Opzelura FDA Approved for Atopic Dermatitis Incyte

Corporation announces US Food and Drug Administration (FDA) approval of Opzelura (ruxolitinib) cream 1.5% for the short-term and noncontinuous chronic treatment of mild to moderate atopic dermatitis (AD) in nonimmunocompromised patients 12 years and older whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. Opzelura is formulated with ruxolitinib, a selective Janus kinase (JAK) 1/JAK2 inhibitor, to target key cytokine signals believed to contribute to itch and inflammation. For more information, visit www.opzelurahcp.com/.

Twyneo FDA Approved for Acne Vulgaris

Sol-Gel Technologies, Ltd, announces US Food and Drug Administration (FDA) approval of Twyneo (tretinoin 0.1% /benzoyl peroxide 3%) cream for the treatment of acne vulgaris in adult and pediatric patients 9 years and older. Tretinoin and benzoyl peroxide are widely prescribed separately for acne vulgaris; however, benzoyl peroxide causes degradation of the tretinoin molecule, thereby potentially reducing its effectiveness if used at the same time or combined in the same formulation. The formulation of Twyneo uses silica (silicon dioxide) core shell structures to separately microencapsulate tretinoin crystals and benzoyl peroxide crystals, enabling inclusion of the 2 active ingredients in the cream. For more information, visit www.sol-gel.com.

If you would like your product included in Product News, please email a press release to the Editorial Office at [email protected].

Opzelura FDA Approved for Atopic Dermatitis Incyte

Corporation announces US Food and Drug Administration (FDA) approval of Opzelura (ruxolitinib) cream 1.5% for the short-term and noncontinuous chronic treatment of mild to moderate atopic dermatitis (AD) in nonimmunocompromised patients 12 years and older whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. Opzelura is formulated with ruxolitinib, a selective Janus kinase (JAK) 1/JAK2 inhibitor, to target key cytokine signals believed to contribute to itch and inflammation. For more information, visit www.opzelurahcp.com/.

Twyneo FDA Approved for Acne Vulgaris

Sol-Gel Technologies, Ltd, announces US Food and Drug Administration (FDA) approval of Twyneo (tretinoin 0.1% /benzoyl peroxide 3%) cream for the treatment of acne vulgaris in adult and pediatric patients 9 years and older. Tretinoin and benzoyl peroxide are widely prescribed separately for acne vulgaris; however, benzoyl peroxide causes degradation of the tretinoin molecule, thereby potentially reducing its effectiveness if used at the same time or combined in the same formulation. The formulation of Twyneo uses silica (silicon dioxide) core shell structures to separately microencapsulate tretinoin crystals and benzoyl peroxide crystals, enabling inclusion of the 2 active ingredients in the cream. For more information, visit www.sol-gel.com.

If you would like your product included in Product News, please email a press release to the Editorial Office at [email protected].

Opzelura FDA Approved for Atopic Dermatitis Incyte

Corporation announces US Food and Drug Administration (FDA) approval of Opzelura (ruxolitinib) cream 1.5% for the short-term and noncontinuous chronic treatment of mild to moderate atopic dermatitis (AD) in nonimmunocompromised patients 12 years and older whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. Opzelura is formulated with ruxolitinib, a selective Janus kinase (JAK) 1/JAK2 inhibitor, to target key cytokine signals believed to contribute to itch and inflammation. For more information, visit www.opzelurahcp.com/.

Twyneo FDA Approved for Acne Vulgaris

Sol-Gel Technologies, Ltd, announces US Food and Drug Administration (FDA) approval of Twyneo (tretinoin 0.1% /benzoyl peroxide 3%) cream for the treatment of acne vulgaris in adult and pediatric patients 9 years and older. Tretinoin and benzoyl peroxide are widely prescribed separately for acne vulgaris; however, benzoyl peroxide causes degradation of the tretinoin molecule, thereby potentially reducing its effectiveness if used at the same time or combined in the same formulation. The formulation of Twyneo uses silica (silicon dioxide) core shell structures to separately microencapsulate tretinoin crystals and benzoyl peroxide crystals, enabling inclusion of the 2 active ingredients in the cream. For more information, visit www.sol-gel.com.

If you would like your product included in Product News, please email a press release to the Editorial Office at [email protected].

Inspired by the ABIM Foundation’s Choosing Wisely^® campaign, the “Things We Do for No Reason” (TWDFNR) series reviews practices that have become common parts of hospital care but may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent clear-cut conclusions or clinical practice standards but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion.

A 56-year-old man with coronary artery disease (CAD) undergoes hospital treatment for diverticulitis. He receives ketorolac for abdominal pain upon arrival to the medical ward despite his known allergy to nonsteroidal anti-inflammatory drugs. Fifteen minutes after administration, he develops lightheadedness and experiences swelling of his lips. On exam, he has tachycardia and a diffuse urticarial rash across his torso. The admitting physician prescribes methylprednisolone, diphenhydramine, and a liter bolus of normal saline for suspected anaphylaxis. Epinephrine is not administered for fear of precipitating an adverse cardiovascular event given the patient’s history of CAD.

Anaphylaxis, a rapid-onset generalized immunoglobulin E (IgE)–mediated hypersensitivity reaction, can lead to significant morbidity and mortality when not managed properly. Patients can present with anaphylaxis in heterogeneous ways. Fulfilling any one of three criteria establishes the diagnosis of anaphylaxis: (1) rapid onset of skin or mucosal symptoms complicated by either respiratory compromise or hypotension; (2) two or more symptoms involving the respiratory, mucosal, cardiovascular, or gastrointestinal systems following exposure to a likely allergen; and (3) reduced blood pressure in response to a known allergen.¹ Up to 5% of the population experiences anaphylaxis in a lifetime. Medication and stinging insects account for the majority of anaphylactic reactions in adults, while food and insect stings commonly trigger it in children and adolescents.²

The majority of anaphylactic reactions, known as uniphasic or monophasic, occur rapidly as single episodes following exposure to a specific trigger and resolve within minutes to hours after treatment. Meanwhile, biphasic, or delayed-phase, anaphylaxis occurs when symptoms recur after an apparent resolution and in the absence of reexposure to the trigger. Symptoms restart within 1 to 72 hours after resolution of an initial anaphylaxis episode, with a median time to onset of 11 hours. Biphasic reactions occur in roughly 5% of patients with anaphylaxis.³

Epinephrine is the only recommended first-line medication for the treatment of anaphylaxis in all age groups.⁴ Epinephrine counteracts the cardiovascular and respiratory compromise induced by anaphylaxis through its α- and β-adrenergic activity and stabilizes mast cells.⁴ Early administration of intramuscular epinephrine decreases the need for additional interventions, reduces the likelihood of hospitalization, and is associated with reduced biphasic reactions.^5-7 Paradoxically, patients receive corticosteroids more often than epinephrine for suspected anaphylaxis, despite no robust evidence for their efficacy.^4,8,9

Corticosteroids act as potent anti-inflammatory medications that modulate mast-cell maturation, activation, and degranulation. Known to work primarily through downregulation of gene transcription responsible for cytokine, chemokine, and arachidonic acid production, their maximal anti-inflammatory effects manifest 2 to 6 hours after administration. Demonstrated efficacy in treating and preventing relapse of other inflammatory conditions, such as asthma and croup, may, in part, explain the widespread glucocorticoid use in anaphylaxis. Some believe that administration of corticosteroids may also help reduce the risk of biphasic or delayed-phase anaphylaxis.¹⁰

Based on their mechanism of action, corticosteroids do not exert any anti-inflammatory effects for several hours, regardless of their route of administration.¹⁰ In contrast, epinephrine exerts an almost immediate effect to increase cardiac output and vascular resistance, to reverse edema and bronchoconstriction, and to stabilize mast cells, preventing release of harmful chemokines and cytokines.⁴

The American Academy of Allergy, Asthma & Immunology (AAAAI) recommends early administration of epinephrine as the first-line treatment of anaphylaxis and emphasizes that evidence does not support routine corticosteroid use in the management of acute anaphylaxis or for prevention of biphasic reactions.⁹ To date, no randomized controlled trials have explored the role of corticosteroids in the treatment of acute anaphylaxis, although one is currently under way looking at whether dexamethasone has an impact on preventing biphasic reactions (Table).¹¹

The AAAAI Joint Task Force on Practice Parameters (JTFPP) conducted a pooled analysis of observational studies that did not find a reduction in biphasic reactions in adult patients receiving corticosteroids (odds ratio [OR], 0.87; 95% CI, 0.74-1.02).⁹ Further, their analysis suggests an association with administration of corticosteroids and an increased likelihood of biphasic reactions in children (OR, 1.55; 95% CI, 1.01-2.38).⁹

An observational study in children across 35 hospitals demonstrated an association with corticosteroid administration and a reduced length of hospital stay for anaphylaxis, but the same study found no reduction in repeat emergency department (ED) visits within 72 hours.¹² Similarly, a retrospective cohort study in adults did not find that corticosteroid administration reduced the 7-day risk of returning to the hospital.¹³ These studies highlight the importance of anticipatory guidance in both ED and hospital discharges for anaphylaxis since the literature does not provide data that corticosteroid administration reduces the likelihood of a biphasic course.

Long-term corticosteroids have well-known deleterious health effects. Recent evidence highlights the possible adverse events associated with even short courses of corticosteroids. A large case series from Taiwan containing 2,623,327 adults administered brief courses (<14 days) of corticosteroids demonstrated increased incidence of gastrointestinal bleeding, sepsis, and heart failure beginning 5 to 30 days after starting corticosteroid treatments for common medical conditions, with respective absolute risk increases of 10.3, 0.1, and 1 per 1000 patient-years for each condition.¹⁴ The same group of researchers found a nearly two-fold increased risk of sepsis, gastrointestinal bleeding, and pneumonia in a nearly 1 million children who had received corticosteroids within the previous year.¹⁵ Other common side effects of short-term corticosteroids include insomnia, agitation, mood disturbances, and hyperglycemia.

A growing body of evidence demonstrates that corticosteroids likely do not alter the natural disease course of anaphylaxis and carry increased risks of significant adverse events. The AAAAI recommends against the use of glucocorticoids as a first-line agent for anaphylaxis and suggests against the use of glucocorticoids to prevent biphasic reactions.⁹

The recent JTFPP analysis of observational studies demonstrated reduced hypersensitivity reactions to chemotherapeutics with corticosteroid premedication (OR, 0.49; 95% CI, 0.37-0.66). The AAAAI favors administration of corticosteroids to reduce the risk of anaphylactoid reactions—non–IgE-mediated mast cell activation—for some chemotherapeutic protocols.⁹

There is robust evidence regarding the benefits of corticosteroids in the treatment of asthma and upper-airway edema.^16,17 Allergen exposures can precipitate significant bronchospasm in individuals with asthma and trigger an exacerbation. Although routine corticosteroid use for anaphylaxis in these populations has not been directly studied, their use as an adjunctive therapy may be beneficial if there is clinical evidence of bronchospasm or significant upper-airway edema.

Rapid administration of epinephrine saves lives, reduces need for adjuvant treatments and hospitalization, and is associated with decreased risk of developing biphasic anaphylactic reactions (OR, 0.2; 95% CI, 0-0.6).^5-7 Some clinicians are apprehensive about using epinephrine owing to fears related to negative side effects, particularly adverse cardiovascular events. Kawano et al¹⁸ performed a retrospective evaluation of 492 ED visits for anaphylaxis and found that epinephrine is administered less often in older patients (age >50 years); however, when administered intramuscularly, there was no significant difference in adverse cardiovascular events in this population compared with younger individuals. The study did demonstrate an increased rate of adverse cardiac events in older patients receiving intravenous epinephrine, an observation that the authors attributed partly to dosing errors that were reported more often with intravenous use.¹⁸

• Always promptly administer intramuscular epinephrine when treating anaphylaxis.
• Routine administration of corticosteroids in the treatment of anaphylaxis is not advised owing to insufficient data supporting their efficacy and potential for adverse events. Some patient populations may derive benefit from corticosteroids, including individuals with history of asthma exhibiting bronchospastic symptoms, individuals with significant upper-airway edema, and those undergoing certain chemotherapy regimens.

In the clinical vignette, the hospitalist withheld the first-line treatment for anaphylaxis, epinephrine. Without the support of evidence in the literature, patients receive corticosteroids and antihistamines more often than epinephrine for suspected anaphylaxis. No evidence supports the routine use of corticosteroids in the management of anaphylaxis or in the prevention of biphasic reactions. Further, recent research demonstrates significant adverse events are associated with even short courses of corticosteroids.

Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason”? Share what you do in your practice and join in the conversation online by retweeting it on Twitter (#TWDFNR) and liking it on Facebook. We invite you to propose ideas for other “Things We Do for No Reason” topics by emailing [email protected].

Inspired by the ABIM Foundation’s Choosing Wisely^® campaign, the “Things We Do for No Reason” (TWDFNR) series reviews practices that have become common parts of hospital care but may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent clear-cut conclusions or clinical practice standards but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion.

A 56-year-old man with coronary artery disease (CAD) undergoes hospital treatment for diverticulitis. He receives ketorolac for abdominal pain upon arrival to the medical ward despite his known allergy to nonsteroidal anti-inflammatory drugs. Fifteen minutes after administration, he develops lightheadedness and experiences swelling of his lips. On exam, he has tachycardia and a diffuse urticarial rash across his torso. The admitting physician prescribes methylprednisolone, diphenhydramine, and a liter bolus of normal saline for suspected anaphylaxis. Epinephrine is not administered for fear of precipitating an adverse cardiovascular event given the patient’s history of CAD.

Anaphylaxis, a rapid-onset generalized immunoglobulin E (IgE)–mediated hypersensitivity reaction, can lead to significant morbidity and mortality when not managed properly. Patients can present with anaphylaxis in heterogeneous ways. Fulfilling any one of three criteria establishes the diagnosis of anaphylaxis: (1) rapid onset of skin or mucosal symptoms complicated by either respiratory compromise or hypotension; (2) two or more symptoms involving the respiratory, mucosal, cardiovascular, or gastrointestinal systems following exposure to a likely allergen; and (3) reduced blood pressure in response to a known allergen.¹ Up to 5% of the population experiences anaphylaxis in a lifetime. Medication and stinging insects account for the majority of anaphylactic reactions in adults, while food and insect stings commonly trigger it in children and adolescents.²

The majority of anaphylactic reactions, known as uniphasic or monophasic, occur rapidly as single episodes following exposure to a specific trigger and resolve within minutes to hours after treatment. Meanwhile, biphasic, or delayed-phase, anaphylaxis occurs when symptoms recur after an apparent resolution and in the absence of reexposure to the trigger. Symptoms restart within 1 to 72 hours after resolution of an initial anaphylaxis episode, with a median time to onset of 11 hours. Biphasic reactions occur in roughly 5% of patients with anaphylaxis.³

Epinephrine is the only recommended first-line medication for the treatment of anaphylaxis in all age groups.⁴ Epinephrine counteracts the cardiovascular and respiratory compromise induced by anaphylaxis through its α- and β-adrenergic activity and stabilizes mast cells.⁴ Early administration of intramuscular epinephrine decreases the need for additional interventions, reduces the likelihood of hospitalization, and is associated with reduced biphasic reactions.^5-7 Paradoxically, patients receive corticosteroids more often than epinephrine for suspected anaphylaxis, despite no robust evidence for their efficacy.^4,8,9

Corticosteroids act as potent anti-inflammatory medications that modulate mast-cell maturation, activation, and degranulation. Known to work primarily through downregulation of gene transcription responsible for cytokine, chemokine, and arachidonic acid production, their maximal anti-inflammatory effects manifest 2 to 6 hours after administration. Demonstrated efficacy in treating and preventing relapse of other inflammatory conditions, such as asthma and croup, may, in part, explain the widespread glucocorticoid use in anaphylaxis. Some believe that administration of corticosteroids may also help reduce the risk of biphasic or delayed-phase anaphylaxis.¹⁰

Based on their mechanism of action, corticosteroids do not exert any anti-inflammatory effects for several hours, regardless of their route of administration.¹⁰ In contrast, epinephrine exerts an almost immediate effect to increase cardiac output and vascular resistance, to reverse edema and bronchoconstriction, and to stabilize mast cells, preventing release of harmful chemokines and cytokines.⁴

The American Academy of Allergy, Asthma & Immunology (AAAAI) recommends early administration of epinephrine as the first-line treatment of anaphylaxis and emphasizes that evidence does not support routine corticosteroid use in the management of acute anaphylaxis or for prevention of biphasic reactions.⁹ To date, no randomized controlled trials have explored the role of corticosteroids in the treatment of acute anaphylaxis, although one is currently under way looking at whether dexamethasone has an impact on preventing biphasic reactions (Table).¹¹

The AAAAI Joint Task Force on Practice Parameters (JTFPP) conducted a pooled analysis of observational studies that did not find a reduction in biphasic reactions in adult patients receiving corticosteroids (odds ratio [OR], 0.87; 95% CI, 0.74-1.02).⁹ Further, their analysis suggests an association with administration of corticosteroids and an increased likelihood of biphasic reactions in children (OR, 1.55; 95% CI, 1.01-2.38).⁹

An observational study in children across 35 hospitals demonstrated an association with corticosteroid administration and a reduced length of hospital stay for anaphylaxis, but the same study found no reduction in repeat emergency department (ED) visits within 72 hours.¹² Similarly, a retrospective cohort study in adults did not find that corticosteroid administration reduced the 7-day risk of returning to the hospital.¹³ These studies highlight the importance of anticipatory guidance in both ED and hospital discharges for anaphylaxis since the literature does not provide data that corticosteroid administration reduces the likelihood of a biphasic course.

Long-term corticosteroids have well-known deleterious health effects. Recent evidence highlights the possible adverse events associated with even short courses of corticosteroids. A large case series from Taiwan containing 2,623,327 adults administered brief courses (<14 days) of corticosteroids demonstrated increased incidence of gastrointestinal bleeding, sepsis, and heart failure beginning 5 to 30 days after starting corticosteroid treatments for common medical conditions, with respective absolute risk increases of 10.3, 0.1, and 1 per 1000 patient-years for each condition.¹⁴ The same group of researchers found a nearly two-fold increased risk of sepsis, gastrointestinal bleeding, and pneumonia in a nearly 1 million children who had received corticosteroids within the previous year.¹⁵ Other common side effects of short-term corticosteroids include insomnia, agitation, mood disturbances, and hyperglycemia.

A growing body of evidence demonstrates that corticosteroids likely do not alter the natural disease course of anaphylaxis and carry increased risks of significant adverse events. The AAAAI recommends against the use of glucocorticoids as a first-line agent for anaphylaxis and suggests against the use of glucocorticoids to prevent biphasic reactions.⁹

The recent JTFPP analysis of observational studies demonstrated reduced hypersensitivity reactions to chemotherapeutics with corticosteroid premedication (OR, 0.49; 95% CI, 0.37-0.66). The AAAAI favors administration of corticosteroids to reduce the risk of anaphylactoid reactions—non–IgE-mediated mast cell activation—for some chemotherapeutic protocols.⁹

There is robust evidence regarding the benefits of corticosteroids in the treatment of asthma and upper-airway edema.^16,17 Allergen exposures can precipitate significant bronchospasm in individuals with asthma and trigger an exacerbation. Although routine corticosteroid use for anaphylaxis in these populations has not been directly studied, their use as an adjunctive therapy may be beneficial if there is clinical evidence of bronchospasm or significant upper-airway edema.

Rapid administration of epinephrine saves lives, reduces need for adjuvant treatments and hospitalization, and is associated with decreased risk of developing biphasic anaphylactic reactions (OR, 0.2; 95% CI, 0-0.6).^5-7 Some clinicians are apprehensive about using epinephrine owing to fears related to negative side effects, particularly adverse cardiovascular events. Kawano et al¹⁸ performed a retrospective evaluation of 492 ED visits for anaphylaxis and found that epinephrine is administered less often in older patients (age >50 years); however, when administered intramuscularly, there was no significant difference in adverse cardiovascular events in this population compared with younger individuals. The study did demonstrate an increased rate of adverse cardiac events in older patients receiving intravenous epinephrine, an observation that the authors attributed partly to dosing errors that were reported more often with intravenous use.¹⁸

• Always promptly administer intramuscular epinephrine when treating anaphylaxis.
• Routine administration of corticosteroids in the treatment of anaphylaxis is not advised owing to insufficient data supporting their efficacy and potential for adverse events. Some patient populations may derive benefit from corticosteroids, including individuals with history of asthma exhibiting bronchospastic symptoms, individuals with significant upper-airway edema, and those undergoing certain chemotherapy regimens.

In the clinical vignette, the hospitalist withheld the first-line treatment for anaphylaxis, epinephrine. Without the support of evidence in the literature, patients receive corticosteroids and antihistamines more often than epinephrine for suspected anaphylaxis. No evidence supports the routine use of corticosteroids in the management of anaphylaxis or in the prevention of biphasic reactions. Further, recent research demonstrates significant adverse events are associated with even short courses of corticosteroids.

Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason”? Share what you do in your practice and join in the conversation online by retweeting it on Twitter (#TWDFNR) and liking it on Facebook. We invite you to propose ideas for other “Things We Do for No Reason” topics by emailing [email protected].

Inspired by the ABIM Foundation’s Choosing Wisely^® campaign, the “Things We Do for No Reason” (TWDFNR) series reviews practices that have become common parts of hospital care but may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent clear-cut conclusions or clinical practice standards but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion.

A 56-year-old man with coronary artery disease (CAD) undergoes hospital treatment for diverticulitis. He receives ketorolac for abdominal pain upon arrival to the medical ward despite his known allergy to nonsteroidal anti-inflammatory drugs. Fifteen minutes after administration, he develops lightheadedness and experiences swelling of his lips. On exam, he has tachycardia and a diffuse urticarial rash across his torso. The admitting physician prescribes methylprednisolone, diphenhydramine, and a liter bolus of normal saline for suspected anaphylaxis. Epinephrine is not administered for fear of precipitating an adverse cardiovascular event given the patient’s history of CAD.

Anaphylaxis, a rapid-onset generalized immunoglobulin E (IgE)–mediated hypersensitivity reaction, can lead to significant morbidity and mortality when not managed properly. Patients can present with anaphylaxis in heterogeneous ways. Fulfilling any one of three criteria establishes the diagnosis of anaphylaxis: (1) rapid onset of skin or mucosal symptoms complicated by either respiratory compromise or hypotension; (2) two or more symptoms involving the respiratory, mucosal, cardiovascular, or gastrointestinal systems following exposure to a likely allergen; and (3) reduced blood pressure in response to a known allergen.¹ Up to 5% of the population experiences anaphylaxis in a lifetime. Medication and stinging insects account for the majority of anaphylactic reactions in adults, while food and insect stings commonly trigger it in children and adolescents.²

The majority of anaphylactic reactions, known as uniphasic or monophasic, occur rapidly as single episodes following exposure to a specific trigger and resolve within minutes to hours after treatment. Meanwhile, biphasic, or delayed-phase, anaphylaxis occurs when symptoms recur after an apparent resolution and in the absence of reexposure to the trigger. Symptoms restart within 1 to 72 hours after resolution of an initial anaphylaxis episode, with a median time to onset of 11 hours. Biphasic reactions occur in roughly 5% of patients with anaphylaxis.³

Epinephrine is the only recommended first-line medication for the treatment of anaphylaxis in all age groups.⁴ Epinephrine counteracts the cardiovascular and respiratory compromise induced by anaphylaxis through its α- and β-adrenergic activity and stabilizes mast cells.⁴ Early administration of intramuscular epinephrine decreases the need for additional interventions, reduces the likelihood of hospitalization, and is associated with reduced biphasic reactions.^5-7 Paradoxically, patients receive corticosteroids more often than epinephrine for suspected anaphylaxis, despite no robust evidence for their efficacy.^4,8,9

Corticosteroids act as potent anti-inflammatory medications that modulate mast-cell maturation, activation, and degranulation. Known to work primarily through downregulation of gene transcription responsible for cytokine, chemokine, and arachidonic acid production, their maximal anti-inflammatory effects manifest 2 to 6 hours after administration. Demonstrated efficacy in treating and preventing relapse of other inflammatory conditions, such as asthma and croup, may, in part, explain the widespread glucocorticoid use in anaphylaxis. Some believe that administration of corticosteroids may also help reduce the risk of biphasic or delayed-phase anaphylaxis.¹⁰

Based on their mechanism of action, corticosteroids do not exert any anti-inflammatory effects for several hours, regardless of their route of administration.¹⁰ In contrast, epinephrine exerts an almost immediate effect to increase cardiac output and vascular resistance, to reverse edema and bronchoconstriction, and to stabilize mast cells, preventing release of harmful chemokines and cytokines.⁴

The American Academy of Allergy, Asthma & Immunology (AAAAI) recommends early administration of epinephrine as the first-line treatment of anaphylaxis and emphasizes that evidence does not support routine corticosteroid use in the management of acute anaphylaxis or for prevention of biphasic reactions.⁹ To date, no randomized controlled trials have explored the role of corticosteroids in the treatment of acute anaphylaxis, although one is currently under way looking at whether dexamethasone has an impact on preventing biphasic reactions (Table).¹¹

The AAAAI Joint Task Force on Practice Parameters (JTFPP) conducted a pooled analysis of observational studies that did not find a reduction in biphasic reactions in adult patients receiving corticosteroids (odds ratio [OR], 0.87; 95% CI, 0.74-1.02).⁹ Further, their analysis suggests an association with administration of corticosteroids and an increased likelihood of biphasic reactions in children (OR, 1.55; 95% CI, 1.01-2.38).⁹

An observational study in children across 35 hospitals demonstrated an association with corticosteroid administration and a reduced length of hospital stay for anaphylaxis, but the same study found no reduction in repeat emergency department (ED) visits within 72 hours.¹² Similarly, a retrospective cohort study in adults did not find that corticosteroid administration reduced the 7-day risk of returning to the hospital.¹³ These studies highlight the importance of anticipatory guidance in both ED and hospital discharges for anaphylaxis since the literature does not provide data that corticosteroid administration reduces the likelihood of a biphasic course.

