THE CASE

Julia* is a 31-year-old woman, gravida 3 para 3, who presents to your office for evaluation after a recent emergency department (ED) visit. Her husband and children are with her. She is 4 months postpartum after an uncomplicated normal spontaneous vaginal delivery. She is breastfeeding her healthy baby boy and is using an intrauterine device for birth control. She went to the ED last week after “choking on a chip” while having lunch with her children. It felt like she “couldn’t breathe.” She called 911 herself. The ED evaluation was unremarkable. Her discharge diagnosis was “panic attack,” and she was sent home with a prescription for lorazepam.

Since the incident, she has been unable to eat any solid foods and has lost 7 pounds. She also reports a globus sensation, extreme fear of swallowing, insomnia, and pervasive thoughts that she could die at any moment and leave her children motherless. She has not taken the lorazepam.

She has a history of self-reported anxiety dating back to high school but no history of panic attacks. She has never been diagnosed with an anxiety disorder and has never before been prescribed anti-anxiety medication. She doesn’t have a history of postpartum depression in prior pregnancies, and a depression screening at her postpartum visit 2 months ago was negative.

● How would you proceed with this patient?

*The patient’s name has been changed to protect her identity.

During the perinatal period, women are particularly vulnerable to affective disorders, and primary care physicians are encouraged to routinely screen for and treat depression in pregnant and postpartum women.¹ However, anxiety disorders have a higher incidence than mood disorders in the general population,² and perinatal anxiety may be more widely underrecognized and undertreated than depression.³ In addition, higher depression scores early in pregnancy have been shown to predict higher anxiety later in pregnancy.⁴

As family physicians, we are well-trained to recognize and treat anxiety disorders in the general patient population; however, we may lack the awareness and tools to identify these conditions in the perinatal period. Given our frequent encounters with both mom and baby in a child’s first year of life, we are uniquely positioned to promptly recognize, diagnose, and treat postpartum anxiety and thereby improve health outcomes for families.

DEFINING PERINATAL ANXIETY

Anxiety disorders (including generalized anxiety disorder, panic, phobia, and social anxiety) are the most common mental health disorders evaluated and treated in the primary care setting, with a lifetime prevalence of close to 30%.²

Continue to: A recent report from...

A recent report from the Centers for Disease Control and Prevention (CDC) estimates that 1 in 9 women experience symptoms of postpartum depression.⁵ The prevalence of anxiety disorders during pregnancy and the early postpartum period is not as well-known, but studies suggest that perinatal anxiety is much more prevalent than depression. In one study, generalized anxiety disorder (GAD) in the pre- and postnatal periods was 15.8% and 17.1%, respectively; an incidence far exceeding that of perinatal depression (3.9% and 4.8%, for the same periods).⁶ Additional evidence suggests that even more women in the postnatal period experience clinically significant levels of anxiety but do not meet full diagnostic criteria for an anxiety disorder.⁷

Consider screening for postpartum anxiety with the GAD-7 or the Edinburgh Postnatal Depression Scale (questions 3-5).

In another study, 9.5% of women met criteria for GAD at some point during pregnancy, with highest anxiety levels in the first trimester.⁸ Women with a history of GAD, lower education, lack of social support, and personal history of child abuse have the highest risk for postpartum anxiety. Women with a history of posttraumatic stress disorder (PTSD) may be twice as likely to develop postpartum anxiety as healthy women.⁹

It has been well-documented that sleep disruption—which is very common in new mothers in the postnatal period—contributes to mood and anxiety disorders.^10,11

Clarifying a diagnosis of postpartum anxiety

The Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5)¹² specifies no diagnosis of postpartum anxiety disorder. And no standardized diagnostic criteria exist. It is likely that in some cases, postpartum anxiety represents an exacerbation of underlying GAD, and in other cases it is a situational disorder brought about by specific circumstances of the peripartum period.

The DSM-5 does, however, provide a helpful diagnostic approach. It defines a diagnosis of postpartum depression as being a variant of major depressive disorder (MDD) in which a woman must 1) meet criteria for a major depressive episode; and 2) occur during pregnancy or within 4 weeks of delivery. In practice, many clinicians extend the second requirement to include the first year postpartum.¹³ There is a “with anxious distress” specifier for major depression in the DSM-5, but the 2 disorders are otherwise unlinked.

Continue to: To apply the...

To apply the DSM-5 principles for postpartum depression to postpartum anxiety, a patient would need to 1) meet the diagnostic criteria for an anxiety disorder that 2) have their onset within a specified perinatal period. Variant presentations of anxiety in the postpartum period might include panic disorder and phobias, which could also interfere with a woman’s ability to care for her child.

The DSM-5 offers the following criteria for GAD¹²:

• excessive worry about a variety of topics
• worry that is experienced as hard to control
• worry associated with at least 3 physical or cognitive symptoms: edginess/restlessness, tiring easily, impaired concentration, irritability
• anxiety, worry, or associated symptoms that make it hard to carry out day-to-day activities and responsibilities
• symptoms that are unrelated to any other medical conditions and cannot be explained by the effect of substances including a prescription medication, alcohol, or recreational drugs
• symptoms that are not better explained by a different mental disorder.

Debilitating effects of postpartum anxiety

Many women experience some level of anxiety during pregnancy and early postpartum—anxiety that may range from normal and adaptive to debilitating.¹⁴ While the challenges of caring for a newborn are likely to bring some level of anxiety, these symptoms should be transient and not interfere with a woman’s capacity to care for her infant, herself, or her family.

Postpartum anxiety has been associated with a prior fear of giving birth, fear of death (of both mother and baby), lack of control, lack of self-confidence, and lack of confidence in the medical system.⁹ The experience of such ongoing disturbing thoughts or feelings of worry and tension that affect a woman’s ability to manage from day to day should indicate an illness state that deserves medical attention.

Consider diagnosing postpartum anxiety when DSM-5 criteria for generalized anxiety disorder are met during the first year postpartum.

Mothers with postpartum anxiety disorders report significantly less bonding with their infants than do mothers without anxiety.¹⁵ A recent narrative review describes numerous studies that illustrate the negative effects of postpartum anxiety on bonding, breastfeeding, infant temperament, early childhood development, and conduct disorders.¹⁶ Anxious women may be less likely to initiate breastfeeding, have more challenges with breastfeeding, and even have a different milk composition.¹⁷ Women with prenatal anxiety are also more likely to stop breastfeeding prematurely.¹⁸ Children of anxious mothers may be more likely to have a difficult temperament and to display more distress.¹⁹ There are small studies demonstrating deficits in early infant development and increases in conduct disorder in the male offspring of anxious women.²⁰

Continue to: SCREENING FOR POSTPARTUM ANXIETY

SCREENING FOR POSTPARTUM ANXIETY

Screening for perinatal depression has become standard of care, and the Edinburgh Postnatal Depression Scale (EPDS) is a widely used instrument.¹ The EPDS, a 10-question self-report scale, was created and validated to screen for perinatal depression, with a cutoff of > 10/30 usually considered a positive result.

Researchers have investigated the utility of the EPDS as a screening tool for perinatal anxiety as well.^21-23 These studies show some promise, but there are questions as to whether a total score or a subscale score of the EPDS is most accurate in detecting anxiety. Women with perinatal anxiety may score low on the total EPDS, yet score higher on 3 anxiety-specific questions (TABLE 1²³). For this reason, several studies propose an EPDS anxiety subscore or subscale (referred to as EPDS-3A).

Of note, there are some women who will score high on the subscale who do not ultimately meet the criteria for an anxiety disorder diagnosis. Clinicians should not over-interpret these scores and should always use sound clinical judgment when making a diagnosis.

Research has also focused on using the GAD 7-item (GAD-7) scale (TABLE 2²⁴),²⁵ and on the development of new tools and screening tools designed specifically for perinatal anxiety, including the Postpartum Worry Scale²⁶ and the Postpartum Specific Anxiety Scale (PSAS).²⁷

Family physicians may consider using the EPDS subscale if they are already using the EPDS, or adding the GAD-7 as a separate screening instrument during a postpartum visit. To date there is no one standard recommendation or screening tool.

Continue to: NONPHARMACOLOGIC TREATMENT

 

 

NONPHARMACOLOGIC TREATMENT

As one would with any patient who has situational anxiety, help new mothers find ways to increase their coping skills, reduce stress, and mobilize social supports and family resources. Given the association between sleep disruption and perinatal anxiety, counsel new mothers, especially those at high risk for postpartum anxiety, to prioritize sleep during this vulnerable time. To that end, consider recommending that they ask partners, family members, or friends to help them take care of the infant at night (or during the day). Such nonmedical interventions may be sufficient for women with mild anxiety.

Very few studies have addressed nonpharmacologic management of postpartum anxiety, but cognitive behavioral therapy (CBT) has been shown to help in managing and treating anxiety disorders outside of pregnancy.²⁸ A few small studies indicate promise for CBT and for mindfulness-based interventions (MBIs) during pregnancy.²⁹

A 2016 systematic review of pharmacologic and nonpharmacologic treatment of anxiety in the perinatal period found support for the use of CBT for panic disorder and specific phobias both in pregnancy and postpartum.³⁰ A very small study found that teaching mothers to massage their preterm infants decreased maternal anxiety.³¹

If the patient is amenable, it is reasonable to start with behavioral interventions like CBT or MBI before pharmacologic treatment—particularly when physicians have mental health professionals embedded in their primary care team.

PHARMACOLOGIC TREATMENT

Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) are considered first-line treatment for moderate to severe anxiety disorders in the perinatal and postnatal period.

Continue to: SSRIs in pregnancy

SSRIs in pregnancy. Lacking support of randomized controlled trials, most recommendations regarding SSRIs in pregnancy come from expert consensus or cohort and case control studies. Studies have raised concerns for an increased rate of congenital heart defects among fetuses exposed to paroxetine³² and primary pulmonary hypertension with all SSRIs.³³ But the absolute risks are quite small. There have also been concerns regarding low birth weight and preterm birth, but it is possible that these outcomes result from the depression itself rather than the medication.³⁴

Many experts believe that not treating anxiety/ depression is more harmful than the fetal effects of SSRIs.

Unfortunately, there are very few studies evaluating the efficacy of SSRIs in treating postpartum depression³⁵ and even fewer that specifically evaluate their effect on perinatal anxiety. Many experts believe that not treating anxiety/depression is actually more harmful than the fetal effects of SSRIs, and that SSRIs are largely safe in both pregnancy and while breastfeeding, with benefits outweighing the risks.

SSRIs while breastfeeding. SSRIs have been found to be present in varying levels in breastmilk but may or may not be present in the serum of nursing infants.³⁶ A 2008 guideline from the American College of Obstetricians and Gynecologists lists paroxetine, sertraline, and fluvoxamine as slightly safer than fluoxetine, escitalopram, and citalopram.³⁷ A 2015 systematic review similarly concluded that sertraline and paroxetine have the most safety data on lactation.³⁸ Lowest effective dose is always recommended to minimize exposure.

Benzodiazepines. As in the general population, benzodiazepines should be reserved for short-term use in acute anxiety and panic because they are associated with such adverse effects as worsening of depression/anxiety and risk of dependence and overdose. Longer-acting benzodiazepines (eg, clonazepam) are generally not recommended in lactation because of reported effects on infants, including sedation. Shorter-acting benzodiazepines (eg, lorazepam) are considered safer in lactation.³⁹

THE CASE

Julia saw her family physician 4 more times, was evaluated by an ear-nose-and-throat specialist for her throat complaints, saw a therapist for CBT and a psychiatrist for medication, had 3 more ED visits, and lost 23 pounds before she finally agreed to start an SSRI for postpartum anxiety. She screened high on the EPDS-3A (9/9) despite scoring low on the full EPDS for perinatal depression (total, 9/30).

Continue to: Because of her swallowing impediments...

Because of her swallowing impediments and because she was breastfeeding, sertraline solution was started at very small doses. It was titrated weekly to obtain therapeutic levels. By 4 weeks, her weight stabilized. By 8 weeks, she started gaining weight and sleeping better. She saw the therapist regularly to continue CBT techniques. Over the next several months she started eating a normal diet. She is currently maintained on her SSRI, is still breastfeeding, and has achieved insight into her perinatal anxiety disorder.

CORRESPONDENCE
Veronica Jordan, MD, 3569 Round Barn Cir #200, Santa Rosa, CA 95403; veronica.a.jordan@gmail.com.

THE CASE

Julia* is a 31-year-old woman, gravida 3 para 3, who presents to your office for evaluation after a recent emergency department (ED) visit. Her husband and children are with her. She is 4 months postpartum after an uncomplicated normal spontaneous vaginal delivery. She is breastfeeding her healthy baby boy and is using an intrauterine device for birth control. She went to the ED last week after “choking on a chip” while having lunch with her children. It felt like she “couldn’t breathe.” She called 911 herself. The ED evaluation was unremarkable. Her discharge diagnosis was “panic attack,” and she was sent home with a prescription for lorazepam.

Since the incident, she has been unable to eat any solid foods and has lost 7 pounds. She also reports a globus sensation, extreme fear of swallowing, insomnia, and pervasive thoughts that she could die at any moment and leave her children motherless. She has not taken the lorazepam.

She has a history of self-reported anxiety dating back to high school but no history of panic attacks. She has never been diagnosed with an anxiety disorder and has never before been prescribed anti-anxiety medication. She doesn’t have a history of postpartum depression in prior pregnancies, and a depression screening at her postpartum visit 2 months ago was negative.

● How would you proceed with this patient?

*The patient’s name has been changed to protect her identity.

During the perinatal period, women are particularly vulnerable to affective disorders, and primary care physicians are encouraged to routinely screen for and treat depression in pregnant and postpartum women.¹ However, anxiety disorders have a higher incidence than mood disorders in the general population,² and perinatal anxiety may be more widely underrecognized and undertreated than depression.³ In addition, higher depression scores early in pregnancy have been shown to predict higher anxiety later in pregnancy.⁴

As family physicians, we are well-trained to recognize and treat anxiety disorders in the general patient population; however, we may lack the awareness and tools to identify these conditions in the perinatal period. Given our frequent encounters with both mom and baby in a child’s first year of life, we are uniquely positioned to promptly recognize, diagnose, and treat postpartum anxiety and thereby improve health outcomes for families.

