals.

Patient Outcomes

At the individual level, PM provide a mechanism to systemically review trainee panel patients with out-of-target clinical measures, and develop new care approaches involving interprofessional strategies and problem solving. PM also helps identify patients who have missed follow-up, reducing the risk that patients with chronic care needs will be lost to clinical engagement if they are not reminded or do not pursue appointments. The PM-trained PACT reaches out to patients who might not otherwise get care before the next clinic visit and provides new care plans. Second, patients have the benefit of a team that manages their health needs. For example, including the clinical pharmacists in the PM sessions ensures timely identification of medication interactions and the potential AEs. Additionally, PM contributes to the care coordination model by involving individuals on the primary care team who know the patient. These members review the patient’s data between visits and initiate team-based changes to the care plan to improve care. More team members connect with a patient, resulting in more intense care and quicker follow-up to determine the effectiveness of a treatment plan.

PM topics have spun off QI projects resulting in new clinic processes and programs, including processes for managing wounds in primary care and to assure timely post-ED visit follow-ups. Areas for expansion include a follow-up QI project to reduce nonacute ED visits by patients on the homeless PACT panel and interventions for better management of care for women veterans with mental health needs. PM also has extended to non-Co- EPCE teams and to other clinic activities, such as strengthening huddles of team members specifically related to panel data and addressing selected patient cases between visits. Pharmacy residents and faculty are more involved in reviewing the panel before patients are seen to review medication lists and identify duplications.

The Future

Under stage 2 of the program, the Seattle CoEPCE intends to lead in the creation of a PM toolkit as well as a data access guide that will allow VA facilities with limited data management expertise to access chronic disease metrics. Second, the CoEPCE will continue its dissemination efforts locally to other residents in the internal medicine residency program in all of its continuity clinics. Additionally, there is high interest by DNP training programs to expand and export longitudinal training experience PM curriculum to non-VA based students.

This article is part of a series that illustrates strategies intended to redesign primary care education at the Veterans Health Administration (VHA), using interprofessional workplace learning. All have been implemented in the VA Centers of Excellence in Primary Care Education (CoEPCE). These models embody visionary transformation of clinical and educational environments that have potential for replication and dissemination throughout VA and other primary care clinical educational environments. For an introduction to the series see Klink K. Transforming primary care clinical learning environments to optimize education, outcomes, and satisfaction. Fed Pract. 2018;35(9):8-10.

Background

In 2011, 5 US Department of Veterans Affairs (VA) medical centers were selected by the VA Office of Academic Affiliations (OAA) to establish Centers of Excellence in Primary Care Education (CoEPCE). Part of the New Models of Care initiative, the 5 CoEPCEs use VA primary care settings to develop and test innovative approaches to prepare physician residents, medical students, advanced practice registered nurses, undergraduate nursing students, and other health professions’ trainees, such as social workers, pharmacists, psychologists, and physician assistants, for improved primary care practice. The CoEPCEs are interprofessional Academic PACTs (iAPACTs) with ≥ 2 professions of trainees engaged in learning on the PACT team.

The VA Puget Sound Seattle CoEPCE curriculum is embedded in a well-established academic VA primary care training site.¹ Trainees include doctor of nursing practice (DNP) students in adult, family, and psychiatric mental health nurse practitioner (NP) programs; NP residents; internal medicine physician residents; postgraduate pharmacy residents; and other health professions’ trainees. A Seattle CoEPCE priority is to provide DNP students, DNP residents, and physician residents with a longitudinal experience in team-based care as well as interprofessional education and collaborative practice (IPECP). Learners spend the majority of CoEPCE time in supervised, direct patient care, including primary care, women’s health, deployment health, homeless care, and home care. Formal IPECP activities comprise about 20% of time, supported by 3 educational strategies: (1) Panel management (PM)/quality improvement (QI); (2) Team building/ communications; and (3) Clinical content seminars to expand trainee clinical knowledge and skills and curriculum developed with the CoEPCE enterprise core domains in mind (Table).

Panel Management

Clinicians are increasingly being required to proactively optimize the health of an assigned population of patients in addition to assessing and managing the health of individual patients presenting for care. To address the objectives of increased accountability for population health outcomes and improved face-to-face care, Seattle CoEPCE developed curriculum for trainees to learn PM, a set of tools and processes that can be applied in the primary care setting.