Long-term corticosteroids have well-known deleterious health effects. Recent evidence highlights the possible adverse events associated with even short courses of corticosteroids. A large case series from Taiwan containing 2,623,327 adults administered brief courses (<14 days) of corticosteroids demonstrated increased incidence of gastrointestinal bleeding, sepsis, and heart failure beginning 5 to 30 days after starting corticosteroid treatments for common medical conditions, with respective absolute risk increases of 10.3, 0.1, and 1 per 1000 patient-years for each condition.¹⁴ The same group of researchers found a nearly two-fold increased risk of sepsis, gastrointestinal bleeding, and pneumonia in a nearly 1 million children who had received corticosteroids within the previous year.¹⁵ Other common side effects of short-term corticosteroids include insomnia, agitation, mood disturbances, and hyperglycemia.

A growing body of evidence demonstrates that corticosteroids likely do not alter the natural disease course of anaphylaxis and carry increased risks of significant adverse events. The AAAAI recommends against the use of glucocorticoids as a first-line agent for anaphylaxis and suggests against the use of glucocorticoids to prevent biphasic reactions.⁹

The recent JTFPP analysis of observational studies demonstrated reduced hypersensitivity reactions to chemotherapeutics with corticosteroid premedication (OR, 0.49; 95% CI, 0.37-0.66). The AAAAI favors administration of corticosteroids to reduce the risk of anaphylactoid reactions—non–IgE-mediated mast cell activation—for some chemotherapeutic protocols.⁹

There is robust evidence regarding the benefits of corticosteroids in the treatment of asthma and upper-airway edema.^16,17 Allergen exposures can precipitate significant bronchospasm in individuals with asthma and trigger an exacerbation. Although routine corticosteroid use for anaphylaxis in these populations has not been directly studied, their use as an adjunctive therapy may be beneficial if there is clinical evidence of bronchospasm or significant upper-airway edema.

Rapid administration of epinephrine saves lives, reduces need for adjuvant treatments and hospitalization, and is associated with decreased risk of developing biphasic anaphylactic reactions (OR, 0.2; 95% CI, 0-0.6).^5-7 Some clinicians are apprehensive about using epinephrine owing to fears related to negative side effects, particularly adverse cardiovascular events. Kawano et al¹⁸ performed a retrospective evaluation of 492 ED visits for anaphylaxis and found that epinephrine is administered less often in older patients (age >50 years); however, when administered intramuscularly, there was no significant difference in adverse cardiovascular events in this population compared with younger individuals. The study did demonstrate an increased rate of adverse cardiac events in older patients receiving intravenous epinephrine, an observation that the authors attributed partly to dosing errors that were reported more often with intravenous use.¹⁸

• Always promptly administer intramuscular epinephrine when treating anaphylaxis.
• Routine administration of corticosteroids in the treatment of anaphylaxis is not advised owing to insufficient data supporting their efficacy and potential for adverse events. Some patient populations may derive benefit from corticosteroids, including individuals with history of asthma exhibiting bronchospastic symptoms, individuals with significant upper-airway edema, and those undergoing certain chemotherapy regimens.

In the clinical vignette, the hospitalist withheld the first-line treatment for anaphylaxis, epinephrine. Without the support of evidence in the literature, patients receive corticosteroids and antihistamines more often than epinephrine for suspected anaphylaxis. No evidence supports the routine use of corticosteroids in the management of anaphylaxis or in the prevention of biphasic reactions. Further, recent research demonstrates significant adverse events are associated with even short courses of corticosteroids.

Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason”? Share what you do in your practice and join in the conversation online by retweeting it on Twitter (#TWDFNR) and liking it on Facebook. We invite you to propose ideas for other “Things We Do for No Reason” topics by emailing [email protected].

Juan, a 50-year-old man with acute myeloid leukemia (AML), sat on the edge of his bed, dejected. Juan’s leukemia had relapsed for a third time, and he was low on options and optimism. Originally from Mexico, he had made the journey to Colorado to work as a mechanic and care for his disabled son. Like millions of other individuals in the United States, he did not obtain a visa and had no affordable options for health insurance. For nearly a decade, that had seemed not to matter, until he became ill. Initially presenting to the emergency department with fatigue and night sweats, Juan was diagnosed with poor-risk AML and underwent emergent induction chemotherapy reimbursed under Emergency Medicaid (Table). Just when his bone marrow biopsy showed remission, however, Juan was told there was no chance to cure him, as his documentation status precluded him from receiving the next recommended therapy: stem cell transplant (SCT). Without transplant, Juan’s leukemia relapsed within a few months. He decided to undergo all the salvage chemotherapy that was offered, worrying about how his son would survive without his father.

For the patient with a new cancer diagnosis, a difference in immigration status may be the difference between life and death. Undocumented immigrants are excluded from federally funded benefits, including those offered under Medicare, most Medicaid programs, and the Patient Protection and Affordable Care Act (Table).¹ The nearly 11 million undocumented immigrants residing in the United States are integral to the workforce and economy. Although they pay taxes that fund Medicaid, contributing approximately $11.7 billion nationally in 2017, undocumented immigrants are ineligible to benefit from such programs.² The inequity of this policy is highlighted by Juan, an undocumented immigrant presenting with a new diagnosis of AML.

The Emergency Medical Treatment and Active Labor Act (EMTALA) is a 1986 federal law which mandates that patients who present to the hospital with an emergency medical condition receive appropriate evaluation and stabilizing treatment. An emergency condition is defined as “manifesting itself by acute symptoms of sufficient severity … such that the absence of immediate medical attention could reasonably be expected to result in (A) placing the patient’s health in serious jeopardy; (B) serious impairment to bodily functions; or (C) serious dysfunction of any bodily organ or part” (Table).^3,4 The Centers for Medicare & Medicaid manual restates the EMTALA definition and notes that services for an emergency medical condition cannot include care related to organ transplantation. Most state Emergency Medicaid programs have adopted the federal definition of what constitutes a medical emergency.⁵ As a result, undocumented individuals who qualify for Medicaid benefits but who do not meet citizenship requirements are eligible to “receive Medical Assistance benefits for emergency medical care only.”³

Similar to our patient Juan, individuals who initially present with an acute leukemia would be eligible for induction chemotherapy, as blast crisis is imminently fatal. Once in remission, however, standard-of-care therapy for patients without disqualifying comorbidities, depending on cytogenetic disease phenotypes, recommends the only current potential cure: allogeneic SCT, a treatment that was far from routine practice at the time EMTALA was enacted.⁶ When preparing for transplant, a patient is stable and no longer fits EMTALA’s “emergency” criteria, even though their health is still in “serious jeopardy,” as their cancer has been incompletely treated. Because most state Emergency Medicaid programs adopt the federal definition of an emergency medical condition, the cure is out of reach.

This policy requires clinicians to deviate from the usual standard of care and results in inferior outcomes. For AML patients in the poor-risk category, allogeneic SCT is recommended following induction chemotherapy.⁷ The risk of relapse is 30% to 40% if consolidation therapy includes SCT, vs 70% to 80% if treated with chemotherapeutic consolidation alone.⁶ AML patients in the intermediate-, and sometimes even favorable- risk categories, have been shown to benefit from allogeneic SCT as well, with risk of relapse half that of a patient who undergoes consolidation without transplant. Undocumented individuals with AML are therefore resigned to inadequate cancer treatment, including lifelong salvage chemotherapy, and have a substantially decreased chance of achieving sustained remission.⁶ Furthermore, providing inequitable care for undocumented patients with other medical conditions, such as end-stage kidney disease (ESKD), has been associated with inferior patient-reported outcomes, higher mortality and hospital costs, and clinician burnout. In many states, undocumented immigrants with ESKD rely on emergency dialysis (dialysis made available only after presenting critically ill to an emergency department). In 2019, Colorado’s Medicaid agency opted to include ESKD as a qualifying condition for Emergency Medicaid, thereby expanding access to scheduled dialysis. This led to improved patient quality of life, a decreased emotional toll on patients and clinicians, and reduced costs.^8,9

Policy discussions must consider cost. The average cost of allogeneic SCT in the United States was approximately $226,000 in 2018, which is often compared to the cost of managing a patient with refractory disease who does not receive transplant.¹⁰ This study reported a cost of active disease without transplant, including chemotherapy and hospitalizations, of approximately $69,000, plus terminal care costs of nearly $89,000; at a total of $158,000, this comes out to $68,000 less than SCT.¹⁰ This cost savings, however, results in a patient’s death rather than an up to 85% chance of long-term, relapse-free survival.⁶

To more completely capture the relationship between the healthcare value and cost-effectiveness of SCT, a second study calculated the incremental cost-effectiveness ratio (ICER) of transplantation in acute leukemias in the first 100 days post transplant, including management of complications, such as hospitalization, acute graft-versus-host disease (GVHD), infection, and blood product transfusions. ICER represents the economic value of an intervention compared to an alternative, calculated as cost per quality-adjusted life years. The ICER of SCT compared to no transplant is $16,346 to $34,360, depending on type of transplant and conditioning regimen.¹¹ An ICER of less than $50,000 is considered an acceptable expense for the value achieved—in this case, a significant opportunity for cure. This finding supports SCT, including management of complications, as an economically valuable intervention. Furthermore, if a sustained remission is achieved with SCT, this difference in expense buys the individual patient potentially decades of productivity to contribute back into society and the economy. According to the National Bureau of Economic Research, undocumented workers as a whole contribute $5 trillion to the US Gross Domestic Product over a 10-year period, or about $45,000 per worker per year.¹² According to the costs cited, curing a single undocumented worker with acute leukemia via SCT and allowing them to return to work would lead to a return on investment in less than 2 years. If the goal is high-quality, high-value, equitable care, it is logical to spend the money upfront and allow all patients the best chance for recovery.

One might suggest that patients instead receive treatment in their country of origin. This proposition, however, is often unrealistic. Latin American countries, for example, lack access to many standard-of-care cancer treatments available domestically. In Mexico, SCT is only available at a single facility in Mexico City, which is unable to track outcomes.¹³ The mortality-to-incidence ratio for cancer, a marker of availability of effective treatment, for Latin America is 0.48, substantially inferior to that of the United States (0.29).¹⁴ Importantly, almost two thirds of undocumented immigrants in the United States have lived in the country for 10 or more years, and 43% are parents of minor children, an increasing proportion of whom are American citizens.¹⁵ This highlights the impracticality of these individuals returning to their country of origin for treatment.

Medicaid laws in several states have made it possible for undocumented immigrants to receive access to standard-of-care therapies. Washington and California have included provisions that enable undocumented immigrants to receive allogeneic SCT if they are otherwise medically eligible. In the course of this policy change, legal arguments from the California Court of Appeals expressed that the language of the law was not intended to deny lifesaving treatment to an individual.¹⁶ California’s Emergency Medicaid policy is comparable to that of other states, but because the courts considered SCT a “continuation of medically necessary inpatient hospital services … directly related to the emergency” for which the patient initially presented, they concluded that it could be covered under California Medicaid. Despite covering SCT for undocumented immigrants, California maintains lower costs for those patients compared to US citizens on Medicaid while providing evidence-based cancer care.¹⁷ This exemplifies sustainable and equitable healthcare policy for the rest of the nation.

A proposed change in policy could occur at either the federal or state level. One option would be to follow the example set by the State of Washington. Under Emergency Medicaid, Washington modified qualifying conditions to include “emergency room care, inpatient admission, or outpatient surgery; a cancer treatment plan; dialysis treatment; anti-rejection medication for an organ transplant” and long-term care services.¹⁸ Federal policy reform for undocumented immigrants would also improve access to care. The US Citizenship Act of 2021, introduced to the House of Representatives in February 2021, offers a path to citizenship for undocumented immigrants, ultimately allowing for undocumented individuals to be eligible for the same programs as citizens, though after a period of up to 8 years.¹⁹ More immediate revisions of qualifying conditions under state Emergency Medicaid programs, coupled with a path to citizenship, would make significant progress towards reducing structural health inequities. Such policy change would also have broader implications. Three quarters of undocumented immigrants in the United States originate from Mexico, Central America, and South America, and the incidence rate of AML for Latinx individuals is 3.6 per 100,000, a figure which can be extrapolated to an estimated 380 cases per year in the US undocumented population.^20-22 In addition to benefiting patients with acute leukemias, the proposed policy change would also benefit numerous others who are frequently hospitalized for acute decompensations of chronic conditions, including congestive heart failure, liver disease, ESKD, and chronic lung conditions. Enabling follow-up care for these diseases under Emergency Medicaid would likewise be expected to reduce costs and improve both quality of care and patient-centered and clinical outcomes.

Hospitalists frequently care for undocumented immigrants with acute leukemias because the hospital can only be reimbursed by Emergency Medicaid when a patient is admitted to the hospital. Patients may ask about what they can expect in the course of their illness and, while details may be left to the oncologist, hospitalists will be faced with responding to many of these questions. Clinicians at our institution hold honest conversations with patients like Juan. We are compelled to provide the care that hospital and state policies allow, and can only offer the best care available to them because of the restrictions of an insurance system to which they contribute financially, yet cannot benefit from, in their time of need. We can tell our undocumented immigrant patients that we find this unacceptable and are actively advocating to change this policy.

The State of Colorado and the nation must amend its healthcare policy to include comprehensive cancer care for everyone. Offering standard-of-care therapy to all patients is not only ethical, but also an economically sound policy benefiting patients, clinicians, and the workforce.

Juan, a 50-year-old man with acute myeloid leukemia (AML), sat on the edge of his bed, dejected. Juan’s leukemia had relapsed for a third time, and he was low on options and optimism. Originally from Mexico, he had made the journey to Colorado to work as a mechanic and care for his disabled son. Like millions of other individuals in the United States, he did not obtain a visa and had no affordable options for health insurance. For nearly a decade, that had seemed not to matter, until he became ill. Initially presenting to the emergency department with fatigue and night sweats, Juan was diagnosed with poor-risk AML and underwent emergent induction chemotherapy reimbursed under Emergency Medicaid (Table). Just when his bone marrow biopsy showed remission, however, Juan was told there was no chance to cure him, as his documentation status precluded him from receiving the next recommended therapy: stem cell transplant (SCT). Without transplant, Juan’s leukemia relapsed within a few months. He decided to undergo all the salvage chemotherapy that was offered, worrying about how his son would survive without his father.

For the patient with a new cancer diagnosis, a difference in immigration status may be the difference between life and death. Undocumented immigrants are excluded from federally funded benefits, including those offered under Medicare, most Medicaid programs, and the Patient Protection and Affordable Care Act (Table).¹ The nearly 11 million undocumented immigrants residing in the United States are integral to the workforce and economy. Although they pay taxes that fund Medicaid, contributing approximately $11.7 billion nationally in 2017, undocumented immigrants are ineligible to benefit from such programs.² The inequity of this policy is highlighted by Juan, an undocumented immigrant presenting with a new diagnosis of AML.

The Emergency Medical Treatment and Active Labor Act (EMTALA) is a 1986 federal law which mandates that patients who present to the hospital with an emergency medical condition receive appropriate evaluation and stabilizing treatment. An emergency condition is defined as “manifesting itself by acute symptoms of sufficient severity … such that the absence of immediate medical attention could reasonably be expected to result in (A) placing the patient’s health in serious jeopardy; (B) serious impairment to bodily functions; or (C) serious dysfunction of any bodily organ or part” (Table).^3,4 The Centers for Medicare & Medicaid manual restates the EMTALA definition and notes that services for an emergency medical condition cannot include care related to organ transplantation. Most state Emergency Medicaid programs have adopted the federal definition of what constitutes a medical emergency.⁵ As a result, undocumented individuals who qualify for Medicaid benefits but who do not meet citizenship requirements are eligible to “receive Medical Assistance benefits for emergency medical care only.”³

Similar to our patient Juan, individuals who initially present with an acute leukemia would be eligible for induction chemotherapy, as blast crisis is imminently fatal. Once in remission, however, standard-of-care therapy for patients without disqualifying comorbidities, depending on cytogenetic disease phenotypes, recommends the only current potential cure: allogeneic SCT, a treatment that was far from routine practice at the time EMTALA was enacted.⁶ When preparing for transplant, a patient is stable and no longer fits EMTALA’s “emergency” criteria, even though their health is still in “serious jeopardy,” as their cancer has been incompletely treated. Because most state Emergency Medicaid programs adopt the federal definition of an emergency medical condition, the cure is out of reach.

This policy requires clinicians to deviate from the usual standard of care and results in inferior outcomes. For AML patients in the poor-risk category, allogeneic SCT is recommended following induction chemotherapy.⁷ The risk of relapse is 30% to 40% if consolidation therapy includes SCT, vs 70% to 80% if treated with chemotherapeutic consolidation alone.⁶ AML patients in the intermediate-, and sometimes even favorable- risk categories, have been shown to benefit from allogeneic SCT as well, with risk of relapse half that of a patient who undergoes consolidation without transplant. Undocumented individuals with AML are therefore resigned to inadequate cancer treatment, including lifelong salvage chemotherapy, and have a substantially decreased chance of achieving sustained remission.⁶ Furthermore, providing inequitable care for undocumented patients with other medical conditions, such as end-stage kidney disease (ESKD), has been associated with inferior patient-reported outcomes, higher mortality and hospital costs, and clinician burnout. In many states, undocumented immigrants with ESKD rely on emergency dialysis (dialysis made available only after presenting critically ill to an emergency department). In 2019, Colorado’s Medicaid agency opted to include ESKD as a qualifying condition for Emergency Medicaid, thereby expanding access to scheduled dialysis. This led to improved patient quality of life, a decreased emotional toll on patients and clinicians, and reduced costs.^8,9

Policy discussions must consider cost. The average cost of allogeneic SCT in the United States was approximately $226,000 in 2018, which is often compared to the cost of managing a patient with refractory disease who does not receive transplant.¹⁰ This study reported a cost of active disease without transplant, including chemotherapy and hospitalizations, of approximately $69,000, plus terminal care costs of nearly $89,000; at a total of $158,000, this comes out to $68,000 less than SCT.¹⁰ This cost savings, however, results in a patient’s death rather than an up to 85% chance of long-term, relapse-free survival.⁶

To more completely capture the relationship between the healthcare value and cost-effectiveness of SCT, a second study calculated the incremental cost-effectiveness ratio (ICER) of transplantation in acute leukemias in the first 100 days post transplant, including management of complications, such as hospitalization, acute graft-versus-host disease (GVHD), infection, and blood product transfusions. ICER represents the economic value of an intervention compared to an alternative, calculated as cost per quality-adjusted life years. The ICER of SCT compared to no transplant is $16,346 to $34,360, depending on type of transplant and conditioning regimen.¹¹ An ICER of less than $50,000 is considered an acceptable expense for the value achieved—in this case, a significant opportunity for cure. This finding supports SCT, including management of complications, as an economically valuable intervention. Furthermore, if a sustained remission is achieved with SCT, this difference in expense buys the individual patient potentially decades of productivity to contribute back into society and the economy. According to the National Bureau of Economic Research, undocumented workers as a whole contribute $5 trillion to the US Gross Domestic Product over a 10-year period, or about $45,000 per worker per year.¹² According to the costs cited, curing a single undocumented worker with acute leukemia via SCT and allowing them to return to work would lead to a return on investment in less than 2 years. If the goal is high-quality, high-value, equitable care, it is logical to spend the money upfront and allow all patients the best chance for recovery.

One might suggest that patients instead receive treatment in their country of origin. This proposition, however, is often unrealistic. Latin American countries, for example, lack access to many standard-of-care cancer treatments available domestically. In Mexico, SCT is only available at a single facility in Mexico City, which is unable to track outcomes.¹³ The mortality-to-incidence ratio for cancer, a marker of availability of effective treatment, for Latin America is 0.48, substantially inferior to that of the United States (0.29).¹⁴ Importantly, almost two thirds of undocumented immigrants in the United States have lived in the country for 10 or more years, and 43% are parents of minor children, an increasing proportion of whom are American citizens.¹⁵ This highlights the impracticality of these individuals returning to their country of origin for treatment.

Medicaid laws in several states have made it possible for undocumented immigrants to receive access to standard-of-care therapies. Washington and California have included provisions that enable undocumented immigrants to receive allogeneic SCT if they are otherwise medically eligible. In the course of this policy change, legal arguments from the California Court of Appeals expressed that the language of the law was not intended to deny lifesaving treatment to an individual.¹⁶ California’s Emergency Medicaid policy is comparable to that of other states, but because the courts considered SCT a “continuation of medically necessary inpatient hospital services … directly related to the emergency” for which the patient initially presented, they concluded that it could be covered under California Medicaid. Despite covering SCT for undocumented immigrants, California maintains lower costs for those patients compared to US citizens on Medicaid while providing evidence-based cancer care.¹⁷ This exemplifies sustainable and equitable healthcare policy for the rest of the nation.

A proposed change in policy could occur at either the federal or state level. One option would be to follow the example set by the State of Washington. Under Emergency Medicaid, Washington modified qualifying conditions to include “emergency room care, inpatient admission, or outpatient surgery; a cancer treatment plan; dialysis treatment; anti-rejection medication for an organ transplant” and long-term care services.¹⁸ Federal policy reform for undocumented immigrants would also improve access to care. The US Citizenship Act of 2021, introduced to the House of Representatives in February 2021, offers a path to citizenship for undocumented immigrants, ultimately allowing for undocumented individuals to be eligible for the same programs as citizens, though after a period of up to 8 years.¹⁹ More immediate revisions of qualifying conditions under state Emergency Medicaid programs, coupled with a path to citizenship, would make significant progress towards reducing structural health inequities. Such policy change would also have broader implications. Three quarters of undocumented immigrants in the United States originate from Mexico, Central America, and South America, and the incidence rate of AML for Latinx individuals is 3.6 per 100,000, a figure which can be extrapolated to an estimated 380 cases per year in the US undocumented population.^20-22 In addition to benefiting patients with acute leukemias, the proposed policy change would also benefit numerous others who are frequently hospitalized for acute decompensations of chronic conditions, including congestive heart failure, liver disease, ESKD, and chronic lung conditions. Enabling follow-up care for these diseases under Emergency Medicaid would likewise be expected to reduce costs and improve both quality of care and patient-centered and clinical outcomes.

Hospitalists frequently care for undocumented immigrants with acute leukemias because the hospital can only be reimbursed by Emergency Medicaid when a patient is admitted to the hospital. Patients may ask about what they can expect in the course of their illness and, while details may be left to the oncologist, hospitalists will be faced with responding to many of these questions. Clinicians at our institution hold honest conversations with patients like Juan. We are compelled to provide the care that hospital and state policies allow, and can only offer the best care available to them because of the restrictions of an insurance system to which they contribute financially, yet cannot benefit from, in their time of need. We can tell our undocumented immigrant patients that we find this unacceptable and are actively advocating to change this policy.

The State of Colorado and the nation must amend its healthcare policy to include comprehensive cancer care for everyone. Offering standard-of-care therapy to all patients is not only ethical, but also an economically sound policy benefiting patients, clinicians, and the workforce.

Juan, a 50-year-old man with acute myeloid leukemia (AML), sat on the edge of his bed, dejected. Juan’s leukemia had relapsed for a third time, and he was low on options and optimism. Originally from Mexico, he had made the journey to Colorado to work as a mechanic and care for his disabled son. Like millions of other individuals in the United States, he did not obtain a visa and had no affordable options for health insurance. For nearly a decade, that had seemed not to matter, until he became ill. Initially presenting to the emergency department with fatigue and night sweats, Juan was diagnosed with poor-risk AML and underwent emergent induction chemotherapy reimbursed under Emergency Medicaid (Table). Just when his bone marrow biopsy showed remission, however, Juan was told there was no chance to cure him, as his documentation status precluded him from receiving the next recommended therapy: stem cell transplant (SCT). Without transplant, Juan’s leukemia relapsed within a few months. He decided to undergo all the salvage chemotherapy that was offered, worrying about how his son would survive without his father.