DEFINING PERINATAL ANXIETY

Anxiety disorders (including generalized anxiety disorder, panic, phobia, and social anxiety) are the most common mental health disorders evaluated and treated in the primary care setting, with a lifetime prevalence of close to 30%.²

Continue to: A recent report from...

A recent report from the Centers for Disease Control and Prevention (CDC) estimates that 1 in 9 women experience symptoms of postpartum depression.⁵ The prevalence of anxiety disorders during pregnancy and the early postpartum period is not as well-known, but studies suggest that perinatal anxiety is much more prevalent than depression. In one study, generalized anxiety disorder (GAD) in the pre- and postnatal periods was 15.8% and 17.1%, respectively; an incidence far exceeding that of perinatal depression (3.9% and 4.8%, for the same periods).⁶ Additional evidence suggests that even more women in the postnatal period experience clinically significant levels of anxiety but do not meet full diagnostic criteria for an anxiety disorder.⁷

Consider screening for postpartum anxiety with the GAD-7 or the Edinburgh Postnatal Depression Scale (questions 3-5).

In another study, 9.5% of women met criteria for GAD at some point during pregnancy, with highest anxiety levels in the first trimester.⁸ Women with a history of GAD, lower education, lack of social support, and personal history of child abuse have the highest risk for postpartum anxiety. Women with a history of posttraumatic stress disorder (PTSD) may be twice as likely to develop postpartum anxiety as healthy women.⁹

It has been well-documented that sleep disruption—which is very common in new mothers in the postnatal period—contributes to mood and anxiety disorders.^10,11

Clarifying a diagnosis of postpartum anxiety

The Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5)¹² specifies no diagnosis of postpartum anxiety disorder. And no standardized diagnostic criteria exist. It is likely that in some cases, postpartum anxiety represents an exacerbation of underlying GAD, and in other cases it is a situational disorder brought about by specific circumstances of the peripartum period.

The DSM-5 does, however, provide a helpful diagnostic approach. It defines a diagnosis of postpartum depression as being a variant of major depressive disorder (MDD) in which a woman must 1) meet criteria for a major depressive episode; and 2) occur during pregnancy or within 4 weeks of delivery. In practice, many clinicians extend the second requirement to include the first year postpartum.¹³ There is a “with anxious distress” specifier for major depression in the DSM-5, but the 2 disorders are otherwise unlinked.

Continue to: To apply the...

To apply the DSM-5 principles for postpartum depression to postpartum anxiety, a patient would need to 1) meet the diagnostic criteria for an anxiety disorder that 2) have their onset within a specified perinatal period. Variant presentations of anxiety in the postpartum period might include panic disorder and phobias, which could also interfere with a woman’s ability to care for her child.

The DSM-5 offers the following criteria for GAD¹²:

• excessive worry about a variety of topics
• worry that is experienced as hard to control
• worry associated with at least 3 physical or cognitive symptoms: edginess/restlessness, tiring easily, impaired concentration, irritability
• anxiety, worry, or associated symptoms that make it hard to carry out day-to-day activities and responsibilities
• symptoms that are unrelated to any other medical conditions and cannot be explained by the effect of substances including a prescription medication, alcohol, or recreational drugs
• symptoms that are not better explained by a different mental disorder.

Debilitating effects of postpartum anxiety

Many women experience some level of anxiety during pregnancy and early postpartum—anxiety that may range from normal and adaptive to debilitating.¹⁴ While the challenges of caring for a newborn are likely to bring some level of anxiety, these symptoms should be transient and not interfere with a woman’s capacity to care for her infant, herself, or her family.

Postpartum anxiety has been associated with a prior fear of giving birth, fear of death (of both mother and baby), lack of control, lack of self-confidence, and lack of confidence in the medical system.⁹ The experience of such ongoing disturbing thoughts or feelings of worry and tension that affect a woman’s ability to manage from day to day should indicate an illness state that deserves medical attention.

Consider diagnosing postpartum anxiety when DSM-5 criteria for generalized anxiety disorder are met during the first year postpartum.

Mothers with postpartum anxiety disorders report significantly less bonding with their infants than do mothers without anxiety.¹⁵ A recent narrative review describes numerous studies that illustrate the negative effects of postpartum anxiety on bonding, breastfeeding, infant temperament, early childhood development, and conduct disorders.¹⁶ Anxious women may be less likely to initiate breastfeeding, have more challenges with breastfeeding, and even have a different milk composition.¹⁷ Women with prenatal anxiety are also more likely to stop breastfeeding prematurely.¹⁸ Children of anxious mothers may be more likely to have a difficult temperament and to display more distress.¹⁹ There are small studies demonstrating deficits in early infant development and increases in conduct disorder in the male offspring of anxious women.²⁰

Continue to: SCREENING FOR POSTPARTUM ANXIETY

SCREENING FOR POSTPARTUM ANXIETY

Screening for perinatal depression has become standard of care, and the Edinburgh Postnatal Depression Scale (EPDS) is a widely used instrument.¹ The EPDS, a 10-question self-report scale, was created and validated to screen for perinatal depression, with a cutoff of > 10/30 usually considered a positive result.

Researchers have investigated the utility of the EPDS as a screening tool for perinatal anxiety as well.^21-23 These studies show some promise, but there are questions as to whether a total score or a subscale score of the EPDS is most accurate in detecting anxiety. Women with perinatal anxiety may score low on the total EPDS, yet score higher on 3 anxiety-specific questions (TABLE 1²³). For this reason, several studies propose an EPDS anxiety subscore or subscale (referred to as EPDS-3A).

Of note, there are some women who will score high on the subscale who do not ultimately meet the criteria for an anxiety disorder diagnosis. Clinicians should not over-interpret these scores and should always use sound clinical judgment when making a diagnosis.

Research has also focused on using the GAD 7-item (GAD-7) scale (TABLE 2²⁴),²⁵ and on the development of new tools and screening tools designed specifically for perinatal anxiety, including the Postpartum Worry Scale²⁶ and the Postpartum Specific Anxiety Scale (PSAS).²⁷

Family physicians may consider using the EPDS subscale if they are already using the EPDS, or adding the GAD-7 as a separate screening instrument during a postpartum visit. To date there is no one standard recommendation or screening tool.

Continue to: NONPHARMACOLOGIC TREATMENT

 

 

NONPHARMACOLOGIC TREATMENT

As one would with any patient who has situational anxiety, help new mothers find ways to increase their coping skills, reduce stress, and mobilize social supports and family resources. Given the association between sleep disruption and perinatal anxiety, counsel new mothers, especially those at high risk for postpartum anxiety, to prioritize sleep during this vulnerable time. To that end, consider recommending that they ask partners, family members, or friends to help them take care of the infant at night (or during the day). Such nonmedical interventions may be sufficient for women with mild anxiety.

Very few studies have addressed nonpharmacologic management of postpartum anxiety, but cognitive behavioral therapy (CBT) has been shown to help in managing and treating anxiety disorders outside of pregnancy.²⁸ A few small studies indicate promise for CBT and for mindfulness-based interventions (MBIs) during pregnancy.²⁹

A 2016 systematic review of pharmacologic and nonpharmacologic treatment of anxiety in the perinatal period found support for the use of CBT for panic disorder and specific phobias both in pregnancy and postpartum.³⁰ A very small study found that teaching mothers to massage their preterm infants decreased maternal anxiety.³¹

If the patient is amenable, it is reasonable to start with behavioral interventions like CBT or MBI before pharmacologic treatment—particularly when physicians have mental health professionals embedded in their primary care team.

PHARMACOLOGIC TREATMENT

Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) are considered first-line treatment for moderate to severe anxiety disorders in the perinatal and postnatal period.

Continue to: SSRIs in pregnancy

SSRIs in pregnancy. Lacking support of randomized controlled trials, most recommendations regarding SSRIs in pregnancy come from expert consensus or cohort and case control studies. Studies have raised concerns for an increased rate of congenital heart defects among fetuses exposed to paroxetine³² and primary pulmonary hypertension with all SSRIs.³³ But the absolute risks are quite small. There have also been concerns regarding low birth weight and preterm birth, but it is possible that these outcomes result from the depression itself rather than the medication.³⁴

Many experts believe that not treating anxiety/ depression is more harmful than the fetal effects of SSRIs.

Unfortunately, there are very few studies evaluating the efficacy of SSRIs in treating postpartum depression³⁵ and even fewer that specifically evaluate their effect on perinatal anxiety. Many experts believe that not treating anxiety/depression is actually more harmful than the fetal effects of SSRIs, and that SSRIs are largely safe in both pregnancy and while breastfeeding, with benefits outweighing the risks.

SSRIs while breastfeeding. SSRIs have been found to be present in varying levels in breastmilk but may or may not be present in the serum of nursing infants.³⁶ A 2008 guideline from the American College of Obstetricians and Gynecologists lists paroxetine, sertraline, and fluvoxamine as slightly safer than fluoxetine, escitalopram, and citalopram.³⁷ A 2015 systematic review similarly concluded that sertraline and paroxetine have the most safety data on lactation.³⁸ Lowest effective dose is always recommended to minimize exposure.

Benzodiazepines. As in the general population, benzodiazepines should be reserved for short-term use in acute anxiety and panic because they are associated with such adverse effects as worsening of depression/anxiety and risk of dependence and overdose. Longer-acting benzodiazepines (eg, clonazepam) are generally not recommended in lactation because of reported effects on infants, including sedation. Shorter-acting benzodiazepines (eg, lorazepam) are considered safer in lactation.³⁹

THE CASE

Julia saw her family physician 4 more times, was evaluated by an ear-nose-and-throat specialist for her throat complaints, saw a therapist for CBT and a psychiatrist for medication, had 3 more ED visits, and lost 23 pounds before she finally agreed to start an SSRI for postpartum anxiety. She screened high on the EPDS-3A (9/9) despite scoring low on the full EPDS for perinatal depression (total, 9/30).

Continue to: Because of her swallowing impediments...

Because of her swallowing impediments and because she was breastfeeding, sertraline solution was started at very small doses. It was titrated weekly to obtain therapeutic levels. By 4 weeks, her weight stabilized. By 8 weeks, she started gaining weight and sleeping better. She saw the therapist regularly to continue CBT techniques. Over the next several months she started eating a normal diet. She is currently maintained on her SSRI, is still breastfeeding, and has achieved insight into her perinatal anxiety disorder.

CORRESPONDENCE
Veronica Jordan, MD, 3569 Round Barn Cir #200, Santa Rosa, CA 95403; veronica.a.jordan@gmail.com.

THE CASE

Julia* is a 31-year-old woman, gravida 3 para 3, who presents to your office for evaluation after a recent emergency department (ED) visit. Her husband and children are with her. She is 4 months postpartum after an uncomplicated normal spontaneous vaginal delivery. She is breastfeeding her healthy baby boy and is using an intrauterine device for birth control. She went to the ED last week after “choking on a chip” while having lunch with her children. It felt like she “couldn’t breathe.” She called 911 herself. The ED evaluation was unremarkable. Her discharge diagnosis was “panic attack,” and she was sent home with a prescription for lorazepam.

Since the incident, she has been unable to eat any solid foods and has lost 7 pounds. She also reports a globus sensation, extreme fear of swallowing, insomnia, and pervasive thoughts that she could die at any moment and leave her children motherless. She has not taken the lorazepam.

She has a history of self-reported anxiety dating back to high school but no history of panic attacks. She has never been diagnosed with an anxiety disorder and has never before been prescribed anti-anxiety medication. She doesn’t have a history of postpartum depression in prior pregnancies, and a depression screening at her postpartum visit 2 months ago was negative.

● How would you proceed with this patient?

*The patient’s name has been changed to protect her identity.

During the perinatal period, women are particularly vulnerable to affective disorders, and primary care physicians are encouraged to routinely screen for and treat depression in pregnant and postpartum women.¹ However, anxiety disorders have a higher incidence than mood disorders in the general population,² and perinatal anxiety may be more widely underrecognized and undertreated than depression.³ In addition, higher depression scores early in pregnancy have been shown to predict higher anxiety later in pregnancy.⁴

As family physicians, we are well-trained to recognize and treat anxiety disorders in the general patient population; however, we may lack the awareness and tools to identify these conditions in the perinatal period. Given our frequent encounters with both mom and baby in a child’s first year of life, we are uniquely positioned to promptly recognize, diagnose, and treat postpartum anxiety and thereby improve health outcomes for families.

DEFINING PERINATAL ANXIETY

Anxiety disorders (including generalized anxiety disorder, panic, phobia, and social anxiety) are the most common mental health disorders evaluated and treated in the primary care setting, with a lifetime prevalence of close to 30%.²

Continue to: A recent report from...

A recent report from the Centers for Disease Control and Prevention (CDC) estimates that 1 in 9 women experience symptoms of postpartum depression.⁵ The prevalence of anxiety disorders during pregnancy and the early postpartum period is not as well-known, but studies suggest that perinatal anxiety is much more prevalent than depression. In one study, generalized anxiety disorder (GAD) in the pre- and postnatal periods was 15.8% and 17.1%, respectively; an incidence far exceeding that of perinatal depression (3.9% and 4.8%, for the same periods).⁶ Additional evidence suggests that even more women in the postnatal period experience clinically significant levels of anxiety but do not meet full diagnostic criteria for an anxiety disorder.⁷

Consider screening for postpartum anxiety with the GAD-7 or the Edinburgh Postnatal Depression Scale (questions 3-5).

In another study, 9.5% of women met criteria for GAD at some point during pregnancy, with highest anxiety levels in the first trimester.⁸ Women with a history of GAD, lower education, lack of social support, and personal history of child abuse have the highest risk for postpartum anxiety. Women with a history of posttraumatic stress disorder (PTSD) may be twice as likely to develop postpartum anxiety as healthy women.⁹

It has been well-documented that sleep disruption—which is very common in new mothers in the postnatal period—contributes to mood and anxiety disorders.^10,11

Clarifying a diagnosis of postpartum anxiety

The Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5)¹² specifies no diagnosis of postpartum anxiety disorder. And no standardized diagnostic criteria exist. It is likely that in some cases, postpartum anxiety represents an exacerbation of underlying GAD, and in other cases it is a situational disorder brought about by specific circumstances of the peripartum period.