PM clinical providers use data to proactively provide care to their patients between traditional clinic visits. The process is proactive in that gaps are identified whether or not an in-person visit occurs and involves an outreach mechanism to increase continuity of care, such as follow-up communications with the patients.² PM also has been associated with improvements in chronic disease care.^3-5

The Seattle CoEPCE developed an interprofessional team approach to PM that teaches trainees about the tools and resources used to close the gaps in care, including the use of clinical team members as health care systems subject matter experts. CoEPCE trainees are taught to analyze the care they provide to their panel of veterans (eg, identifying patients who have not refilled chronic medications or those who use the emergency department [ED] for nonacute conditions) and take action to improve care. PM yields rich discussions on systems resources and processes and is easily applied to a range of health conditions as well as delivery system issues. PM gives learners the tools they can use to close these gaps, such as the expertise of their peers, clinical team, and specialists.⁶

Planning and Implementation

In addition to completing a literature review to determine the state of PM practice and models, CoEPCE faculty polled recent graduates inquiring about strategies they did not learn prior to graduation. Based on their responses, CoEPCE faculty identified 2 skill deficits: management of chronic diseases and proficiency with data and statistics about performance improvement in panel patient care over time. Addressing these unmet needs became the impetus for developing curriculum for conducting PM. Planning and launching the CoEPCE approach to PM took about 3 months and involved CoEPCE faculty, a data manager, and administrative support. The learning objectives of Seattle’s PM initiative are to:

• Promote preventive health and chronic disease care by use performance data;
• Develop individual- and populationfocused action plans;
• Work collaboratively, strategically, and effectively with an interprofessional care team; and
• Learn how to effectively use system resources.

Curriculum

The PM curriculum is a longitudinal, experiential approach to learning how to manage chronic diseases between visits by using patient data. It is designed for trainees in a continuity clinic to review the care of their patients on a regular basis. Seattle CoEPCE medicine residents are assigned patient panels, which increase from 70 patients in the first year to about 140 patients by the end of the third year. DNP postgraduate trainees are assigned an initial panel of 50 patients that increases incrementally over the year-long residency.

CoEPCE faculty determined the focus of PM sessions to be diabetes mellitus (DM), hypertension, obesity, chronic opioid therapy, and low-acuity ED use. Because PM sessions are designed to allow participants to identify systems issues that may affect multiple patients, some of these topics have expanded into QI projects. PM sessions run 2 to 3 hours per session and are held 4 to 6 times a year. Each session is repeated twice to accommodate diverse trainee schedules. PM participants must have their patient visit time blocked for each session (Appendix).

Faculty Roles and Development

PM faculty involved in any individual session may include a combination of a CoEPCE clinical pharmacy specialist, a registered nurse (RN) care manager, a social worker, a NP, a physician, a clinical psychologist, and a medicine outpatient chief resident (PGY4, termed clinician-teacher fellow at Seattle VA medical center). The chief resident is a medicine residency graduate and takes on teaching responsibilities depending on the topic of the session. The CoEPCE clinical pharmacist role varies depending on the session topic: They may facilitate the session or provide recommendations for medication management for individual cases. The RN care manager often knows the patients and brings a unique perspective that complements that of the primary care providers and ideally participates in every session. The patients of multiple RN care managers may be presented at each session, and it was not feasible to include all RN care managers in every session. After case discussions, trainees often communicated with the RN care managers about the case, using instant messaging, and CoEPCE provides other avenues for patient care discussion through huddles involving the provider, RN care manager, clinical pharmacist, and other clinical professions.

Resources

The primary resource required to support PM is an information technology (IT) system that provides relevant health outcome and health care utilization data on patients assigned to trainees. PM sessions include teaching trainees how to access patient data. Since discussion about the care of panel patients during the learning sessions often results in real-time adjustments in the care plan, modest administrative support required post-PM sessions, such as clerical scheduling of the requested clinic or telephone follow-up with the physician, nurse, or pharmacist.

Monitoring and Assessment

Panel performance is evaluated at each educational session. To assess the CoEPCE PM curriculum, participants provide feedback in 8 questions over 3 domains: trainee perception of curriculum content, confidence in performing PM involving completion of a PM workshop, and likelihood of using PM techniques in the future. CoEPCE faculty use the feedback to improve their instruction of panel management skill and develop new sessions that target additional population groups. Evaluation of the curriculum also includes monitoring of panel patients’ chronic disease measures.

Several partnerships have contributed to the success and integrations of PM into facility activities. First, having the primary care clinic director as a member of the Co- EPCE faculty has encouraged faculty and staff to operationalize and implement PM broadly by distributing data monthly to all clinic staff. Second, high facility staff interest outside the CoEPCE and primary care clinic has facilitated establishing communications outside the CoEPCE regarding clinic data.