For the patient with a new cancer diagnosis, a difference in immigration status may be the difference between life and death. Undocumented immigrants are excluded from federally funded benefits, including those offered under Medicare, most Medicaid programs, and the Patient Protection and Affordable Care Act (Table).¹ The nearly 11 million undocumented immigrants residing in the United States are integral to the workforce and economy. Although they pay taxes that fund Medicaid, contributing approximately $11.7 billion nationally in 2017, undocumented immigrants are ineligible to benefit from such programs.² The inequity of this policy is highlighted by Juan, an undocumented immigrant presenting with a new diagnosis of AML.

The Emergency Medical Treatment and Active Labor Act (EMTALA) is a 1986 federal law which mandates that patients who present to the hospital with an emergency medical condition receive appropriate evaluation and stabilizing treatment. An emergency condition is defined as “manifesting itself by acute symptoms of sufficient severity … such that the absence of immediate medical attention could reasonably be expected to result in (A) placing the patient’s health in serious jeopardy; (B) serious impairment to bodily functions; or (C) serious dysfunction of any bodily organ or part” (Table).^3,4 The Centers for Medicare & Medicaid manual restates the EMTALA definition and notes that services for an emergency medical condition cannot include care related to organ transplantation. Most state Emergency Medicaid programs have adopted the federal definition of what constitutes a medical emergency.⁵ As a result, undocumented individuals who qualify for Medicaid benefits but who do not meet citizenship requirements are eligible to “receive Medical Assistance benefits for emergency medical care only.”³

Similar to our patient Juan, individuals who initially present with an acute leukemia would be eligible for induction chemotherapy, as blast crisis is imminently fatal. Once in remission, however, standard-of-care therapy for patients without disqualifying comorbidities, depending on cytogenetic disease phenotypes, recommends the only current potential cure: allogeneic SCT, a treatment that was far from routine practice at the time EMTALA was enacted.⁶ When preparing for transplant, a patient is stable and no longer fits EMTALA’s “emergency” criteria, even though their health is still in “serious jeopardy,” as their cancer has been incompletely treated. Because most state Emergency Medicaid programs adopt the federal definition of an emergency medical condition, the cure is out of reach.

This policy requires clinicians to deviate from the usual standard of care and results in inferior outcomes. For AML patients in the poor-risk category, allogeneic SCT is recommended following induction chemotherapy.⁷ The risk of relapse is 30% to 40% if consolidation therapy includes SCT, vs 70% to 80% if treated with chemotherapeutic consolidation alone.⁶ AML patients in the intermediate-, and sometimes even favorable- risk categories, have been shown to benefit from allogeneic SCT as well, with risk of relapse half that of a patient who undergoes consolidation without transplant. Undocumented individuals with AML are therefore resigned to inadequate cancer treatment, including lifelong salvage chemotherapy, and have a substantially decreased chance of achieving sustained remission.⁶ Furthermore, providing inequitable care for undocumented patients with other medical conditions, such as end-stage kidney disease (ESKD), has been associated with inferior patient-reported outcomes, higher mortality and hospital costs, and clinician burnout. In many states, undocumented immigrants with ESKD rely on emergency dialysis (dialysis made available only after presenting critically ill to an emergency department). In 2019, Colorado’s Medicaid agency opted to include ESKD as a qualifying condition for Emergency Medicaid, thereby expanding access to scheduled dialysis. This led to improved patient quality of life, a decreased emotional toll on patients and clinicians, and reduced costs.^8,9

Policy discussions must consider cost. The average cost of allogeneic SCT in the United States was approximately $226,000 in 2018, which is often compared to the cost of managing a patient with refractory disease who does not receive transplant.¹⁰ This study reported a cost of active disease without transplant, including chemotherapy and hospitalizations, of approximately $69,000, plus terminal care costs of nearly $89,000; at a total of $158,000, this comes out to $68,000 less than SCT.¹⁰ This cost savings, however, results in a patient’s death rather than an up to 85% chance of long-term, relapse-free survival.⁶

To more completely capture the relationship between the healthcare value and cost-effectiveness of SCT, a second study calculated the incremental cost-effectiveness ratio (ICER) of transplantation in acute leukemias in the first 100 days post transplant, including management of complications, such as hospitalization, acute graft-versus-host disease (GVHD), infection, and blood product transfusions. ICER represents the economic value of an intervention compared to an alternative, calculated as cost per quality-adjusted life years. The ICER of SCT compared to no transplant is $16,346 to $34,360, depending on type of transplant and conditioning regimen.¹¹ An ICER of less than $50,000 is considered an acceptable expense for the value achieved—in this case, a significant opportunity for cure. This finding supports SCT, including management of complications, as an economically valuable intervention. Furthermore, if a sustained remission is achieved with SCT, this difference in expense buys the individual patient potentially decades of productivity to contribute back into society and the economy. According to the National Bureau of Economic Research, undocumented workers as a whole contribute $5 trillion to the US Gross Domestic Product over a 10-year period, or about $45,000 per worker per year.¹² According to the costs cited, curing a single undocumented worker with acute leukemia via SCT and allowing them to return to work would lead to a return on investment in less than 2 years. If the goal is high-quality, high-value, equitable care, it is logical to spend the money upfront and allow all patients the best chance for recovery.

One might suggest that patients instead receive treatment in their country of origin. This proposition, however, is often unrealistic. Latin American countries, for example, lack access to many standard-of-care cancer treatments available domestically. In Mexico, SCT is only available at a single facility in Mexico City, which is unable to track outcomes.¹³ The mortality-to-incidence ratio for cancer, a marker of availability of effective treatment, for Latin America is 0.48, substantially inferior to that of the United States (0.29).¹⁴ Importantly, almost two thirds of undocumented immigrants in the United States have lived in the country for 10 or more years, and 43% are parents of minor children, an increasing proportion of whom are American citizens.¹⁵ This highlights the impracticality of these individuals returning to their country of origin for treatment.

Medicaid laws in several states have made it possible for undocumented immigrants to receive access to standard-of-care therapies. Washington and California have included provisions that enable undocumented immigrants to receive allogeneic SCT if they are otherwise medically eligible. In the course of this policy change, legal arguments from the California Court of Appeals expressed that the language of the law was not intended to deny lifesaving treatment to an individual.¹⁶ California’s Emergency Medicaid policy is comparable to that of other states, but because the courts considered SCT a “continuation of medically necessary inpatient hospital services … directly related to the emergency” for which the patient initially presented, they concluded that it could be covered under California Medicaid. Despite covering SCT for undocumented immigrants, California maintains lower costs for those patients compared to US citizens on Medicaid while providing evidence-based cancer care.¹⁷ This exemplifies sustainable and equitable healthcare policy for the rest of the nation.

A proposed change in policy could occur at either the federal or state level. One option would be to follow the example set by the State of Washington. Under Emergency Medicaid, Washington modified qualifying conditions to include “emergency room care, inpatient admission, or outpatient surgery; a cancer treatment plan; dialysis treatment; anti-rejection medication for an organ transplant” and long-term care services.¹⁸ Federal policy reform for undocumented immigrants would also improve access to care. The US Citizenship Act of 2021, introduced to the House of Representatives in February 2021, offers a path to citizenship for undocumented immigrants, ultimately allowing for undocumented individuals to be eligible for the same programs as citizens, though after a period of up to 8 years.¹⁹ More immediate revisions of qualifying conditions under state Emergency Medicaid programs, coupled with a path to citizenship, would make significant progress towards reducing structural health inequities. Such policy change would also have broader implications. Three quarters of undocumented immigrants in the United States originate from Mexico, Central America, and South America, and the incidence rate of AML for Latinx individuals is 3.6 per 100,000, a figure which can be extrapolated to an estimated 380 cases per year in the US undocumented population.^20-22 In addition to benefiting patients with acute leukemias, the proposed policy change would also benefit numerous others who are frequently hospitalized for acute decompensations of chronic conditions, including congestive heart failure, liver disease, ESKD, and chronic lung conditions. Enabling follow-up care for these diseases under Emergency Medicaid would likewise be expected to reduce costs and improve both quality of care and patient-centered and clinical outcomes.

Hospitalists frequently care for undocumented immigrants with acute leukemias because the hospital can only be reimbursed by Emergency Medicaid when a patient is admitted to the hospital. Patients may ask about what they can expect in the course of their illness and, while details may be left to the oncologist, hospitalists will be faced with responding to many of these questions. Clinicians at our institution hold honest conversations with patients like Juan. We are compelled to provide the care that hospital and state policies allow, and can only offer the best care available to them because of the restrictions of an insurance system to which they contribute financially, yet cannot benefit from, in their time of need. We can tell our undocumented immigrant patients that we find this unacceptable and are actively advocating to change this policy.

The State of Colorado and the nation must amend its healthcare policy to include comprehensive cancer care for everyone. Offering standard-of-care therapy to all patients is not only ethical, but also an economically sound policy benefiting patients, clinicians, and the workforce.

Inspired by the ABIM Foundation’s Choosing Wisely^® campaign, the “Things We Do for No Reason^™” (TWDFNR) series reviews practices that have become common parts of hospital care but may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent clear-cut conclusions or clinical practice standards but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion.

An 87-year-old hospitalized man has lost 7% of his body weight in the past year. His family and the inpatient nutritionist ask about a prescription appetite stimulant.

Unintentional weight loss—the loss of more than 10 lb or 5% of usual body weight over 6 to 12 months—affects up to 27% of older adults in the community and 50% to 60% of older adults in nursing homes.^1,2 Patients who report weight loss on hospital admission have an almost four times greater risk of death in the 12 months following discharge.³ To address unintentional weight loss, clinicians may prescribe appetite stimulants.

Megestrol acetate is approved by the US Food and Drug Administration (FDA) for the treatment of weight loss in patients with AIDS.⁴ Megestrol acetate promotes weight gain through inhibition of cytokines, interleukin-6, and tumor necrosis factor-alpha, which are increased in older adults. In a randomized, placebo-controlled trial of 69 nursing home residents with ≥6 months’ life expectancy and Karnofsky score of ≥40%, patients treated with megestrol acetate for 12 weeks reported increased appetite and well-being. They achieved significant weight gain (>1.82 kg), but not until 3 months after therapy ended.⁵ No significant adverse events were reported; however, adverse event monitoring continued only for the 12-week treatment period. This follow-up duration may have been insufficient to identify some adverse events, such as venous thromboembolism.

Mirtazapine, an antidepressant and serotonin receptor antagonist, reduces levels of serotonin, a neurotransmitter that promotes early satiety.⁶ In a meta-analysis of 11 trials comparing mirtazapine to selective serotonin reuptake inhibitors for depression, patients treated with mirtazapine demonstrated an increase in the composite secondary outcome of weight gain or increased appetite.⁷ The amount of weight gain was not specified. Weight gain is more common with low-dose mirtazapine, potentially due to increased antihistamine activity at lower doses.⁸ Overall, mirtazapine is well-tolerated and efficacious in the treatment of depression and may benefit older adults with concomitant weight loss.⁶

Cyproheptadine is a first-generation antihistamine with appetite-stimulating effects. It has been found to increase weight or appetite in various disease states, particularly in the pediatric population,⁹ including cystic fibrosis¹⁰ and malignancy.¹¹ Given this evidence, there has been interest in its use in the geriatric population with unintentional weight loss.

Dronabinol is an orally active cannabinoid approved for anorexia-associated weight loss in patients with AIDS.¹² In a randomized, placebo-controlled trial in patients with AIDS-related anorexia and weight loss, participants receiving dronabinol had a statistically significant increase in appetite but no change in weight. Participants receiving dronabinol also experienced more nervous system-related adverse events, including dizziness, thinking abnormalities, and somnolence.¹³

Weight gain may not improve clinically meaningful outcomes. The absence of consistent evidence that prescription appetite stimulants improve patient-centered outcomes, such as quality of life or functional status, and the potential morbidity and mortality of these medications make prescribing appetite stimulants in older adults concerning.

Megestrol Acetate

A 2018 systematic review of randomized controlled trials studying megestrol acetate for treatment of anorexia-cachexia, primarily in adults with AIDS and cancer, found that treatment resulted in a 2.25-kg weight gain, with no improvement in quality of life and an increased risk of adverse events.¹⁴

Three prospective trials studied the effect of megestrol acetate in older adults (Appendix Table). One trial randomized 47 patients receiving skilled nursing services following an admission for acute illness to megestrol acetate vs placebo. While the investigators noted increases in appetite at higher doses of megestrol acetate, there was no change in weight or clinically relevant outcomes.¹⁵ In a second randomized controlled trial, 29 patients with illness-induced functional decline were enrolled in a strength training program in addition to being assigned to megestrol acetate or placebo. While patients receiving megestrol acetate with the exercise program had significant increases in weight and nutritional intake, they suffered a deterioration in physical function.¹⁶ In a pilot study, 17 nursing home residents who consistently ate less than 75% of their meals received megestrol acetate plus standard or optimal feeding assistance. The percentage of meals consumed increased only when patients received optimal feeding assistance in conjunction with megestrol acetate.¹⁷

The largest case-control study examining megestrol acetate for unintentional weight loss in older adults compared 709 residents in a multistate nursing home system treated with megestrol acetate to matched untreated controls. After 6 months of treatment, the median weight and change in weight did not differ significantly. Patients receiving megestrol acetate had a significant increase in mortality, surviving an average of 23.9 months, compared to 31.2 months for controls (P < .001).¹⁸

Additionally, two retrospective reviews of nursing home patients who were prescribed megestrol acetate showed incidences of venous thrombosis of 5% and 32%.^19,20 Other potentially significant adverse effects include adrenal insufficiency and fluid retention.⁶ In 2019, the American Geriatrics Society’s Beers Criteria included megestrol acetate as a medication to avoid given its “minimal effect on weight; increases [in] risk of thrombotic events and possibly death in older adults.”²¹

Mirtazapine

No studies have evaluated mirtazapine for weight gain without concomitant depression. In older adults with depression, mirtazapine has minimal impact on promoting weight gain compared to other antidepressants. In two retrospective studies of older patients with depression and weight loss, researchers found no difference in weight gain in those treated with mirtazapine vs sertraline or other nontricyclic antidepressants, excluding fluoxetine.^22,23

Cyproheptadine

There have been no controlled trials evaluating the use of cyproheptadine in older adults, in part due to anticholinergic side effects. In a trial of cancer patients, sedation and dizziness were common adverse effects.¹¹ The 2019 American Geriatrics Society’s Beers Criteria include cyproheptadine as a medication to avoid based upon the “risk of confusion, dry mouth, constipation, and other anticholinergic effects or toxicity.”²¹

Dronabinol

In a retrospective cohort study of 28 long-term care residents with anorexia and weight loss, participants receiving dronabinol for 12 weeks had no statistically significant weight gain.²⁴ The FDA cautions against prescribing dronabinol for older adults due to neurological side effects.¹² A systematic review of randomized controlled trials found that cannabinoid-based medications in patients older than 50 years were associated with a significant increase in dizziness or lightheadedness and thinking or perception disorder.²⁵

In the Choosing Wisely^® initiative, the American Geriatrics Society recommends avoiding prescription appetite stimulants for patients with anorexia or cachexia.²⁶ Instead, hospitalists should evaluate older patients for causes of unintentional weight loss, including malignancy, nonmalignant gastrointestinal disorders, depression, and dementia. Hospitalists can identify most causes based on the history, physical exam, and laboratory studies and initiate treatment for modifiable causes, such as constipation and depression.²

Hospitalists should work with an interprofessional team to develop an individualized plan to optimize caloric intake in the hospital (Table).²⁷ One in five hospitalized older adults has insufficient caloric intake during admission, which is associated with increased risk for in-hospital and 90-day mortality.²⁸ Removing dietary restrictions, increasing the variety of foods offered, and assisted eating may increase food intake.^27,29 Hospitalists should also consider discontinuing or changing medications with gastrointestinal side effects, such as metformin, cholinesterase inhibitors, bisphosphonates, and oral iron supplements. Dietitians may recommend oral nutrition supplements; if started, patients should be offered supplements after discharge.^27,29 For patients with limited access to food, social workers can help optimize social supports and identify community resources following discharge. Finally, hospitalists should coordinate with outpatient providers to monitor weight long-term.

• Recognize and address unintentional weight loss in older adults in the hospital.
• Do not prescribe appetite stimulants for unintentional weight loss in hospitalized older adults as they have no proven benefit for improving long-term outcomes and, in the case of megestrol acetate, may increase mortality.
• Work with an interprofessional team to address factors contributing to unintentional weight loss using nonpharmacologic options for improving food intake.

After discussing the lack of evidence supporting prescription appetite stimulants and the potential risks, we shifted the focus to optimizing oral intake. The team worked with the patient and the patient’s family to optimize nutrition following discharge and communicated the need for ongoing monitoring to the primary care provider.

Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason^™”? Share what you do in your practice and join in the conversation online by retweeting it on Twitter (#TWDFNR) and liking it on Facebook. We invite you to propose ideas for other “Things We Do for No Reason^™” topics by emailing [email protected]

The authors thank Claire Campbell, MD, for her review of this manuscript.

Inspired by the ABIM Foundation’s Choosing Wisely^® campaign, the “Things We Do for No Reason^™” (TWDFNR) series reviews practices that have become common parts of hospital care but may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent clear-cut conclusions or clinical practice standards but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion.

An 87-year-old hospitalized man has lost 7% of his body weight in the past year. His family and the inpatient nutritionist ask about a prescription appetite stimulant.

Unintentional weight loss—the loss of more than 10 lb or 5% of usual body weight over 6 to 12 months—affects up to 27% of older adults in the community and 50% to 60% of older adults in nursing homes.^1,2 Patients who report weight loss on hospital admission have an almost four times greater risk of death in the 12 months following discharge.³ To address unintentional weight loss, clinicians may prescribe appetite stimulants.

Megestrol acetate is approved by the US Food and Drug Administration (FDA) for the treatment of weight loss in patients with AIDS.⁴ Megestrol acetate promotes weight gain through inhibition of cytokines, interleukin-6, and tumor necrosis factor-alpha, which are increased in older adults. In a randomized, placebo-controlled trial of 69 nursing home residents with ≥6 months’ life expectancy and Karnofsky score of ≥40%, patients treated with megestrol acetate for 12 weeks reported increased appetite and well-being. They achieved significant weight gain (>1.82 kg), but not until 3 months after therapy ended.⁵ No significant adverse events were reported; however, adverse event monitoring continued only for the 12-week treatment period. This follow-up duration may have been insufficient to identify some adverse events, such as venous thromboembolism.

Mirtazapine, an antidepressant and serotonin receptor antagonist, reduces levels of serotonin, a neurotransmitter that promotes early satiety.⁶ In a meta-analysis of 11 trials comparing mirtazapine to selective serotonin reuptake inhibitors for depression, patients treated with mirtazapine demonstrated an increase in the composite secondary outcome of weight gain or increased appetite.⁷ The amount of weight gain was not specified. Weight gain is more common with low-dose mirtazapine, potentially due to increased antihistamine activity at lower doses.⁸ Overall, mirtazapine is well-tolerated and efficacious in the treatment of depression and may benefit older adults with concomitant weight loss.⁶

Cyproheptadine is a first-generation antihistamine with appetite-stimulating effects. It has been found to increase weight or appetite in various disease states, particularly in the pediatric population,⁹ including cystic fibrosis¹⁰ and malignancy.¹¹ Given this evidence, there has been interest in its use in the geriatric population with unintentional weight loss.

Dronabinol is an orally active cannabinoid approved for anorexia-associated weight loss in patients with AIDS.¹² In a randomized, placebo-controlled trial in patients with AIDS-related anorexia and weight loss, participants receiving dronabinol had a statistically significant increase in appetite but no change in weight. Participants receiving dronabinol also experienced more nervous system-related adverse events, including dizziness, thinking abnormalities, and somnolence.¹³

Weight gain may not improve clinically meaningful outcomes. The absence of consistent evidence that prescription appetite stimulants improve patient-centered outcomes, such as quality of life or functional status, and the potential morbidity and mortality of these medications make prescribing appetite stimulants in older adults concerning.

Megestrol Acetate

A 2018 systematic review of randomized controlled trials studying megestrol acetate for treatment of anorexia-cachexia, primarily in adults with AIDS and cancer, found that treatment resulted in a 2.25-kg weight gain, with no improvement in quality of life and an increased risk of adverse events.¹⁴

Three prospective trials studied the effect of megestrol acetate in older adults (Appendix Table). One trial randomized 47 patients receiving skilled nursing services following an admission for acute illness to megestrol acetate vs placebo. While the investigators noted increases in appetite at higher doses of megestrol acetate, there was no change in weight or clinically relevant outcomes.¹⁵ In a second randomized controlled trial, 29 patients with illness-induced functional decline were enrolled in a strength training program in addition to being assigned to megestrol acetate or placebo. While patients receiving megestrol acetate with the exercise program had significant increases in weight and nutritional intake, they suffered a deterioration in physical function.¹⁶ In a pilot study, 17 nursing home residents who consistently ate less than 75% of their meals received megestrol acetate plus standard or optimal feeding assistance. The percentage of meals consumed increased only when patients received optimal feeding assistance in conjunction with megestrol acetate.¹⁷

The largest case-control study examining megestrol acetate for unintentional weight loss in older adults compared 709 residents in a multistate nursing home system treated with megestrol acetate to matched untreated controls. After 6 months of treatment, the median weight and change in weight did not differ significantly. Patients receiving megestrol acetate had a significant increase in mortality, surviving an average of 23.9 months, compared to 31.2 months for controls (P < .001).¹⁸

Additionally, two retrospective reviews of nursing home patients who were prescribed megestrol acetate showed incidences of venous thrombosis of 5% and 32%.^19,20 Other potentially significant adverse effects include adrenal insufficiency and fluid retention.⁶ In 2019, the American Geriatrics Society’s Beers Criteria included megestrol acetate as a medication to avoid given its “minimal effect on weight; increases [in] risk of thrombotic events and possibly death in older adults.”²¹

Mirtazapine

No studies have evaluated mirtazapine for weight gain without concomitant depression. In older adults with depression, mirtazapine has minimal impact on promoting weight gain compared to other antidepressants. In two retrospective studies of older patients with depression and weight loss, researchers found no difference in weight gain in those treated with mirtazapine vs sertraline or other nontricyclic antidepressants, excluding fluoxetine.^22,23

Cyproheptadine

There have been no controlled trials evaluating the use of cyproheptadine in older adults, in part due to anticholinergic side effects. In a trial of cancer patients, sedation and dizziness were common adverse effects.¹¹ The 2019 American Geriatrics Society’s Beers Criteria include cyproheptadine as a medication to avoid based upon the “risk of confusion, dry mouth, constipation, and other anticholinergic effects or toxicity.”²¹

Dronabinol

In a retrospective cohort study of 28 long-term care residents with anorexia and weight loss, participants receiving dronabinol for 12 weeks had no statistically significant weight gain.²⁴ The FDA cautions against prescribing dronabinol for older adults due to neurological side effects.¹² A systematic review of randomized controlled trials found that cannabinoid-based medications in patients older than 50 years were associated with a significant increase in dizziness or lightheadedness and thinking or perception disorder.²⁵

In the Choosing Wisely^® initiative, the American Geriatrics Society recommends avoiding prescription appetite stimulants for patients with anorexia or cachexia.²⁶ Instead, hospitalists should evaluate older patients for causes of unintentional weight loss, including malignancy, nonmalignant gastrointestinal disorders, depression, and dementia. Hospitalists can identify most causes based on the history, physical exam, and laboratory studies and initiate treatment for modifiable causes, such as constipation and depression.²

Hospitalists should work with an interprofessional team to develop an individualized plan to optimize caloric intake in the hospital (Table).²⁷ One in five hospitalized older adults has insufficient caloric intake during admission, which is associated with increased risk for in-hospital and 90-day mortality.²⁸ Removing dietary restrictions, increasing the variety of foods offered, and assisted eating may increase food intake.^27,29 Hospitalists should also consider discontinuing or changing medications with gastrointestinal side effects, such as metformin, cholinesterase inhibitors, bisphosphonates, and oral iron supplements. Dietitians may recommend oral nutrition supplements; if started, patients should be offered supplements after discharge.^27,29 For patients with limited access to food, social workers can help optimize social supports and identify community resources following discharge. Finally, hospitalists should coordinate with outpatient providers to monitor weight long-term.