The DSM-5 does, however, provide a helpful diagnostic approach. It defines a diagnosis of postpartum depression as being a variant of major depressive disorder (MDD) in which a woman must 1) meet criteria for a major depressive episode; and 2) occur during pregnancy or within 4 weeks of delivery. In practice, many clinicians extend the second requirement to include the first year postpartum.¹³ There is a “with anxious distress” specifier for major depression in the DSM-5, but the 2 disorders are otherwise unlinked.

Continue to: To apply the...

To apply the DSM-5 principles for postpartum depression to postpartum anxiety, a patient would need to 1) meet the diagnostic criteria for an anxiety disorder that 2) have their onset within a specified perinatal period. Variant presentations of anxiety in the postpartum period might include panic disorder and phobias, which could also interfere with a woman’s ability to care for her child.

The DSM-5 offers the following criteria for GAD¹²:

• excessive worry about a variety of topics
• worry that is experienced as hard to control
• worry associated with at least 3 physical or cognitive symptoms: edginess/restlessness, tiring easily, impaired concentration, irritability
• anxiety, worry, or associated symptoms that make it hard to carry out day-to-day activities and responsibilities
• symptoms that are unrelated to any other medical conditions and cannot be explained by the effect of substances including a prescription medication, alcohol, or recreational drugs
• symptoms that are not better explained by a different mental disorder.

Debilitating effects of postpartum anxiety

Many women experience some level of anxiety during pregnancy and early postpartum—anxiety that may range from normal and adaptive to debilitating.¹⁴ While the challenges of caring for a newborn are likely to bring some level of anxiety, these symptoms should be transient and not interfere with a woman’s capacity to care for her infant, herself, or her family.

Postpartum anxiety has been associated with a prior fear of giving birth, fear of death (of both mother and baby), lack of control, lack of self-confidence, and lack of confidence in the medical system.⁹ The experience of such ongoing disturbing thoughts or feelings of worry and tension that affect a woman’s ability to manage from day to day should indicate an illness state that deserves medical attention.

Consider diagnosing postpartum anxiety when DSM-5 criteria for generalized anxiety disorder are met during the first year postpartum.

Mothers with postpartum anxiety disorders report significantly less bonding with their infants than do mothers without anxiety.¹⁵ A recent narrative review describes numerous studies that illustrate the negative effects of postpartum anxiety on bonding, breastfeeding, infant temperament, early childhood development, and conduct disorders.¹⁶ Anxious women may be less likely to initiate breastfeeding, have more challenges with breastfeeding, and even have a different milk composition.¹⁷ Women with prenatal anxiety are also more likely to stop breastfeeding prematurely.¹⁸ Children of anxious mothers may be more likely to have a difficult temperament and to display more distress.¹⁹ There are small studies demonstrating deficits in early infant development and increases in conduct disorder in the male offspring of anxious women.²⁰

Continue to: SCREENING FOR POSTPARTUM ANXIETY

SCREENING FOR POSTPARTUM ANXIETY

Screening for perinatal depression has become standard of care, and the Edinburgh Postnatal Depression Scale (EPDS) is a widely used instrument.¹ The EPDS, a 10-question self-report scale, was created and validated to screen for perinatal depression, with a cutoff of > 10/30 usually considered a positive result.

Researchers have investigated the utility of the EPDS as a screening tool for perinatal anxiety as well.^21-23 These studies show some promise, but there are questions as to whether a total score or a subscale score of the EPDS is most accurate in detecting anxiety. Women with perinatal anxiety may score low on the total EPDS, yet score higher on 3 anxiety-specific questions (TABLE 1²³). For this reason, several studies propose an EPDS anxiety subscore or subscale (referred to as EPDS-3A).

Of note, there are some women who will score high on the subscale who do not ultimately meet the criteria for an anxiety disorder diagnosis. Clinicians should not over-interpret these scores and should always use sound clinical judgment when making a diagnosis.

Research has also focused on using the GAD 7-item (GAD-7) scale (TABLE 2²⁴),²⁵ and on the development of new tools and screening tools designed specifically for perinatal anxiety, including the Postpartum Worry Scale²⁶ and the Postpartum Specific Anxiety Scale (PSAS).²⁷

Family physicians may consider using the EPDS subscale if they are already using the EPDS, or adding the GAD-7 as a separate screening instrument during a postpartum visit. To date there is no one standard recommendation or screening tool.

Continue to: NONPHARMACOLOGIC TREATMENT

 

 

NONPHARMACOLOGIC TREATMENT

As one would with any patient who has situational anxiety, help new mothers find ways to increase their coping skills, reduce stress, and mobilize social supports and family resources. Given the association between sleep disruption and perinatal anxiety, counsel new mothers, especially those at high risk for postpartum anxiety, to prioritize sleep during this vulnerable time. To that end, consider recommending that they ask partners, family members, or friends to help them take care of the infant at night (or during the day). Such nonmedical interventions may be sufficient for women with mild anxiety.

Very few studies have addressed nonpharmacologic management of postpartum anxiety, but cognitive behavioral therapy (CBT) has been shown to help in managing and treating anxiety disorders outside of pregnancy.²⁸ A few small studies indicate promise for CBT and for mindfulness-based interventions (MBIs) during pregnancy.²⁹

A 2016 systematic review of pharmacologic and nonpharmacologic treatment of anxiety in the perinatal period found support for the use of CBT for panic disorder and specific phobias both in pregnancy and postpartum.³⁰ A very small study found that teaching mothers to massage their preterm infants decreased maternal anxiety.³¹

If the patient is amenable, it is reasonable to start with behavioral interventions like CBT or MBI before pharmacologic treatment—particularly when physicians have mental health professionals embedded in their primary care team.

PHARMACOLOGIC TREATMENT

Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) are considered first-line treatment for moderate to severe anxiety disorders in the perinatal and postnatal period.

Continue to: SSRIs in pregnancy

SSRIs in pregnancy. Lacking support of randomized controlled trials, most recommendations regarding SSRIs in pregnancy come from expert consensus or cohort and case control studies. Studies have raised concerns for an increased rate of congenital heart defects among fetuses exposed to paroxetine³² and primary pulmonary hypertension with all SSRIs.³³ But the absolute risks are quite small. There have also been concerns regarding low birth weight and preterm birth, but it is possible that these outcomes result from the depression itself rather than the medication.³⁴

Many experts believe that not treating anxiety/ depression is more harmful than the fetal effects of SSRIs.

Unfortunately, there are very few studies evaluating the efficacy of SSRIs in treating postpartum depression³⁵ and even fewer that specifically evaluate their effect on perinatal anxiety. Many experts believe that not treating anxiety/depression is actually more harmful than the fetal effects of SSRIs, and that SSRIs are largely safe in both pregnancy and while breastfeeding, with benefits outweighing the risks.

SSRIs while breastfeeding. SSRIs have been found to be present in varying levels in breastmilk but may or may not be present in the serum of nursing infants.³⁶ A 2008 guideline from the American College of Obstetricians and Gynecologists lists paroxetine, sertraline, and fluvoxamine as slightly safer than fluoxetine, escitalopram, and citalopram.³⁷ A 2015 systematic review similarly concluded that sertraline and paroxetine have the most safety data on lactation.³⁸ Lowest effective dose is always recommended to minimize exposure.

Benzodiazepines. As in the general population, benzodiazepines should be reserved for short-term use in acute anxiety and panic because they are associated with such adverse effects as worsening of depression/anxiety and risk of dependence and overdose. Longer-acting benzodiazepines (eg, clonazepam) are generally not recommended in lactation because of reported effects on infants, including sedation. Shorter-acting benzodiazepines (eg, lorazepam) are considered safer in lactation.³⁹

THE CASE

Julia saw her family physician 4 more times, was evaluated by an ear-nose-and-throat specialist for her throat complaints, saw a therapist for CBT and a psychiatrist for medication, had 3 more ED visits, and lost 23 pounds before she finally agreed to start an SSRI for postpartum anxiety. She screened high on the EPDS-3A (9/9) despite scoring low on the full EPDS for perinatal depression (total, 9/30).

Continue to: Because of her swallowing impediments...

Because of her swallowing impediments and because she was breastfeeding, sertraline solution was started at very small doses. It was titrated weekly to obtain therapeutic levels. By 4 weeks, her weight stabilized. By 8 weeks, she started gaining weight and sleeping better. She saw the therapist regularly to continue CBT techniques. Over the next several months she started eating a normal diet. She is currently maintained on her SSRI, is still breastfeeding, and has achieved insight into her perinatal anxiety disorder.

CORRESPONDENCE
Veronica Jordan, MD, 3569 Round Barn Cir #200, Santa Rosa, CA 95403; veronica.a.jordan@gmail.com.

ILLUSTRATIVE CASE

A 60-year-old man is seen in your clinic 30 days after he was hospitalized for acute coronary syndrome (ACS) due to ST-elevation myocardial infarction (STEMI). He underwent percutaneous coronary intervention (PCI) with placement of one stent. He received aspirin and a loading dose of ticagrelor for antiplatelet therapy. He was discharged on dual antiplatelet therapy (DAPT) consisting of daily aspirin and ticagrelor. He asks about the risk of bleeding associated with these medications. Should you recommend any changes?

Platelet inhibition during and after ACS to prevent recurrent ischemic events is a cornerstone of treatment for patients after myocardial infarction (MI).² Current American Cardiology Association and European Society of Cardiology guidelines recommend patients with coronary artery disease who have had a recent MI continue DAPT with aspirin and a P2Y12 blocker (ie, clopidogrel, ticlopidine, ticagrelor, prasugrel, or cangrelor) for 12 months following ACSto reduce recurrent ischemia.^2-4

Studies have shown that using the newer P2Y12 inhibitors (ie, prasugrel and ticagrelor) after PCI leads to a significant reduction in recurrent ischemic events when compared to clopidogrel.^5-7 These data led to a guideline change recommending the use of the newer agents over clopidogrel for 12 months following PCI.² Follow-up studies evaluating the newer P2Y12 agents continue to show strong evidence for their use in the first month following PCI, while also demonstrating an increased bleeding risk in the maintenance phase (from 30 days to 12 months post-PCI).^6,7 This increased risk is the basis for the current study, which tested switching from a newer P2Y12 agent to clopidogrel after the initial 30-day period following PCI.

STUDY SUMMARY

Switched DAPT is superior to unchanged DAPT

This open-label RCT (N = 646) examined changing DAPT from aspirin plus a newer P2Y12 blocker (prasugrel or ticagrelor) to a combination of aspirin and clopidogrel after the first month of DAPT post-ACS.¹ Prior to PCI, all patients received a loading dose of ticagrelor 180 mg or prasugrel 60 mg. Subsequently, all patients in the trial took aspirin (75 mg/d) and one of the newer P2Y12 inhibitors (prasugrel 10 mg/d or ticagrelor 90 mg BID) for 1 month. For those enrollees who had no adverse events after 30 days, half were randomly switched to aspirin and clopidogrel 75 mg/d and the other half remained on aspirin and their newer P2Y12 blocker in a 1:1 ratio. For the next year, researchers examined the composite outcome of cardiovascular death, urgent revascularization, stroke, and major bleeding (as defined by the Bleeding Academic Research Consortium [BARC] classification ≥ Type 2 at 1 year post-ACS).

Implementing this practice change is facilitated by the fact that, currently, clopidogrel is less expensive than the newer P2Y12 blockers.

The average age of the participants was 60 years; 40% had experienced a STEMI and 60% had a non–STEMI. Overall, 43% of patients were prescribed ticagrelor and 57% prasugrel. At 1 year, 86% of the switched DAPT group and 75% of the unchanged DAPT group were still taking their medication. At the 1-year follow-up, the composite outcome was lower in the switched group, compared with the unchanged group (13% vs 26%; hazard ratio [HR] = 0.48; 95% confidence interval [CI], 0.34-0.68; number needed to treat [NNT] = 8).

All bleeding events (ranging from minimal to fatal) were lower in the switched group (9% vs 24%; HR = 0.39; 95% CI, 0.27-0.57; NNT = 7), and bleeding events identified as BARC ≥ Type 2 (defined as needing medical treatment) were also lower in the switched group (4% vs 15%; HR = 0.30, 95% CI, 0.18-0.50; NNT = 9). There were no significant differences in reported recurrent cardiovascular ischemic events (9.3% vs 11.5%; HR = 0.80, 95% CI, 0.50-1.29).

WHAT’S NEW

Fewer bleeding events without an increase in ischemic events

Cardiology guidelines recommend the newer P2Y12 blockers as part of DAPT after ACS, but this trial showed switching to clopidogrel for DAPT after 30 days of treatment lowers bleeding events with no difference in recurrent ischemic events.^2-4

Continue to: CAVEATS

 

 

CAVEATS

Less-than-ideal study methods

This trial was an open-label, unblinded study. The investigators who adjudicated critical events were blinded to the treatment allocation, but some events, such as minor bleeding and medication discontinuation, could be self-reported by patients. In addition, the investigators used a less-than-ideal method (opaque envelopes) to conceal allocation at enrollment.

CHALLENGES TO IMPLEMENTATION

Implementation may require changing a cardiologist’s prescription

Implementing this practice change is facilitated by the fact that clopidogrel is currently less expensive than the newer P2Y12 blockers. However, after ACS and PCI treatment, cardiologists usually initiate antiplatelet therapy and may continue to manage patients after discharge. So the family physician (FP) may not be responsible for the DAPT switch initially. Further, switching may necessitate coordination with the cardiologist, as FPs may be hesitant to change cardiologists’ prescriptions. Lastly, guidelines currently recommend using the newer P2Y12 blockers for 12 months.²

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 60-year-old man is seen in your clinic 30 days after he was hospitalized for acute coronary syndrome (ACS) due to ST-elevation myocardial infarction (STEMI). He underwent percutaneous coronary intervention (PCI) with placement of one stent. He received aspirin and a loading dose of ticagrelor for antiplatelet therapy. He was discharged on dual antiplatelet therapy (DAPT) consisting of daily aspirin and ticagrelor. He asks about the risk of bleeding associated with these medications. Should you recommend any changes?