Challenges and Solutions

Trainees at earlier academic levels often desire more instruction in clinical knowledge, such as treatment options for DM or goals of therapy in hypertension. In contrast, advanced trainees are able to review patient data, brainstorm, and optimize solutions. Seattle CoEPCE balances these different learning needs via a flexible approach to the 3-hour sessions. For example, advanced trainees progress from structured short lectures to informal sessions, which train them to perform PM on their own. In addition, the flexible design integrates trainees with diverse schedules, particularly among DNP students and residents, pharmacy residents, and physician residents. Some of this work falls on the RN care management team and administrative support staff.

Competing Priorities

The demand for direct patient care points to the importance of indirect patient care activities like PM to demonstrate improved results. Managing chronic conditions and matching appropriate services and resources should improve clinical outcomes and efficiency longterm. In the interim, it is important to note that PM demonstrates the continuous aspect of clinical care, particularly for trainees who have strict guidelines defining clinical care for the experiences to count toward eligibility for licensure. Additionally, PM results in trainees who are making decisions with VA patients and are more efficiently providing and supporting patient care. Therefore, it is critical to secure important resources, such as provider time for conducting PM.

Data Access

No single data system in VA covers the broad range of topics covered in the PM sessions, and not all trainees have their own assigned panels. For example, health professions students are not assigned a panel of patients. While they do not have access to panel data such as those generated by Primary Care Almanac in VSSC (a data source in the VA Support Service Center database),the Seattle CoEPCE data manager pulls a set of patient data from the students’ paired faculty preceptors’ panels for review. Thus they learn PM principles and strategies for improving patient care via PM as part of the unique VA longitudinal clinic experience and the opportunity to learn from a multidisciplinary team that is not available at other clinical sites. Postgraduate NP residents in CoEPCE training have their own panels of patients and thus the ability to directly access their panel performance data.

Success Factors

A key success factor includes CoEPCE faculty’s ability to develop and operationalize a panel management model that simultaneously aligns with the educational goals of an interprofessional education training program and supports VA adoption of the medical home or patient aligned care teams (PACT). The CoEPCE contributes staff expertise in accessing and reporting patient data, accessing appropriate teaching space, managing panels of patients with chronic diseases, and facilitating a team-based approach to care. Additionally, the CoEPCE brand is helpful for getting buy-in from the clinical and academic stakeholders necessary for moving PM forward.

Colocating CoEPCE trainees and faculty in the primary care clinic promotes team identity around the RN care managers and facilitated communications with non-CoEPCE clinical teams that have trainees from other professions. RN care managers serve as the locus of highquality PM since they share patient panels with the trainees and already track admissions, ED visits, and numerous chronic health care metrics. RN care managers offer a level of insight into chronic disease that other providers may not possess, such as the specific details on medication adherence and the impact of adverse effects (AEs) for that particular patient. RN care managers are able to teach about their team role and responsibilities, strengthening the model.

PM is an opportunity to expand CoEPCE interprofessional education capacity by creating colocation of different trainee and faculty professions during the PM sessions; the sharing of data with trainees; and sharing and reflecting on data, strengthening communications between professions and within the PACT. The Seattle CoEPCE now has systems in place that allow the RN care manager to send notes to a physician and DNP resident, and the resident is expected to respond. In addition, the PM approach provides experience with analyzing data to improve care in an interprofessional team setting, which is a requirement of the Accreditation Council for Graduate Medical Education.

Interprofessional Collaboration

PM sessions are intentionally designed to improve communication among team members and foster a team approach to care. PM sessions provide an opportunity for trainees and clinician faculty to be together and learn about each profession’s perspectives. For example, early in the process physician and DNP trainees learn about the importance of clinical pharmacists to the team who prescribe and make medication adjustments within their scope of practice as well as the importance of making appropriate pharmacy referrals. Additionally, the RN care manager and clinical pharmacy specialists who serve as faculty in the CoEPCE provide pertinent information on individual patients, increasing integration with the PACT. Finally, there is anecdotal evidence that faculty also are learning more about interprofessional education and expanding their own skills.

Clinical Performance

CoEPCE trainees, non-CoEPCE physician residents, and CoEPCE faculty participants regularly receive patient data with which they can proactively develop or amend a treatment plan between visits. PM has resulted in improved data sharing with providers. Instead of once a year, providers and clinic staff now receive patient data monthly on chronic conditions from the clinic director. Trainees on ambulatory rotations are expected to review their panel data at least a half day per week. CoEPCE staff evaluate trainee likelihood to use PM and ability to identify patients who benefit from team-based care.