• Recognize and address unintentional weight loss in older adults in the hospital.
• Do not prescribe appetite stimulants for unintentional weight loss in hospitalized older adults as they have no proven benefit for improving long-term outcomes and, in the case of megestrol acetate, may increase mortality.
• Work with an interprofessional team to address factors contributing to unintentional weight loss using nonpharmacologic options for improving food intake.

After discussing the lack of evidence supporting prescription appetite stimulants and the potential risks, we shifted the focus to optimizing oral intake. The team worked with the patient and the patient’s family to optimize nutrition following discharge and communicated the need for ongoing monitoring to the primary care provider.

Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason^™”? Share what you do in your practice and join in the conversation online by retweeting it on Twitter (#TWDFNR) and liking it on Facebook. We invite you to propose ideas for other “Things We Do for No Reason^™” topics by emailing [email protected]

The authors thank Claire Campbell, MD, for her review of this manuscript.

Inspired by the ABIM Foundation’s Choosing Wisely^® campaign, the “Things We Do for No Reason^™” (TWDFNR) series reviews practices that have become common parts of hospital care but may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent clear-cut conclusions or clinical practice standards but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion.

An 87-year-old hospitalized man has lost 7% of his body weight in the past year. His family and the inpatient nutritionist ask about a prescription appetite stimulant.

Unintentional weight loss—the loss of more than 10 lb or 5% of usual body weight over 6 to 12 months—affects up to 27% of older adults in the community and 50% to 60% of older adults in nursing homes.^1,2 Patients who report weight loss on hospital admission have an almost four times greater risk of death in the 12 months following discharge.³ To address unintentional weight loss, clinicians may prescribe appetite stimulants.

Megestrol acetate is approved by the US Food and Drug Administration (FDA) for the treatment of weight loss in patients with AIDS.⁴ Megestrol acetate promotes weight gain through inhibition of cytokines, interleukin-6, and tumor necrosis factor-alpha, which are increased in older adults. In a randomized, placebo-controlled trial of 69 nursing home residents with ≥6 months’ life expectancy and Karnofsky score of ≥40%, patients treated with megestrol acetate for 12 weeks reported increased appetite and well-being. They achieved significant weight gain (>1.82 kg), but not until 3 months after therapy ended.⁵ No significant adverse events were reported; however, adverse event monitoring continued only for the 12-week treatment period. This follow-up duration may have been insufficient to identify some adverse events, such as venous thromboembolism.

Mirtazapine, an antidepressant and serotonin receptor antagonist, reduces levels of serotonin, a neurotransmitter that promotes early satiety.⁶ In a meta-analysis of 11 trials comparing mirtazapine to selective serotonin reuptake inhibitors for depression, patients treated with mirtazapine demonstrated an increase in the composite secondary outcome of weight gain or increased appetite.⁷ The amount of weight gain was not specified. Weight gain is more common with low-dose mirtazapine, potentially due to increased antihistamine activity at lower doses.⁸ Overall, mirtazapine is well-tolerated and efficacious in the treatment of depression and may benefit older adults with concomitant weight loss.⁶

Cyproheptadine is a first-generation antihistamine with appetite-stimulating effects. It has been found to increase weight or appetite in various disease states, particularly in the pediatric population,⁹ including cystic fibrosis¹⁰ and malignancy.¹¹ Given this evidence, there has been interest in its use in the geriatric population with unintentional weight loss.

Dronabinol is an orally active cannabinoid approved for anorexia-associated weight loss in patients with AIDS.¹² In a randomized, placebo-controlled trial in patients with AIDS-related anorexia and weight loss, participants receiving dronabinol had a statistically significant increase in appetite but no change in weight. Participants receiving dronabinol also experienced more nervous system-related adverse events, including dizziness, thinking abnormalities, and somnolence.¹³

Weight gain may not improve clinically meaningful outcomes. The absence of consistent evidence that prescription appetite stimulants improve patient-centered outcomes, such as quality of life or functional status, and the potential morbidity and mortality of these medications make prescribing appetite stimulants in older adults concerning.

Megestrol Acetate

A 2018 systematic review of randomized controlled trials studying megestrol acetate for treatment of anorexia-cachexia, primarily in adults with AIDS and cancer, found that treatment resulted in a 2.25-kg weight gain, with no improvement in quality of life and an increased risk of adverse events.¹⁴

Three prospective trials studied the effect of megestrol acetate in older adults (Appendix Table). One trial randomized 47 patients receiving skilled nursing services following an admission for acute illness to megestrol acetate vs placebo. While the investigators noted increases in appetite at higher doses of megestrol acetate, there was no change in weight or clinically relevant outcomes.¹⁵ In a second randomized controlled trial, 29 patients with illness-induced functional decline were enrolled in a strength training program in addition to being assigned to megestrol acetate or placebo. While patients receiving megestrol acetate with the exercise program had significant increases in weight and nutritional intake, they suffered a deterioration in physical function.¹⁶ In a pilot study, 17 nursing home residents who consistently ate less than 75% of their meals received megestrol acetate plus standard or optimal feeding assistance. The percentage of meals consumed increased only when patients received optimal feeding assistance in conjunction with megestrol acetate.¹⁷

The largest case-control study examining megestrol acetate for unintentional weight loss in older adults compared 709 residents in a multistate nursing home system treated with megestrol acetate to matched untreated controls. After 6 months of treatment, the median weight and change in weight did not differ significantly. Patients receiving megestrol acetate had a significant increase in mortality, surviving an average of 23.9 months, compared to 31.2 months for controls (P < .001).¹⁸

Additionally, two retrospective reviews of nursing home patients who were prescribed megestrol acetate showed incidences of venous thrombosis of 5% and 32%.^19,20 Other potentially significant adverse effects include adrenal insufficiency and fluid retention.⁶ In 2019, the American Geriatrics Society’s Beers Criteria included megestrol acetate as a medication to avoid given its “minimal effect on weight; increases [in] risk of thrombotic events and possibly death in older adults.”²¹

Mirtazapine

No studies have evaluated mirtazapine for weight gain without concomitant depression. In older adults with depression, mirtazapine has minimal impact on promoting weight gain compared to other antidepressants. In two retrospective studies of older patients with depression and weight loss, researchers found no difference in weight gain in those treated with mirtazapine vs sertraline or other nontricyclic antidepressants, excluding fluoxetine.^22,23

Cyproheptadine

There have been no controlled trials evaluating the use of cyproheptadine in older adults, in part due to anticholinergic side effects. In a trial of cancer patients, sedation and dizziness were common adverse effects.¹¹ The 2019 American Geriatrics Society’s Beers Criteria include cyproheptadine as a medication to avoid based upon the “risk of confusion, dry mouth, constipation, and other anticholinergic effects or toxicity.”²¹

Dronabinol

In a retrospective cohort study of 28 long-term care residents with anorexia and weight loss, participants receiving dronabinol for 12 weeks had no statistically significant weight gain.²⁴ The FDA cautions against prescribing dronabinol for older adults due to neurological side effects.¹² A systematic review of randomized controlled trials found that cannabinoid-based medications in patients older than 50 years were associated with a significant increase in dizziness or lightheadedness and thinking or perception disorder.²⁵

In the Choosing Wisely^® initiative, the American Geriatrics Society recommends avoiding prescription appetite stimulants for patients with anorexia or cachexia.²⁶ Instead, hospitalists should evaluate older patients for causes of unintentional weight loss, including malignancy, nonmalignant gastrointestinal disorders, depression, and dementia. Hospitalists can identify most causes based on the history, physical exam, and laboratory studies and initiate treatment for modifiable causes, such as constipation and depression.²

Hospitalists should work with an interprofessional team to develop an individualized plan to optimize caloric intake in the hospital (Table).²⁷ One in five hospitalized older adults has insufficient caloric intake during admission, which is associated with increased risk for in-hospital and 90-day mortality.²⁸ Removing dietary restrictions, increasing the variety of foods offered, and assisted eating may increase food intake.^27,29 Hospitalists should also consider discontinuing or changing medications with gastrointestinal side effects, such as metformin, cholinesterase inhibitors, bisphosphonates, and oral iron supplements. Dietitians may recommend oral nutrition supplements; if started, patients should be offered supplements after discharge.^27,29 For patients with limited access to food, social workers can help optimize social supports and identify community resources following discharge. Finally, hospitalists should coordinate with outpatient providers to monitor weight long-term.

• Recognize and address unintentional weight loss in older adults in the hospital.
• Do not prescribe appetite stimulants for unintentional weight loss in hospitalized older adults as they have no proven benefit for improving long-term outcomes and, in the case of megestrol acetate, may increase mortality.
• Work with an interprofessional team to address factors contributing to unintentional weight loss using nonpharmacologic options for improving food intake.

After discussing the lack of evidence supporting prescription appetite stimulants and the potential risks, we shifted the focus to optimizing oral intake. The team worked with the patient and the patient’s family to optimize nutrition following discharge and communicated the need for ongoing monitoring to the primary care provider.

Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason^™”? Share what you do in your practice and join in the conversation online by retweeting it on Twitter (#TWDFNR) and liking it on Facebook. We invite you to propose ideas for other “Things We Do for No Reason^™” topics by emailing [email protected]

The authors thank Claire Campbell, MD, for her review of this manuscript.

Asthma is a heterogeneous condition characterized by airway hyperresponsiveness and obstruction, with associated airway inflammation and remodeling.² Asthma affects 25 million people in the United States and 334 million people worldwide, with significant healthcare disparities across race and ethnicity.^2-6 Asthma is the third most common reason for hospitalizations in pediatrics, accounting for 180,000 annual hospitalizations for children and adults.^3,7 In 2020, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel provided a focused update to the Asthma Management Guidelines, centered on six topics with sufficient new evidence. The management of status asthmaticus was not included in this update. We spotlight four of the recommendations applicable to the practice of pediatric hospital medicine.

Recommendation 1. Children 0 to 4 years old with recurrent wheezing triggered by a respiratory tract infection (RTI) and no wheezing between infections should receive a short course of daily inhaled corticosteroids (ICS) at the onset of a RTI, with an as-needed short-acting beta agonist (SABA) for quick-relief therapy compared to SABA alone (evidence quality: high; recommendation strength: conditional).

Recurrent wheezing is defined as clinically significant periods of wheezing that are reversible or consistent with bronchospasm and as ≥3 episodes in a lifetime or 2 episodes in the past year. It is important to adhere to this definition to prevent inappropriate use of ICS for bronchiolitis. This treatment is associated with a reduction of use of systemic steroids (relative risk [RR], 0.67; 95% CI, 0.46-0.98) without a statistical decrease in acute care visits (RR, 0.90; 95% CI, 0.77-1.05) or hospitalizations (RR, 0.77; 95% CI, 0.06-9.68). Improved transition of care is essential between the primary care provider, hospitalist, and family to ensure an understanding of how/when to initiate ICS at the onset of a RTI. Potential harms include effect on growth and overprescribing. Growth should be monitored because data are conflicting.

Recommendation 2. Individuals ages 12 years and older with mild persistent asthma should use as-needed SABA and may use either daily low-dose ICS or as-needed ICS when symptoms flare (evidence quality: moderate; recommendation strength: conditional).

In intermittent therapy, patients take a SABA followed by an ICS as needed for acute asthma symptoms. This recommendation is driven by asthma-control and quality-of-life outcomes, with caregivers reporting that intermittent dosing could “offer flexibility and potentially reduce side effects.” There were no differences between management regimens with respect to systemic steroid use (RR, 0.70; 95% CI, 0.30-1.64) or urgent care visits (RR, 0.25; 95% CI, 0.05-1.16). Differing perception of symptoms by individuals may lead to undertreating or overtreating, and intermittent administration makes it challenging for clinicians to assess the need to adjust therapy.

Recommendation 3. Children 4 years and older with moderate to severe persistent asthma should use ICS-formoterol in a single inhaler used as both daily controller and reliever therapy compared to either (a) higher-dose ICS as daily controller therapy and SABA for quick-relief therapy or (b) a same-dose ICS-long-acting beta agonist (LABA) as daily controller therapy and SABA for quick-relief therapy (evidence quality: high for ages ≥12 years, moderate for ages 4-11 years; recommendation strength: strong).

For children 4 years and older, it is recommended to use “single maintenance and reliever therapy” (SMART) with a single-inhaler containing either low- or medium-dose ICS and formoterol when stepping up from Step 2 (daily low-dose ICS and as-needed SABA) to Step 3 (daily and as-needed low-dose ICS-formoterol) and Step 4 (daily and as-needed medium-dose ICS-formoterol). It is preferred to use this single inhaler as needed when symptoms flare rather than an additional as-needed SABA. However, this may be impractical if insurance does not cover multiple prescriptions per month. Formoterol is specified because it is the only LABA studied. Studies have shown reductions in hospitalizations, systemic corticosteroids, and ED visits with this regimen. “ICS-formoterol should be administered as maintenance therapy with 1-2 puffs once to twice daily and 1-2 puffs as needed for asthma symptoms. The maximum number of puffs per day is 12 (54 mcg formoterol) for individuals ages 12 years and older and 8 (36 mcg formoterol) for children ages 4-11 years.”¹

Recommendation 4. If individuals with asthma have symptoms related to indoor allergens, confirmed by history or allergy testing, they should use a multicomponent allergen-specific mitigation intervention. Allergen mitigation interventions should not be a part of routine asthma management for individuals with asthma who do not have symptoms related to exposure to specific indoor allergens (evidence quality: low; recommendation strength: conditional).

Providers often emphasize exposure to potential indoor allergens such as carpets and pets when taking an asthma history and counsel removal of these triggers. However, all recommendations related to allergies in the 2020 updates have low-moderate evidence quality and conditional recommendation strength. Hospitalists should instead focus their questions on allergy symptoms and triggers and recommend multicomponent mitigation intervention only if there is a confirmed allergy history. Families should continue routine good practices such as house cleaning and laundering, but other interventions are not evidence-based.

Methods

The Expert Panel included a diverse group of clinicians, a pharmacist, and health policy experts. In 2015, a needs assessment identified 6 out of 17 priority topics with sufficient new information for updates. Key questions were drafted, and systematic reviews were published through 2018. The Expert Panel made its recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. The Expert Panel informed its recommendations with input from focus groups, including individuals with asthma and caregivers. The NHLBI posted the draft report for public review, and comments were considered. We believe these methods effectively developed evidence-based recommendations, and the diversity of stakeholders increases the value of this guideline. However, the infrequency of updates limits the utility of the NHLBI guidelines as compared with annual GINA (Global Initiative for Asthma) updates.

There are important considerations in assessing these guidelines. Specifically, the validity of systemic steroid courses as an outcome for children ages 0 to 4 years is controversial. Second, the studies cited in defense of intermittent ICS use in children >12 years of age excluded pediatric patients and did not include readmissions as a primary outcome, which is of particular interest to the hospitalist.

Potential Conflicts for Guideline Authors

The Expert Panel reported all potential conflicts of interest (COIs), which were rated by the Expert Panel Chair and Journal of Allergy and Clinical Immunology editors. Individuals with high COIs were excluded from the Expert Panel. Those with moderate COIs were recused for that topic. Low COIs were not related to the guideline.

Generalizability of the Guideline

These guidelines are based on systematic reviews with large sample sizes and patients of all ages. They are generalizable. However, the authors recognize that variations in asthma require individualized approaches. They identify this as a reason for the lack of strong recommendations for asthma standards of care.

Biologics have progressed considerably since revision of the guidelines. The 2020 guidelines did not address these to prevent delay of the guideline release, but recommendations should be included in future guidelines. Future studies should address healthcare disparities in asthma, barriers to equitable care, and how to eliminate them, as guided by the President’s Task Force.⁸ Status asthmaticus should be included in future updates.

Asthma is a heterogeneous condition characterized by airway hyperresponsiveness and obstruction, with associated airway inflammation and remodeling.² Asthma affects 25 million people in the United States and 334 million people worldwide, with significant healthcare disparities across race and ethnicity.^2-6 Asthma is the third most common reason for hospitalizations in pediatrics, accounting for 180,000 annual hospitalizations for children and adults.^3,7 In 2020, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel provided a focused update to the Asthma Management Guidelines, centered on six topics with sufficient new evidence. The management of status asthmaticus was not included in this update. We spotlight four of the recommendations applicable to the practice of pediatric hospital medicine.

Recommendation 1. Children 0 to 4 years old with recurrent wheezing triggered by a respiratory tract infection (RTI) and no wheezing between infections should receive a short course of daily inhaled corticosteroids (ICS) at the onset of a RTI, with an as-needed short-acting beta agonist (SABA) for quick-relief therapy compared to SABA alone (evidence quality: high; recommendation strength: conditional).

Recurrent wheezing is defined as clinically significant periods of wheezing that are reversible or consistent with bronchospasm and as ≥3 episodes in a lifetime or 2 episodes in the past year. It is important to adhere to this definition to prevent inappropriate use of ICS for bronchiolitis. This treatment is associated with a reduction of use of systemic steroids (relative risk [RR], 0.67; 95% CI, 0.46-0.98) without a statistical decrease in acute care visits (RR, 0.90; 95% CI, 0.77-1.05) or hospitalizations (RR, 0.77; 95% CI, 0.06-9.68). Improved transition of care is essential between the primary care provider, hospitalist, and family to ensure an understanding of how/when to initiate ICS at the onset of a RTI. Potential harms include effect on growth and overprescribing. Growth should be monitored because data are conflicting.

Recommendation 2. Individuals ages 12 years and older with mild persistent asthma should use as-needed SABA and may use either daily low-dose ICS or as-needed ICS when symptoms flare (evidence quality: moderate; recommendation strength: conditional).

In intermittent therapy, patients take a SABA followed by an ICS as needed for acute asthma symptoms. This recommendation is driven by asthma-control and quality-of-life outcomes, with caregivers reporting that intermittent dosing could “offer flexibility and potentially reduce side effects.” There were no differences between management regimens with respect to systemic steroid use (RR, 0.70; 95% CI, 0.30-1.64) or urgent care visits (RR, 0.25; 95% CI, 0.05-1.16). Differing perception of symptoms by individuals may lead to undertreating or overtreating, and intermittent administration makes it challenging for clinicians to assess the need to adjust therapy.

Recommendation 3. Children 4 years and older with moderate to severe persistent asthma should use ICS-formoterol in a single inhaler used as both daily controller and reliever therapy compared to either (a) higher-dose ICS as daily controller therapy and SABA for quick-relief therapy or (b) a same-dose ICS-long-acting beta agonist (LABA) as daily controller therapy and SABA for quick-relief therapy (evidence quality: high for ages ≥12 years, moderate for ages 4-11 years; recommendation strength: strong).

For children 4 years and older, it is recommended to use “single maintenance and reliever therapy” (SMART) with a single-inhaler containing either low- or medium-dose ICS and formoterol when stepping up from Step 2 (daily low-dose ICS and as-needed SABA) to Step 3 (daily and as-needed low-dose ICS-formoterol) and Step 4 (daily and as-needed medium-dose ICS-formoterol). It is preferred to use this single inhaler as needed when symptoms flare rather than an additional as-needed SABA. However, this may be impractical if insurance does not cover multiple prescriptions per month. Formoterol is specified because it is the only LABA studied. Studies have shown reductions in hospitalizations, systemic corticosteroids, and ED visits with this regimen. “ICS-formoterol should be administered as maintenance therapy with 1-2 puffs once to twice daily and 1-2 puffs as needed for asthma symptoms. The maximum number of puffs per day is 12 (54 mcg formoterol) for individuals ages 12 years and older and 8 (36 mcg formoterol) for children ages 4-11 years.”¹

Recommendation 4. If individuals with asthma have symptoms related to indoor allergens, confirmed by history or allergy testing, they should use a multicomponent allergen-specific mitigation intervention. Allergen mitigation interventions should not be a part of routine asthma management for individuals with asthma who do not have symptoms related to exposure to specific indoor allergens (evidence quality: low; recommendation strength: conditional).

Providers often emphasize exposure to potential indoor allergens such as carpets and pets when taking an asthma history and counsel removal of these triggers. However, all recommendations related to allergies in the 2020 updates have low-moderate evidence quality and conditional recommendation strength. Hospitalists should instead focus their questions on allergy symptoms and triggers and recommend multicomponent mitigation intervention only if there is a confirmed allergy history. Families should continue routine good practices such as house cleaning and laundering, but other interventions are not evidence-based.

Methods

The Expert Panel included a diverse group of clinicians, a pharmacist, and health policy experts. In 2015, a needs assessment identified 6 out of 17 priority topics with sufficient new information for updates. Key questions were drafted, and systematic reviews were published through 2018. The Expert Panel made its recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. The Expert Panel informed its recommendations with input from focus groups, including individuals with asthma and caregivers. The NHLBI posted the draft report for public review, and comments were considered. We believe these methods effectively developed evidence-based recommendations, and the diversity of stakeholders increases the value of this guideline. However, the infrequency of updates limits the utility of the NHLBI guidelines as compared with annual GINA (Global Initiative for Asthma) updates.

There are important considerations in assessing these guidelines. Specifically, the validity of systemic steroid courses as an outcome for children ages 0 to 4 years is controversial. Second, the studies cited in defense of intermittent ICS use in children >12 years of age excluded pediatric patients and did not include readmissions as a primary outcome, which is of particular interest to the hospitalist.

Potential Conflicts for Guideline Authors

The Expert Panel reported all potential conflicts of interest (COIs), which were rated by the Expert Panel Chair and Journal of Allergy and Clinical Immunology editors. Individuals with high COIs were excluded from the Expert Panel. Those with moderate COIs were recused for that topic. Low COIs were not related to the guideline.

Generalizability of the Guideline

These guidelines are based on systematic reviews with large sample sizes and patients of all ages. They are generalizable. However, the authors recognize that variations in asthma require individualized approaches. They identify this as a reason for the lack of strong recommendations for asthma standards of care.

Biologics have progressed considerably since revision of the guidelines. The 2020 guidelines did not address these to prevent delay of the guideline release, but recommendations should be included in future guidelines. Future studies should address healthcare disparities in asthma, barriers to equitable care, and how to eliminate them, as guided by the President’s Task Force.⁸ Status asthmaticus should be included in future updates.

Asthma is a heterogeneous condition characterized by airway hyperresponsiveness and obstruction, with associated airway inflammation and remodeling.² Asthma affects 25 million people in the United States and 334 million people worldwide, with significant healthcare disparities across race and ethnicity.^2-6 Asthma is the third most common reason for hospitalizations in pediatrics, accounting for 180,000 annual hospitalizations for children and adults.^3,7 In 2020, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel provided a focused update to the Asthma Management Guidelines, centered on six topics with sufficient new evidence. The management of status asthmaticus was not included in this update. We spotlight four of the recommendations applicable to the practice of pediatric hospital medicine.

Recommendation 1. Children 0 to 4 years old with recurrent wheezing triggered by a respiratory tract infection (RTI) and no wheezing between infections should receive a short course of daily inhaled corticosteroids (ICS) at the onset of a RTI, with an as-needed short-acting beta agonist (SABA) for quick-relief therapy compared to SABA alone (evidence quality: high; recommendation strength: conditional).

Recurrent wheezing is defined as clinically significant periods of wheezing that are reversible or consistent with bronchospasm and as ≥3 episodes in a lifetime or 2 episodes in the past year. It is important to adhere to this definition to prevent inappropriate use of ICS for bronchiolitis. This treatment is associated with a reduction of use of systemic steroids (relative risk [RR], 0.67; 95% CI, 0.46-0.98) without a statistical decrease in acute care visits (RR, 0.90; 95% CI, 0.77-1.05) or hospitalizations (RR, 0.77; 95% CI, 0.06-9.68). Improved transition of care is essential between the primary care provider, hospitalist, and family to ensure an understanding of how/when to initiate ICS at the onset of a RTI. Potential harms include effect on growth and overprescribing. Growth should be monitored because data are conflicting.

Recommendation 2. Individuals ages 12 years and older with mild persistent asthma should use as-needed SABA and may use either daily low-dose ICS or as-needed ICS when symptoms flare (evidence quality: moderate; recommendation strength: conditional).

In intermittent therapy, patients take a SABA followed by an ICS as needed for acute asthma symptoms. This recommendation is driven by asthma-control and quality-of-life outcomes, with caregivers reporting that intermittent dosing could “offer flexibility and potentially reduce side effects.” There were no differences between management regimens with respect to systemic steroid use (RR, 0.70; 95% CI, 0.30-1.64) or urgent care visits (RR, 0.25; 95% CI, 0.05-1.16). Differing perception of symptoms by individuals may lead to undertreating or overtreating, and intermittent administration makes it challenging for clinicians to assess the need to adjust therapy.

Recommendation 3. Children 4 years and older with moderate to severe persistent asthma should use ICS-formoterol in a single inhaler used as both daily controller and reliever therapy compared to either (a) higher-dose ICS as daily controller therapy and SABA for quick-relief therapy or (b) a same-dose ICS-long-acting beta agonist (LABA) as daily controller therapy and SABA for quick-relief therapy (evidence quality: high for ages ≥12 years, moderate for ages 4-11 years; recommendation strength: strong).