Platelet inhibition during and after ACS to prevent recurrent ischemic events is a cornerstone of treatment for patients after myocardial infarction (MI).² Current American Cardiology Association and European Society of Cardiology guidelines recommend patients with coronary artery disease who have had a recent MI continue DAPT with aspirin and a P2Y12 blocker (ie, clopidogrel, ticlopidine, ticagrelor, prasugrel, or cangrelor) for 12 months following ACSto reduce recurrent ischemia.^2-4

Studies have shown that using the newer P2Y12 inhibitors (ie, prasugrel and ticagrelor) after PCI leads to a significant reduction in recurrent ischemic events when compared to clopidogrel.^5-7 These data led to a guideline change recommending the use of the newer agents over clopidogrel for 12 months following PCI.² Follow-up studies evaluating the newer P2Y12 agents continue to show strong evidence for their use in the first month following PCI, while also demonstrating an increased bleeding risk in the maintenance phase (from 30 days to 12 months post-PCI).^6,7 This increased risk is the basis for the current study, which tested switching from a newer P2Y12 agent to clopidogrel after the initial 30-day period following PCI.

STUDY SUMMARY

Switched DAPT is superior to unchanged DAPT

This open-label RCT (N = 646) examined changing DAPT from aspirin plus a newer P2Y12 blocker (prasugrel or ticagrelor) to a combination of aspirin and clopidogrel after the first month of DAPT post-ACS.¹ Prior to PCI, all patients received a loading dose of ticagrelor 180 mg or prasugrel 60 mg. Subsequently, all patients in the trial took aspirin (75 mg/d) and one of the newer P2Y12 inhibitors (prasugrel 10 mg/d or ticagrelor 90 mg BID) for 1 month. For those enrollees who had no adverse events after 30 days, half were randomly switched to aspirin and clopidogrel 75 mg/d and the other half remained on aspirin and their newer P2Y12 blocker in a 1:1 ratio. For the next year, researchers examined the composite outcome of cardiovascular death, urgent revascularization, stroke, and major bleeding (as defined by the Bleeding Academic Research Consortium [BARC] classification ≥ Type 2 at 1 year post-ACS).

Implementing this practice change is facilitated by the fact that, currently, clopidogrel is less expensive than the newer P2Y12 blockers.

The average age of the participants was 60 years; 40% had experienced a STEMI and 60% had a non–STEMI. Overall, 43% of patients were prescribed ticagrelor and 57% prasugrel. At 1 year, 86% of the switched DAPT group and 75% of the unchanged DAPT group were still taking their medication. At the 1-year follow-up, the composite outcome was lower in the switched group, compared with the unchanged group (13% vs 26%; hazard ratio [HR] = 0.48; 95% confidence interval [CI], 0.34-0.68; number needed to treat [NNT] = 8).

All bleeding events (ranging from minimal to fatal) were lower in the switched group (9% vs 24%; HR = 0.39; 95% CI, 0.27-0.57; NNT = 7), and bleeding events identified as BARC ≥ Type 2 (defined as needing medical treatment) were also lower in the switched group (4% vs 15%; HR = 0.30, 95% CI, 0.18-0.50; NNT = 9). There were no significant differences in reported recurrent cardiovascular ischemic events (9.3% vs 11.5%; HR = 0.80, 95% CI, 0.50-1.29).

WHAT’S NEW

Fewer bleeding events without an increase in ischemic events

Cardiology guidelines recommend the newer P2Y12 blockers as part of DAPT after ACS, but this trial showed switching to clopidogrel for DAPT after 30 days of treatment lowers bleeding events with no difference in recurrent ischemic events.^2-4

Continue to: CAVEATS

 

 

CAVEATS

Less-than-ideal study methods

This trial was an open-label, unblinded study. The investigators who adjudicated critical events were blinded to the treatment allocation, but some events, such as minor bleeding and medication discontinuation, could be self-reported by patients. In addition, the investigators used a less-than-ideal method (opaque envelopes) to conceal allocation at enrollment.

CHALLENGES TO IMPLEMENTATION

Implementation may require changing a cardiologist’s prescription

Implementing this practice change is facilitated by the fact that clopidogrel is currently less expensive than the newer P2Y12 blockers. However, after ACS and PCI treatment, cardiologists usually initiate antiplatelet therapy and may continue to manage patients after discharge. So the family physician (FP) may not be responsible for the DAPT switch initially. Further, switching may necessitate coordination with the cardiologist, as FPs may be hesitant to change cardiologists’ prescriptions. Lastly, guidelines currently recommend using the newer P2Y12 blockers for 12 months.²

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 60-year-old man is seen in your clinic 30 days after he was hospitalized for acute coronary syndrome (ACS) due to ST-elevation myocardial infarction (STEMI). He underwent percutaneous coronary intervention (PCI) with placement of one stent. He received aspirin and a loading dose of ticagrelor for antiplatelet therapy. He was discharged on dual antiplatelet therapy (DAPT) consisting of daily aspirin and ticagrelor. He asks about the risk of bleeding associated with these medications. Should you recommend any changes?

Platelet inhibition during and after ACS to prevent recurrent ischemic events is a cornerstone of treatment for patients after myocardial infarction (MI).² Current American Cardiology Association and European Society of Cardiology guidelines recommend patients with coronary artery disease who have had a recent MI continue DAPT with aspirin and a P2Y12 blocker (ie, clopidogrel, ticlopidine, ticagrelor, prasugrel, or cangrelor) for 12 months following ACSto reduce recurrent ischemia.^2-4

Studies have shown that using the newer P2Y12 inhibitors (ie, prasugrel and ticagrelor) after PCI leads to a significant reduction in recurrent ischemic events when compared to clopidogrel.^5-7 These data led to a guideline change recommending the use of the newer agents over clopidogrel for 12 months following PCI.² Follow-up studies evaluating the newer P2Y12 agents continue to show strong evidence for their use in the first month following PCI, while also demonstrating an increased bleeding risk in the maintenance phase (from 30 days to 12 months post-PCI).^6,7 This increased risk is the basis for the current study, which tested switching from a newer P2Y12 agent to clopidogrel after the initial 30-day period following PCI.

STUDY SUMMARY

Switched DAPT is superior to unchanged DAPT

This open-label RCT (N = 646) examined changing DAPT from aspirin plus a newer P2Y12 blocker (prasugrel or ticagrelor) to a combination of aspirin and clopidogrel after the first month of DAPT post-ACS.¹ Prior to PCI, all patients received a loading dose of ticagrelor 180 mg or prasugrel 60 mg. Subsequently, all patients in the trial took aspirin (75 mg/d) and one of the newer P2Y12 inhibitors (prasugrel 10 mg/d or ticagrelor 90 mg BID) for 1 month. For those enrollees who had no adverse events after 30 days, half were randomly switched to aspirin and clopidogrel 75 mg/d and the other half remained on aspirin and their newer P2Y12 blocker in a 1:1 ratio. For the next year, researchers examined the composite outcome of cardiovascular death, urgent revascularization, stroke, and major bleeding (as defined by the Bleeding Academic Research Consortium [BARC] classification ≥ Type 2 at 1 year post-ACS).

Implementing this practice change is facilitated by the fact that, currently, clopidogrel is less expensive than the newer P2Y12 blockers.

The average age of the participants was 60 years; 40% had experienced a STEMI and 60% had a non–STEMI. Overall, 43% of patients were prescribed ticagrelor and 57% prasugrel. At 1 year, 86% of the switched DAPT group and 75% of the unchanged DAPT group were still taking their medication. At the 1-year follow-up, the composite outcome was lower in the switched group, compared with the unchanged group (13% vs 26%; hazard ratio [HR] = 0.48; 95% confidence interval [CI], 0.34-0.68; number needed to treat [NNT] = 8).

All bleeding events (ranging from minimal to fatal) were lower in the switched group (9% vs 24%; HR = 0.39; 95% CI, 0.27-0.57; NNT = 7), and bleeding events identified as BARC ≥ Type 2 (defined as needing medical treatment) were also lower in the switched group (4% vs 15%; HR = 0.30, 95% CI, 0.18-0.50; NNT = 9). There were no significant differences in reported recurrent cardiovascular ischemic events (9.3% vs 11.5%; HR = 0.80, 95% CI, 0.50-1.29).

WHAT’S NEW

Fewer bleeding events without an increase in ischemic events

Cardiology guidelines recommend the newer P2Y12 blockers as part of DAPT after ACS, but this trial showed switching to clopidogrel for DAPT after 30 days of treatment lowers bleeding events with no difference in recurrent ischemic events.^2-4

Continue to: CAVEATS

 

 

CAVEATS

Less-than-ideal study methods

This trial was an open-label, unblinded study. The investigators who adjudicated critical events were blinded to the treatment allocation, but some events, such as minor bleeding and medication discontinuation, could be self-reported by patients. In addition, the investigators used a less-than-ideal method (opaque envelopes) to conceal allocation at enrollment.

CHALLENGES TO IMPLEMENTATION

Implementation may require changing a cardiologist’s prescription

Implementing this practice change is facilitated by the fact that clopidogrel is currently less expensive than the newer P2Y12 blockers. However, after ACS and PCI treatment, cardiologists usually initiate antiplatelet therapy and may continue to manage patients after discharge. So the family physician (FP) may not be responsible for the DAPT switch initially. Further, switching may necessitate coordination with the cardiologist, as FPs may be hesitant to change cardiologists’ prescriptions. Lastly, guidelines currently recommend using the newer P2Y12 blockers for 12 months.²

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

SEATTLE – Female sex, young age, residing in a rural location, black race, and Medicaid insurance were all associated with reduced adherence to HIV pre-exposure prophylaxis in a study from the Centers for Disease Control and Prevention.

M. Alexander Otto/MDedge News

Daily pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir (Truvada) prevents infection, but not everyone sticks with it. The investigators wanted to find out who struggles the most with adherence to help focus future intervention efforts.

The team identified 7,250 commercially insured and 349 Medicaid PrEP users in IBM MarketScan databases during 2011-2016. They tracked them from their initial PrEP prescription until there was a gap of 30 days or more in their PrEP refills, at which point they met the study’s definition of nonpersistence.

Overall, “commercially insured nonpersistent PrEP users were young, female, and rural. Medicaid insured nonpersistent users were young, female, and black,” said lead investigator Ya-Lin Huang, PhD, a health scientist in the CDC Division of HIV/AIDS Prevention.

“It is concerning that some populations with low persistence were among those with the highest rates of HIV diagnosis, such as young, black men. Research is needed to understand reasons for discontinuing PrEP. Interventions tailored for priority populations are needed to improve PrEP persistence,” she said at the Conference on Retroviruses and Opportunistic Infections.

Her team found that commercially insured patients stuck with PrEP longer than did those on Medicaid, a median of 14.5 months, with 56% still filling their prescriptions after a year, versus a median Medicaid persistence of 7.6 months, with only a third of Medicaid patients still on PrEP after 12 months.

Men were more persistent with PrEP than were women in both groups, as were older people versus younger. The median length of adherence among commercially insured patients aged 45-54 years, for instance, was 20.5 months, versus 8.6 months among people aged 18-24 years. Older PrEP users persisted longer among Medicaid patients as well, a median of 10 versus 4 months.

Also in the Medicaid group, white patients stuck with PrEP longer than did black patients, a median of 8.5 months versus 4.1 months. There were no racial differences with commercial insurance.

The findings held even when the team used gaps of 60 and 90 days, instead of 30 days, to define nonpersistence.

The study says nothing about why people stopped PrEP, or why there were such stark differences between the groups.

Perhaps, in some cases, people quit risky behavior or entered new relationships. Maybe PrEP was too expensive for some, or transportation to the clinic was an issue. Side effects might have been a problem, or people could have lost their insurance coverage, or maybe didn’t want to deal with the hassle. It’s impossible to know from the data, Dr. Huang said.

She said her team wants to figure it out, so they can help people overcome barriers to treatment, which likely vary across subgroups.

The study also was limited to patients who were enrolled in coverage at least 6 months before and 6 months after their first PrEP prescription; the investigators want to exam the situation for people with less consistent coverage, and no coverage at all.

The work was funded by the Centers for Disease Control and Prevention. The investigators had no disclosures.

aotto@mdedge.com

SOURCE: Huang YA et al. CROI 2019, Abstract 106.

SEATTLE – Female sex, young age, residing in a rural location, black race, and Medicaid insurance were all associated with reduced adherence to HIV pre-exposure prophylaxis in a study from the Centers for Disease Control and Prevention.

M. Alexander Otto/MDedge News

Daily pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir (Truvada) prevents infection, but not everyone sticks with it. The investigators wanted to find out who struggles the most with adherence to help focus future intervention efforts.

The team identified 7,250 commercially insured and 349 Medicaid PrEP users in IBM MarketScan databases during 2011-2016. They tracked them from their initial PrEP prescription until there was a gap of 30 days or more in their PrEP refills, at which point they met the study’s definition of nonpersistence.

Overall, “commercially insured nonpersistent PrEP users were young, female, and rural. Medicaid insured nonpersistent users were young, female, and black,” said lead investigator Ya-Lin Huang, PhD, a health scientist in the CDC Division of HIV/AIDS Prevention.

“It is concerning that some populations with low persistence were among those with the highest rates of HIV diagnosis, such as young, black men. Research is needed to understand reasons for discontinuing PrEP. Interventions tailored for priority populations are needed to improve PrEP persistence,” she said at the Conference on Retroviruses and Opportunistic Infections.

Her team found that commercially insured patients stuck with PrEP longer than did those on Medicaid, a median of 14.5 months, with 56% still filling their prescriptions after a year, versus a median Medicaid persistence of 7.6 months, with only a third of Medicaid patients still on PrEP after 12 months.

Men were more persistent with PrEP than were women in both groups, as were older people versus younger. The median length of adherence among commercially insured patients aged 45-54 years, for instance, was 20.5 months, versus 8.6 months among people aged 18-24 years. Older PrEP users persisted longer among Medicaid patients as well, a median of 10 versus 4 months.

Also in the Medicaid group, white patients stuck with PrEP longer than did black patients, a median of 8.5 months versus 4.1 months. There were no racial differences with commercial insurance.