At the population level of chronic disease management, preliminary evidence demonstrates that primary care clinic patient panels are increasingly within target for DM and blood pressure measures, as assessed by periodic clinical reports to providers. Some of the PM topics have resulted in systems-level improvements, such as reducing unnecessary ED use for nonacute conditions and better opioid prescription monitoring. Moreover, PM supports everyone working at the top of his/her professional capability. For example, the RN care manager has the impetus to initiate DM education with a particular patient.

Since CoEPCE began teaching PM, the Seattle primary care clinic has committed to the regular access and review of data. This has encouraged the alignment of standards of care for chronic disease management so that all care providers are working toward the same benchmark goals.

Patient Outcomes

At the individual level, PM provide a mechanism to systemically review trainee panel patients with out-of-target clinical measures, and develop new care approaches involving interprofessional strategies and problem solving. PM also helps identify patients who have missed follow-up, reducing the risk that patients with chronic care needs will be lost to clinical engagement if they are not reminded or do not pursue appointments. The PM-trained PACT reaches out to patients who might not otherwise get care before the next clinic visit and provides new care plans. Second, patients have the benefit of a team that manages their health needs. For example, including the clinical pharmacists in the PM sessions ensures timely identification of medication interactions and the potential AEs. Additionally, PM contributes to the care coordination model by involving individuals on the primary care team who know the patient. These members review the patient’s data between visits and initiate team-based changes to the care plan to improve care. More team members connect with a patient, resulting in more intense care and quicker follow-up to determine the effectiveness of a treatment plan.

PM topics have spun off QI projects resulting in new clinic processes and programs, including processes for managing wounds in primary care and to assure timely post-ED visit follow-ups. Areas for expansion include a follow-up QI project to reduce nonacute ED visits by patients on the homeless PACT panel and interventions for better management of care for women veterans with mental health needs. PM also has extended to non-Co- EPCE teams and to other clinic activities, such as strengthening huddles of team members specifically related to panel data and addressing selected patient cases between visits. Pharmacy residents and faculty are more involved in reviewing the panel before patients are seen to review medication lists and identify duplications.

The Future

Under stage 2 of the program, the Seattle CoEPCE intends to lead in the creation of a PM toolkit as well as a data access guide that will allow VA facilities with limited data management expertise to access chronic disease metrics. Second, the CoEPCE will continue its dissemination efforts locally to other residents in the internal medicine residency program in all of its continuity clinics. Additionally, there is high interest by DNP training programs to expand and export longitudinal training experience PM curriculum to non-VA based students.

The viscous homemade children’s plaything known as “slime” has been associated with allergic, as well as irritant, contact dermatitis of the hands thanks to an array of possible compounds with which it can be made, according to a case report in Pediatric Dermatology. The report details many possible compounds causing the dermatitis reactions seen by health care professionals.

In the case, which was reported by L. Elizabeth Anderson, MD, of the Children’s Hospital of Philadelphia and colleagues, an 11-year-old girl with a history of atopic dermatitis presented with hand dermatitis that was suspected to be related to playing with slime. After her dermatitis failed to respond to strong topical steroids, she was referred for patch testing, with positivity for methylchloroisothiazolinone/methylisothiazolinone (MCI/MI). After all contact with any products containing MCI/MI was eliminated, her hand dermatitis cleared, and bodywide atopic dermatitis improved some as well.

MCI/MI and MI are among the most commonly suspected culprits in cases of slime-related contact dermatitis. Although most cases are irritant contact dermatitis, some are allergic and can be detected using patch tests. MCI/MI is included in the T.R.U.E. Test, but according to the case report, 37% of patients with allergy to MI alone will not have positive response with the T.R.U.E. Test because of the low concentrations of MI in that test. The authors of this case report also listed many other the potential allergens in popular slime recipes; however, many are not included in the T.R.U.E. Test.

“While the T.R.U.E. Test does not capture most of the potential allergens in popular slime recipes, the recently published Pediatric Baseline Patch Test Series by Yu et al. [Dermatitis. 2018;29:206-12] does and is recommended for use in patients suspected of having dermatitis secondary to slime,” Dr. Anderson and associates wrote.

cpalmer@mdedge.com

SOURCE: Anderson LE et al. Pediatr Dermatol. 2019 Mar 13. doi: 10.1111/pde.13792.