For children 4 years and older, it is recommended to use “single maintenance and reliever therapy” (SMART) with a single-inhaler containing either low- or medium-dose ICS and formoterol when stepping up from Step 2 (daily low-dose ICS and as-needed SABA) to Step 3 (daily and as-needed low-dose ICS-formoterol) and Step 4 (daily and as-needed medium-dose ICS-formoterol). It is preferred to use this single inhaler as needed when symptoms flare rather than an additional as-needed SABA. However, this may be impractical if insurance does not cover multiple prescriptions per month. Formoterol is specified because it is the only LABA studied. Studies have shown reductions in hospitalizations, systemic corticosteroids, and ED visits with this regimen. “ICS-formoterol should be administered as maintenance therapy with 1-2 puffs once to twice daily and 1-2 puffs as needed for asthma symptoms. The maximum number of puffs per day is 12 (54 mcg formoterol) for individuals ages 12 years and older and 8 (36 mcg formoterol) for children ages 4-11 years.”¹

Recommendation 4. If individuals with asthma have symptoms related to indoor allergens, confirmed by history or allergy testing, they should use a multicomponent allergen-specific mitigation intervention. Allergen mitigation interventions should not be a part of routine asthma management for individuals with asthma who do not have symptoms related to exposure to specific indoor allergens (evidence quality: low; recommendation strength: conditional).

Providers often emphasize exposure to potential indoor allergens such as carpets and pets when taking an asthma history and counsel removal of these triggers. However, all recommendations related to allergies in the 2020 updates have low-moderate evidence quality and conditional recommendation strength. Hospitalists should instead focus their questions on allergy symptoms and triggers and recommend multicomponent mitigation intervention only if there is a confirmed allergy history. Families should continue routine good practices such as house cleaning and laundering, but other interventions are not evidence-based.

Methods

The Expert Panel included a diverse group of clinicians, a pharmacist, and health policy experts. In 2015, a needs assessment identified 6 out of 17 priority topics with sufficient new information for updates. Key questions were drafted, and systematic reviews were published through 2018. The Expert Panel made its recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. The Expert Panel informed its recommendations with input from focus groups, including individuals with asthma and caregivers. The NHLBI posted the draft report for public review, and comments were considered. We believe these methods effectively developed evidence-based recommendations, and the diversity of stakeholders increases the value of this guideline. However, the infrequency of updates limits the utility of the NHLBI guidelines as compared with annual GINA (Global Initiative for Asthma) updates.

There are important considerations in assessing these guidelines. Specifically, the validity of systemic steroid courses as an outcome for children ages 0 to 4 years is controversial. Second, the studies cited in defense of intermittent ICS use in children >12 years of age excluded pediatric patients and did not include readmissions as a primary outcome, which is of particular interest to the hospitalist.

Potential Conflicts for Guideline Authors

The Expert Panel reported all potential conflicts of interest (COIs), which were rated by the Expert Panel Chair and Journal of Allergy and Clinical Immunology editors. Individuals with high COIs were excluded from the Expert Panel. Those with moderate COIs were recused for that topic. Low COIs were not related to the guideline.

Generalizability of the Guideline

These guidelines are based on systematic reviews with large sample sizes and patients of all ages. They are generalizable. However, the authors recognize that variations in asthma require individualized approaches. They identify this as a reason for the lack of strong recommendations for asthma standards of care.

Biologics have progressed considerably since revision of the guidelines. The 2020 guidelines did not address these to prevent delay of the guideline release, but recommendations should be included in future guidelines. Future studies should address healthcare disparities in asthma, barriers to equitable care, and how to eliminate them, as guided by the President’s Task Force.⁸ Status asthmaticus should be included in future updates.

Inspired by the ABIM Foundation’s Choosing Wisely^® campaign, the “Things We Do for No Reason^™” (TWDFNR) series reviews practices that have become common parts of hospital care but may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent clear-cut conclusions or clinical practice standards but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion.

A 56-year-old man with alcohol use disorder (AUD) is admitted with decompensated heart failure and experiences alcohol withdrawal during the hospitalization. He improves with guideline-directed heart failure therapy and benzodiazepines for alcohol withdrawal. Discharge medications are metoprolol succinate, lisinopril, furosemide, aspirin, atorvastatin, thiamine, folic acid, and a multivitamin. No medications are offered for AUD treatment. At follow-up a week later, he presents with dyspnea and reports poor medication adherence and a return to heavy drinking.

AUD is common among hospitalized patients.¹ AUD increases the risk of vitamin deficiencies due to the toxic effects of alcohol on the gastrointestinal tract and liver, causing impaired digestion, reduced absorption, and increased degradation of key micronutrients.^2,3 Other risk factors for AUD-associated vitamin deficiencies include food insecurity and the replacement of nutrient-rich food with alcohol. Since the body does not readily store water-soluble vitamins, including thiamine (vitamin B₁) and folate (vitamin B₉), people require regular dietary replenishment of these nutrients. Thus, if individuals with AUD eat less fortified food, they risk developing thiamine, folate, niacin, and other vitamin deficiencies. Since AUD puts patients at risk for vitamin deficiencies, hospitalized patients typically receive vitamin supplementation, including thiamine, folic acid, and a multivitamin (most formulations contain water-soluble vitamins B and C and micronutrients).¹ Hospitalists often continue these medications at discharge.

Thiamine deficiency may manifest as Wernicke encephalopathy (WE), peripheral neuropathy, or a high-output heart failure state. Untreated, acute WE can progress to irreversible Korsakoff psychosis. Given the serious morbidity and mortality of unrecognized and untreated WE, hospitalists often start high-dose intravenous (IV) thiamine at 200 to 500 mg every 8 hours for at least 72 hours for patients with WE risk factors (including AUD) or those with suspected WE based on clinical presentation.^4,5

Hospitalists empirically treat with thiamine, folate, and other vitamins upon hospital admission with the intent of reducing morbidity associated with nutritional deficiencies.¹ Repletion poses few risks to patients since the kidneys eliminate water-soluble vitamins. Multivitamins also have a low potential for direct harm and a low cost. Given the consequences of missing a deficiency, alcohol withdrawal–management order sets commonly embed vitamin repletion orders.⁶

Hospitalists often reflexively continue vitamin supplementation on discharge. Unfortunately, there is no evidence that prescribing vitamin supplementation leads to clinically significant improvements for people with AUD, and patients can experience harms.

Literature and specialty guidelines lack consensus on rational vitamin supplementation in patients with AUD.^2,7,8 Folate testing is not recommended due to inaccuracies.⁹ In fact, clinical data, such as body mass index, more accurately predict alcohol-related cognitive impairment than blood levels of vitamins.¹⁰ In one small study of vitamin deficiencies among patients with acute alcohol intoxication, none had low B₁₂ or folate levels.¹¹ A systematic review among people experiencing homelessness with unhealthy alcohol use showed no clear pattern of vitamin deficiencies across studies, although vitamin C and thiamine deficiencies predominated.¹²

In the absence of reliable thiamine and folate testing to confirm deficiencies, clinicians must use their clinical assessment skills. Clinicians rarely evaluate patients with AUD for vitamin deficiency risk factors and instead reflexively prescribe vitamin supplementation. An AUD diagnosis may serve as a sensitive, but not specific, risk factor for those in need of vitamin supplementation. Once the diagnosis of AUD is made, further investigation can help discern which AUD patients will benefit from vitamins after discharge.

Other limitations make prescribing oral vitamins reflexively at discharge a low-value practice. Thiamine, often prescribed orally in the hospital and on discharge, has poor oral bioavailability.¹³ Unfortunately, people with AUD have decreased and variable thiamine absorption. To prevent WE, thiamine must cross the blood-brain barrier, and the literature provides insufficient evidence to guide clinicians on an appropriate oral thiamine dose, frequency, or duration of treatment.¹⁴ While early high-dose IV thiamine may treat or prevent WE during hospitalization, low-dose oral thiamine may not provide benefit to patients with AUD.⁵

The literature also provides sparse evidence for folate supplementation and its optimal dose. Since 1998, when the United States mandated fortifying grain products with folic acid, people rarely have low serum folate levels. Though patients with AUD have lower folate levels relative to the general population,¹⁵ this difference does not seem clinically significant. While limited data show an association between oral multivitamin supplementation and improved serum nutrient levels among people with AUD, we lack evidence on clinical outcomes.¹⁶

Most importantly, for a practice lacking strong evidence, prescribing multiple vitamins at discharge may result in harm from polypharmacy and unnecessary costs for the recently hospitalized patient. Alcohol use is associated with decreased adherence to medications for chronic conditions,¹⁷ including HIV, hypertension, hyperlipidemia, and psychiatric diseases. In addition, research shows an association between an increased number of discharge medications and higher risk for hospital readmission. The harm may actually correlate with the number of medications and complexity of the regimen rather than the risk profile of the medications themselves.¹⁸ Providers underestimate the impact of adding multiple vitamins at discharge, especially for patients who have several co-occurring medical conditions that require other medications. Furthermore, insurance rarely covers vitamins, leading hospitals or patients to incur the costs at discharge.

When treating patients with AUD, consider the potential benefit of vitamin supplementation for the individual. If a patient with regular, heavy alcohol use is at high risk of vitamin deficiencies due to ongoing risk factors (Table), hospitalists should discuss vitamin therapy via a patient-centered risk-benefit process.

When considering discharge vitamins, make concurrent efforts to enhance patient nutrition via decreased alcohol consumption and improved healthy food intake. While some patients do not have a goal of abstaining from alcohol, providing resources to food access may help decrease the harms of drinking. Education may help patients learn that vitamin deficiencies can result from heavy alcohol use.

Multivitamin formulations have variable doses of vitamins but can contain 100% or more of the daily value of thiamine and folic acid. For patients with AUD at lower risk of vitamin deficiencies (ie, mild alcohol use disorder with a healthy diet), discuss risks and benefits of supplementation. If they desire supplementation, a single thiamine-containing vitamin alone may be highest yield since it is the most morbid vitamin deficiency. Conversely, a patient with heavy alcohol intake and other risk factors for malnutrition may benefit from a higher dose of supplementation, achieved by prescribing a multivitamin alongside additional doses of thiamine and folate. However, the literature lacks evidence to guide clinicians on optimal vitamin dosing and formulations.

Instead of reflexively prescribing thiamine, folate, and multivitamin, clinicians can assess patients for AUD, provide motivational interviewing, and offer AUD treatment. Hospitalists should initiate and prescribe evidence-based medications for AUD for patients interested in reducing or stopping their alcohol intake. We can choose from Food and Drug Administration–approved AUD medications, including naltrexone and acamprosate. Unfortunately, less than 3% of patients with AUD receive medication therapy.¹⁹ Our healthcare systems can also refer individuals to community psychosocial treatment.

For patients with risk factors, prescribe empiric IV thiamine during hospitalization. Clinicians should then perform a risk-benefit assessment rather than reflexively prescribe vitamins to patients with AUD at discharge. We should also counsel patients to eat food when drinking to decrease alcohol-related harms.²⁰ Patients experiencing food insecurity should be linked to food resources through inpatient nutritional and social work consultations.

Elicit patient preference around vitamin supplementation after discharge. For patients with AUD who desire supplementation without risk factors for malnutrition (Table), consider prescribing a single thiamine-containing vitamin for prevention of thiamine deficiency, which, unlike other vitamin deficiencies, has the potential to be irreversible and life-threatening. Though no evidence currently supports this practice, it stands to reason that prescribing a single tablet could decrease the number of pills for patients who struggle with pill burden.

• Offer evidence-based medication treatment for AUD.
• Connect patients experiencing food insecurity with appropriate resources.
• For patients initiated on a multivitamin, folate, and high-dose IV thiamine at admission, perform vitamin de-escalation during hospitalization.
• Risk-stratify hospitalized patients with AUD for additional risk factors for vitamin deficiencies (Table). In those with additional risk factors, offer supplementation if consistent with patient preference. Balance the benefits of vitamin supplementation with the risks of polypharmacy, particularly if the patient has conditions requiring multiple medications.

Returning to our case, the hospitalist initiates IV thiamine, folate, and a multivitamin at admission and assesses the patient’s nutritional status and food insecurity. The hospitalist deems the patient—who eats regular, balanced meals—to be at low risk for vitamin deficiencies. The medical team discontinues folate and multivitamins before discharge and continues IV thiamine throughout the 3-day hospitalization. The patient and clinician agree that unaddressed AUD played a key role in the patient’s heart failure exacerbation. The clinician elicits the patient’s goals around their alcohol use, discusses AUD treatment, and initiates naltrexone for AUD.

Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason™”? Share what you do in your practice and join in the conversation online by retweeting it on Twitter (#TWDFNR) and liking it on Facebook. We invite you to propose ideas for other “Things We Do for No Reason™” topics by emailing [email protected].

Inspired by the ABIM Foundation’s Choosing Wisely^® campaign, the “Things We Do for No Reason^™” (TWDFNR) series reviews practices that have become common parts of hospital care but may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent clear-cut conclusions or clinical practice standards but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion.

A 56-year-old man with alcohol use disorder (AUD) is admitted with decompensated heart failure and experiences alcohol withdrawal during the hospitalization. He improves with guideline-directed heart failure therapy and benzodiazepines for alcohol withdrawal. Discharge medications are metoprolol succinate, lisinopril, furosemide, aspirin, atorvastatin, thiamine, folic acid, and a multivitamin. No medications are offered for AUD treatment. At follow-up a week later, he presents with dyspnea and reports poor medication adherence and a return to heavy drinking.

AUD is common among hospitalized patients.¹ AUD increases the risk of vitamin deficiencies due to the toxic effects of alcohol on the gastrointestinal tract and liver, causing impaired digestion, reduced absorption, and increased degradation of key micronutrients.^2,3 Other risk factors for AUD-associated vitamin deficiencies include food insecurity and the replacement of nutrient-rich food with alcohol. Since the body does not readily store water-soluble vitamins, including thiamine (vitamin B₁) and folate (vitamin B₉), people require regular dietary replenishment of these nutrients. Thus, if individuals with AUD eat less fortified food, they risk developing thiamine, folate, niacin, and other vitamin deficiencies. Since AUD puts patients at risk for vitamin deficiencies, hospitalized patients typically receive vitamin supplementation, including thiamine, folic acid, and a multivitamin (most formulations contain water-soluble vitamins B and C and micronutrients).¹ Hospitalists often continue these medications at discharge.

Thiamine deficiency may manifest as Wernicke encephalopathy (WE), peripheral neuropathy, or a high-output heart failure state. Untreated, acute WE can progress to irreversible Korsakoff psychosis. Given the serious morbidity and mortality of unrecognized and untreated WE, hospitalists often start high-dose intravenous (IV) thiamine at 200 to 500 mg every 8 hours for at least 72 hours for patients with WE risk factors (including AUD) or those with suspected WE based on clinical presentation.^4,5

Hospitalists empirically treat with thiamine, folate, and other vitamins upon hospital admission with the intent of reducing morbidity associated with nutritional deficiencies.¹ Repletion poses few risks to patients since the kidneys eliminate water-soluble vitamins. Multivitamins also have a low potential for direct harm and a low cost. Given the consequences of missing a deficiency, alcohol withdrawal–management order sets commonly embed vitamin repletion orders.⁶

Hospitalists often reflexively continue vitamin supplementation on discharge. Unfortunately, there is no evidence that prescribing vitamin supplementation leads to clinically significant improvements for people with AUD, and patients can experience harms.

Literature and specialty guidelines lack consensus on rational vitamin supplementation in patients with AUD.^2,7,8 Folate testing is not recommended due to inaccuracies.⁹ In fact, clinical data, such as body mass index, more accurately predict alcohol-related cognitive impairment than blood levels of vitamins.¹⁰ In one small study of vitamin deficiencies among patients with acute alcohol intoxication, none had low B₁₂ or folate levels.¹¹ A systematic review among people experiencing homelessness with unhealthy alcohol use showed no clear pattern of vitamin deficiencies across studies, although vitamin C and thiamine deficiencies predominated.¹²

In the absence of reliable thiamine and folate testing to confirm deficiencies, clinicians must use their clinical assessment skills. Clinicians rarely evaluate patients with AUD for vitamin deficiency risk factors and instead reflexively prescribe vitamin supplementation. An AUD diagnosis may serve as a sensitive, but not specific, risk factor for those in need of vitamin supplementation. Once the diagnosis of AUD is made, further investigation can help discern which AUD patients will benefit from vitamins after discharge.

Other limitations make prescribing oral vitamins reflexively at discharge a low-value practice. Thiamine, often prescribed orally in the hospital and on discharge, has poor oral bioavailability.¹³ Unfortunately, people with AUD have decreased and variable thiamine absorption. To prevent WE, thiamine must cross the blood-brain barrier, and the literature provides insufficient evidence to guide clinicians on an appropriate oral thiamine dose, frequency, or duration of treatment.¹⁴ While early high-dose IV thiamine may treat or prevent WE during hospitalization, low-dose oral thiamine may not provide benefit to patients with AUD.⁵

The literature also provides sparse evidence for folate supplementation and its optimal dose. Since 1998, when the United States mandated fortifying grain products with folic acid, people rarely have low serum folate levels. Though patients with AUD have lower folate levels relative to the general population,¹⁵ this difference does not seem clinically significant. While limited data show an association between oral multivitamin supplementation and improved serum nutrient levels among people with AUD, we lack evidence on clinical outcomes.¹⁶

Most importantly, for a practice lacking strong evidence, prescribing multiple vitamins at discharge may result in harm from polypharmacy and unnecessary costs for the recently hospitalized patient. Alcohol use is associated with decreased adherence to medications for chronic conditions,¹⁷ including HIV, hypertension, hyperlipidemia, and psychiatric diseases. In addition, research shows an association between an increased number of discharge medications and higher risk for hospital readmission. The harm may actually correlate with the number of medications and complexity of the regimen rather than the risk profile of the medications themselves.¹⁸ Providers underestimate the impact of adding multiple vitamins at discharge, especially for patients who have several co-occurring medical conditions that require other medications. Furthermore, insurance rarely covers vitamins, leading hospitals or patients to incur the costs at discharge.

When treating patients with AUD, consider the potential benefit of vitamin supplementation for the individual. If a patient with regular, heavy alcohol use is at high risk of vitamin deficiencies due to ongoing risk factors (Table), hospitalists should discuss vitamin therapy via a patient-centered risk-benefit process.

When considering discharge vitamins, make concurrent efforts to enhance patient nutrition via decreased alcohol consumption and improved healthy food intake. While some patients do not have a goal of abstaining from alcohol, providing resources to food access may help decrease the harms of drinking. Education may help patients learn that vitamin deficiencies can result from heavy alcohol use.

Multivitamin formulations have variable doses of vitamins but can contain 100% or more of the daily value of thiamine and folic acid. For patients with AUD at lower risk of vitamin deficiencies (ie, mild alcohol use disorder with a healthy diet), discuss risks and benefits of supplementation. If they desire supplementation, a single thiamine-containing vitamin alone may be highest yield since it is the most morbid vitamin deficiency. Conversely, a patient with heavy alcohol intake and other risk factors for malnutrition may benefit from a higher dose of supplementation, achieved by prescribing a multivitamin alongside additional doses of thiamine and folate. However, the literature lacks evidence to guide clinicians on optimal vitamin dosing and formulations.

Instead of reflexively prescribing thiamine, folate, and multivitamin, clinicians can assess patients for AUD, provide motivational interviewing, and offer AUD treatment. Hospitalists should initiate and prescribe evidence-based medications for AUD for patients interested in reducing or stopping their alcohol intake. We can choose from Food and Drug Administration–approved AUD medications, including naltrexone and acamprosate. Unfortunately, less than 3% of patients with AUD receive medication therapy.¹⁹ Our healthcare systems can also refer individuals to community psychosocial treatment.

For patients with risk factors, prescribe empiric IV thiamine during hospitalization. Clinicians should then perform a risk-benefit assessment rather than reflexively prescribe vitamins to patients with AUD at discharge. We should also counsel patients to eat food when drinking to decrease alcohol-related harms.²⁰ Patients experiencing food insecurity should be linked to food resources through inpatient nutritional and social work consultations.

Elicit patient preference around vitamin supplementation after discharge. For patients with AUD who desire supplementation without risk factors for malnutrition (Table), consider prescribing a single thiamine-containing vitamin for prevention of thiamine deficiency, which, unlike other vitamin deficiencies, has the potential to be irreversible and life-threatening. Though no evidence currently supports this practice, it stands to reason that prescribing a single tablet could decrease the number of pills for patients who struggle with pill burden.

• Offer evidence-based medication treatment for AUD.
• Connect patients experiencing food insecurity with appropriate resources.
• For patients initiated on a multivitamin, folate, and high-dose IV thiamine at admission, perform vitamin de-escalation during hospitalization.
• Risk-stratify hospitalized patients with AUD for additional risk factors for vitamin deficiencies (Table). In those with additional risk factors, offer supplementation if consistent with patient preference. Balance the benefits of vitamin supplementation with the risks of polypharmacy, particularly if the patient has conditions requiring multiple medications.

Returning to our case, the hospitalist initiates IV thiamine, folate, and a multivitamin at admission and assesses the patient’s nutritional status and food insecurity. The hospitalist deems the patient—who eats regular, balanced meals—to be at low risk for vitamin deficiencies. The medical team discontinues folate and multivitamins before discharge and continues IV thiamine throughout the 3-day hospitalization. The patient and clinician agree that unaddressed AUD played a key role in the patient’s heart failure exacerbation. The clinician elicits the patient’s goals around their alcohol use, discusses AUD treatment, and initiates naltrexone for AUD.

Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason™”? Share what you do in your practice and join in the conversation online by retweeting it on Twitter (#TWDFNR) and liking it on Facebook. We invite you to propose ideas for other “Things We Do for No Reason™” topics by emailing [email protected].

Inspired by the ABIM Foundation’s Choosing Wisely^® campaign, the “Things We Do for No Reason^™” (TWDFNR) series reviews practices that have become common parts of hospital care but may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent clear-cut conclusions or clinical practice standards but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion.

A 56-year-old man with alcohol use disorder (AUD) is admitted with decompensated heart failure and experiences alcohol withdrawal during the hospitalization. He improves with guideline-directed heart failure therapy and benzodiazepines for alcohol withdrawal. Discharge medications are metoprolol succinate, lisinopril, furosemide, aspirin, atorvastatin, thiamine, folic acid, and a multivitamin. No medications are offered for AUD treatment. At follow-up a week later, he presents with dyspnea and reports poor medication adherence and a return to heavy drinking.

AUD is common among hospitalized patients.¹ AUD increases the risk of vitamin deficiencies due to the toxic effects of alcohol on the gastrointestinal tract and liver, causing impaired digestion, reduced absorption, and increased degradation of key micronutrients.^2,3 Other risk factors for AUD-associated vitamin deficiencies include food insecurity and the replacement of nutrient-rich food with alcohol. Since the body does not readily store water-soluble vitamins, including thiamine (vitamin B₁) and folate (vitamin B₉), people require regular dietary replenishment of these nutrients. Thus, if individuals with AUD eat less fortified food, they risk developing thiamine, folate, niacin, and other vitamin deficiencies. Since AUD puts patients at risk for vitamin deficiencies, hospitalized patients typically receive vitamin supplementation, including thiamine, folic acid, and a multivitamin (most formulations contain water-soluble vitamins B and C and micronutrients).¹ Hospitalists often continue these medications at discharge.

Thiamine deficiency may manifest as Wernicke encephalopathy (WE), peripheral neuropathy, or a high-output heart failure state. Untreated, acute WE can progress to irreversible Korsakoff psychosis. Given the serious morbidity and mortality of unrecognized and untreated WE, hospitalists often start high-dose intravenous (IV) thiamine at 200 to 500 mg every 8 hours for at least 72 hours for patients with WE risk factors (including AUD) or those with suspected WE based on clinical presentation.^4,5

Hospitalists empirically treat with thiamine, folate, and other vitamins upon hospital admission with the intent of reducing morbidity associated with nutritional deficiencies.¹ Repletion poses few risks to patients since the kidneys eliminate water-soluble vitamins. Multivitamins also have a low potential for direct harm and a low cost. Given the consequences of missing a deficiency, alcohol withdrawal–management order sets commonly embed vitamin repletion orders.⁶

Hospitalists often reflexively continue vitamin supplementation on discharge. Unfortunately, there is no evidence that prescribing vitamin supplementation leads to clinically significant improvements for people with AUD, and patients can experience harms.