The findings held even when the team used gaps of 60 and 90 days, instead of 30 days, to define nonpersistence.

The study says nothing about why people stopped PrEP, or why there were such stark differences between the groups.

Perhaps, in some cases, people quit risky behavior or entered new relationships. Maybe PrEP was too expensive for some, or transportation to the clinic was an issue. Side effects might have been a problem, or people could have lost their insurance coverage, or maybe didn’t want to deal with the hassle. It’s impossible to know from the data, Dr. Huang said.

She said her team wants to figure it out, so they can help people overcome barriers to treatment, which likely vary across subgroups.

The study also was limited to patients who were enrolled in coverage at least 6 months before and 6 months after their first PrEP prescription; the investigators want to exam the situation for people with less consistent coverage, and no coverage at all.

The work was funded by the Centers for Disease Control and Prevention. The investigators had no disclosures.

aotto@mdedge.com

SOURCE: Huang YA et al. CROI 2019, Abstract 106.

SEATTLE – Female sex, young age, residing in a rural location, black race, and Medicaid insurance were all associated with reduced adherence to HIV pre-exposure prophylaxis in a study from the Centers for Disease Control and Prevention.

M. Alexander Otto/MDedge News

Daily pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir (Truvada) prevents infection, but not everyone sticks with it. The investigators wanted to find out who struggles the most with adherence to help focus future intervention efforts.

The team identified 7,250 commercially insured and 349 Medicaid PrEP users in IBM MarketScan databases during 2011-2016. They tracked them from their initial PrEP prescription until there was a gap of 30 days or more in their PrEP refills, at which point they met the study’s definition of nonpersistence.

Overall, “commercially insured nonpersistent PrEP users were young, female, and rural. Medicaid insured nonpersistent users were young, female, and black,” said lead investigator Ya-Lin Huang, PhD, a health scientist in the CDC Division of HIV/AIDS Prevention.

“It is concerning that some populations with low persistence were among those with the highest rates of HIV diagnosis, such as young, black men. Research is needed to understand reasons for discontinuing PrEP. Interventions tailored for priority populations are needed to improve PrEP persistence,” she said at the Conference on Retroviruses and Opportunistic Infections.

Her team found that commercially insured patients stuck with PrEP longer than did those on Medicaid, a median of 14.5 months, with 56% still filling their prescriptions after a year, versus a median Medicaid persistence of 7.6 months, with only a third of Medicaid patients still on PrEP after 12 months.

Men were more persistent with PrEP than were women in both groups, as were older people versus younger. The median length of adherence among commercially insured patients aged 45-54 years, for instance, was 20.5 months, versus 8.6 months among people aged 18-24 years. Older PrEP users persisted longer among Medicaid patients as well, a median of 10 versus 4 months.

Also in the Medicaid group, white patients stuck with PrEP longer than did black patients, a median of 8.5 months versus 4.1 months. There were no racial differences with commercial insurance.

The findings held even when the team used gaps of 60 and 90 days, instead of 30 days, to define nonpersistence.

The study says nothing about why people stopped PrEP, or why there were such stark differences between the groups.

Perhaps, in some cases, people quit risky behavior or entered new relationships. Maybe PrEP was too expensive for some, or transportation to the clinic was an issue. Side effects might have been a problem, or people could have lost their insurance coverage, or maybe didn’t want to deal with the hassle. It’s impossible to know from the data, Dr. Huang said.

She said her team wants to figure it out, so they can help people overcome barriers to treatment, which likely vary across subgroups.

The study also was limited to patients who were enrolled in coverage at least 6 months before and 6 months after their first PrEP prescription; the investigators want to exam the situation for people with less consistent coverage, and no coverage at all.

The work was funded by the Centers for Disease Control and Prevention. The investigators had no disclosures.

aotto@mdedge.com

SOURCE: Huang YA et al. CROI 2019, Abstract 106.

Hospitals that performed more transcatheter aortic valve replacements continued to outperform low-volume centers for 30-day postprocedure survival, in data collected from more than 113,000 transcatheter aortic valves replaced during 2015-2017.

Bruce Jancin/MDedge News

During that time, 113,662 transcatheter aortic valve replacement (TAVR) procedures occurred in the United States and were entered into a registry maintained by the Society of Thoracic Surgeons and American College of Cardiology. The new analysis focused on the more than 96,000 valve placements done via a transfemoral approach. The analysis divided these patients into quartiles based on total annual TAVR volume at each of the 554 centers where the procedures occurred, and this showed that 30-day mortality, after adjustment for 39 demographic and clinical variables, was 3.19% among patients treated at centers in the lowest-volume quartile and 2.66% in patients treated at centers in the highest-volume quartile. This translated to a 21% relative risk increase in 30-day mortality at the lowest volume centers that was statistically significant, Sreekanth Vemulapalli, MD, and his associates reported in an article published online on April 3 in the New England Journal of Medicine.

The mean annual volume among centers in the lowest-volume quartile during the 3 years studied was 27 procedures/year, while the average volume among the 25% highest-volume centers was 143 TAVRs each year, reported Dr. Vemulapalli, an interventional cardiologist at Duke University in Durham, N.C., and his associates. After excluding the first 12 months of TAVR performance for each center during the study period, the adjusted 30-day mortality averaged 3.10% in the lowest-volume tertile and 2.61% in centers in the highest-volume tertile. That meant the lowest-volume centers saw a 19% relative increase in mortality that was statistically significant.


This is not the first study to show a significant link between TAVR procedure volumes at individual centers and patient outcomes, and since 2012 the Centers for Medicare & Medicaid Services has stipulated that eligibility for Medicare coverage of TAVR requires that it be done at a center that performs at least 20 TAVR procedures annually or at least 40 during the most recent 2 years. A prior report showing a similar volume-outcome link looked at U.S. TAVR cases during 2011-2015 (J Am Coll Cardiol. 2017 July;70[1]:29-41), and reports of volume-outcome relationships have also come out for other catheter-based intravascular procedures.

“Our results suggest that raising the minimum volume requirements for TAVR centers may improve the quality of outcomes. However, this potential improvement in quality needs to be balanced against access to care in general, and for underserved and underrepresented populations in particular,” Dr. Vemulapalli said in an interview. The data suggested that a significant number of patients from underserved populations are treated at lower-volume TAVR centers. It’s unclear what impact raising the threshold volume [by CMS] might have on these underserved populations,” he explained.

Dr. Vemulapalli conceded that his analysis may have been affected by several potential confounding variables that did not receive adjustment in the analyses he and his associates ran. The variables of hospital size and teaching status both showed an association with TAVR volume. Hospitals with a greater number of beds and those that were teaching hospitals were also the places where TAVR volumes were highest, while lower-volume centers tended to be smaller, nonteaching institutions. But the variables of size and teaching status did not receive adjustment. Both are “difficult to tease apart from TAVR volume,” he noted.

The CMS mandated Transcatheter Valve Therapy Registry also functions as a quality-improvement mechanism in which U.S. TAVR sites receive quarterly feedback on their performance and are benchmarked against other programs in a risk-adjusted way. The registry also disseminates best practices as part of the quality improvement process, Dr. Vemulapalli said.

Results from two TAVR trials reported at the American College of Cardiology’s annual meeting in March, PARTNER 3 and Evolut Low Risk, documented the efficacy and safety of TAVR compared with surgery in low-risk patients, findings that will soon substantially increase the volume of TAVR cases performed (N Engl J Med. 2019 Mar 16. doi: 10.1056/NEJMoa1814052 and doi: 10.1056/NEJMoa1816885).

When the impact of TAVR moving to low-risk patients starts to kick in, “the findings from our analysis will become even more relevant,” Dr. Vemulapalli predicted. “As TAVR moves to low-risk, healthier patients, and more patients undergo the procedure, a firm commitment to measuring and ensuring quality while balancing access to care will be pivotal. The data in our study regarding the association between TAVR volume and outcomes and the characteristics of low- and high-volume hospitals and the patients they treat are fundamental to striking this balance.”

mzoler@mdedge.com

SOURCE: Vemulapalli S. et al. N Engl J Med. 2019 Apr 3.doi: 10.1056/NEJMsa1901109.

Hospitals that performed more transcatheter aortic valve replacements continued to outperform low-volume centers for 30-day postprocedure survival, in data collected from more than 113,000 transcatheter aortic valves replaced during 2015-2017.

Bruce Jancin/MDedge News

During that time, 113,662 transcatheter aortic valve replacement (TAVR) procedures occurred in the United States and were entered into a registry maintained by the Society of Thoracic Surgeons and American College of Cardiology. The new analysis focused on the more than 96,000 valve placements done via a transfemoral approach. The analysis divided these patients into quartiles based on total annual TAVR volume at each of the 554 centers where the procedures occurred, and this showed that 30-day mortality, after adjustment for 39 demographic and clinical variables, was 3.19% among patients treated at centers in the lowest-volume quartile and 2.66% in patients treated at centers in the highest-volume quartile. This translated to a 21% relative risk increase in 30-day mortality at the lowest volume centers that was statistically significant, Sreekanth Vemulapalli, MD, and his associates reported in an article published online on April 3 in the New England Journal of Medicine.

The mean annual volume among centers in the lowest-volume quartile during the 3 years studied was 27 procedures/year, while the average volume among the 25% highest-volume centers was 143 TAVRs each year, reported Dr. Vemulapalli, an interventional cardiologist at Duke University in Durham, N.C., and his associates. After excluding the first 12 months of TAVR performance for each center during the study period, the adjusted 30-day mortality averaged 3.10% in the lowest-volume tertile and 2.61% in centers in the highest-volume tertile. That meant the lowest-volume centers saw a 19% relative increase in mortality that was statistically significant.


This is not the first study to show a significant link between TAVR procedure volumes at individual centers and patient outcomes, and since 2012 the Centers for Medicare & Medicaid Services has stipulated that eligibility for Medicare coverage of TAVR requires that it be done at a center that performs at least 20 TAVR procedures annually or at least 40 during the most recent 2 years. A prior report showing a similar volume-outcome link looked at U.S. TAVR cases during 2011-2015 (J Am Coll Cardiol. 2017 July;70[1]:29-41), and reports of volume-outcome relationships have also come out for other catheter-based intravascular procedures.

“Our results suggest that raising the minimum volume requirements for TAVR centers may improve the quality of outcomes. However, this potential improvement in quality needs to be balanced against access to care in general, and for underserved and underrepresented populations in particular,” Dr. Vemulapalli said in an interview. The data suggested that a significant number of patients from underserved populations are treated at lower-volume TAVR centers. It’s unclear what impact raising the threshold volume [by CMS] might have on these underserved populations,” he explained.

Dr. Vemulapalli conceded that his analysis may have been affected by several potential confounding variables that did not receive adjustment in the analyses he and his associates ran. The variables of hospital size and teaching status both showed an association with TAVR volume. Hospitals with a greater number of beds and those that were teaching hospitals were also the places where TAVR volumes were highest, while lower-volume centers tended to be smaller, nonteaching institutions. But the variables of size and teaching status did not receive adjustment. Both are “difficult to tease apart from TAVR volume,” he noted.

The CMS mandated Transcatheter Valve Therapy Registry also functions as a quality-improvement mechanism in which U.S. TAVR sites receive quarterly feedback on their performance and are benchmarked against other programs in a risk-adjusted way. The registry also disseminates best practices as part of the quality improvement process, Dr. Vemulapalli said.

Results from two TAVR trials reported at the American College of Cardiology’s annual meeting in March, PARTNER 3 and Evolut Low Risk, documented the efficacy and safety of TAVR compared with surgery in low-risk patients, findings that will soon substantially increase the volume of TAVR cases performed (N Engl J Med. 2019 Mar 16. doi: 10.1056/NEJMoa1814052 and doi: 10.1056/NEJMoa1816885).

When the impact of TAVR moving to low-risk patients starts to kick in, “the findings from our analysis will become even more relevant,” Dr. Vemulapalli predicted. “As TAVR moves to low-risk, healthier patients, and more patients undergo the procedure, a firm commitment to measuring and ensuring quality while balancing access to care will be pivotal. The data in our study regarding the association between TAVR volume and outcomes and the characteristics of low- and high-volume hospitals and the patients they treat are fundamental to striking this balance.”

mzoler@mdedge.com

SOURCE: Vemulapalli S. et al. N Engl J Med. 2019 Apr 3.doi: 10.1056/NEJMsa1901109.

Hospitals that performed more transcatheter aortic valve replacements continued to outperform low-volume centers for 30-day postprocedure survival, in data collected from more than 113,000 transcatheter aortic valves replaced during 2015-2017.

Bruce Jancin/MDedge News

During that time, 113,662 transcatheter aortic valve replacement (TAVR) procedures occurred in the United States and were entered into a registry maintained by the Society of Thoracic Surgeons and American College of Cardiology. The new analysis focused on the more than 96,000 valve placements done via a transfemoral approach. The analysis divided these patients into quartiles based on total annual TAVR volume at each of the 554 centers where the procedures occurred, and this showed that 30-day mortality, after adjustment for 39 demographic and clinical variables, was 3.19% among patients treated at centers in the lowest-volume quartile and 2.66% in patients treated at centers in the highest-volume quartile. This translated to a 21% relative risk increase in 30-day mortality at the lowest volume centers that was statistically significant, Sreekanth Vemulapalli, MD, and his associates reported in an article published online on April 3 in the New England Journal of Medicine.

The mean annual volume among centers in the lowest-volume quartile during the 3 years studied was 27 procedures/year, while the average volume among the 25% highest-volume centers was 143 TAVRs each year, reported Dr. Vemulapalli, an interventional cardiologist at Duke University in Durham, N.C., and his associates. After excluding the first 12 months of TAVR performance for each center during the study period, the adjusted 30-day mortality averaged 3.10% in the lowest-volume tertile and 2.61% in centers in the highest-volume tertile. That meant the lowest-volume centers saw a 19% relative increase in mortality that was statistically significant.


This is not the first study to show a significant link between TAVR procedure volumes at individual centers and patient outcomes, and since 2012 the Centers for Medicare & Medicaid Services has stipulated that eligibility for Medicare coverage of TAVR requires that it be done at a center that performs at least 20 TAVR procedures annually or at least 40 during the most recent 2 years. A prior report showing a similar volume-outcome link looked at U.S. TAVR cases during 2011-2015 (J Am Coll Cardiol. 2017 July;70[1]:29-41), and reports of volume-outcome relationships have also come out for other catheter-based intravascular procedures.