The viscous homemade children’s plaything known as “slime” has been associated with allergic, as well as irritant, contact dermatitis of the hands thanks to an array of possible compounds with which it can be made, according to a case report in Pediatric Dermatology. The report details many possible compounds causing the dermatitis reactions seen by health care professionals.

In the case, which was reported by L. Elizabeth Anderson, MD, of the Children’s Hospital of Philadelphia and colleagues, an 11-year-old girl with a history of atopic dermatitis presented with hand dermatitis that was suspected to be related to playing with slime. After her dermatitis failed to respond to strong topical steroids, she was referred for patch testing, with positivity for methylchloroisothiazolinone/methylisothiazolinone (MCI/MI). After all contact with any products containing MCI/MI was eliminated, her hand dermatitis cleared, and bodywide atopic dermatitis improved some as well.

MCI/MI and MI are among the most commonly suspected culprits in cases of slime-related contact dermatitis. Although most cases are irritant contact dermatitis, some are allergic and can be detected using patch tests. MCI/MI is included in the T.R.U.E. Test, but according to the case report, 37% of patients with allergy to MI alone will not have positive response with the T.R.U.E. Test because of the low concentrations of MI in that test. The authors of this case report also listed many other the potential allergens in popular slime recipes; however, many are not included in the T.R.U.E. Test.

“While the T.R.U.E. Test does not capture most of the potential allergens in popular slime recipes, the recently published Pediatric Baseline Patch Test Series by Yu et al. [Dermatitis. 2018;29:206-12] does and is recommended for use in patients suspected of having dermatitis secondary to slime,” Dr. Anderson and associates wrote.

cpalmer@mdedge.com

SOURCE: Anderson LE et al. Pediatr Dermatol. 2019 Mar 13. doi: 10.1111/pde.13792.

The viscous homemade children’s plaything known as “slime” has been associated with allergic, as well as irritant, contact dermatitis of the hands thanks to an array of possible compounds with which it can be made, according to a case report in Pediatric Dermatology. The report details many possible compounds causing the dermatitis reactions seen by health care professionals.

In the case, which was reported by L. Elizabeth Anderson, MD, of the Children’s Hospital of Philadelphia and colleagues, an 11-year-old girl with a history of atopic dermatitis presented with hand dermatitis that was suspected to be related to playing with slime. After her dermatitis failed to respond to strong topical steroids, she was referred for patch testing, with positivity for methylchloroisothiazolinone/methylisothiazolinone (MCI/MI). After all contact with any products containing MCI/MI was eliminated, her hand dermatitis cleared, and bodywide atopic dermatitis improved some as well.

MCI/MI and MI are among the most commonly suspected culprits in cases of slime-related contact dermatitis. Although most cases are irritant contact dermatitis, some are allergic and can be detected using patch tests. MCI/MI is included in the T.R.U.E. Test, but according to the case report, 37% of patients with allergy to MI alone will not have positive response with the T.R.U.E. Test because of the low concentrations of MI in that test. The authors of this case report also listed many other the potential allergens in popular slime recipes; however, many are not included in the T.R.U.E. Test.

“While the T.R.U.E. Test does not capture most of the potential allergens in popular slime recipes, the recently published Pediatric Baseline Patch Test Series by Yu et al. [Dermatitis. 2018;29:206-12] does and is recommended for use in patients suspected of having dermatitis secondary to slime,” Dr. Anderson and associates wrote.

cpalmer@mdedge.com

SOURCE: Anderson LE et al. Pediatr Dermatol. 2019 Mar 13. doi: 10.1111/pde.13792.

A potent oral inhibitor of acetyl-coenzyme-A carboxylase approximately halved the production of facial sebum, most of which arises from de novo lipogenesis, researchers reported.

The production of sebum triglycerides, wax esters, and free fatty acids all depend on local flux through this de novo lipogenesis (DNL) pathway in sebocytes, explained William P. Esler, PhD, and associates. Oral treatment with the investigational agent PF-05175157, a potent inhibitor of acetyl-coenzyme-A carboxylase (ACC) 1 and 2, reduced levels of these sebum components by about 66%, but did not affect levels of compounds that do not depend on the DNL pathway. The results of their mechanistic studies “identify sebocyte DNL as a pathway of importance in the biology of human skin and in the pathogenesis of acne vulgaris,” the researchers wrote in Science Translational Medicine. “Moreover, the observed dependence of human sebum production on local DNL flux and the effectiveness of DNL inhibition by an ACC inhibitor to suppress sebum production in humans indicate that clinical evaluation of this pathway for the treatment of acne may be warranted.”