Literature and specialty guidelines lack consensus on rational vitamin supplementation in patients with AUD.^2,7,8 Folate testing is not recommended due to inaccuracies.⁹ In fact, clinical data, such as body mass index, more accurately predict alcohol-related cognitive impairment than blood levels of vitamins.¹⁰ In one small study of vitamin deficiencies among patients with acute alcohol intoxication, none had low B₁₂ or folate levels.¹¹ A systematic review among people experiencing homelessness with unhealthy alcohol use showed no clear pattern of vitamin deficiencies across studies, although vitamin C and thiamine deficiencies predominated.¹²

In the absence of reliable thiamine and folate testing to confirm deficiencies, clinicians must use their clinical assessment skills. Clinicians rarely evaluate patients with AUD for vitamin deficiency risk factors and instead reflexively prescribe vitamin supplementation. An AUD diagnosis may serve as a sensitive, but not specific, risk factor for those in need of vitamin supplementation. Once the diagnosis of AUD is made, further investigation can help discern which AUD patients will benefit from vitamins after discharge.

Other limitations make prescribing oral vitamins reflexively at discharge a low-value practice. Thiamine, often prescribed orally in the hospital and on discharge, has poor oral bioavailability.¹³ Unfortunately, people with AUD have decreased and variable thiamine absorption. To prevent WE, thiamine must cross the blood-brain barrier, and the literature provides insufficient evidence to guide clinicians on an appropriate oral thiamine dose, frequency, or duration of treatment.¹⁴ While early high-dose IV thiamine may treat or prevent WE during hospitalization, low-dose oral thiamine may not provide benefit to patients with AUD.⁵

The literature also provides sparse evidence for folate supplementation and its optimal dose. Since 1998, when the United States mandated fortifying grain products with folic acid, people rarely have low serum folate levels. Though patients with AUD have lower folate levels relative to the general population,¹⁵ this difference does not seem clinically significant. While limited data show an association between oral multivitamin supplementation and improved serum nutrient levels among people with AUD, we lack evidence on clinical outcomes.¹⁶

Most importantly, for a practice lacking strong evidence, prescribing multiple vitamins at discharge may result in harm from polypharmacy and unnecessary costs for the recently hospitalized patient. Alcohol use is associated with decreased adherence to medications for chronic conditions,¹⁷ including HIV, hypertension, hyperlipidemia, and psychiatric diseases. In addition, research shows an association between an increased number of discharge medications and higher risk for hospital readmission. The harm may actually correlate with the number of medications and complexity of the regimen rather than the risk profile of the medications themselves.¹⁸ Providers underestimate the impact of adding multiple vitamins at discharge, especially for patients who have several co-occurring medical conditions that require other medications. Furthermore, insurance rarely covers vitamins, leading hospitals or patients to incur the costs at discharge.

When treating patients with AUD, consider the potential benefit of vitamin supplementation for the individual. If a patient with regular, heavy alcohol use is at high risk of vitamin deficiencies due to ongoing risk factors (Table), hospitalists should discuss vitamin therapy via a patient-centered risk-benefit process.

When considering discharge vitamins, make concurrent efforts to enhance patient nutrition via decreased alcohol consumption and improved healthy food intake. While some patients do not have a goal of abstaining from alcohol, providing resources to food access may help decrease the harms of drinking. Education may help patients learn that vitamin deficiencies can result from heavy alcohol use.

Multivitamin formulations have variable doses of vitamins but can contain 100% or more of the daily value of thiamine and folic acid. For patients with AUD at lower risk of vitamin deficiencies (ie, mild alcohol use disorder with a healthy diet), discuss risks and benefits of supplementation. If they desire supplementation, a single thiamine-containing vitamin alone may be highest yield since it is the most morbid vitamin deficiency. Conversely, a patient with heavy alcohol intake and other risk factors for malnutrition may benefit from a higher dose of supplementation, achieved by prescribing a multivitamin alongside additional doses of thiamine and folate. However, the literature lacks evidence to guide clinicians on optimal vitamin dosing and formulations.

Instead of reflexively prescribing thiamine, folate, and multivitamin, clinicians can assess patients for AUD, provide motivational interviewing, and offer AUD treatment. Hospitalists should initiate and prescribe evidence-based medications for AUD for patients interested in reducing or stopping their alcohol intake. We can choose from Food and Drug Administration–approved AUD medications, including naltrexone and acamprosate. Unfortunately, less than 3% of patients with AUD receive medication therapy.¹⁹ Our healthcare systems can also refer individuals to community psychosocial treatment.

For patients with risk factors, prescribe empiric IV thiamine during hospitalization. Clinicians should then perform a risk-benefit assessment rather than reflexively prescribe vitamins to patients with AUD at discharge. We should also counsel patients to eat food when drinking to decrease alcohol-related harms.²⁰ Patients experiencing food insecurity should be linked to food resources through inpatient nutritional and social work consultations.

Elicit patient preference around vitamin supplementation after discharge. For patients with AUD who desire supplementation without risk factors for malnutrition (Table), consider prescribing a single thiamine-containing vitamin for prevention of thiamine deficiency, which, unlike other vitamin deficiencies, has the potential to be irreversible and life-threatening. Though no evidence currently supports this practice, it stands to reason that prescribing a single tablet could decrease the number of pills for patients who struggle with pill burden.

• Offer evidence-based medication treatment for AUD.
• Connect patients experiencing food insecurity with appropriate resources.
• For patients initiated on a multivitamin, folate, and high-dose IV thiamine at admission, perform vitamin de-escalation during hospitalization.
• Risk-stratify hospitalized patients with AUD for additional risk factors for vitamin deficiencies (Table). In those with additional risk factors, offer supplementation if consistent with patient preference. Balance the benefits of vitamin supplementation with the risks of polypharmacy, particularly if the patient has conditions requiring multiple medications.

Returning to our case, the hospitalist initiates IV thiamine, folate, and a multivitamin at admission and assesses the patient’s nutritional status and food insecurity. The hospitalist deems the patient—who eats regular, balanced meals—to be at low risk for vitamin deficiencies. The medical team discontinues folate and multivitamins before discharge and continues IV thiamine throughout the 3-day hospitalization. The patient and clinician agree that unaddressed AUD played a key role in the patient’s heart failure exacerbation. The clinician elicits the patient’s goals around their alcohol use, discusses AUD treatment, and initiates naltrexone for AUD.

Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason™”? Share what you do in your practice and join in the conversation online by retweeting it on Twitter (#TWDFNR) and liking it on Facebook. We invite you to propose ideas for other “Things We Do for No Reason™” topics by emailing [email protected].

Inspired by the ABIM Foundation’s Choosing Wisely^® campaign, the “Things We Do for No Reason^™” (TWDFNR) series reviews practices that have become common parts of hospital care but may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent clear-cut conclusions or clinical practice standards but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion.

The hospitalist admits an 80-year-old man for a chronic obstructive pulmonary disease exacerbation. The patient’s history is significant for chronic right knee pain. While hospitalized, the patient reports worsening of his knee pain. Radiographs of the right knee show severe osteoarthritic changes. Since acetaminophen does not relieve the patient’s pain, the hospitalist orders tramadol as needed.

Hospitalists, who commonly evaluate and treat acute and chronic pain in the inpatient setting, have a wide selection of interventions from which to choose, including tramadol. Tramadol hydrochloride is a synthetic, central-acting analgesic with multiple mechanisms of action. It is a serotonin-norepinephrine reuptake inhibitor (SNRI) with a structure similar to venlafaxine and produces antineuropathic analgesic effects.¹ Tramadol and its primary active metabolite O-desmethyltramadol (also known as the M1 metabolite) mediate its effects by binding at the mu-opioid receptor.² Phase I metabolism in the liver by cytochrome P450 isoenzyme 2D6 (CYP2D6) facilitates conversion of tramadol to M1 (Figure). Importantly, genetic polymorphisms in CYP2D6 result in individual variations in gene expression, which impacts the metabolism of tramadol.²

Although tramadol is available over the counter in some countries, in the United States it is a Schedule IV controlled substance. Tramadol consistently ranks among the top 50 prescribed medications in the United States.³

Given the growing concerns regarding the use of opioids, the pharmaceutical industry has marketed tramadol as a safer opioid option for pain management. Tramadol binds at the mu-opioid receptor with an affinity that is less than 4000-fold that of morphine; the binding potency of M1, the metabolite of tramadol, is less than 5-fold that of morphine.⁴ Due to its lower binding affinity at the mu-opioid receptor, tramadol is considered a weak opioid, one believed to have minimal withdrawal symptoms and a lower potential for overdose or misuse compared to other opioids.^1,5 Based on this characterization, many clinicians prescribe tramadol for elderly patients or patients otherwise at risk for medication misuse or adverse effects of opioids.⁶ In addition, hospitalized patients often have contraindications to nonopioid medications (eg, acetaminophen, nonsteroidal anti-inflammatory drugs [NSAIDs]), limiting their options for pain management.

Despite being marketed as an effective and safe medication, tramadol has an unpredictable metabolism, complex pharmacology, and drug-drug interactions that can cause significant adverse effects. Similar to other opioids, tramadol is associated with a risk of misuse, physiologic dependency, and overdose. In addition, tramadol has a black box warning for addiction, misuse, respiratory depression, ultra-rapid metabolism, neonatal opioid withdrawal syndrome, CYP450 drug interactions, and interactions with other central nervous system depressants.

While tramadol has multiple mechanisms of action, the literature lacks high-quality evidence (eg, large randomized controlled trials) supporting its use, especially in hospitalized medical patients. A recent retrospective study of tramadol looked at the diagnoses of 250 hospitalized patients who received tramadol for pain management. While this study did not examine efficacy, it found mild-to-moderate acute noncancer pain to be the primary reason for prescribing tramadol.⁷ This study also showed the risk of severe drug-drug interactions increased the longer patients were on tramadol.⁷

As a result of the limited evidence in hospitalized patients, hospitalists must rely on outpatient studies.^8-10 The size and quality of these studies, especially given the magnitude of tramadol prescribing in the United States, make them less useful. A series of Cochrane reviews examining the beneficial effects of tramadol for neuropathic pain, osteoarthritis, and cancer pain show insufficient evidence for tramadol when compared to placebo or active controls such as acetaminophen, NSAIDs, or other opioids.^8-10

The side-effect profile of tramadol outweighs its mild analgesic effects. The 2019 American Geriatric Society Beers criteria for potentially inappropriate medication use in older adults strongly recommends clinicians use caution when prescribing tramadol to older adult patients, as tramadol may worsen or cause hyponatremia.¹¹ In one large, population-based study, the use of tramadol doubled patients’ risk of hospitalization for hyponatremia when compared to codeine, though the incidence remains rather low at 4.6 per 10,000 person-months.¹² Studies have also demonstrated an increased risk of hospitalization for hypoglycemia in nondiabetic patients receiving tramadol.¹³ A large propensity-score matched cohort study of patients with osteoarthritis found tramadol to have an associated higher all-cause mortality compared to NSAIDs; however, these differences may be due to confounding variables.¹ In addition to hyponatremia and all-cause mortality, patients taking tramadol also have an associated increased risk of falls and hip fractures when compared to codeine or NSAIDs.¹⁴

The increased serotonergic activity associated with tramadol can lead to serotonin syndrome (serotonin toxicity), a rare but serious condition. Although serotonin syndrome can develop in patients taking tramadol as a monotherapy, the risk for this toxidrome increases when tramadol is taken in combination with other serotonergic agents or agents that inhibit metabolism of tramadol at CYP2D6.⁵ Seizures may also occur with tramadol at therapeutic and supratherapeutic doses. Population-based studies estimate seizures occur in 0.15% to 0.86% of patients receiving tramadol, which is two to six times the risk of those not on tramadol.⁵ Patients concurrently taking tramadol with a tricyclic antidepressant (TCA) or selective serotonin reuptake inhibitor (SSRI) are estimated to have seizures five to nine times more often than patients not taking a TCA or SSRI.⁵ Risk factors for tramadol-induced seizure include tramadol misuse or overdose, tramadol doses >1000 mg daily (maximum recommended dose is 400 mg/day), chronic tramadol use, concurrent use of a serotonergic agent or medications that inhibit CYP2D6, and history of epilepsy, renal disease, stroke, or traumatic brain injury.⁵ 

Differences in the genetic polymorphisms of CYP2D6 can produce a range of CYP2D6 activity from “poor metabolizers” (little-to-no analgesic effect) to “ultra-rapid metabolizers” (enhanced analgesia and increased risk of adverse effects), leading to unpredictable pharmacodynamic effects of tramadol.² In North Africa and the Arabian peninsula, more than 25% of the population rapidly metabolizes tramadol; these pharmacogenomic effects result in higher rates of tramadol addiction and overdose in these regions.⁵ An estimated 7% to 10% of Caucasians slowly metabolize tramadol, which may place them at risk of adverse effects from tramadol in addition to inadequate analgesia.¹⁵ In contrast, Ethiopian populations have the highest rate of ultra-rapid tramadol metabolism at 29%.¹⁵

Drugs that induce CYP2D6 (eg, dexamethasone, rifampin) or inhibit CYP2D6 (eg, bupropion, fluoxetine) also impact tramadol efficacy, pharmacokinetics, and pharmacodynamics.^16,17 Patients taking strong CYP2D6 inhibitors require significantly higher doses of tramadol to achieve analgesic effects.¹⁷ Tramadol undergoes extensive hepatic metabolism, producing several active metabolites, including M1 (Figure). Hepatic impairment increases the elimination half-life of tramadol and its metabolites.¹⁸ The majority of tramadol and its metabolites are eliminated through the kidneys. Accumulation of tramadol and its metabolites may occur in patients with renal impairment, placing them at increased risk of adverse effects.²

Finally, although some clinicians assume that tramadol has lower rates of misuse, diversion, or overdose compared to other opioids, rates of nonprescription use have increased with its proliferation.^19,20 The US Substance Abuse and Mental Health Services Administration estimates that 1,287,000 persons misused tramadol in 2019.²¹ Patients may exhibit symptoms of physiologic opioid dependence and withdrawal from chronic tramadol use.^2,22 In one study, patients prescribed tramadol monotherapy for acute pain from elective surgery had an increased risk for prolonged opioid use compared to patients prescribed other short-acting opioids.²²

Clinicians should determine the nature of the patient’s pain by obtaining a complete medical history, performing a thorough physical examination, and ordering diagnostic tests and imaging studies, as necessary. After consulting with the patient’s primary care physician, the clinician should employ a multimodal approach to pain that includes topical agents, psychotherapy, injections or interventions, and nonopioid medications. Patients with neuropathic pain may benefit from adjuvant analgesics such as gabapentinoids, TCAs, or SNRIs. In patients with evidence-based indications for opioid therapy (eg, pancreatitis, cancer pain, postsurgical pain), the hospitalist should assess the risk for opioid misuse and discuss risks and benefits with the patient before considering a time-limited trial of opioid therapy. If available and when indicated, clinicians should consult with specialists in pain management or palliative care. For cases wherein clinicians have already prescribed tramadol to the patient, they should discuss deprescribing strategies and alternative analgesic options with the patient and the patient’s primary care physician. Finally, before initiating tramadol therapy for hospitalized patients with pain, hospitalists should consider the risks, benefits, and alternative approaches to prescribing tramadol.

• For hospitalized patients reporting pain, complete a pain assessment by history, physical exam, chart review, and diagnostic studies to examine the etiology of the pain.
• Utilize multiple modalities for pain control when possible, including acetaminophen, NSAIDs, topical agents, ice or heat, neuropathic pain medications, and interventions such as injections, psychotherapy, or radiation, if indicated.
• Avoid prescribing tramadol due to unpredictable pharmacodynamics, adverse effects, and lack of quality evidence for efficacy in hospitalized medical patients.

Tramadol is a commonly used opioid medication associated with adverse effects and unpredictable analgesia. Regarding this case scenario, the use of tramadol in this patient places him at risk for drug-drug interactions, hyponatremia, hypoglycemia, serotonin syndrome, seizures, and pronounced side effects of opioid medications. Moderate quality evidence in the outpatient setting suggests that tramadol is unlikely to provide significant analgesia for his osteoarthritic pain.⁹ Instead of prescribing tramadol, the hospitalist should consider alternative treatments for this patient’s pain, such as intraarticular glucocorticoids, a short course of oral NSAIDs (unless contraindicated), topical treatments (eg, menthol, capsaicin, NSAIDs), physical therapy, and close follow-up with an orthopedist after hospital discharge. Further randomized controlled studies of tramadol vs active controls are needed.

Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason™”? Share what you do in your practice and join in the conversation online by retweeting it on Twitter (#TWDFNR) and liking it on Facebook. We invite you to propose ideas for other “Things We Do for No Reason™” topics by emailing [email protected].

Inspired by the ABIM Foundation’s Choosing Wisely^® campaign, the “Things We Do for No Reason^™” (TWDFNR) series reviews practices that have become common parts of hospital care but may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent clear-cut conclusions or clinical practice standards but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion.

The hospitalist admits an 80-year-old man for a chronic obstructive pulmonary disease exacerbation. The patient’s history is significant for chronic right knee pain. While hospitalized, the patient reports worsening of his knee pain. Radiographs of the right knee show severe osteoarthritic changes. Since acetaminophen does not relieve the patient’s pain, the hospitalist orders tramadol as needed.

Hospitalists, who commonly evaluate and treat acute and chronic pain in the inpatient setting, have a wide selection of interventions from which to choose, including tramadol. Tramadol hydrochloride is a synthetic, central-acting analgesic with multiple mechanisms of action. It is a serotonin-norepinephrine reuptake inhibitor (SNRI) with a structure similar to venlafaxine and produces antineuropathic analgesic effects.¹ Tramadol and its primary active metabolite O-desmethyltramadol (also known as the M1 metabolite) mediate its effects by binding at the mu-opioid receptor.² Phase I metabolism in the liver by cytochrome P450 isoenzyme 2D6 (CYP2D6) facilitates conversion of tramadol to M1 (Figure). Importantly, genetic polymorphisms in CYP2D6 result in individual variations in gene expression, which impacts the metabolism of tramadol.²

Although tramadol is available over the counter in some countries, in the United States it is a Schedule IV controlled substance. Tramadol consistently ranks among the top 50 prescribed medications in the United States.³

Given the growing concerns regarding the use of opioids, the pharmaceutical industry has marketed tramadol as a safer opioid option for pain management. Tramadol binds at the mu-opioid receptor with an affinity that is less than 4000-fold that of morphine; the binding potency of M1, the metabolite of tramadol, is less than 5-fold that of morphine.⁴ Due to its lower binding affinity at the mu-opioid receptor, tramadol is considered a weak opioid, one believed to have minimal withdrawal symptoms and a lower potential for overdose or misuse compared to other opioids.^1,5 Based on this characterization, many clinicians prescribe tramadol for elderly patients or patients otherwise at risk for medication misuse or adverse effects of opioids.⁶ In addition, hospitalized patients often have contraindications to nonopioid medications (eg, acetaminophen, nonsteroidal anti-inflammatory drugs [NSAIDs]), limiting their options for pain management.

Despite being marketed as an effective and safe medication, tramadol has an unpredictable metabolism, complex pharmacology, and drug-drug interactions that can cause significant adverse effects. Similar to other opioids, tramadol is associated with a risk of misuse, physiologic dependency, and overdose. In addition, tramadol has a black box warning for addiction, misuse, respiratory depression, ultra-rapid metabolism, neonatal opioid withdrawal syndrome, CYP450 drug interactions, and interactions with other central nervous system depressants.

While tramadol has multiple mechanisms of action, the literature lacks high-quality evidence (eg, large randomized controlled trials) supporting its use, especially in hospitalized medical patients. A recent retrospective study of tramadol looked at the diagnoses of 250 hospitalized patients who received tramadol for pain management. While this study did not examine efficacy, it found mild-to-moderate acute noncancer pain to be the primary reason for prescribing tramadol.⁷ This study also showed the risk of severe drug-drug interactions increased the longer patients were on tramadol.⁷

As a result of the limited evidence in hospitalized patients, hospitalists must rely on outpatient studies.^8-10 The size and quality of these studies, especially given the magnitude of tramadol prescribing in the United States, make them less useful. A series of Cochrane reviews examining the beneficial effects of tramadol for neuropathic pain, osteoarthritis, and cancer pain show insufficient evidence for tramadol when compared to placebo or active controls such as acetaminophen, NSAIDs, or other opioids.^8-10

The side-effect profile of tramadol outweighs its mild analgesic effects. The 2019 American Geriatric Society Beers criteria for potentially inappropriate medication use in older adults strongly recommends clinicians use caution when prescribing tramadol to older adult patients, as tramadol may worsen or cause hyponatremia.¹¹ In one large, population-based study, the use of tramadol doubled patients’ risk of hospitalization for hyponatremia when compared to codeine, though the incidence remains rather low at 4.6 per 10,000 person-months.¹² Studies have also demonstrated an increased risk of hospitalization for hypoglycemia in nondiabetic patients receiving tramadol.¹³ A large propensity-score matched cohort study of patients with osteoarthritis found tramadol to have an associated higher all-cause mortality compared to NSAIDs; however, these differences may be due to confounding variables.¹ In addition to hyponatremia and all-cause mortality, patients taking tramadol also have an associated increased risk of falls and hip fractures when compared to codeine or NSAIDs.¹⁴

The increased serotonergic activity associated with tramadol can lead to serotonin syndrome (serotonin toxicity), a rare but serious condition. Although serotonin syndrome can develop in patients taking tramadol as a monotherapy, the risk for this toxidrome increases when tramadol is taken in combination with other serotonergic agents or agents that inhibit metabolism of tramadol at CYP2D6.⁵ Seizures may also occur with tramadol at therapeutic and supratherapeutic doses. Population-based studies estimate seizures occur in 0.15% to 0.86% of patients receiving tramadol, which is two to six times the risk of those not on tramadol.⁵ Patients concurrently taking tramadol with a tricyclic antidepressant (TCA) or selective serotonin reuptake inhibitor (SSRI) are estimated to have seizures five to nine times more often than patients not taking a TCA or SSRI.⁵ Risk factors for tramadol-induced seizure include tramadol misuse or overdose, tramadol doses >1000 mg daily (maximum recommended dose is 400 mg/day), chronic tramadol use, concurrent use of a serotonergic agent or medications that inhibit CYP2D6, and history of epilepsy, renal disease, stroke, or traumatic brain injury.⁵ 

Differences in the genetic polymorphisms of CYP2D6 can produce a range of CYP2D6 activity from “poor metabolizers” (little-to-no analgesic effect) to “ultra-rapid metabolizers” (enhanced analgesia and increased risk of adverse effects), leading to unpredictable pharmacodynamic effects of tramadol.² In North Africa and the Arabian peninsula, more than 25% of the population rapidly metabolizes tramadol; these pharmacogenomic effects result in higher rates of tramadol addiction and overdose in these regions.⁵ An estimated 7% to 10% of Caucasians slowly metabolize tramadol, which may place them at risk of adverse effects from tramadol in addition to inadequate analgesia.¹⁵ In contrast, Ethiopian populations have the highest rate of ultra-rapid tramadol metabolism at 29%.¹⁵

Drugs that induce CYP2D6 (eg, dexamethasone, rifampin) or inhibit CYP2D6 (eg, bupropion, fluoxetine) also impact tramadol efficacy, pharmacokinetics, and pharmacodynamics.^16,17 Patients taking strong CYP2D6 inhibitors require significantly higher doses of tramadol to achieve analgesic effects.¹⁷ Tramadol undergoes extensive hepatic metabolism, producing several active metabolites, including M1 (Figure). Hepatic impairment increases the elimination half-life of tramadol and its metabolites.¹⁸ The majority of tramadol and its metabolites are eliminated through the kidneys. Accumulation of tramadol and its metabolites may occur in patients with renal impairment, placing them at increased risk of adverse effects.²

Finally, although some clinicians assume that tramadol has lower rates of misuse, diversion, or overdose compared to other opioids, rates of nonprescription use have increased with its proliferation.^19,20 The US Substance Abuse and Mental Health Services Administration estimates that 1,287,000 persons misused tramadol in 2019.²¹ Patients may exhibit symptoms of physiologic opioid dependence and withdrawal from chronic tramadol use.^2,22 In one study, patients prescribed tramadol monotherapy for acute pain from elective surgery had an increased risk for prolonged opioid use compared to patients prescribed other short-acting opioids.²²

Clinicians should determine the nature of the patient’s pain by obtaining a complete medical history, performing a thorough physical examination, and ordering diagnostic tests and imaging studies, as necessary. After consulting with the patient’s primary care physician, the clinician should employ a multimodal approach to pain that includes topical agents, psychotherapy, injections or interventions, and nonopioid medications. Patients with neuropathic pain may benefit from adjuvant analgesics such as gabapentinoids, TCAs, or SNRIs. In patients with evidence-based indications for opioid therapy (eg, pancreatitis, cancer pain, postsurgical pain), the hospitalist should assess the risk for opioid misuse and discuss risks and benefits with the patient before considering a time-limited trial of opioid therapy. If available and when indicated, clinicians should consult with specialists in pain management or palliative care. For cases wherein clinicians have already prescribed tramadol to the patient, they should discuss deprescribing strategies and alternative analgesic options with the patient and the patient’s primary care physician. Finally, before initiating tramadol therapy for hospitalized patients with pain, hospitalists should consider the risks, benefits, and alternative approaches to prescribing tramadol.