“Our results suggest that raising the minimum volume requirements for TAVR centers may improve the quality of outcomes. However, this potential improvement in quality needs to be balanced against access to care in general, and for underserved and underrepresented populations in particular,” Dr. Vemulapalli said in an interview. The data suggested that a significant number of patients from underserved populations are treated at lower-volume TAVR centers. It’s unclear what impact raising the threshold volume [by CMS] might have on these underserved populations,” he explained.

Dr. Vemulapalli conceded that his analysis may have been affected by several potential confounding variables that did not receive adjustment in the analyses he and his associates ran. The variables of hospital size and teaching status both showed an association with TAVR volume. Hospitals with a greater number of beds and those that were teaching hospitals were also the places where TAVR volumes were highest, while lower-volume centers tended to be smaller, nonteaching institutions. But the variables of size and teaching status did not receive adjustment. Both are “difficult to tease apart from TAVR volume,” he noted.

The CMS mandated Transcatheter Valve Therapy Registry also functions as a quality-improvement mechanism in which U.S. TAVR sites receive quarterly feedback on their performance and are benchmarked against other programs in a risk-adjusted way. The registry also disseminates best practices as part of the quality improvement process, Dr. Vemulapalli said.

Results from two TAVR trials reported at the American College of Cardiology’s annual meeting in March, PARTNER 3 and Evolut Low Risk, documented the efficacy and safety of TAVR compared with surgery in low-risk patients, findings that will soon substantially increase the volume of TAVR cases performed (N Engl J Med. 2019 Mar 16. doi: 10.1056/NEJMoa1814052 and doi: 10.1056/NEJMoa1816885).

When the impact of TAVR moving to low-risk patients starts to kick in, “the findings from our analysis will become even more relevant,” Dr. Vemulapalli predicted. “As TAVR moves to low-risk, healthier patients, and more patients undergo the procedure, a firm commitment to measuring and ensuring quality while balancing access to care will be pivotal. The data in our study regarding the association between TAVR volume and outcomes and the characteristics of low- and high-volume hospitals and the patients they treat are fundamental to striking this balance.”

mzoler@mdedge.com

SOURCE: Vemulapalli S. et al. N Engl J Med. 2019 Apr 3.doi: 10.1056/NEJMsa1901109.

Habitual use of opioids “rewires” the brain’s reward system. In the study, researchers will be testing ANS-6637 (Amygdala Neurosciences), a drug that may inhibit the dopamine surge of opioid use, without affecting the levels of dopamine needed for normal brain function.

The phase 1 trial will enroll up to 50 healthy adults aged 18 to 65 years. On the first day of the 10-day study, they will receive a single dose of midazolam, chosen to act as a template for liver metabolism. After a drug-free day 2, on days 3 through 7 they will receive 600 mg/d of ANS-6637. On day 8, the participants will be given the 2 drugs together to determine how the investigational drug affects midazolam levels, which also will help the researchers understand how ANS-6637 is processed in the body. The volunteers will return for a final outpatient visit after 1 week.

At present, few pharmacologic interventions target opioid-related cravings, says researcher Henry Masur, MD, chief of the Clinical Center’s Critical Care Medicine Department. If proven effective, the researchers say, ANS-6637 could be part of a comprehensive package of services, including harm reduction, opioid agonist therapy, and behavioral interventions.

The study is funded through NIH’s Helping to End Addiction Long-Term (HEAL) Initiative, an “aggressive, trans-agency effort to speed scientific solutions” to the opioid crisis.

Habitual use of opioids “rewires” the brain’s reward system. In the study, researchers will be testing ANS-6637 (Amygdala Neurosciences), a drug that may inhibit the dopamine surge of opioid use, without affecting the levels of dopamine needed for normal brain function.

The phase 1 trial will enroll up to 50 healthy adults aged 18 to 65 years. On the first day of the 10-day study, they will receive a single dose of midazolam, chosen to act as a template for liver metabolism. After a drug-free day 2, on days 3 through 7 they will receive 600 mg/d of ANS-6637. On day 8, the participants will be given the 2 drugs together to determine how the investigational drug affects midazolam levels, which also will help the researchers understand how ANS-6637 is processed in the body. The volunteers will return for a final outpatient visit after 1 week.

At present, few pharmacologic interventions target opioid-related cravings, says researcher Henry Masur, MD, chief of the Clinical Center’s Critical Care Medicine Department. If proven effective, the researchers say, ANS-6637 could be part of a comprehensive package of services, including harm reduction, opioid agonist therapy, and behavioral interventions.

The study is funded through NIH’s Helping to End Addiction Long-Term (HEAL) Initiative, an “aggressive, trans-agency effort to speed scientific solutions” to the opioid crisis.

Habitual use of opioids “rewires” the brain’s reward system. In the study, researchers will be testing ANS-6637 (Amygdala Neurosciences), a drug that may inhibit the dopamine surge of opioid use, without affecting the levels of dopamine needed for normal brain function.

The phase 1 trial will enroll up to 50 healthy adults aged 18 to 65 years. On the first day of the 10-day study, they will receive a single dose of midazolam, chosen to act as a template for liver metabolism. After a drug-free day 2, on days 3 through 7 they will receive 600 mg/d of ANS-6637. On day 8, the participants will be given the 2 drugs together to determine how the investigational drug affects midazolam levels, which also will help the researchers understand how ANS-6637 is processed in the body. The volunteers will return for a final outpatient visit after 1 week.

At present, few pharmacologic interventions target opioid-related cravings, says researcher Henry Masur, MD, chief of the Clinical Center’s Critical Care Medicine Department. If proven effective, the researchers say, ANS-6637 could be part of a comprehensive package of services, including harm reduction, opioid agonist therapy, and behavioral interventions.

The study is funded through NIH’s Helping to End Addiction Long-Term (HEAL) Initiative, an “aggressive, trans-agency effort to speed scientific solutions” to the opioid crisis.

About 80% of new HIV transmissions are from people who do not know they have HIV or are not receiving regular care, according to a CDC report. That makes improvements in early detection and “rapid entry into care” key to ending the HIV epidemic within 10 years—the current US Department of Health and Human Services goal.

Recent studies have shown that viral suppression prevents sexual transmission of HIV, the researchers say. The studies found no HIV transmissions attributable to sex between HIV-discordant couples when the HIV-infected partner was maintaining viral suppression through treatment—even when the HIV-negative partner was not using preexposure prophylaxis. Those findings mean HIV transmission can become a “rare event,” the researchers say.

Today’s treatments have gotten simpler than the hills of pills that patients used to take. Sometimes the patient needs only a single-tablet regimen. Most people, according to the CDC, can achieve viral suppression within 6 months of starting treatment.

But many of the 1.1 million people with HIV infection are not effectively treated. In 2015, the CDC researchers say, 14.5% of people with HIV infection did not have a diagnosis, and 37.2% were not in care (receiving ≥ 1 CD4 tests in a measurement year). Nearly half were not virally suppressed. Lack of effective treatment results in worse outcomes and higher rates of transmission: It was associated with 38,700 new HIV infections in 2016.

The researchers used a model to estimate transmission rates in 2016 along the HIV continuum of care. Overall, the rate was 3.5 per 100 person-years. Among 9,600 people who were acutely infected and unaware of their infection, the rate was 16.1 per 100 person-years. Among 154,400 people who were nonacutely infected and unaware, the rate was 8.4.

Of the nearly 250,000 people who were aware of HIV infection but not in care, 16,500 transmissions were generated (6.6/100 person-years). Among the 125,300 who were receiving HIV care but not virally suppressed, 7,700 transmissions were generated (6.1).

The transmission rate was 0 for patients who were virally suppressed. The researchers note that 100% efficacy was assumed based on trial results for sexual transmission; no data are available on the efficacy of viral suppression on reducing HIV transmission from IV drug use.

Better detection and linkage to treatment will address most of the problem, but what about the patients who do not maintain viral suppression? Among patients in clinical care, about 80% were virally suppressed at their most recent visit, but about one-third did not sustain viral suppression over 1 year. For those patients, the researchers say, a tailored approach aimed at the barriers that are most relevant for the patient is critical to improving adherence.

The CDC recommends routine screening of all Americans aged 13 to 64 years at least once in their life and at least annual testing for those at high risk. In addition, the researchers say, it is important to spread the word that maintaining viral suppression prevents sexual transmission. Sharing this knowledge more generally might reduce the stigma associated with HIV and help engage patients in consistent care.

About 80% of new HIV transmissions are from people who do not know they have HIV or are not receiving regular care, according to a CDC report. That makes improvements in early detection and “rapid entry into care” key to ending the HIV epidemic within 10 years—the current US Department of Health and Human Services goal.

Recent studies have shown that viral suppression prevents sexual transmission of HIV, the researchers say. The studies found no HIV transmissions attributable to sex between HIV-discordant couples when the HIV-infected partner was maintaining viral suppression through treatment—even when the HIV-negative partner was not using preexposure prophylaxis. Those findings mean HIV transmission can become a “rare event,” the researchers say.

Today’s treatments have gotten simpler than the hills of pills that patients used to take. Sometimes the patient needs only a single-tablet regimen. Most people, according to the CDC, can achieve viral suppression within 6 months of starting treatment.

But many of the 1.1 million people with HIV infection are not effectively treated. In 2015, the CDC researchers say, 14.5% of people with HIV infection did not have a diagnosis, and 37.2% were not in care (receiving ≥ 1 CD4 tests in a measurement year). Nearly half were not virally suppressed. Lack of effective treatment results in worse outcomes and higher rates of transmission: It was associated with 38,700 new HIV infections in 2016.

The researchers used a model to estimate transmission rates in 2016 along the HIV continuum of care. Overall, the rate was 3.5 per 100 person-years. Among 9,600 people who were acutely infected and unaware of their infection, the rate was 16.1 per 100 person-years. Among 154,400 people who were nonacutely infected and unaware, the rate was 8.4.

Of the nearly 250,000 people who were aware of HIV infection but not in care, 16,500 transmissions were generated (6.6/100 person-years). Among the 125,300 who were receiving HIV care but not virally suppressed, 7,700 transmissions were generated (6.1).

The transmission rate was 0 for patients who were virally suppressed. The researchers note that 100% efficacy was assumed based on trial results for sexual transmission; no data are available on the efficacy of viral suppression on reducing HIV transmission from IV drug use.

Better detection and linkage to treatment will address most of the problem, but what about the patients who do not maintain viral suppression? Among patients in clinical care, about 80% were virally suppressed at their most recent visit, but about one-third did not sustain viral suppression over 1 year. For those patients, the researchers say, a tailored approach aimed at the barriers that are most relevant for the patient is critical to improving adherence.

The CDC recommends routine screening of all Americans aged 13 to 64 years at least once in their life and at least annual testing for those at high risk. In addition, the researchers say, it is important to spread the word that maintaining viral suppression prevents sexual transmission. Sharing this knowledge more generally might reduce the stigma associated with HIV and help engage patients in consistent care.

About 80% of new HIV transmissions are from people who do not know they have HIV or are not receiving regular care, according to a CDC report. That makes improvements in early detection and “rapid entry into care” key to ending the HIV epidemic within 10 years—the current US Department of Health and Human Services goal.

Recent studies have shown that viral suppression prevents sexual transmission of HIV, the researchers say. The studies found no HIV transmissions attributable to sex between HIV-discordant couples when the HIV-infected partner was maintaining viral suppression through treatment—even when the HIV-negative partner was not using preexposure prophylaxis. Those findings mean HIV transmission can become a “rare event,” the researchers say.

Today’s treatments have gotten simpler than the hills of pills that patients used to take. Sometimes the patient needs only a single-tablet regimen. Most people, according to the CDC, can achieve viral suppression within 6 months of starting treatment.

But many of the 1.1 million people with HIV infection are not effectively treated. In 2015, the CDC researchers say, 14.5% of people with HIV infection did not have a diagnosis, and 37.2% were not in care (receiving ≥ 1 CD4 tests in a measurement year). Nearly half were not virally suppressed. Lack of effective treatment results in worse outcomes and higher rates of transmission: It was associated with 38,700 new HIV infections in 2016.

The researchers used a model to estimate transmission rates in 2016 along the HIV continuum of care. Overall, the rate was 3.5 per 100 person-years. Among 9,600 people who were acutely infected and unaware of their infection, the rate was 16.1 per 100 person-years. Among 154,400 people who were nonacutely infected and unaware, the rate was 8.4.

Of the nearly 250,000 people who were aware of HIV infection but not in care, 16,500 transmissions were generated (6.6/100 person-years). Among the 125,300 who were receiving HIV care but not virally suppressed, 7,700 transmissions were generated (6.1).

The transmission rate was 0 for patients who were virally suppressed. The researchers note that 100% efficacy was assumed based on trial results for sexual transmission; no data are available on the efficacy of viral suppression on reducing HIV transmission from IV drug use.

Better detection and linkage to treatment will address most of the problem, but what about the patients who do not maintain viral suppression? Among patients in clinical care, about 80% were virally suppressed at their most recent visit, but about one-third did not sustain viral suppression over 1 year. For those patients, the researchers say, a tailored approach aimed at the barriers that are most relevant for the patient is critical to improving adherence.

The CDC recommends routine screening of all Americans aged 13 to 64 years at least once in their life and at least annual testing for those at high risk. In addition, the researchers say, it is important to spread the word that maintaining viral suppression prevents sexual transmission. Sharing this knowledge more generally might reduce the stigma associated with HIV and help engage patients in consistent care.

Poor oral health was significantly associated with poor academic performance in children aged 6-17 years, based on data from more than 45,000 children in the United States.

AGrigorjeva/Thinkstock

The study, published in the Journal of Pediatrics, updates an assessment from 2007 of a similarly representative sample of U.S. children.

“Providing an updated analysis is especially important to understand the dynamics between children’s oral health status and academic performance, given reported improvements in dental care use among children and dental treatment quality and the implementation or expansion of some state-level preventive strategies,” wrote Carol Cristina Guarnizo-Herreño, DDS, PhD, of Universidad Nacional de Colombia, Bogotá, and her colleagues.