Sebum helps moisturize and protect human skin, but increased production is linked to acne vulgaris severity. While sebaceous glands contain ACC and undergo DNL, the role of this pathway in sebum production relative to the recycling of circulating lipids was unknown. For the study, Dr. Esler of Pfizer Global Research and Development in Cambridge, Mass., and associates administered heavy water to 22 healthy volunteers to measure how much stable isotope was incorporated into newly synthesized fatty acids in sebocytes. They found that most skin sebum originated from local flux through the DNL pathway, including 80% of sebum palmitate and more than 80% of sebum sapienate. Furthermore, compared with 10 individuals with acne-free skin, 9 patients with acne vulgaris had about 20% greater sebum production and DNL pathway flux.


Oral therapy for 2 weeks with the ACC inhibitor (200 mg twice daily) was well tolerated and reduced baseline sebum production by 49% when administered to 10 healthy volunteers, the investigators wrote. This effect was not observed in a small placebo comparator group. Importantly, studies of hamsters and guinea pigs failed to implicate the DNL pathway in sebum production, even though these animals have been widely used to model sebum production in humans.

The researchers recommended studying the effects of ACC inhibition in patients with acne vulgaris, the effects of topical ACC inhibition on sebum production, and whether DNL pathway inhibition reduces the number and severity of acne lesions.

Pfizer provided funding; Dr. Esler and 12 coinvestigators are Pfizer employees and stockholders. Two additional coinvestigators are former Pfizer employees while three are current or prior scientific consultants for Pfizer.

SOURCE: Esler WP et al. Sci Transl Med. 2019 May 15. doi: 10.1126/scitranslmed.aau8465.
 

A potent oral inhibitor of acetyl-coenzyme-A carboxylase approximately halved the production of facial sebum, most of which arises from de novo lipogenesis, researchers reported.

The production of sebum triglycerides, wax esters, and free fatty acids all depend on local flux through this de novo lipogenesis (DNL) pathway in sebocytes, explained William P. Esler, PhD, and associates. Oral treatment with the investigational agent PF-05175157, a potent inhibitor of acetyl-coenzyme-A carboxylase (ACC) 1 and 2, reduced levels of these sebum components by about 66%, but did not affect levels of compounds that do not depend on the DNL pathway. The results of their mechanistic studies “identify sebocyte DNL as a pathway of importance in the biology of human skin and in the pathogenesis of acne vulgaris,” the researchers wrote in Science Translational Medicine. “Moreover, the observed dependence of human sebum production on local DNL flux and the effectiveness of DNL inhibition by an ACC inhibitor to suppress sebum production in humans indicate that clinical evaluation of this pathway for the treatment of acne may be warranted.”

Sebum helps moisturize and protect human skin, but increased production is linked to acne vulgaris severity. While sebaceous glands contain ACC and undergo DNL, the role of this pathway in sebum production relative to the recycling of circulating lipids was unknown. For the study, Dr. Esler of Pfizer Global Research and Development in Cambridge, Mass., and associates administered heavy water to 22 healthy volunteers to measure how much stable isotope was incorporated into newly synthesized fatty acids in sebocytes. They found that most skin sebum originated from local flux through the DNL pathway, including 80% of sebum palmitate and more than 80% of sebum sapienate. Furthermore, compared with 10 individuals with acne-free skin, 9 patients with acne vulgaris had about 20% greater sebum production and DNL pathway flux.


Oral therapy for 2 weeks with the ACC inhibitor (200 mg twice daily) was well tolerated and reduced baseline sebum production by 49% when administered to 10 healthy volunteers, the investigators wrote. This effect was not observed in a small placebo comparator group. Importantly, studies of hamsters and guinea pigs failed to implicate the DNL pathway in sebum production, even though these animals have been widely used to model sebum production in humans.

The researchers recommended studying the effects of ACC inhibition in patients with acne vulgaris, the effects of topical ACC inhibition on sebum production, and whether DNL pathway inhibition reduces the number and severity of acne lesions.

Pfizer provided funding; Dr. Esler and 12 coinvestigators are Pfizer employees and stockholders. Two additional coinvestigators are former Pfizer employees while three are current or prior scientific consultants for Pfizer.

SOURCE: Esler WP et al. Sci Transl Med. 2019 May 15. doi: 10.1126/scitranslmed.aau8465.
 