• For hospitalized patients reporting pain, complete a pain assessment by history, physical exam, chart review, and diagnostic studies to examine the etiology of the pain.
• Utilize multiple modalities for pain control when possible, including acetaminophen, NSAIDs, topical agents, ice or heat, neuropathic pain medications, and interventions such as injections, psychotherapy, or radiation, if indicated.
• Avoid prescribing tramadol due to unpredictable pharmacodynamics, adverse effects, and lack of quality evidence for efficacy in hospitalized medical patients.

Tramadol is a commonly used opioid medication associated with adverse effects and unpredictable analgesia. Regarding this case scenario, the use of tramadol in this patient places him at risk for drug-drug interactions, hyponatremia, hypoglycemia, serotonin syndrome, seizures, and pronounced side effects of opioid medications. Moderate quality evidence in the outpatient setting suggests that tramadol is unlikely to provide significant analgesia for his osteoarthritic pain.⁹ Instead of prescribing tramadol, the hospitalist should consider alternative treatments for this patient’s pain, such as intraarticular glucocorticoids, a short course of oral NSAIDs (unless contraindicated), topical treatments (eg, menthol, capsaicin, NSAIDs), physical therapy, and close follow-up with an orthopedist after hospital discharge. Further randomized controlled studies of tramadol vs active controls are needed.

Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason™”? Share what you do in your practice and join in the conversation online by retweeting it on Twitter (#TWDFNR) and liking it on Facebook. We invite you to propose ideas for other “Things We Do for No Reason™” topics by emailing [email protected].

Inspired by the ABIM Foundation’s Choosing Wisely^® campaign, the “Things We Do for No Reason^™” (TWDFNR) series reviews practices that have become common parts of hospital care but may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent clear-cut conclusions or clinical practice standards but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion.

The hospitalist admits an 80-year-old man for a chronic obstructive pulmonary disease exacerbation. The patient’s history is significant for chronic right knee pain. While hospitalized, the patient reports worsening of his knee pain. Radiographs of the right knee show severe osteoarthritic changes. Since acetaminophen does not relieve the patient’s pain, the hospitalist orders tramadol as needed.

Hospitalists, who commonly evaluate and treat acute and chronic pain in the inpatient setting, have a wide selection of interventions from which to choose, including tramadol. Tramadol hydrochloride is a synthetic, central-acting analgesic with multiple mechanisms of action. It is a serotonin-norepinephrine reuptake inhibitor (SNRI) with a structure similar to venlafaxine and produces antineuropathic analgesic effects.¹ Tramadol and its primary active metabolite O-desmethyltramadol (also known as the M1 metabolite) mediate its effects by binding at the mu-opioid receptor.² Phase I metabolism in the liver by cytochrome P450 isoenzyme 2D6 (CYP2D6) facilitates conversion of tramadol to M1 (Figure). Importantly, genetic polymorphisms in CYP2D6 result in individual variations in gene expression, which impacts the metabolism of tramadol.²

Although tramadol is available over the counter in some countries, in the United States it is a Schedule IV controlled substance. Tramadol consistently ranks among the top 50 prescribed medications in the United States.³

Given the growing concerns regarding the use of opioids, the pharmaceutical industry has marketed tramadol as a safer opioid option for pain management. Tramadol binds at the mu-opioid receptor with an affinity that is less than 4000-fold that of morphine; the binding potency of M1, the metabolite of tramadol, is less than 5-fold that of morphine.⁴ Due to its lower binding affinity at the mu-opioid receptor, tramadol is considered a weak opioid, one believed to have minimal withdrawal symptoms and a lower potential for overdose or misuse compared to other opioids.^1,5 Based on this characterization, many clinicians prescribe tramadol for elderly patients or patients otherwise at risk for medication misuse or adverse effects of opioids.⁶ In addition, hospitalized patients often have contraindications to nonopioid medications (eg, acetaminophen, nonsteroidal anti-inflammatory drugs [NSAIDs]), limiting their options for pain management.

Despite being marketed as an effective and safe medication, tramadol has an unpredictable metabolism, complex pharmacology, and drug-drug interactions that can cause significant adverse effects. Similar to other opioids, tramadol is associated with a risk of misuse, physiologic dependency, and overdose. In addition, tramadol has a black box warning for addiction, misuse, respiratory depression, ultra-rapid metabolism, neonatal opioid withdrawal syndrome, CYP450 drug interactions, and interactions with other central nervous system depressants.

While tramadol has multiple mechanisms of action, the literature lacks high-quality evidence (eg, large randomized controlled trials) supporting its use, especially in hospitalized medical patients. A recent retrospective study of tramadol looked at the diagnoses of 250 hospitalized patients who received tramadol for pain management. While this study did not examine efficacy, it found mild-to-moderate acute noncancer pain to be the primary reason for prescribing tramadol.⁷ This study also showed the risk of severe drug-drug interactions increased the longer patients were on tramadol.⁷

As a result of the limited evidence in hospitalized patients, hospitalists must rely on outpatient studies.^8-10 The size and quality of these studies, especially given the magnitude of tramadol prescribing in the United States, make them less useful. A series of Cochrane reviews examining the beneficial effects of tramadol for neuropathic pain, osteoarthritis, and cancer pain show insufficient evidence for tramadol when compared to placebo or active controls such as acetaminophen, NSAIDs, or other opioids.^8-10

The side-effect profile of tramadol outweighs its mild analgesic effects. The 2019 American Geriatric Society Beers criteria for potentially inappropriate medication use in older adults strongly recommends clinicians use caution when prescribing tramadol to older adult patients, as tramadol may worsen or cause hyponatremia.¹¹ In one large, population-based study, the use of tramadol doubled patients’ risk of hospitalization for hyponatremia when compared to codeine, though the incidence remains rather low at 4.6 per 10,000 person-months.¹² Studies have also demonstrated an increased risk of hospitalization for hypoglycemia in nondiabetic patients receiving tramadol.¹³ A large propensity-score matched cohort study of patients with osteoarthritis found tramadol to have an associated higher all-cause mortality compared to NSAIDs; however, these differences may be due to confounding variables.¹ In addition to hyponatremia and all-cause mortality, patients taking tramadol also have an associated increased risk of falls and hip fractures when compared to codeine or NSAIDs.¹⁴

The increased serotonergic activity associated with tramadol can lead to serotonin syndrome (serotonin toxicity), a rare but serious condition. Although serotonin syndrome can develop in patients taking tramadol as a monotherapy, the risk for this toxidrome increases when tramadol is taken in combination with other serotonergic agents or agents that inhibit metabolism of tramadol at CYP2D6.⁵ Seizures may also occur with tramadol at therapeutic and supratherapeutic doses. Population-based studies estimate seizures occur in 0.15% to 0.86% of patients receiving tramadol, which is two to six times the risk of those not on tramadol.⁵ Patients concurrently taking tramadol with a tricyclic antidepressant (TCA) or selective serotonin reuptake inhibitor (SSRI) are estimated to have seizures five to nine times more often than patients not taking a TCA or SSRI.⁵ Risk factors for tramadol-induced seizure include tramadol misuse or overdose, tramadol doses >1000 mg daily (maximum recommended dose is 400 mg/day), chronic tramadol use, concurrent use of a serotonergic agent or medications that inhibit CYP2D6, and history of epilepsy, renal disease, stroke, or traumatic brain injury.⁵ 

Differences in the genetic polymorphisms of CYP2D6 can produce a range of CYP2D6 activity from “poor metabolizers” (little-to-no analgesic effect) to “ultra-rapid metabolizers” (enhanced analgesia and increased risk of adverse effects), leading to unpredictable pharmacodynamic effects of tramadol.² In North Africa and the Arabian peninsula, more than 25% of the population rapidly metabolizes tramadol; these pharmacogenomic effects result in higher rates of tramadol addiction and overdose in these regions.⁵ An estimated 7% to 10% of Caucasians slowly metabolize tramadol, which may place them at risk of adverse effects from tramadol in addition to inadequate analgesia.¹⁵ In contrast, Ethiopian populations have the highest rate of ultra-rapid tramadol metabolism at 29%.¹⁵

Drugs that induce CYP2D6 (eg, dexamethasone, rifampin) or inhibit CYP2D6 (eg, bupropion, fluoxetine) also impact tramadol efficacy, pharmacokinetics, and pharmacodynamics.^16,17 Patients taking strong CYP2D6 inhibitors require significantly higher doses of tramadol to achieve analgesic effects.¹⁷ Tramadol undergoes extensive hepatic metabolism, producing several active metabolites, including M1 (Figure). Hepatic impairment increases the elimination half-life of tramadol and its metabolites.¹⁸ The majority of tramadol and its metabolites are eliminated through the kidneys. Accumulation of tramadol and its metabolites may occur in patients with renal impairment, placing them at increased risk of adverse effects.²

Finally, although some clinicians assume that tramadol has lower rates of misuse, diversion, or overdose compared to other opioids, rates of nonprescription use have increased with its proliferation.^19,20 The US Substance Abuse and Mental Health Services Administration estimates that 1,287,000 persons misused tramadol in 2019.²¹ Patients may exhibit symptoms of physiologic opioid dependence and withdrawal from chronic tramadol use.^2,22 In one study, patients prescribed tramadol monotherapy for acute pain from elective surgery had an increased risk for prolonged opioid use compared to patients prescribed other short-acting opioids.²²

Clinicians should determine the nature of the patient’s pain by obtaining a complete medical history, performing a thorough physical examination, and ordering diagnostic tests and imaging studies, as necessary. After consulting with the patient’s primary care physician, the clinician should employ a multimodal approach to pain that includes topical agents, psychotherapy, injections or interventions, and nonopioid medications. Patients with neuropathic pain may benefit from adjuvant analgesics such as gabapentinoids, TCAs, or SNRIs. In patients with evidence-based indications for opioid therapy (eg, pancreatitis, cancer pain, postsurgical pain), the hospitalist should assess the risk for opioid misuse and discuss risks and benefits with the patient before considering a time-limited trial of opioid therapy. If available and when indicated, clinicians should consult with specialists in pain management or palliative care. For cases wherein clinicians have already prescribed tramadol to the patient, they should discuss deprescribing strategies and alternative analgesic options with the patient and the patient’s primary care physician. Finally, before initiating tramadol therapy for hospitalized patients with pain, hospitalists should consider the risks, benefits, and alternative approaches to prescribing tramadol.

• For hospitalized patients reporting pain, complete a pain assessment by history, physical exam, chart review, and diagnostic studies to examine the etiology of the pain.
• Utilize multiple modalities for pain control when possible, including acetaminophen, NSAIDs, topical agents, ice or heat, neuropathic pain medications, and interventions such as injections, psychotherapy, or radiation, if indicated.
• Avoid prescribing tramadol due to unpredictable pharmacodynamics, adverse effects, and lack of quality evidence for efficacy in hospitalized medical patients.

Tramadol is a commonly used opioid medication associated with adverse effects and unpredictable analgesia. Regarding this case scenario, the use of tramadol in this patient places him at risk for drug-drug interactions, hyponatremia, hypoglycemia, serotonin syndrome, seizures, and pronounced side effects of opioid medications. Moderate quality evidence in the outpatient setting suggests that tramadol is unlikely to provide significant analgesia for his osteoarthritic pain.⁹ Instead of prescribing tramadol, the hospitalist should consider alternative treatments for this patient’s pain, such as intraarticular glucocorticoids, a short course of oral NSAIDs (unless contraindicated), topical treatments (eg, menthol, capsaicin, NSAIDs), physical therapy, and close follow-up with an orthopedist after hospital discharge. Further randomized controlled studies of tramadol vs active controls are needed.

Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason™”? Share what you do in your practice and join in the conversation online by retweeting it on Twitter (#TWDFNR) and liking it on Facebook. We invite you to propose ideas for other “Things We Do for No Reason™” topics by emailing [email protected].

When pediatricians and other pediatric providers are given training and resource materials, levels of firearm screenings and anticipatory guidance about firearm safety increase significantly, according to two new studies presented at the annual meeting of the American Academy of Pediatrics.

“With the rise in firearm sales and injuries during the COVID-19 pandemic, it is more important than ever that pediatricians address the firearm epidemic,” said Alexandra Byrne, MD, a pediatric resident at the University of Florida in Gainesville, who presented one of the studies.

There were 4.3 million more firearms purchased from March through July 2020 than expected, a recent study estimates, and 4,075 more firearm injuries than expected from April through July 2020.

In states with more excess purchases, firearm injuries related to domestic violence increased in April (rate ratio, 2.60; 95% CI, 1.32-5.93) and May (RR, 1.79; 95% CI, 1.19-2.91) 2020. However, excess gun purchases had no effect on rates of firearm violence outside the home.

In addition to the link between firearms in the home and domestic violence, they are also linked to a three- to fourfold greater risk for teen suicide, and both depression and suicidal thoughts have risen in teens during the pandemic.

“The data are pretty clear that if you have an unlocked, loaded weapon in your home, and you have a kid who’s depressed or anxious or dysregulated or doing maladaptive things for the pandemic, they’re much more likely to inadvertently take their own or someone else’s life by grabbing [a gun],” said Cora Breuner, MD, MPH, professor of pediatrics at Seattle Children’s Hospital.

However, there is no difference in gun ownership or gun-safety measures between homes with and without at-risk children, previous research shows.
 

Training, guidance, and locks

Previous research has also shown that there has been a reluctance by pediatricians to conduct firearm screenings and counsel parents about gun safety in the home.

For their two-step program, Dr. Byrne’s team used a plan-do-study-act approach. They started by providing training on firearm safety, evidence-based recommendations for firearm screening, and anticipatory guidance regarding safe firearm storage to members of the general pediatrics division at the University of Florida. And they supplied clinics with free firearm locks.

Next they supplied clinics with posters and educational cards from the Be SMART campaign, an initiative of the Everytown for Gun Safety Support Fund, which provides materials for anyone, including physicians, to use.

During their study, the researchers sent three anonymous six-question online surveys – at baseline and 3 to 4 months after each of the two steps – to pediatric residents, physician assistants, advanced practice registered nurses, and attendings to assess the project. There were 52 responses to the first survey, for a response rate of 58.4%, 42 responses to the second survey, for a response rate of 47.2%, and 23 responses to the third survey, for a rate of response 25.8%.

The program nearly doubled screenings during well-child visits and dramatically increased the proportion of families who received a firearm lock when they told providers they had a firearm at home.

Adding a social-history component

A program to increase firearm screening was also presented at the AAP conference.

After random review of medical records from 30 patients admitted to the hospital documented zero firearm screenings, Marjorie Farrington, MD, and Samantha Gunkelman, MD, from Akron Children’s Hospital in Ohio, implemented a program that they hope will increase firearm screenings during inpatient admissions to at least 50%.

They started their ongoing program in April 2020 by adding a social-history component to the history and physical (H&P) exam template and educating residents on how to screen and included guidance on safe firearm storage.

They also had physicians with firearm expertise give gun-safety lectures, and they plan to involve the Family Resource Center at their hospital in the creation of resources that can be incorporated into discharge instructions.

From April 2020 to June 2021, after the addition to the H&P template, 63% of the 5196 patients admitted to the hospital underwent a firearm screening. Of the 25% of patients who reported guns at home, 3% were not storing their firearms safely.

The pair used the “Store It Safe” Physician Handout provided by the Ohio chapter of the AAP.

Many pediatricians and pediatric trainees are not comfortable counseling on firearm safety, often a result of inadequate training on the topic.

The BulletPoints Project — developed by the Violence Prevention Research Program at the University of California, Davis — can also help physicians talk to patients about guns.

“Many pediatricians and pediatric trainees are not comfortable counseling on firearm safety, often a result of inadequate training on the topic,” Dr. Byrne said in an interview. “Additionally, it is a challenging topic that can often be met with resistance from patients and families. Lack of time during visits is also a huge barrier.”

Lack of training is an obstacle to greater firearm screenings, Dr. Greeley agreed, as are the feeling that guidance simply won’t make a difference and concerns about political pressure and divineness. The lack of research on firearm injuries and the impact of firearm screenings and anticipatory guidance is a challenge, he added, although that is starting to change.

Pediatricians need education on how to make a difference when it comes to firearm safety, and should follow AAP guidelines, Dr. Greeley said.

Counseling on firearm safety is in the same category as immunizations, seatbelts, substance use, helmets, and other public-health issues that are important to address at visits, regardless of how difficult it might be, Dr. Breuner told this news organization.

“It is our mission, as pediatricians, to provide every ounce of prevention in our well-child and anticipatory guidance visits,” she said. “It’s our job, so we shouldn’t shy away from it even though it’s hard.”

Doctors are more comfortable discussing firearm safety if they are firearm owners, previous research has shown, so she advises pediatricians who feel unqualified to discuss firearms to seek guidance from their peers on how to approach screenings and anticipatory guidance, she noted.

The firearm study being done in an academic center gives me great pause. The populations are often very different than private practice.

Both of these studies were conducted at single institutions and might not reflect what would work in private clinics.

“The firearm study being done in an academic center gives me great pause,” Dr. Greeley said. “The populations are often very different than private practice. I think that there is still a lot that remains unknown about decreasing household firearm injury and death.”

And the degree to which findings from these two gun-safety programs can be generalized to other academic centers or children’s hospitals is unclear.

“There are states where, I suspect, firearm screening is much more common. Some states have very pro-firearm cultures and others are anti-firearm,” Dr. Greeley said. “There are also likely differences within states,” particularly between urban and rural regions.

“Firearms are often a very personal issue for families, and pediatricians in ‘pro-firearm’ communities may have greater resistance to working on this,” he pointed out.

Nevertheless, Dr. Greeley said, “this is a promising strategy that could be part of a broad injury prevention initiative.”

Neither study noted any external funding. Dr. Byrne is a member of the Moms Demand Action Gainesville Chapter, which donated the firearm locks for the project. Dr. Breuner, Dr. Greeley, and Dr. Farrington have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

When pediatricians and other pediatric providers are given training and resource materials, levels of firearm screenings and anticipatory guidance about firearm safety increase significantly, according to two new studies presented at the annual meeting of the American Academy of Pediatrics.

“With the rise in firearm sales and injuries during the COVID-19 pandemic, it is more important than ever that pediatricians address the firearm epidemic,” said Alexandra Byrne, MD, a pediatric resident at the University of Florida in Gainesville, who presented one of the studies.

There were 4.3 million more firearms purchased from March through July 2020 than expected, a recent study estimates, and 4,075 more firearm injuries than expected from April through July 2020.

In states with more excess purchases, firearm injuries related to domestic violence increased in April (rate ratio, 2.60; 95% CI, 1.32-5.93) and May (RR, 1.79; 95% CI, 1.19-2.91) 2020. However, excess gun purchases had no effect on rates of firearm violence outside the home.

In addition to the link between firearms in the home and domestic violence, they are also linked to a three- to fourfold greater risk for teen suicide, and both depression and suicidal thoughts have risen in teens during the pandemic.

“The data are pretty clear that if you have an unlocked, loaded weapon in your home, and you have a kid who’s depressed or anxious or dysregulated or doing maladaptive things for the pandemic, they’re much more likely to inadvertently take their own or someone else’s life by grabbing [a gun],” said Cora Breuner, MD, MPH, professor of pediatrics at Seattle Children’s Hospital.

However, there is no difference in gun ownership or gun-safety measures between homes with and without at-risk children, previous research shows.
 

Training, guidance, and locks

Previous research has also shown that there has been a reluctance by pediatricians to conduct firearm screenings and counsel parents about gun safety in the home.

For their two-step program, Dr. Byrne’s team used a plan-do-study-act approach. They started by providing training on firearm safety, evidence-based recommendations for firearm screening, and anticipatory guidance regarding safe firearm storage to members of the general pediatrics division at the University of Florida. And they supplied clinics with free firearm locks.

Next they supplied clinics with posters and educational cards from the Be SMART campaign, an initiative of the Everytown for Gun Safety Support Fund, which provides materials for anyone, including physicians, to use.

During their study, the researchers sent three anonymous six-question online surveys – at baseline and 3 to 4 months after each of the two steps – to pediatric residents, physician assistants, advanced practice registered nurses, and attendings to assess the project. There were 52 responses to the first survey, for a response rate of 58.4%, 42 responses to the second survey, for a response rate of 47.2%, and 23 responses to the third survey, for a rate of response 25.8%.

The program nearly doubled screenings during well-child visits and dramatically increased the proportion of families who received a firearm lock when they told providers they had a firearm at home.

Adding a social-history component

A program to increase firearm screening was also presented at the AAP conference.

After random review of medical records from 30 patients admitted to the hospital documented zero firearm screenings, Marjorie Farrington, MD, and Samantha Gunkelman, MD, from Akron Children’s Hospital in Ohio, implemented a program that they hope will increase firearm screenings during inpatient admissions to at least 50%.

They started their ongoing program in April 2020 by adding a social-history component to the history and physical (H&P) exam template and educating residents on how to screen and included guidance on safe firearm storage.

They also had physicians with firearm expertise give gun-safety lectures, and they plan to involve the Family Resource Center at their hospital in the creation of resources that can be incorporated into discharge instructions.

From April 2020 to June 2021, after the addition to the H&P template, 63% of the 5196 patients admitted to the hospital underwent a firearm screening. Of the 25% of patients who reported guns at home, 3% were not storing their firearms safely.

The pair used the “Store It Safe” Physician Handout provided by the Ohio chapter of the AAP.

Many pediatricians and pediatric trainees are not comfortable counseling on firearm safety, often a result of inadequate training on the topic.

The BulletPoints Project — developed by the Violence Prevention Research Program at the University of California, Davis — can also help physicians talk to patients about guns.

“Many pediatricians and pediatric trainees are not comfortable counseling on firearm safety, often a result of inadequate training on the topic,” Dr. Byrne said in an interview. “Additionally, it is a challenging topic that can often be met with resistance from patients and families. Lack of time during visits is also a huge barrier.”

Lack of training is an obstacle to greater firearm screenings, Dr. Greeley agreed, as are the feeling that guidance simply won’t make a difference and concerns about political pressure and divineness. The lack of research on firearm injuries and the impact of firearm screenings and anticipatory guidance is a challenge, he added, although that is starting to change.

Pediatricians need education on how to make a difference when it comes to firearm safety, and should follow AAP guidelines, Dr. Greeley said.

Counseling on firearm safety is in the same category as immunizations, seatbelts, substance use, helmets, and other public-health issues that are important to address at visits, regardless of how difficult it might be, Dr. Breuner told this news organization.

“It is our mission, as pediatricians, to provide every ounce of prevention in our well-child and anticipatory guidance visits,” she said. “It’s our job, so we shouldn’t shy away from it even though it’s hard.”

Doctors are more comfortable discussing firearm safety if they are firearm owners, previous research has shown, so she advises pediatricians who feel unqualified to discuss firearms to seek guidance from their peers on how to approach screenings and anticipatory guidance, she noted.

The firearm study being done in an academic center gives me great pause. The populations are often very different than private practice.

Both of these studies were conducted at single institutions and might not reflect what would work in private clinics.

“The firearm study being done in an academic center gives me great pause,” Dr. Greeley said. “The populations are often very different than private practice. I think that there is still a lot that remains unknown about decreasing household firearm injury and death.”

And the degree to which findings from these two gun-safety programs can be generalized to other academic centers or children’s hospitals is unclear.

“There are states where, I suspect, firearm screening is much more common. Some states have very pro-firearm cultures and others are anti-firearm,” Dr. Greeley said. “There are also likely differences within states,” particularly between urban and rural regions.

“Firearms are often a very personal issue for families, and pediatricians in ‘pro-firearm’ communities may have greater resistance to working on this,” he pointed out.

Nevertheless, Dr. Greeley said, “this is a promising strategy that could be part of a broad injury prevention initiative.”

Neither study noted any external funding. Dr. Byrne is a member of the Moms Demand Action Gainesville Chapter, which donated the firearm locks for the project. Dr. Breuner, Dr. Greeley, and Dr. Farrington have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

When pediatricians and other pediatric providers are given training and resource materials, levels of firearm screenings and anticipatory guidance about firearm safety increase significantly, according to two new studies presented at the annual meeting of the American Academy of Pediatrics.

“With the rise in firearm sales and injuries during the COVID-19 pandemic, it is more important than ever that pediatricians address the firearm epidemic,” said Alexandra Byrne, MD, a pediatric resident at the University of Florida in Gainesville, who presented one of the studies.

There were 4.3 million more firearms purchased from March through July 2020 than expected, a recent study estimates, and 4,075 more firearm injuries than expected from April through July 2020.