The researchers analyzed data from the 2016 and 2017 versions of National Survey of Children’s Health that included 45,711 children aged 6-17 years. Survey data were collected from parents or other primary caregivers. In the study population, 16% of the children had a least one dental problem, defined as toothache, tooth decay or cavities, or bleeding gums, and 25% of the children had school problems: 67% missed any school, 23% missed more than 3 days of school, and 10% missed more than 6 days of school.

Overall, children with at least 1 dental problem were significantly more likely than those without dental problems to have problems at school (odds ratio, 1.56) or miss at least 1 school day (OR, 1.54) – more than 50% more likely. In addition, children with at least one dental problem were approximately 40% more likely to miss more than 3 days or more than 6 days of school (OR, 1.39 for both).

The association increased when the investigators used children’s oral health ratings; those with oral health rated as poor/fair were approximately 80% more likely to have school problems (OR, 1.77), almost 60% more likely to miss more than 3 days of school (OR, 1.56), and 90% more likely to miss more than 6 days of school, compared with children with oral health rankings of good, very good, or excellent.

Despite some variations in subgroups when the population was stratified by age, sex, race, household income, and health insurance, the associations between oral health problems and academic problems showed “remarkable stability,” across demographic and socioeconomic categories, the researchers said.

The study results were limited by several factors including the inability to identify the mechanisms behind the oral health and academic outcomes relationship, as well as the potential errors in parent or caregiver reports of children’s oral health and school performance, Dr. Guarnizo-Herreño and her associates said. However, the findings support those from an earlier study using 2007 data, and suggest that the link between poor oral health and poor academic performance has lasted for the past decade.

“The relationship between oral health and academic achievement is complex and likely involves multiple and intertwined pathways,” such as the impact of oral pain or discomfort on eating and sleeping that may affect academic performance, they said.

“These findings highlight the need for broad population-wide policies and integrated approaches to promote children’s development and reduce academic deficits that include among other components initiatives to improve oral health through prevention and treatment access strategies,” Dr. Guarnizo-Herreño and her associates concluded.

The study was supported by the National Institute of Dental and Craniofacial Research. The researchers had no financial conflicts to disclose.

SOURCE: Guarnizo-Herreño C et al. J Pediatr. 2019. doi: 10.1016/j.jpeds.2019.01.045.

Poor oral health was significantly associated with poor academic performance in children aged 6-17 years, based on data from more than 45,000 children in the United States.

AGrigorjeva/Thinkstock

The study, published in the Journal of Pediatrics, updates an assessment from 2007 of a similarly representative sample of U.S. children.

“Providing an updated analysis is especially important to understand the dynamics between children’s oral health status and academic performance, given reported improvements in dental care use among children and dental treatment quality and the implementation or expansion of some state-level preventive strategies,” wrote Carol Cristina Guarnizo-Herreño, DDS, PhD, of Universidad Nacional de Colombia, Bogotá, and her colleagues.

The researchers analyzed data from the 2016 and 2017 versions of National Survey of Children’s Health that included 45,711 children aged 6-17 years. Survey data were collected from parents or other primary caregivers. In the study population, 16% of the children had a least one dental problem, defined as toothache, tooth decay or cavities, or bleeding gums, and 25% of the children had school problems: 67% missed any school, 23% missed more than 3 days of school, and 10% missed more than 6 days of school.

Overall, children with at least 1 dental problem were significantly more likely than those without dental problems to have problems at school (odds ratio, 1.56) or miss at least 1 school day (OR, 1.54) – more than 50% more likely. In addition, children with at least one dental problem were approximately 40% more likely to miss more than 3 days or more than 6 days of school (OR, 1.39 for both).

The association increased when the investigators used children’s oral health ratings; those with oral health rated as poor/fair were approximately 80% more likely to have school problems (OR, 1.77), almost 60% more likely to miss more than 3 days of school (OR, 1.56), and 90% more likely to miss more than 6 days of school, compared with children with oral health rankings of good, very good, or excellent.

Despite some variations in subgroups when the population was stratified by age, sex, race, household income, and health insurance, the associations between oral health problems and academic problems showed “remarkable stability,” across demographic and socioeconomic categories, the researchers said.

The study results were limited by several factors including the inability to identify the mechanisms behind the oral health and academic outcomes relationship, as well as the potential errors in parent or caregiver reports of children’s oral health and school performance, Dr. Guarnizo-Herreño and her associates said. However, the findings support those from an earlier study using 2007 data, and suggest that the link between poor oral health and poor academic performance has lasted for the past decade.

“The relationship between oral health and academic achievement is complex and likely involves multiple and intertwined pathways,” such as the impact of oral pain or discomfort on eating and sleeping that may affect academic performance, they said.

“These findings highlight the need for broad population-wide policies and integrated approaches to promote children’s development and reduce academic deficits that include among other components initiatives to improve oral health through prevention and treatment access strategies,” Dr. Guarnizo-Herreño and her associates concluded.

The study was supported by the National Institute of Dental and Craniofacial Research. The researchers had no financial conflicts to disclose.

SOURCE: Guarnizo-Herreño C et al. J Pediatr. 2019. doi: 10.1016/j.jpeds.2019.01.045.

Poor oral health was significantly associated with poor academic performance in children aged 6-17 years, based on data from more than 45,000 children in the United States.

AGrigorjeva/Thinkstock

The study, published in the Journal of Pediatrics, updates an assessment from 2007 of a similarly representative sample of U.S. children.

“Providing an updated analysis is especially important to understand the dynamics between children’s oral health status and academic performance, given reported improvements in dental care use among children and dental treatment quality and the implementation or expansion of some state-level preventive strategies,” wrote Carol Cristina Guarnizo-Herreño, DDS, PhD, of Universidad Nacional de Colombia, Bogotá, and her colleagues.

The researchers analyzed data from the 2016 and 2017 versions of National Survey of Children’s Health that included 45,711 children aged 6-17 years. Survey data were collected from parents or other primary caregivers. In the study population, 16% of the children had a least one dental problem, defined as toothache, tooth decay or cavities, or bleeding gums, and 25% of the children had school problems: 67% missed any school, 23% missed more than 3 days of school, and 10% missed more than 6 days of school.

Overall, children with at least 1 dental problem were significantly more likely than those without dental problems to have problems at school (odds ratio, 1.56) or miss at least 1 school day (OR, 1.54) – more than 50% more likely. In addition, children with at least one dental problem were approximately 40% more likely to miss more than 3 days or more than 6 days of school (OR, 1.39 for both).

The association increased when the investigators used children’s oral health ratings; those with oral health rated as poor/fair were approximately 80% more likely to have school problems (OR, 1.77), almost 60% more likely to miss more than 3 days of school (OR, 1.56), and 90% more likely to miss more than 6 days of school, compared with children with oral health rankings of good, very good, or excellent.

Despite some variations in subgroups when the population was stratified by age, sex, race, household income, and health insurance, the associations between oral health problems and academic problems showed “remarkable stability,” across demographic and socioeconomic categories, the researchers said.

The study results were limited by several factors including the inability to identify the mechanisms behind the oral health and academic outcomes relationship, as well as the potential errors in parent or caregiver reports of children’s oral health and school performance, Dr. Guarnizo-Herreño and her associates said. However, the findings support those from an earlier study using 2007 data, and suggest that the link between poor oral health and poor academic performance has lasted for the past decade.

“The relationship between oral health and academic achievement is complex and likely involves multiple and intertwined pathways,” such as the impact of oral pain or discomfort on eating and sleeping that may affect academic performance, they said.

“These findings highlight the need for broad population-wide policies and integrated approaches to promote children’s development and reduce academic deficits that include among other components initiatives to improve oral health through prevention and treatment access strategies,” Dr. Guarnizo-Herreño and her associates concluded.

The study was supported by the National Institute of Dental and Craniofacial Research. The researchers had no financial conflicts to disclose.

SOURCE: Guarnizo-Herreño C et al. J Pediatr. 2019. doi: 10.1016/j.jpeds.2019.01.045.

TUCSON, ARIZ. – After pelvic reconstructive surgery, a pain management program consisting of ice, Toradol, and Tylenol led to a significant reduction in narcotics intake, compared with a standard regimen, with no difference in patient satisfaction scores.

Jim Kling/MDedge News

The new study extends findings from other surgical procedures to pelvic reconstructive surgery.

“This can limit both inpatient and outpatient narcotic use. It uses oral Toradol on an outpatient basis. It’s totally underutilized. People are afraid of it, people think it causes more bleeding, and maybe there’s a cost issue,” Andrey Petrikovets, MD, a urogynecologist in Los Angeles, said in an interview.

The regimen, which he calls ICE-T, relies in part on 16 tablets of Toradol sent home with the patient – 4 days’ worth. “It’s just 16 tablets, so it’s cheap, and patients do great with it. If you really use Toradol appropriately, especially on an outpatient basis, you can pretty much eliminate outpatient narcotic use,” said Dr. Petrikovets, who presented the work at the annual scientific meeting of the Society of Gynecologic Surgeons.

He believes that ICE-T is a good option for vaginal surgery. It’s a possibility for benign laparoscopic and perhaps robotic surgery, although those applications need to be studied. ICE-T should be avoided in patients with chronic pain, as well as patients with contraindications to any of the regimen’s medications, Dr. Petrikovets said.

According to the protocol, until hospital discharge, patients receive 20 minutes of ice to the perineum every 2 hours, 30 mg IV Toradol every 6 hours, 1,000 mg oral Tylenol every 6 hours, and 0.2 mg IV Dilaudid every 3 hours as needed for breakthrough pain. The constant pain management is important, said Dr. Petrikovets. “Patients don’t have an opportunity for the pain to get really high,” he said. At-home management includes 1,000 mg oral Tylenol every 6 hours, as needed (pain level 1-5, 60 tablets), and 10 mg Toradol every 6 hours as needed (pain level 6-10, 16 tablets).

The trial was conducted at two centers, where 63 patients were randomized to ICE-T or a standard regimen, which at the hospital included 600 mg ibuprofen every 6 hours as needed for pain levels 1-3, one tablet of Percocet (5/325 mg) every 4-6 hours as needed for pain levels 4-6, two tablets of Percocet for pain levels 7-10, and 0.2 mg IV Dilaudid every 3 hours as needed for breakthrough pain. At-home management consisted of 600 mg ibuprofen every 6 hours for pain levels 1-5 (60 tablets), and Percocet 5/325 mg every 6 hours for pain levels 6-10 (16 tablets).

Using the visual analog scale, researchers found that the 30 patients in the ICE-T arm of the study had less morning pain (VAS score, 20 mm vs. 40 mm; P = .03), and lower numerical pain score at 96 hours (2 vs. 3; P = .04). During the mornings and at 96 hours, the two groups had similar quality of recovery and satisfaction scores.

Narcotic use, measured as oral morphine equivalents, was significantly lower in the ICE-T arm between exit from the postanesthesia care unit (PACU) and hospital discharge (3 vs. 20; P less than .001) and through PACU all the way to discharge (17 vs. 38; P less than .001); 70% of patients in the ICE-T arm required no narcotics after PACU discharge, compared with 12% in the standard care arm (P less than .001).

At 96 hours, there was no significant difference between the two groups in the number of emergency department visits, percentage who had a bowel movement since surgery, or the number of Percocet/Toradol tablets taken. The ICE-T group took more Tylenol tablets than did the standard group took ibuprofen (11 vs. 6; P = .012).

SOURCE: Petrikovets A et al. SGS 2019, Abstract 07.
 

TUCSON, ARIZ. – After pelvic reconstructive surgery, a pain management program consisting of ice, Toradol, and Tylenol led to a significant reduction in narcotics intake, compared with a standard regimen, with no difference in patient satisfaction scores.

Jim Kling/MDedge News

The new study extends findings from other surgical procedures to pelvic reconstructive surgery.

“This can limit both inpatient and outpatient narcotic use. It uses oral Toradol on an outpatient basis. It’s totally underutilized. People are afraid of it, people think it causes more bleeding, and maybe there’s a cost issue,” Andrey Petrikovets, MD, a urogynecologist in Los Angeles, said in an interview.

The regimen, which he calls ICE-T, relies in part on 16 tablets of Toradol sent home with the patient – 4 days’ worth. “It’s just 16 tablets, so it’s cheap, and patients do great with it. If you really use Toradol appropriately, especially on an outpatient basis, you can pretty much eliminate outpatient narcotic use,” said Dr. Petrikovets, who presented the work at the annual scientific meeting of the Society of Gynecologic Surgeons.

He believes that ICE-T is a good option for vaginal surgery. It’s a possibility for benign laparoscopic and perhaps robotic surgery, although those applications need to be studied. ICE-T should be avoided in patients with chronic pain, as well as patients with contraindications to any of the regimen’s medications, Dr. Petrikovets said.

According to the protocol, until hospital discharge, patients receive 20 minutes of ice to the perineum every 2 hours, 30 mg IV Toradol every 6 hours, 1,000 mg oral Tylenol every 6 hours, and 0.2 mg IV Dilaudid every 3 hours as needed for breakthrough pain. The constant pain management is important, said Dr. Petrikovets. “Patients don’t have an opportunity for the pain to get really high,” he said. At-home management includes 1,000 mg oral Tylenol every 6 hours, as needed (pain level 1-5, 60 tablets), and 10 mg Toradol every 6 hours as needed (pain level 6-10, 16 tablets).

The trial was conducted at two centers, where 63 patients were randomized to ICE-T or a standard regimen, which at the hospital included 600 mg ibuprofen every 6 hours as needed for pain levels 1-3, one tablet of Percocet (5/325 mg) every 4-6 hours as needed for pain levels 4-6, two tablets of Percocet for pain levels 7-10, and 0.2 mg IV Dilaudid every 3 hours as needed for breakthrough pain. At-home management consisted of 600 mg ibuprofen every 6 hours for pain levels 1-5 (60 tablets), and Percocet 5/325 mg every 6 hours for pain levels 6-10 (16 tablets).