A potent oral inhibitor of acetyl-coenzyme-A carboxylase approximately halved the production of facial sebum, most of which arises from de novo lipogenesis, researchers reported.

The production of sebum triglycerides, wax esters, and free fatty acids all depend on local flux through this de novo lipogenesis (DNL) pathway in sebocytes, explained William P. Esler, PhD, and associates. Oral treatment with the investigational agent PF-05175157, a potent inhibitor of acetyl-coenzyme-A carboxylase (ACC) 1 and 2, reduced levels of these sebum components by about 66%, but did not affect levels of compounds that do not depend on the DNL pathway. The results of their mechanistic studies “identify sebocyte DNL as a pathway of importance in the biology of human skin and in the pathogenesis of acne vulgaris,” the researchers wrote in Science Translational Medicine. “Moreover, the observed dependence of human sebum production on local DNL flux and the effectiveness of DNL inhibition by an ACC inhibitor to suppress sebum production in humans indicate that clinical evaluation of this pathway for the treatment of acne may be warranted.”

Sebum helps moisturize and protect human skin, but increased production is linked to acne vulgaris severity. While sebaceous glands contain ACC and undergo DNL, the role of this pathway in sebum production relative to the recycling of circulating lipids was unknown. For the study, Dr. Esler of Pfizer Global Research and Development in Cambridge, Mass., and associates administered heavy water to 22 healthy volunteers to measure how much stable isotope was incorporated into newly synthesized fatty acids in sebocytes. They found that most skin sebum originated from local flux through the DNL pathway, including 80% of sebum palmitate and more than 80% of sebum sapienate. Furthermore, compared with 10 individuals with acne-free skin, 9 patients with acne vulgaris had about 20% greater sebum production and DNL pathway flux.


Oral therapy for 2 weeks with the ACC inhibitor (200 mg twice daily) was well tolerated and reduced baseline sebum production by 49% when administered to 10 healthy volunteers, the investigators wrote. This effect was not observed in a small placebo comparator group. Importantly, studies of hamsters and guinea pigs failed to implicate the DNL pathway in sebum production, even though these animals have been widely used to model sebum production in humans.

The researchers recommended studying the effects of ACC inhibition in patients with acne vulgaris, the effects of topical ACC inhibition on sebum production, and whether DNL pathway inhibition reduces the number and severity of acne lesions.

Pfizer provided funding; Dr. Esler and 12 coinvestigators are Pfizer employees and stockholders. Two additional coinvestigators are former Pfizer employees while three are current or prior scientific consultants for Pfizer.

SOURCE: Esler WP et al. Sci Transl Med. 2019 May 15. doi: 10.1126/scitranslmed.aau8465.
 

LJUBLJANA, SLOVENIA – A “surprisingly low” prevalence of protective antibodies against measles is present in adolescents and adults living with HIV infection despite their prior vaccination against the resurgent disease, Raquel M. Simakawa, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

“With the present concern about the global reemergence of measles, we should consider measuring measles antibodies in people living with HIV, especially those who acquired the infection vertically, and then revaccinating those with low titers,” said Dr. Simakawa of the Federal University of São Paolo.

She presented interim findings of an ongoing study of the measles immunologic status of persons living with HIV, which for this analysis included 57 patients who acquired HIV from their mother via vertical transmission and 24 with horizontally acquired HIV. The vertical-transmission group was significantly younger, with a median age of 20 years, compared with 31 years in the horizontal group, who were diagnosed with HIV infection at an average age of 24 years. The vast majority of subjects were on combination antiretroviral therapy. No detectable HIV viral load had been present for a median of 70 months in the vertical group and 25 months in the horizontal group.

Only a mere 7% of the vertical transmission group had protective levels of measles IgG antibodies as measured by enzyme-linked immunosorbent assay, as did 29% of the horizontal group. The likely explanation for the higher rate of protection in the horizontal group, she said, is that they received their routine measles vaccination before they acquired HIV infection, and some of them didn’t lose their protective antibodies during their immune system’s fight against HIV infection.

Session chair Nico G. Hartwig, MD, of Franciscus Hospital in Rotterdam, the Netherlands, posed a question: Given the sky-high rate of measles seronegativity status among the vertically transmitted HIV-positive group – the patient population pediatricians focus on – why bother to measure their measles antibody level? Why not just give them all a measles booster?