In states with more excess purchases, firearm injuries related to domestic violence increased in April (rate ratio, 2.60; 95% CI, 1.32-5.93) and May (RR, 1.79; 95% CI, 1.19-2.91) 2020. However, excess gun purchases had no effect on rates of firearm violence outside the home.

In addition to the link between firearms in the home and domestic violence, they are also linked to a three- to fourfold greater risk for teen suicide, and both depression and suicidal thoughts have risen in teens during the pandemic.

“The data are pretty clear that if you have an unlocked, loaded weapon in your home, and you have a kid who’s depressed or anxious or dysregulated or doing maladaptive things for the pandemic, they’re much more likely to inadvertently take their own or someone else’s life by grabbing [a gun],” said Cora Breuner, MD, MPH, professor of pediatrics at Seattle Children’s Hospital.

However, there is no difference in gun ownership or gun-safety measures between homes with and without at-risk children, previous research shows.
 

Training, guidance, and locks

Previous research has also shown that there has been a reluctance by pediatricians to conduct firearm screenings and counsel parents about gun safety in the home.

For their two-step program, Dr. Byrne’s team used a plan-do-study-act approach. They started by providing training on firearm safety, evidence-based recommendations for firearm screening, and anticipatory guidance regarding safe firearm storage to members of the general pediatrics division at the University of Florida. And they supplied clinics with free firearm locks.

Next they supplied clinics with posters and educational cards from the Be SMART campaign, an initiative of the Everytown for Gun Safety Support Fund, which provides materials for anyone, including physicians, to use.

During their study, the researchers sent three anonymous six-question online surveys – at baseline and 3 to 4 months after each of the two steps – to pediatric residents, physician assistants, advanced practice registered nurses, and attendings to assess the project. There were 52 responses to the first survey, for a response rate of 58.4%, 42 responses to the second survey, for a response rate of 47.2%, and 23 responses to the third survey, for a rate of response 25.8%.

The program nearly doubled screenings during well-child visits and dramatically increased the proportion of families who received a firearm lock when they told providers they had a firearm at home.

Adding a social-history component

A program to increase firearm screening was also presented at the AAP conference.

After random review of medical records from 30 patients admitted to the hospital documented zero firearm screenings, Marjorie Farrington, MD, and Samantha Gunkelman, MD, from Akron Children’s Hospital in Ohio, implemented a program that they hope will increase firearm screenings during inpatient admissions to at least 50%.

They started their ongoing program in April 2020 by adding a social-history component to the history and physical (H&P) exam template and educating residents on how to screen and included guidance on safe firearm storage.

They also had physicians with firearm expertise give gun-safety lectures, and they plan to involve the Family Resource Center at their hospital in the creation of resources that can be incorporated into discharge instructions.

From April 2020 to June 2021, after the addition to the H&P template, 63% of the 5196 patients admitted to the hospital underwent a firearm screening. Of the 25% of patients who reported guns at home, 3% were not storing their firearms safely.

The pair used the “Store It Safe” Physician Handout provided by the Ohio chapter of the AAP.

Many pediatricians and pediatric trainees are not comfortable counseling on firearm safety, often a result of inadequate training on the topic.

The BulletPoints Project — developed by the Violence Prevention Research Program at the University of California, Davis — can also help physicians talk to patients about guns.

“Many pediatricians and pediatric trainees are not comfortable counseling on firearm safety, often a result of inadequate training on the topic,” Dr. Byrne said in an interview. “Additionally, it is a challenging topic that can often be met with resistance from patients and families. Lack of time during visits is also a huge barrier.”

Lack of training is an obstacle to greater firearm screenings, Dr. Greeley agreed, as are the feeling that guidance simply won’t make a difference and concerns about political pressure and divineness. The lack of research on firearm injuries and the impact of firearm screenings and anticipatory guidance is a challenge, he added, although that is starting to change.

Pediatricians need education on how to make a difference when it comes to firearm safety, and should follow AAP guidelines, Dr. Greeley said.

Counseling on firearm safety is in the same category as immunizations, seatbelts, substance use, helmets, and other public-health issues that are important to address at visits, regardless of how difficult it might be, Dr. Breuner told this news organization.

“It is our mission, as pediatricians, to provide every ounce of prevention in our well-child and anticipatory guidance visits,” she said. “It’s our job, so we shouldn’t shy away from it even though it’s hard.”

Doctors are more comfortable discussing firearm safety if they are firearm owners, previous research has shown, so she advises pediatricians who feel unqualified to discuss firearms to seek guidance from their peers on how to approach screenings and anticipatory guidance, she noted.

The firearm study being done in an academic center gives me great pause. The populations are often very different than private practice.

Both of these studies were conducted at single institutions and might not reflect what would work in private clinics.

“The firearm study being done in an academic center gives me great pause,” Dr. Greeley said. “The populations are often very different than private practice. I think that there is still a lot that remains unknown about decreasing household firearm injury and death.”

And the degree to which findings from these two gun-safety programs can be generalized to other academic centers or children’s hospitals is unclear.

“There are states where, I suspect, firearm screening is much more common. Some states have very pro-firearm cultures and others are anti-firearm,” Dr. Greeley said. “There are also likely differences within states,” particularly between urban and rural regions.

“Firearms are often a very personal issue for families, and pediatricians in ‘pro-firearm’ communities may have greater resistance to working on this,” he pointed out.

Nevertheless, Dr. Greeley said, “this is a promising strategy that could be part of a broad injury prevention initiative.”

Neither study noted any external funding. Dr. Byrne is a member of the Moms Demand Action Gainesville Chapter, which donated the firearm locks for the project. Dr. Breuner, Dr. Greeley, and Dr. Farrington have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The prevalence of homicide was 16% higher in pregnant women or postpartum women than nonpregnant or nonpostpartum women in the United States, according to 2018 and 2019 mortality data from the National Center for Health Statistics.

Homicide has long been identified as a leading cause of death during pregnancy, but homicide is not counted in estimates of maternal mortality, nor is it emphasized as a target for prevention and intervention, wrote Maeve Wallace, PhD, of Tulane University, New Orleans, and colleagues.

Data on maternal mortality (defined as “death while pregnant or within 42 days of the end of pregnancy from causes related to or aggravated by pregnancy”) were limited until the addition of pregnancy to the U.S. Standard Certificate of Death in 2003; all 50 states had adopted it by 2018, the researchers noted.

In a study published in Obstetrics & Gynecology, the researchers analyzed the first 2 years of nationally available data to identify pregnancy-associated mortality and characterize other risk factors such as age and race.

The researchers identified 4,705 female homicides in 2018 and 2019. Of these, 273 (5.8%) occurred in women who were pregnant or within a year of the end of pregnancy. Approximately half (50.2%) of the pregnant or postpartum victims were non-Hispanic Black, 30% were non-Hispanic white, 9.5% were Hispanic, and 10.3% were other races; approximately one-third (35.5%) were in the 20- to 24-year age group.

Overall, the ratio was 3.62 homicides per 100,000 live births among females who were either pregnant or within 1 year post partum, compared to 3.12 homicides per 100,000 live births in nonpregnant, nonpostpartum females aged 10-44 years (P = .05).

“Patterns were similar in further stratification by both race and age such that pregnancy was associated with more than a doubled risk of homicide among girls and women aged 10–24 in both the non-Hispanic White and non-Hispanic Black populations,” the researchers wrote.

The findings are consistent with previous studies, which “implicates health and social system failures. Although we are unable to directly evaluate the involvement of intimate partner violence (IPV) in this report, we did find that a majority of pregnancy-associated homicides occurred in the home, implicating the likelihood of involvement by persons known to the victim,” they noted. In addition, the data showed that approximately 70% of the incidents of homicide in pregnant and postpartum women involved a firearm, an increase over previous estimates.

The study findings were limited by several factors including the lack of circumstantial information and incomplete data on victim characteristics, the researchers noted. Other key limitations included the potential for false-positives and false-negatives when recording pregnancy status, which could lead to underestimates of pregnancy-associated homicides, and the lack of data on pregnancy outcomes for women who experienced live birth, abortion, or miscarriage within a year of death.

However, the results highlight the need for increased awareness and training of physicians in completing the pregnancy checkbox on death certificates, and the need for action on recommendations and interventions to prevent maternal deaths from homicide, they emphasized.

“Although encouraging, a commitment to the actual implementation of policies and investments known to be effective at protecting and the promoting the health and safety of girls and women must follow,” they concluded.
 

Data highlight disparities

“This study could not be done effectively prior to now, as the adoption of the pregnancy checkbox on the U.S. Standard Certificate of Death was only available in all 50 states as of 2018,” Sarah W. Prager, MD, of the University of Washington, Seattle, said in an interview.

“This study also demonstrates what was already known, which is that pregnancy is a high-risk time period for intimate partner violence, including homicide. The differences in homicide rates based on race and ethnicity also highlight the clear disparities in maternal mortality in the U.S. that are attributable to racism. There is more attention being paid to maternal mortality and the differential experience based on race, and this demonstrates that simply addressing medical management during pregnancy is not enough – we need to address root causes of racism if we truly want to reduce maternal mortality,” Dr. Prager said. 

“The primary take-home message for clinicians is to ascertain safety from every patient, and to try to reduce the impacts of racism on health care for patients, especially during pregnancy,” she said. 

Although more detailed records would help with elucidating causes versus associations, “more research is not the answer,” Dr. Prager stated. “The real solution here is to have better gun safety laws, and to put significant resources toward reducing the impacts of racism on health care and our society.”

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The researchers had no financial conflicts to disclose. Dr. Prager had no financial conflicts to disclose, but serves on the editorial advisory board of Ob.Gyn News.

The prevalence of homicide was 16% higher in pregnant women or postpartum women than nonpregnant or nonpostpartum women in the United States, according to 2018 and 2019 mortality data from the National Center for Health Statistics.

Homicide has long been identified as a leading cause of death during pregnancy, but homicide is not counted in estimates of maternal mortality, nor is it emphasized as a target for prevention and intervention, wrote Maeve Wallace, PhD, of Tulane University, New Orleans, and colleagues.

Data on maternal mortality (defined as “death while pregnant or within 42 days of the end of pregnancy from causes related to or aggravated by pregnancy”) were limited until the addition of pregnancy to the U.S. Standard Certificate of Death in 2003; all 50 states had adopted it by 2018, the researchers noted.

In a study published in Obstetrics & Gynecology, the researchers analyzed the first 2 years of nationally available data to identify pregnancy-associated mortality and characterize other risk factors such as age and race.

The researchers identified 4,705 female homicides in 2018 and 2019. Of these, 273 (5.8%) occurred in women who were pregnant or within a year of the end of pregnancy. Approximately half (50.2%) of the pregnant or postpartum victims were non-Hispanic Black, 30% were non-Hispanic white, 9.5% were Hispanic, and 10.3% were other races; approximately one-third (35.5%) were in the 20- to 24-year age group.

Overall, the ratio was 3.62 homicides per 100,000 live births among females who were either pregnant or within 1 year post partum, compared to 3.12 homicides per 100,000 live births in nonpregnant, nonpostpartum females aged 10-44 years (P = .05).

“Patterns were similar in further stratification by both race and age such that pregnancy was associated with more than a doubled risk of homicide among girls and women aged 10–24 in both the non-Hispanic White and non-Hispanic Black populations,” the researchers wrote.

The findings are consistent with previous studies, which “implicates health and social system failures. Although we are unable to directly evaluate the involvement of intimate partner violence (IPV) in this report, we did find that a majority of pregnancy-associated homicides occurred in the home, implicating the likelihood of involvement by persons known to the victim,” they noted. In addition, the data showed that approximately 70% of the incidents of homicide in pregnant and postpartum women involved a firearm, an increase over previous estimates.

The study findings were limited by several factors including the lack of circumstantial information and incomplete data on victim characteristics, the researchers noted. Other key limitations included the potential for false-positives and false-negatives when recording pregnancy status, which could lead to underestimates of pregnancy-associated homicides, and the lack of data on pregnancy outcomes for women who experienced live birth, abortion, or miscarriage within a year of death.

However, the results highlight the need for increased awareness and training of physicians in completing the pregnancy checkbox on death certificates, and the need for action on recommendations and interventions to prevent maternal deaths from homicide, they emphasized.

“Although encouraging, a commitment to the actual implementation of policies and investments known to be effective at protecting and the promoting the health and safety of girls and women must follow,” they concluded.
 

Data highlight disparities

“This study could not be done effectively prior to now, as the adoption of the pregnancy checkbox on the U.S. Standard Certificate of Death was only available in all 50 states as of 2018,” Sarah W. Prager, MD, of the University of Washington, Seattle, said in an interview.

“This study also demonstrates what was already known, which is that pregnancy is a high-risk time period for intimate partner violence, including homicide. The differences in homicide rates based on race and ethnicity also highlight the clear disparities in maternal mortality in the U.S. that are attributable to racism. There is more attention being paid to maternal mortality and the differential experience based on race, and this demonstrates that simply addressing medical management during pregnancy is not enough – we need to address root causes of racism if we truly want to reduce maternal mortality,” Dr. Prager said. 

“The primary take-home message for clinicians is to ascertain safety from every patient, and to try to reduce the impacts of racism on health care for patients, especially during pregnancy,” she said. 

Although more detailed records would help with elucidating causes versus associations, “more research is not the answer,” Dr. Prager stated. “The real solution here is to have better gun safety laws, and to put significant resources toward reducing the impacts of racism on health care and our society.”

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The researchers had no financial conflicts to disclose. Dr. Prager had no financial conflicts to disclose, but serves on the editorial advisory board of Ob.Gyn News.

The prevalence of homicide was 16% higher in pregnant women or postpartum women than nonpregnant or nonpostpartum women in the United States, according to 2018 and 2019 mortality data from the National Center for Health Statistics.

Homicide has long been identified as a leading cause of death during pregnancy, but homicide is not counted in estimates of maternal mortality, nor is it emphasized as a target for prevention and intervention, wrote Maeve Wallace, PhD, of Tulane University, New Orleans, and colleagues.

Data on maternal mortality (defined as “death while pregnant or within 42 days of the end of pregnancy from causes related to or aggravated by pregnancy”) were limited until the addition of pregnancy to the U.S. Standard Certificate of Death in 2003; all 50 states had adopted it by 2018, the researchers noted.

In a study published in Obstetrics & Gynecology, the researchers analyzed the first 2 years of nationally available data to identify pregnancy-associated mortality and characterize other risk factors such as age and race.

The researchers identified 4,705 female homicides in 2018 and 2019. Of these, 273 (5.8%) occurred in women who were pregnant or within a year of the end of pregnancy. Approximately half (50.2%) of the pregnant or postpartum victims were non-Hispanic Black, 30% were non-Hispanic white, 9.5% were Hispanic, and 10.3% were other races; approximately one-third (35.5%) were in the 20- to 24-year age group.

Overall, the ratio was 3.62 homicides per 100,000 live births among females who were either pregnant or within 1 year post partum, compared to 3.12 homicides per 100,000 live births in nonpregnant, nonpostpartum females aged 10-44 years (P = .05).

“Patterns were similar in further stratification by both race and age such that pregnancy was associated with more than a doubled risk of homicide among girls and women aged 10–24 in both the non-Hispanic White and non-Hispanic Black populations,” the researchers wrote.

The findings are consistent with previous studies, which “implicates health and social system failures. Although we are unable to directly evaluate the involvement of intimate partner violence (IPV) in this report, we did find that a majority of pregnancy-associated homicides occurred in the home, implicating the likelihood of involvement by persons known to the victim,” they noted. In addition, the data showed that approximately 70% of the incidents of homicide in pregnant and postpartum women involved a firearm, an increase over previous estimates.

The study findings were limited by several factors including the lack of circumstantial information and incomplete data on victim characteristics, the researchers noted. Other key limitations included the potential for false-positives and false-negatives when recording pregnancy status, which could lead to underestimates of pregnancy-associated homicides, and the lack of data on pregnancy outcomes for women who experienced live birth, abortion, or miscarriage within a year of death.

However, the results highlight the need for increased awareness and training of physicians in completing the pregnancy checkbox on death certificates, and the need for action on recommendations and interventions to prevent maternal deaths from homicide, they emphasized.

“Although encouraging, a commitment to the actual implementation of policies and investments known to be effective at protecting and the promoting the health and safety of girls and women must follow,” they concluded.
 

Data highlight disparities

“This study could not be done effectively prior to now, as the adoption of the pregnancy checkbox on the U.S. Standard Certificate of Death was only available in all 50 states as of 2018,” Sarah W. Prager, MD, of the University of Washington, Seattle, said in an interview.

“This study also demonstrates what was already known, which is that pregnancy is a high-risk time period for intimate partner violence, including homicide. The differences in homicide rates based on race and ethnicity also highlight the clear disparities in maternal mortality in the U.S. that are attributable to racism. There is more attention being paid to maternal mortality and the differential experience based on race, and this demonstrates that simply addressing medical management during pregnancy is not enough – we need to address root causes of racism if we truly want to reduce maternal mortality,” Dr. Prager said. 

“The primary take-home message for clinicians is to ascertain safety from every patient, and to try to reduce the impacts of racism on health care for patients, especially during pregnancy,” she said. 

Although more detailed records would help with elucidating causes versus associations, “more research is not the answer,” Dr. Prager stated. “The real solution here is to have better gun safety laws, and to put significant resources toward reducing the impacts of racism on health care and our society.”

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The researchers had no financial conflicts to disclose. Dr. Prager had no financial conflicts to disclose, but serves on the editorial advisory board of Ob.Gyn News.

The first patient of the afternoon is a 4-month-old in for his health maintenance visit. You’ve known his 20-year-old mother since she was a toddler. This infant has a 2-year-old sister. Also in the exam room is a young man you don’t recognize whom the mother introduces as Jason, her new boyfriend. He never makes eye contact and despite your best efforts you can’t get him to engage.

At the child’s next visit you are relieved to see the 6-month-old is alive and well and learn that your former patient and her two children have moved back in with her parents and Jason is no longer in the picture.

You don’t have to have been doing pediatrics very long to have learned that a “family” that includes an infant and a young adult male who is probably not the father is an environment in which the infant’s health and well-being is at significant risk. It is a situation in which child abuse even to the point of infanticide should be waving a red flag in your face.

Infanticide occurs in many animal species including our own. As abhorrent we may find the act, it occurs often enough to be, if not normal, at least not unexpected in certain circumstances. Theories abound as to what advantage the act of infanticide might convey to the success of a species. However, little if anything is known about any possible mechanisms that would allow it to occur.

Recently, a professor of molecular and cellular biology at Harvard University discovered a specific set of neurons in the mouse brain that controls aggressive behavior toward infants (Biological triggers for infant abuse, by Juan Siliezar, The Harvard Gazette, Sept 27, 2021). This same set of neurons also appears to trigger avoidance and neglect behaviors as well.

Research in other animal species has found that these antiparental behaviors occur in both virgins and sexually mature males who are strangers to the group. Interestingly, the behaviors switch off once individuals have their own offspring or have had the opportunity to familiarize themselves with infants. Not surprisingly, other studies have found that in some species environmental stress such as food shortage or threats of predation have triggered females to attack or ignore their offspring.

I think it is safe to assume a similar collection of neurons controlling aggressive behavior also exists in humans. One can imagine some well-read defense attorney dredging up this study and claiming that because his client had not yet fathered a child of his own that it was his nervous system’s normal response that made him toss his girlfriend’s baby against the wall.

The lead author of the study intends to study this collection of neurons in more depth to discover more about the process. It is conceivable that with more information her initial findings may help in the development of treatment and specific prevention strategies. Until that happens, we must rely on our intuition and keep our antennae tuned and alert for high-risk scenarios like the one I described at the opening of this letter.

We are left with leaning heavily on our community social work networks to keep close tabs on these high-risk families, offering both financial and emotional support. Parenting classes may be helpful, but some of this research leads me to suspect that immersing these young parents-to-be in hands-on child care situations might provide the best protection we can offer.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

The first patient of the afternoon is a 4-month-old in for his health maintenance visit. You’ve known his 20-year-old mother since she was a toddler. This infant has a 2-year-old sister. Also in the exam room is a young man you don’t recognize whom the mother introduces as Jason, her new boyfriend. He never makes eye contact and despite your best efforts you can’t get him to engage.

At the child’s next visit you are relieved to see the 6-month-old is alive and well and learn that your former patient and her two children have moved back in with her parents and Jason is no longer in the picture.

You don’t have to have been doing pediatrics very long to have learned that a “family” that includes an infant and a young adult male who is probably not the father is an environment in which the infant’s health and well-being is at significant risk. It is a situation in which child abuse even to the point of infanticide should be waving a red flag in your face.

Infanticide occurs in many animal species including our own. As abhorrent we may find the act, it occurs often enough to be, if not normal, at least not unexpected in certain circumstances. Theories abound as to what advantage the act of infanticide might convey to the success of a species. However, little if anything is known about any possible mechanisms that would allow it to occur.

Recently, a professor of molecular and cellular biology at Harvard University discovered a specific set of neurons in the mouse brain that controls aggressive behavior toward infants (Biological triggers for infant abuse, by Juan Siliezar, The Harvard Gazette, Sept 27, 2021). This same set of neurons also appears to trigger avoidance and neglect behaviors as well.

Research in other animal species has found that these antiparental behaviors occur in both virgins and sexually mature males who are strangers to the group. Interestingly, the behaviors switch off once individuals have their own offspring or have had the opportunity to familiarize themselves with infants. Not surprisingly, other studies have found that in some species environmental stress such as food shortage or threats of predation have triggered females to attack or ignore their offspring.

I think it is safe to assume a similar collection of neurons controlling aggressive behavior also exists in humans. One can imagine some well-read defense attorney dredging up this study and claiming that because his client had not yet fathered a child of his own that it was his nervous system’s normal response that made him toss his girlfriend’s baby against the wall.

The lead author of the study intends to study this collection of neurons in more depth to discover more about the process. It is conceivable that with more information her initial findings may help in the development of treatment and specific prevention strategies. Until that happens, we must rely on our intuition and keep our antennae tuned and alert for high-risk scenarios like the one I described at the opening of this letter.

We are left with leaning heavily on our community social work networks to keep close tabs on these high-risk families, offering both financial and emotional support. Parenting classes may be helpful, but some of this research leads me to suspect that immersing these young parents-to-be in hands-on child care situations might provide the best protection we can offer.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

The first patient of the afternoon is a 4-month-old in for his health maintenance visit. You’ve known his 20-year-old mother since she was a toddler. This infant has a 2-year-old sister. Also in the exam room is a young man you don’t recognize whom the mother introduces as Jason, her new boyfriend. He never makes eye contact and despite your best efforts you can’t get him to engage.

At the child’s next visit you are relieved to see the 6-month-old is alive and well and learn that your former patient and her two children have moved back in with her parents and Jason is no longer in the picture.

You don’t have to have been doing pediatrics very long to have learned that a “family” that includes an infant and a young adult male who is probably not the father is an environment in which the infant’s health and well-being is at significant risk. It is a situation in which child abuse even to the point of infanticide should be waving a red flag in your face.

Infanticide occurs in many animal species including our own. As abhorrent we may find the act, it occurs often enough to be, if not normal, at least not unexpected in certain circumstances. Theories abound as to what advantage the act of infanticide might convey to the success of a species. However, little if anything is known about any possible mechanisms that would allow it to occur.

Recently, a professor of molecular and cellular biology at Harvard University discovered a specific set of neurons in the mouse brain that controls aggressive behavior toward infants (Biological triggers for infant abuse, by Juan Siliezar, The Harvard Gazette, Sept 27, 2021). This same set of neurons also appears to trigger avoidance and neglect behaviors as well.

Research in other animal species has found that these antiparental behaviors occur in both virgins and sexually mature males who are strangers to the group. Interestingly, the behaviors switch off once individuals have their own offspring or have had the opportunity to familiarize themselves with infants. Not surprisingly, other studies have found that in some species environmental stress such as food shortage or threats of predation have triggered females to attack or ignore their offspring.

I think it is safe to assume a similar collection of neurons controlling aggressive behavior also exists in humans. One can imagine some well-read defense attorney dredging up this study and claiming that because his client had not yet fathered a child of his own that it was his nervous system’s normal response that made him toss his girlfriend’s baby against the wall.

The lead author of the study intends to study this collection of neurons in more depth to discover more about the process. It is conceivable that with more information her initial findings may help in the development of treatment and specific prevention strategies. Until that happens, we must rely on our intuition and keep our antennae tuned and alert for high-risk scenarios like the one I described at the opening of this letter.

We are left with leaning heavily on our community social work networks to keep close tabs on these high-risk families, offering both financial and emotional support. Parenting classes may be helpful, but some of this research leads me to suspect that immersing these young parents-to-be in hands-on child care situations might provide the best protection we can offer.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].