Using the visual analog scale, researchers found that the 30 patients in the ICE-T arm of the study had less morning pain (VAS score, 20 mm vs. 40 mm; P = .03), and lower numerical pain score at 96 hours (2 vs. 3; P = .04). During the mornings and at 96 hours, the two groups had similar quality of recovery and satisfaction scores.

Narcotic use, measured as oral morphine equivalents, was significantly lower in the ICE-T arm between exit from the postanesthesia care unit (PACU) and hospital discharge (3 vs. 20; P less than .001) and through PACU all the way to discharge (17 vs. 38; P less than .001); 70% of patients in the ICE-T arm required no narcotics after PACU discharge, compared with 12% in the standard care arm (P less than .001).

At 96 hours, there was no significant difference between the two groups in the number of emergency department visits, percentage who had a bowel movement since surgery, or the number of Percocet/Toradol tablets taken. The ICE-T group took more Tylenol tablets than did the standard group took ibuprofen (11 vs. 6; P = .012).

SOURCE: Petrikovets A et al. SGS 2019, Abstract 07.
 

TUCSON, ARIZ. – After pelvic reconstructive surgery, a pain management program consisting of ice, Toradol, and Tylenol led to a significant reduction in narcotics intake, compared with a standard regimen, with no difference in patient satisfaction scores.

Jim Kling/MDedge News

The new study extends findings from other surgical procedures to pelvic reconstructive surgery.

“This can limit both inpatient and outpatient narcotic use. It uses oral Toradol on an outpatient basis. It’s totally underutilized. People are afraid of it, people think it causes more bleeding, and maybe there’s a cost issue,” Andrey Petrikovets, MD, a urogynecologist in Los Angeles, said in an interview.

The regimen, which he calls ICE-T, relies in part on 16 tablets of Toradol sent home with the patient – 4 days’ worth. “It’s just 16 tablets, so it’s cheap, and patients do great with it. If you really use Toradol appropriately, especially on an outpatient basis, you can pretty much eliminate outpatient narcotic use,” said Dr. Petrikovets, who presented the work at the annual scientific meeting of the Society of Gynecologic Surgeons.

He believes that ICE-T is a good option for vaginal surgery. It’s a possibility for benign laparoscopic and perhaps robotic surgery, although those applications need to be studied. ICE-T should be avoided in patients with chronic pain, as well as patients with contraindications to any of the regimen’s medications, Dr. Petrikovets said.

According to the protocol, until hospital discharge, patients receive 20 minutes of ice to the perineum every 2 hours, 30 mg IV Toradol every 6 hours, 1,000 mg oral Tylenol every 6 hours, and 0.2 mg IV Dilaudid every 3 hours as needed for breakthrough pain. The constant pain management is important, said Dr. Petrikovets. “Patients don’t have an opportunity for the pain to get really high,” he said. At-home management includes 1,000 mg oral Tylenol every 6 hours, as needed (pain level 1-5, 60 tablets), and 10 mg Toradol every 6 hours as needed (pain level 6-10, 16 tablets).

The trial was conducted at two centers, where 63 patients were randomized to ICE-T or a standard regimen, which at the hospital included 600 mg ibuprofen every 6 hours as needed for pain levels 1-3, one tablet of Percocet (5/325 mg) every 4-6 hours as needed for pain levels 4-6, two tablets of Percocet for pain levels 7-10, and 0.2 mg IV Dilaudid every 3 hours as needed for breakthrough pain. At-home management consisted of 600 mg ibuprofen every 6 hours for pain levels 1-5 (60 tablets), and Percocet 5/325 mg every 6 hours for pain levels 6-10 (16 tablets).

Using the visual analog scale, researchers found that the 30 patients in the ICE-T arm of the study had less morning pain (VAS score, 20 mm vs. 40 mm; P = .03), and lower numerical pain score at 96 hours (2 vs. 3; P = .04). During the mornings and at 96 hours, the two groups had similar quality of recovery and satisfaction scores.

Narcotic use, measured as oral morphine equivalents, was significantly lower in the ICE-T arm between exit from the postanesthesia care unit (PACU) and hospital discharge (3 vs. 20; P less than .001) and through PACU all the way to discharge (17 vs. 38; P less than .001); 70% of patients in the ICE-T arm required no narcotics after PACU discharge, compared with 12% in the standard care arm (P less than .001).

At 96 hours, there was no significant difference between the two groups in the number of emergency department visits, percentage who had a bowel movement since surgery, or the number of Percocet/Toradol tablets taken. The ICE-T group took more Tylenol tablets than did the standard group took ibuprofen (11 vs. 6; P = .012).

SOURCE: Petrikovets A et al. SGS 2019, Abstract 07.
 

NEW ORLEANS – In a large community-based study that evaluated sex hormone levels in older men, higher levels of estradiol correlated strongly with longer telomere length, a measure of biologic age, suggesting that sex hormones influence the aging process.

“There was a large effect size, comparable with being 2 or 3 years younger for those with relatively high levels of estradiol, compared with those with lower levels of the hormone,” said Bu Yeap, MBBS, PhD, professor of medicine, University of Western Australia Medical School, Perth, who reported the results at the annual meeting of the Endocrine Society.

In a video interview conducted at the meeting, Dr. Yeap explained the basis of the study, which is the variety of evidence showing that decline in sex hormones correlates with higher rates of age-related disease processes. For example, increasing rates of cardiovascular disease, dementia, and mortality in men all correlate with declining levels of testosterone.

In the study, 2,913 men between the ages of 70 and 89 years and living in the community were recruited. The average age of the men was 77 years. Serum levels of testosterone, dihydrotestosterone, and estradiol were measured. Telomere length was calculated with a polymerase chain reaction test.

Serum levels of testosterone and dihydrotestosterone did not correlate with telomere length, but incremental increases in serum estradiol levels were associated with incremental increases in telomere length.

“Telomeres are both a mediator and a biomarker for biological aging,” according to Dr. Yeap, who added that the telomeres protect chromosomes from degradation. As the telomeres shorten, cell senescence is increased along with an array of age-related diseases.

The next step for researchers is to evaluate whether administering exogenous sex hormones can favorably alter telomere length. If such an effect is demonstrated, then it could provide a step toward understanding how to slow the aging process, he said.

Dr Yeap and his colleagues reported no disclosures or financial conflicts of interest.

Vidyard Video

NEW ORLEANS – In a large community-based study that evaluated sex hormone levels in older men, higher levels of estradiol correlated strongly with longer telomere length, a measure of biologic age, suggesting that sex hormones influence the aging process.

“There was a large effect size, comparable with being 2 or 3 years younger for those with relatively high levels of estradiol, compared with those with lower levels of the hormone,” said Bu Yeap, MBBS, PhD, professor of medicine, University of Western Australia Medical School, Perth, who reported the results at the annual meeting of the Endocrine Society.

In a video interview conducted at the meeting, Dr. Yeap explained the basis of the study, which is the variety of evidence showing that decline in sex hormones correlates with higher rates of age-related disease processes. For example, increasing rates of cardiovascular disease, dementia, and mortality in men all correlate with declining levels of testosterone.

In the study, 2,913 men between the ages of 70 and 89 years and living in the community were recruited. The average age of the men was 77 years. Serum levels of testosterone, dihydrotestosterone, and estradiol were measured. Telomere length was calculated with a polymerase chain reaction test.

Serum levels of testosterone and dihydrotestosterone did not correlate with telomere length, but incremental increases in serum estradiol levels were associated with incremental increases in telomere length.

“Telomeres are both a mediator and a biomarker for biological aging,” according to Dr. Yeap, who added that the telomeres protect chromosomes from degradation. As the telomeres shorten, cell senescence is increased along with an array of age-related diseases.

The next step for researchers is to evaluate whether administering exogenous sex hormones can favorably alter telomere length. If such an effect is demonstrated, then it could provide a step toward understanding how to slow the aging process, he said.

Dr Yeap and his colleagues reported no disclosures or financial conflicts of interest.

Vidyard Video

NEW ORLEANS – In a large community-based study that evaluated sex hormone levels in older men, higher levels of estradiol correlated strongly with longer telomere length, a measure of biologic age, suggesting that sex hormones influence the aging process.

“There was a large effect size, comparable with being 2 or 3 years younger for those with relatively high levels of estradiol, compared with those with lower levels of the hormone,” said Bu Yeap, MBBS, PhD, professor of medicine, University of Western Australia Medical School, Perth, who reported the results at the annual meeting of the Endocrine Society.

In a video interview conducted at the meeting, Dr. Yeap explained the basis of the study, which is the variety of evidence showing that decline in sex hormones correlates with higher rates of age-related disease processes. For example, increasing rates of cardiovascular disease, dementia, and mortality in men all correlate with declining levels of testosterone.

In the study, 2,913 men between the ages of 70 and 89 years and living in the community were recruited. The average age of the men was 77 years. Serum levels of testosterone, dihydrotestosterone, and estradiol were measured. Telomere length was calculated with a polymerase chain reaction test.

Serum levels of testosterone and dihydrotestosterone did not correlate with telomere length, but incremental increases in serum estradiol levels were associated with incremental increases in telomere length.

“Telomeres are both a mediator and a biomarker for biological aging,” according to Dr. Yeap, who added that the telomeres protect chromosomes from degradation. As the telomeres shorten, cell senescence is increased along with an array of age-related diseases.

The next step for researchers is to evaluate whether administering exogenous sex hormones can favorably alter telomere length. If such an effect is demonstrated, then it could provide a step toward understanding how to slow the aging process, he said.

Dr Yeap and his colleagues reported no disclosures or financial conflicts of interest.

Vidyard Video

Cigna and Express Scripts have announced a new patient assistance program aimed at ensuring that patients with diabetes are not prevented by cost-related issues from getting access to insulin.

KatarzynaBialasiewicz/Thinkstock

The new program, open to Cigna members who are covered in commercial plans, would cap out-of-pocket costs for a 30-day supply of insulin at $25. For plan members, the only eligibility requirement is having an out-of-pocket cost higher than $25, according to a press release.

For a member to participate in the program, the plan administrator at the member’s place of employment has to opt in to it. There are no eligibility requirements imposed on the employer, other than a willingness to opt in.

A spokeswoman for Express Scripts said that there is no charge to sign up for the program, and most plans will not see an additional cost to get the copayment to $25 for the patient.

The announcement comes in the wake of the first of two hearings by the House Committee on Energy & Commerce aimed at understanding why insulin prices have spiked in recent years. The first hearing, held on April 2, examined the impact that the high list price of insulin is having on patients, and how out-of-pocket expenses are limiting access to this life-saving drug. The second hearing, expected to occur during the week of April 8 (the date had not been scheduled as of press time), will bring together various players in the supply chain, including the three major manufacturers of insulin.

“We are confident that our new program will remove cost as a barrier for people in participating plans who need insulin,” Steve Miller, MD, executive vice president and chief clinical officer at Cigna, said in a statement.

The Express Scripts spokeswoman noted that there were more than 700,000 people in a commercially insured plan across Cigna and Express Scripts who had a claim for insulin in 2018. The average out-of-pocket cost of a 30-day supply of insulin in 2018 across this population was $41.50.

gtwachtman@mdedge.com

Cigna and Express Scripts have announced a new patient assistance program aimed at ensuring that patients with diabetes are not prevented by cost-related issues from getting access to insulin.

KatarzynaBialasiewicz/Thinkstock

The new program, open to Cigna members who are covered in commercial plans, would cap out-of-pocket costs for a 30-day supply of insulin at $25. For plan members, the only eligibility requirement is having an out-of-pocket cost higher than $25, according to a press release.

For a member to participate in the program, the plan administrator at the member’s place of employment has to opt in to it. There are no eligibility requirements imposed on the employer, other than a willingness to opt in.

A spokeswoman for Express Scripts said that there is no charge to sign up for the program, and most plans will not see an additional cost to get the copayment to $25 for the patient.

The announcement comes in the wake of the first of two hearings by the House Committee on Energy & Commerce aimed at understanding why insulin prices have spiked in recent years. The first hearing, held on April 2, examined the impact that the high list price of insulin is having on patients, and how out-of-pocket expenses are limiting access to this life-saving drug. The second hearing, expected to occur during the week of April 8 (the date had not been scheduled as of press time), will bring together various players in the supply chain, including the three major manufacturers of insulin.

“We are confident that our new program will remove cost as a barrier for people in participating plans who need insulin,” Steve Miller, MD, executive vice president and chief clinical officer at Cigna, said in a statement.

The Express Scripts spokeswoman noted that there were more than 700,000 people in a commercially insured plan across Cigna and Express Scripts who had a claim for insulin in 2018. The average out-of-pocket cost of a 30-day supply of insulin in 2018 across this population was $41.50.

gtwachtman@mdedge.com

Cigna and Express Scripts have announced a new patient assistance program aimed at ensuring that patients with diabetes are not prevented by cost-related issues from getting access to insulin.

KatarzynaBialasiewicz/Thinkstock

The new program, open to Cigna members who are covered in commercial plans, would cap out-of-pocket costs for a 30-day supply of insulin at $25. For plan members, the only eligibility requirement is having an out-of-pocket cost higher than $25, according to a press release.

For a member to participate in the program, the plan administrator at the member’s place of employment has to opt in to it. There are no eligibility requirements imposed on the employer, other than a willingness to opt in.

A spokeswoman for Express Scripts said that there is no charge to sign up for the program, and most plans will not see an additional cost to get the copayment to $25 for the patient.

The announcement comes in the wake of the first of two hearings by the House Committee on Energy & Commerce aimed at understanding why insulin prices have spiked in recent years. The first hearing, held on April 2, examined the impact that the high list price of insulin is having on patients, and how out-of-pocket expenses are limiting access to this life-saving drug. The second hearing, expected to occur during the week of April 8 (the date had not been scheduled as of press time), will bring together various players in the supply chain, including the three major manufacturers of insulin.

“We are confident that our new program will remove cost as a barrier for people in participating plans who need insulin,” Steve Miller, MD, executive vice president and chief clinical officer at Cigna, said in a statement.

The Express Scripts spokeswoman noted that there were more than 700,000 people in a commercially insured plan across Cigna and Express Scripts who had a claim for insulin in 2018. The average out-of-pocket cost of a 30-day supply of insulin in 2018 across this population was $41.50.

gtwachtman@mdedge.com