Dr. Simakawa replied that that’s worth considering in routine clinical practice now that her study has shown that this group is more vulnerable to measles because of their poor response to immunization. But the study is ongoing, with larger numbers of patients to be enrolled. Also, in the second phase of the study, which will include a control group, measles IgG antibodies will be remeasured 1 month after administration of a new dose of measles vaccine.

She reported having no financial conflicts regarding this study, conducted free of commercial support.

bjancin@mdedge.com

LJUBLJANA, SLOVENIA – A “surprisingly low” prevalence of protective antibodies against measles is present in adolescents and adults living with HIV infection despite their prior vaccination against the resurgent disease, Raquel M. Simakawa, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

“With the present concern about the global reemergence of measles, we should consider measuring measles antibodies in people living with HIV, especially those who acquired the infection vertically, and then revaccinating those with low titers,” said Dr. Simakawa of the Federal University of São Paolo.

She presented interim findings of an ongoing study of the measles immunologic status of persons living with HIV, which for this analysis included 57 patients who acquired HIV from their mother via vertical transmission and 24 with horizontally acquired HIV. The vertical-transmission group was significantly younger, with a median age of 20 years, compared with 31 years in the horizontal group, who were diagnosed with HIV infection at an average age of 24 years. The vast majority of subjects were on combination antiretroviral therapy. No detectable HIV viral load had been present for a median of 70 months in the vertical group and 25 months in the horizontal group.

Only a mere 7% of the vertical transmission group had protective levels of measles IgG antibodies as measured by enzyme-linked immunosorbent assay, as did 29% of the horizontal group. The likely explanation for the higher rate of protection in the horizontal group, she said, is that they received their routine measles vaccination before they acquired HIV infection, and some of them didn’t lose their protective antibodies during their immune system’s fight against HIV infection.

Session chair Nico G. Hartwig, MD, of Franciscus Hospital in Rotterdam, the Netherlands, posed a question: Given the sky-high rate of measles seronegativity status among the vertically transmitted HIV-positive group – the patient population pediatricians focus on – why bother to measure their measles antibody level? Why not just give them all a measles booster?

Dr. Simakawa replied that that’s worth considering in routine clinical practice now that her study has shown that this group is more vulnerable to measles because of their poor response to immunization. But the study is ongoing, with larger numbers of patients to be enrolled. Also, in the second phase of the study, which will include a control group, measles IgG antibodies will be remeasured 1 month after administration of a new dose of measles vaccine.

She reported having no financial conflicts regarding this study, conducted free of commercial support.

bjancin@mdedge.com

LJUBLJANA, SLOVENIA – A “surprisingly low” prevalence of protective antibodies against measles is present in adolescents and adults living with HIV infection despite their prior vaccination against the resurgent disease, Raquel M. Simakawa, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

“With the present concern about the global reemergence of measles, we should consider measuring measles antibodies in people living with HIV, especially those who acquired the infection vertically, and then revaccinating those with low titers,” said Dr. Simakawa of the Federal University of São Paolo.

She presented interim findings of an ongoing study of the measles immunologic status of persons living with HIV, which for this analysis included 57 patients who acquired HIV from their mother via vertical transmission and 24 with horizontally acquired HIV. The vertical-transmission group was significantly younger, with a median age of 20 years, compared with 31 years in the horizontal group, who were diagnosed with HIV infection at an average age of 24 years. The vast majority of subjects were on combination antiretroviral therapy. No detectable HIV viral load had been present for a median of 70 months in the vertical group and 25 months in the horizontal group.

Only a mere 7% of the vertical transmission group had protective levels of measles IgG antibodies as measured by enzyme-linked immunosorbent assay, as did 29% of the horizontal group. The likely explanation for the higher rate of protection in the horizontal group, she said, is that they received their routine measles vaccination before they acquired HIV infection, and some of them didn’t lose their protective antibodies during their immune system’s fight against HIV infection.

Session chair Nico G. Hartwig, MD, of Franciscus Hospital in Rotterdam, the Netherlands, posed a question: Given the sky-high rate of measles seronegativity status among the vertically transmitted HIV-positive group – the patient population pediatricians focus on – why bother to measure their measles antibody level? Why not just give them all a measles booster?

Dr. Simakawa replied that that’s worth considering in routine clinical practice now that her study has shown that this group is more vulnerable to measles because of their poor response to immunization. But the study is ongoing, with larger numbers of patients to be enrolled. Also, in the second phase of the study, which will include a control group, measles IgG antibodies will be remeasured 1 month after administration of a new dose of measles vaccine.

She reported having no financial conflicts regarding this study, conducted free of commercial support.

bjancin@mdedge.com